2013 rrc4

ISSN: 1583-2996
President: Ioan M. Coman

President elect: Gabriel Tatu-Chioiu
Former president: Dan E. Deleanu
Vice-presidents: Drago Vinereanu
Radu Ciudin
Secretary: Bogdan A. Popescu
Treasurer: Ovidiu Chioncel
Members: Eduard Apetrei
erban Blnescu
Mircea Cintez
Marian Croitoru
Dan Gai
Daniel Gherasim
Ioana Ghiorghiu
Carmen Ginghin
Adriana Ilieiu
Daniel Lighezan
Florin Mitu
Clin Pop
Radu Vtescu
Drago Vinereanu
THE ROMANIAN SOCIETY OF CARDIOLOGY BOARD
EDITORIAL STAFF
Editor-in chief
Eduard Apetrei
Deputy Editor
Carmen Ginghin
Editors
Radu Cplneanu
Cezar Macarie
Founding editor
Costin Carp
Associate editors
Mihaela Rugin
Ruxandra Jurcu
Bogdan A. Popescu
Costel Matei
EDITORIAL BOARD
erban Blnescu - Bucureti
Luigi Paolo Badano - Italia
Ion V. Bruckner - Bucureti
Alexandru Cmpeanu - Bucureti
Gheorghe Cerin - Italia
Mircea Cintez - Bucureti
Radu Ciudin - Bucureti
D. V. Cokkinos - Grecia
Ioan Mircea Coman - Bucureti
G. Andrei Dan - Bucureti
Dan Deleanu - Bucureti
Genevieve Derumeaux - Frana
Doina Dimulescu - Bucureti
Maria Dorobanu - Bucureti
tefan Iosif Drgulescu -
Timioara
Guy Fontaine - Frana
Alan Fraser - Anglia
Ctlina Arsenescu-Georgescu -
Iai
Mihai Gheorghiade - USA
Leonida Gherasim - Bucureti
Aurel Grosu - Chiinu,
R. Moldova
Assen R. Goudev - Bulgaria
Anthony Heagerty - Marea
Britanie
Alexandru Ioan - Bucureti
Dan Dominic Ionescu -
Craiova
Gabriel Kamensky - Slovacia
Andre Keren - Israel
Michel Komajda, Frana
Giuseppe Mancia - Italia
Ioan Maniiu - Sibiu
Athanasios Manolis - Grecia
Martin S. Martin - SUA
Gerald A. Maurer - Austria
erban Mihileanu - Frana
Tiberiu Nanea, Bucureti
Gian Luigi Nicolosi - Italia
Peter Nilsson - Suedia
Nour Olinic - Cluj-Napoca
Fausto Pinto - Portugalia
Clin Pop - Baia Mare
Josep Redon - Spania
Willem J. Remme - Olanda
Michal Tendera - Polonia
Ion intoiu - Bucureti
Panagiotis Vardas - Grecia
Margus Viigimaa - Estonia
Drago Vinereanu - Bucureti
Marius Vintil - Bucureti
Dumitru Zdrenghea -
Cluj-Napoca
Issue editor
Bogdan A. Popescu
Secretary
Mihaela Slgean
TECHNICAL INFORMATION
Responsibility for the contents of the published articles falls entirely on the authors. Opinions, ideas, results of studies published in the Ro-
manian Journal of Cardiology are those of the authors and do not refect the position and politics of the Romanian Society of Cardiology. No
part of this publication can be reproduced, registered, transmitted under any form or means (electronic, mechanic, photocopied, recorded)
without the previous written permission of the editor.
All rights reserved to the Romanian Society of Cardiology
Contact: Societatea Romn de Cardiologie
Str. Avrig nr. 63, Sector 2, Bucureti
Tel./Fax: +40.21.250 01 00, +40.21.250 50 86, +40.21.250 50 87;
E-mail: of ce@cardioportal.ro
"Carol Davila" University of Medicine and Pharmacy, Bucharest,
"CC Iliescu" Department of Cardiology - A short history 315
E. Apetrei
Investigation of patients adherence to Angiotensin II Receptor
Blockers drug treatment for hypertensive patients in primary medical
care (I ADHERE) 323
D. Gherasim, M. Iurciuc, C. Voiculet, A. Giuca, V. Petrescu, F. Maghiar, A. Gherghina, A.Tase, C. Ginghin
Te study of vascular reactivity on the ascending aorta afer aortic
coarctation corrective surgery 332
I. A. Ghiorghiu, M. E. Iancu, M. erban, C. Ginghin
Almanac 2013: acute coronary syndromes 339
P. Meier, A. J. Lansky, A. Baumbach
Almanac 2013: heart failure 348
A. L. Clark
Almanac 2013: cardiac arrhythmias and pacing an editorial overview
of selected research that has driven recent advances in clinical cardiology 354
R. Liew
Fostering Difusion of Scientifc Contents of National Societies
Cardiovascular Journals: Te New ESC Search Engine 367
F. Alfonso, L. Gonalves, F. Pinto, A. Timmis, H. Hector, G. Ambrosio, P. Vardas
Surprising awakening of a sleeping heart 376
A. Scridon, R. C. erban, A. Elkahlout, M. Opri , D. Dobreanu
Endovascular treatment in a case of transplant renal artery stenosis 381
A. Buc a, C. Buc a, C. Matei, C. Chirion, M. Croitoru
Echocardiography - Complex cardiac malformation in a young pregnant
woman 384
O. N stase, R. Enache, B. A. Popescu, C. Ginghin , R. Jurcu
Vascular Doppler - Ultrasound imaging of a bilateral carotid body
paraganglioma 387
R. O. Darabont
Updates in Cardiology 390
National and international cardiology agenda 2014 396
Reviewers 2013 399
Instructions for authors 400
Vol. 23, No. 4, 2013
ORIGINAL ARTICLES
REVIEWS
CASE PRESENTATIONS
IMAGES IN CARDIOLOGY
UPDATES IN CARDIOLOGY
AGENDA
REVIEWERS
INSTRUCTIONS FOR
AUTHORS
THE WORLD OF
CARDIOLOGY
Universitatea de Medicin i Farmacie "Carol Davila Bucureti,
Clinica de Cardiologie "CC Iliescu" Scurt istoric 315
E. Apetrei
Evaluarea complianei la tratamentul cu blocani ai receptorilor de
angiotensin II la pacienii hipertensivi n centrele de medicin
primar (I ADHERE) 323
D. Gherasim, M. Iurciuc, C. Voiculet, A. Giuca, V. Petrescu, F. Maghiar, A. Gherghina, A.Tase, C. Ginghin
Studiul reactivitii vasculare la nivelul aortei ascendente post corecia
coarctaiei de aort 332
I. A. Ghiorghiu, M. E. Iancu, M. erban, C. Ginghin
Almanac 2013: sindroame coronariene acute 339
P. Meier, A. J. Lansky, A. Baumbach
Almanac 2013: insufciena cardiac 348
A. L. Clark
Almanac 2013: aritmii cardiace i cardiostimularea 354
R. Liew
Fostering Difusion of Scientifc Contents of National Societies
Cardiovascular Journals: Te New ESC Search Engine 367
F. Alfonso, L. Gonalves, F. Pinto, A. Timmis, H. Hector, G. Ambrosio, P. Vardas
Trezirea surprinztoare a unei inimi adormite 376
A. Scridon, R. C. erban, A. Elkahlout, M. Opri , D. Dobreanu
Tratamentul endovascular n cazul stenozelor de arter renal
posttransplant 381
A. Buc a, C. Buc a, C. Matei, C. Chirion, M. Croitoru
Ecocardiografe - Malformaie cardiac complex la o gravid tnr 384
O. N stase, R. Enache, B. A. Popescu, C. Ginghin , R. Jurcu
Doppler vascular - Imagini ecografce n tumora glomic carotidian
bilateral 387
R. O. Darabont
Actualiti n cardiologie 390
Calendarul manifestrilor tiinifce cardiologice 2013 396
Refereni 2013 399
Instruciuni pentru autori 400
PREZENTRI DE CAZ
REFERATE
ARTICOLE ORIGINALE
AGENDA
REFERENI
INSTRUCIUNI PENTRU
AUTORI
IMAGINI N CARDIOLOGIE
Vol. XXII, Nr. 1, 2007
Vol. 23, No. 4, 2013
ACTUALITI N
CARDIOLOGIE
DIN LUMEA
CARDIOLOGIEI
Romanian Journal of Cardiology | Vol. 23, No. 4, 2013
815
THE WORLD OF CARDIOLOGY
"CC Iliescu" Department of Cardiology - A short history
Eduard Apetrei
C
ardiology was defned as a separate medical speci-
alty in our country faster than in other countries,
in the 1960. A crucial role in this was played by the
founder of Romanian cardiology, Prof. Dr. CC Iliescu.
Te frst cardiology clinic in Romania was founded
in 1959 and it was named Te ASCAR Cardiology Cli-
nic.
Te clinic was part of the Faculty for the Training and
Specialization of Doctors and Pharmacists (FPSMF),
within the Medicine and Pharmacy Institute - Bucha-
rest. Te faculty for Training and Specialization was
founded in 1958 by turning the Institute for Training
and Specialization for Doctors and Pharmacists (de-
pendant on the Ministry of Health) - founded in 1952 -
into a Faculty. Te newly founded faculty was naturally
included in the Institute for Medicine and Pharmacy,
Bucharest.
Te one who strived and fnally succeeded in foun-
ding this school was Prof. Dr. Constantin C. Iliescu.
He was then named head of the clinic, occupying this
position until 1962, when he retired. Te cardiology
clinic was named ASCAR Cardiology Clinic because
it was within the ASCAR Hospital (CARdiac Assistan-
ce ASistenta CARdiacilor). Te ASCAR institution
was founded in 1945. A centre for the care of cardiac
patients was a novelty not only for Romania, but for
the entire world. It was the frst institution of its kind in
Europe, and the second in the entire world.
Besides the care for cardiovascular diseases it was
also necessary to train doctors and specialists in car-
diology for the entire country. Tus, the ASCAR cli-
nic had a determining role in contouring cardiology in
Romania. In the frst year the clinic held specialization
courses in cardiology for internal medicine specialists
and later, for pediatricians. Te duration of the courses
was 9 months and 120 doctors graduated until 1965. In
this way a cardiology network was created all around
the country.
It is important to note that during this period, Prof.
Iliescu used to visit newly inaugurated cardiology de-
partments in order to see how the medical activity is
being managed and to give an impulse through his pre-
sence. I can remember such a visit from 1963, from the
Onesti hospital, where Dr. Florin Anghelescu, a fresh
graduate of the specialization courses, was working.
I resident in internal medicine there during that year
and this visit determined me to choose cardiology as
a specialization. During the same period, 30 day cour-
ses for the initiation and study of the electrocardiogram
were organized. During the 1965/1966 academic year
the speciality in for perfecting various areas of cardio-
logy was launched. Tus, a few areas such as congenital
diseases, valvulopathies, ischemic heart diseases cardi-
omyopathy and later, phonocardiography were intro-
duced in this program. Tese 1-2 month courses goal
was to refresh the existing know ledge and train specia-
lists in the diferent subspecialties of cardiology. 3 week
electrocardiography courses were also held in other
centres in the country, such as Sibiu, Slatina, Craiova.
Starting with 1965, internal medicine interns (nowa-
days residents) were allowed to participate to these co-
urses, in order to become cardiologists. I am one of the
graduates of this frst course organized for interns. Te
9 month specialization courses respected the following
schedule: in the beginning a few introductory noti-
ons about the anatomy of the heart and large vessels,
cardiovascular physiopathology, cardiovascular semi-
ology and clinical examination. Tis was followed by
a period dedicated to learning electrocardiogram (5
hours/day - without clinical activity) - 3 weeks; pho-
nocardiography - 2 weeks; radiology - 10 days. Ten,
clinical activity was resumed and theory classes were
held daily at 13:00 hours, except for Wednesdays, whi-
ch were reserved to the presentation of a clinical case.
Te clinical cases presentation was done by a resident,
respecting the exam methodology: 20 minutes to exa-
minate the patients, 20 minutes to structure the case, 20
minutes for the presentation (this methodology is now
well known and still applied). Te second participant/
resident (afore named) made diferent comments and
remarks in completion to the presentation, followed
by questions and discussions with the colleagues in
the class. Te theoretical courses were held by the pro-
fessor and lecturers. Some courses were assigned to
the little ones. Professor Iliescu, or one of the lectu-
rers (L. Kleinerman and E. Viciu), took part in these
courses held by the assistants. Te course was followed
by a private discussion behind closed doors with 2
Eduard Apetrei
Romanian Journal of Cardiology
Vol. 23, No. 4, 2013
816
partners. Te course was analyzed regarding the way it
was structured, correctness of the disseminated infor-
mation, whether or not it was updated information and
how the course should be. Tese lessons cannot be for-
gotten and it would be important if they were repeated
nowadays. During the training period the participants
worked for 5 months in the patient wards (ASCAR had
3 sections, with a total of 120 beds) and 2 month in
the ambulatory (this had 8 consultation rooms). Every
Saturday, in the ambulatory, Prof. Iliescu commented
on some particular cases and paid great attention to
how the charts were completed. Every case had a chart
and congenital heart diseases and cardiac failure had
special charts. Tis summed up to 110.000 charts. Te
doctors were encouraged to go with the patients to the
electrocardiography laboratories (there were 3 such la-
boratories, 2 in the ambulatory and one for the patient
wards), to the phonocardiography laboratories, radio-
logy or heart catheterism. Regular testing was perfor-
med throughout the training period (especially ECG,
Phono and later echocardiography) in order to evalua-
te the participants. Tests were also administered at the
beginning of the training period, in order to assess the
level of those entering the course. Tis made possible a
comparison between the level of knowledge at the be-
ginning and at the end of the training course. At the
end of the course a committee appointed by the Health
Ministry was appointed and the graduates who passed
the examination (they usually passed) became specia-
list in cardiology. Some of the trainees were also invol-
ved in the clinics scientifc activity, which was mostly
concentrated on congenital heart diseases - clinical and
hemodynamic studies, valvulopathies, arrhythmias
(one of Prof. Iliescus greatest passions), myocardial
infarction, arterial hypertension (I have forgotten to
mention that in the ambulatory there was a special ca-
binet for patients with arterial hypertension). During
this period the members of the clinic published a series
of monographies: Infectious Endocarditis, cardiovas-
cular functional exploration, Cardiomyopathies, Mitral
Stenosis, Chronic Pulmonary Heart Disease, Arterial
Hypertension etc (see Annex). Te cardiology clinic
and the whole of ASCAR rapidly became the centre
of national education in cardiology, the place of origin
for the cardiology network, the place where specialists
were trained and methodology books were elaborated
for training purposes. During this time, respecting the
model of the hospital ASCAR several subsidiaries were
inaugurated in Timisoara, Craiova and many cardio-
logy departments were founded all around the coun-
try. Te ASCAR cardiology clinic was visited by many
personalities from the world of cardiology, such as Paul
Dudley White - the patriarch of american cardiology,
De Bakey, L.Turner, Eliot Corday, O.Abbott, R.Bing,
A.De Maria, etc. PD White wrote in the ASCAR Hono-
ur Book: ASCAR is performing a pioneering activity in
the vital feld of preventing heart diseases. In 1960 the
cardiology clinic had the following confguration: Prof.
Dr. CC Iliescu head of clinic, Associate professor Dr.
Lazar Kleinerman, Associate Professor Emil Viciu, Dr.
Matei Iliescu - lecturer, Dr. Radian Petrescu - assistant,
Dr. Georgeta Domocos - assistant, Dr. Constantin Ba-
ciu - assistant, Dr. Paul Iacobini - assistant. Prof. Dr. CC
Iliescu was also chairman of the newly founded Cardi-
ology subsection of subsection of the Internal Medici-
ne Section of the Medical Sciences Societies in Roma-
nia. In 1962 the subsection becomes an independent
section, named the Cardiology Society - chairman, Dr.
Petronela Vintila - secretary. Starting with 1961, annu-
al cardiology conferences are being organized. A great
role in the organization of these conferences was pla-
yed by the Cardiology Clinic and ASCAR Hospital. In
the future, most of the presidents and secretaries of the
Cardiology Societies will come from this clinic.
Between 1962 and 1966 the clinic was ran by Associ-
ate Professor L. Kleinerman and by Associate Professor
Emil Viciu (they ran the clinic alternatively). During
this period the didactic activity aimed at training doc-
tors continued, new laboratories were created (like the
hemodynamics laboratory - led by Associate Prof. Klei-
nerman) and the electrocardiography laboratories were
expanded - Dr. I Loebel wrote the frst romanian book
on electrocardiography, Dr. P Dumitru, Dr. Olga Du-
Figure 1. Prof. CC Iliescu and some of his collaborators (1974)
From lef to right: Dr. C Parlog, Dr. R. Enescu, Dr. Hortensia Cionca, Dr.
Anca Iliescu, Dr. P Andreescu, Dr. Maria Moman, Dr. Lucia Serafm, Dr.
Munteanu.
Vol. 23, No. 4, 2013
81I
Eduard Apetrei
mitrescu. Associate Prof. Viciu continued the studies
on clinical and experimental electrocardiography, fna-
lized with the editing, in collaboration with Dr. B Fotia-
de and Dr. R Zamfrescu of a comprehensive treaty on
electrocardiography. In 1964, the frst coronary intensi-
ve care unit in Romania was inaugurated (by Prof. C. C.
Iliescu), the frst electrical conversions were performed
and the frst Romanian built pacemaker (built by Eng.
Goldis, Dr. D. Draghici si Dr. Gh. Bunghez - 1965) was
implanted.
In 1966 Prof. A Moga was named head of the clinic.
He came from Cluj to occupy the function of health
minister (1966 - 1969). During this period the clinic
had the following componence: Aurel Moga - pro-
fessor, head of clinic; Lazar Kleinerman - associate pro-
fessor; Emil Viciu associate professor, Matei Iliescu
- lecturer, Ion Orha - lecturer, Radian Petrescu - assis-
tant professor, Georgeta Domocos - assistant professor,
Constantin Baciu - assistant professor, Paul Iacobini-
assistant professor, Oprisan Alexandrina - preparator,
Eduard Apetrei-preparator.
Dr. Ion Orha - lecturer and Dr. Niculae Stancioiu -
Prof. Mogas PhD student, were also transferred from
Cluj. Dr. N Stancioiu was later appointed assistant pro-
fessor and in 1974 he became lecturer. Dr. N. Stancioiu
activated in the clinic until 1981 when he was trans-
ferred to Cluj as Assistant Professor, initially in a Me-
dical clinic and soon afer, in the newly founded Car-
diology clinic, due to personal eforts (the Cardiology
clinic from Cluj was the second Cardiology clinic in the
country). In the frst few months afer he became head
of the clinic, Prof. A Moga presented the idea of turning
the Cardiology clinic into an Internal Medicine Clinic,
specialized in Cardiology. He was probably considering
the model of the Cluj clinic where he activated until he
came to Bucharest and where (and why hide the fact)
he was worshiped by his collaborators, being one of the
most well-known medical personalities in Romania.
Despite all the infuence he had at that time, as Health
minister and then, President of the Romanian Medical
Sciences Academy (until 1974) he did not succeed in
fulflling his plan. Prof. Iliescu was still active, he came
to the clinic every day and still had enough infuence
to oppose such a project, unwanted by the entire staf.
Cardiology was rapidly evolving towards indepen-
dence from Internal Medicine.
In this period, due to the eforts of Dr. I Orha exerci-
se testing for coronary patients was started and the re-
habilitation program was initiated. In the beginning the
efort tests were done at the Center for Sports Medicine
and then, in our clinic. Afer the death of Prof. Moga
in 1973, Assistant Prof. L. Kleinerman became once
more the head of the clinic. Te ASCAR Cardiology
clinic functioned since its foundation in the ASCAR
building in Cosmonauts Square (nowadays Lahovary
Square). Due to the eforts of some personalities from
the romanian medical world with political inclinations
the Cardiology clinic and the entire ASCAR hospital
were relocated in 1976 in the Fundeni Hospital. It is im-
portant to note that next to the ASCAR building there
was a space destinated (and all plans were made and
approved) for a new building, in order to expand the
ambulatory and include a Cardiovascular surgery cli-
nic. Te plans were app roved and the construction was
ready to begin. During this period the head of the clinic
was Associate Professor L. Kleinerman, a good doctor
and teacher and Dr. C. Parlog was manager of the AS-
CAR hospital. Tey accepted the relocation of the clinic
without great opposition, but during those times not
much could be done if a decision was made at the top.
Te clinics relocation also had positive aspects, but we
are not going to discuss this matter in this article.
At the time of its relocation to Fundeni Hospital the
clinic had the following confguration: Assoc. Prof. L
Kleinerman - head of clinic, Dr. Matei Iliescu - leturer,
Figure 2. Prof. C.C. Iliescu
Te painting is now in the Meeting Room of the University of Medicine,
Bucharest.
Eduard Apetrei
Vol. 23, No. 4, 2013
818
Dr. Ion Orha - lecturer, Dr.Radian Petrescu - lecturer,
Dr. Georgeta Domocos - assistant, Dr. Petre Dumitru -
assistant, Dr. Alexandrina Oprisan - assistant, Dr. Edu-
ard Apetrei - assistant, Dr.Niculae Stancioiu - assistant.
Along with the relocation the clinic received a new
name: Te Fundeni Cardiology Clinic. Te clinic con-
tinued its didactic activities within the Faculty for the
Training and Specialization of Doctors and Pharma-
cists (FPSMF). Assoc. Prof. L. Kleinerman retires in
1976, the same year when the clinic was relocated to
Fundeni and Dr. Matei Iliescu - lecturer is appointed
to run the clinic. During those years academic promo-
tions were frozen, so many doctors were blocked in
the same positions for many years. Tis was also the
case of Dr. Matei Iliescu. He competently ran the clinic
for almost 2 years, in a slightly hostile atmosphere (2
other lecturers were working in the clinic), but the ge-
neral activity of the clinic did not sufer. Didactic acti-
vities went on without any impediments. In 1978 Prof.
Costin Carp was put in charge of the clinic. He came
from the Caritas hospital. Although Prof. Costin Carp
was not a collaborator of CC Iliescu and he had never
worked in ASCAR, he managed to run the clinic in the
ASCAR spirit, ensuring without a doubt, its continuity.
During this period the clinic continued to consolidate
its position as a training and specialization center. Most
specialists working in Cardiology or cardiology subf-
elds, such as echocardiography, phonocardiography or
invasive cardiology were trained in the Fundeni clinic.
Prof. C. Carp was a very good clinician and he mana-
ged in a relatively short period of time to impose pro-
fessionalism, sobriety and responsibility in the medical
act. Te medical act could not sufer from any political
intervention. Ten, as today, politicians (the party)
wanted to control everything (it was also a very dif -
cult period), but this desire was not fulflled regarding
the medical feld. Medical research was continued in
the felds of epidemiology and rehabilitation (depart-
ment led by Dr. I. Orha - this department took part in
international programs such as the OMS program for
myocardial infarction or the MONICA program), ar-
rhythmias (one of Prof. Carps favorite preoccupations),
valvulopathies, cardiomyopathies, congenital diseases,
arterial hypertension, etc. New diagnostic methods
are introduced - initiated and developed by members
of the clinic (an example is echocardiography - Dr. E.
Apetrei). Te frst echocardiography cours in Romania
are organized starting with 1982 and then, our clinic
organizes National Symposiums on echocardiography,
beginning with 1984.
Our involvement in the international cardiology sce-
ne is increasingly higher because of the eforts and sti-
mulation of Prof. Dr. C. Carp.
In Romania, the Fundeni Cardiology Clinic plays an
important role in the reorganization of the Romanian
Society of Cardiology and in 1990 Prof. Carp is elected
president of the Society of Cardiology and Dr. E. Ape-
trei is elected secretary.
Afer Prof. Carps retirement in 1992 his position as
head of the Fundeni Cardiology Clinic becomes vacant
and is occupied afer public competition by Conf. Dr.
E. Apetrei.
In 1993 the academic staf of the Cardiology Clinic
consisted of: Prof. Dr. Eduard Apetrei head of clinic,
Prof Dr. Costin Carp - consulting professor, Assoc.
Prof. Dr. Radian Petrescu, Dr.Petre Dumitru - assistant
professor, Dr. Ioana Stoian - assistant professor, R Ciu-
din- assistant professor, I Coman - assistant professor.
Assoc. Prof. Dr. I. Orha moved in 1991 at the Flo-
reasca Emergency Hospital as a Professor, head of the
Medical Clinic. Te didactic activities concerning trai-
ning and specialization continued without interrup-
tion. Courses for resident doctors respect a program
recommended by the European Union of Medical Spe-
cialties (UEMS) - Section Cardiology (Prof. E. Apetrei
was in the board of this European forum between 1994
and 2011 and Prof. Dr. Carmen Ginghina is a member
of this board since 2011). New courses were introduced
- transesophageal echocardiography - 2002, vascular
Doppler ultrasound - 2003, invasive cardiology - 2002.
A totasl of 6-8 specialization courses are organized each
year. A course of echocardiography was organized in
Milan for 1 month in 1994 and 1995, with the support
of Dr. Faletra. 24 cardiologists from the clinic and from
other cardiology clinics in the country participated, to
this training period. In 1993 the university courses for
medical students were introduced for the frst time in
the clinic. At frst 3 series of students were taught here
each year, but later only 2series were accepted (the cli-
nic was overcrowded with residents and specialists).
Shorter specialization courses were introduced (7 days
and even 2 days, in week-ends). Attendance for these
courses is still high. Te clinic was visited by numerous
personalities coming here for conferences, courses, de-
bates, new methods of treatment. Some of the members
of the clinic (Dr. R. Ciudin, Dr. I. Coman, Dr. A Mereu-
ta, Dr. C. Matei) went abroad for specialization courses,
facilitating the introduction of new diagnostic methods
and treatment. Research continues, books and cardio-
logy treaties are written (see Annex 1). Te Cardiology
Clinic becomes in 2001 a CENTER FOR EXCELLEN-
Vol. 23, No. 4, 2013
819
Eduard Apetrei
Adrian Mereuta Assistant Professor, Dr. Monica Rota-
reasa Assistant Professor, Dr. Matei Costel preparator.
In 2002 a second Professors position is opened and
Assoc. Prof. C. Macarie occupies it afer an open com-
petition. In 2003 a third position of Professor is opened
and is occupied by Assoc. Prof. Dr. Carmen Ginghi-
na, afer a public competition. In October 2003 Prof.
Dr. E. Apetrei retires and Prof. Dr. C. Macarie becomes
the head of Fundeni cardiology Clinic. Afer 1 year,
elections are organized in order to choose the heads
of clinics for the entire University of Medicine and
Pharmacy and Prof. Dr. Carmen Ginghina is elected as
head of the Fundeni cardiology clinic and is currently
running in this position. During this time the clinic
continued to be involved in numerous activities. Te
clinics activity with 4
th
year students was continued, as
well as courses for residents in the 3
rd
year. Residents
from the CC Iliescu Cardiology clinic and from Car-
diology clinics all around the country participate at
these courses. Training course for trans-thoracic and
trans-esophageal ultrasound, vascular Doppler and in-
terventional cardiology are organized twice a year. A
total of 14 courses are organized in the clinic each year,
excepting the courses for students and residents. Prof.
Dr. Carmen Ginghina is very active from a professional
and scientifc point of view and she stimulated her col-
leagues and and residents to take an active interest in
research and publishing quality papers. Te residents,
under the direct guidance of the head of the the clinic
help publish a yearly volume entitled Cardiac patients
Imagistics, continuing with a modern approach the se-
ries Commented and Illustrated cases in Cardiology.
Several books and monographies were published (see
Annex). Te level of scientifc activity is very high, an
important role in this aspect being held by the Cardiac
Ultrasound Laboratory, with a European accreditation.
Over 200 ISI credited publications were published in
the last 10 years. Some of the members of the clinic are
part of the boards of the national scientifc organizati-
ons such as the Romanian Society of Cardiology and
the Societys work Groups (see the volume Te Roma-
nian Society of Cardiology - short history - no. 56, An-
nex I) and in the European Society of Cardiology and
Echocardiography. Te current leadership of the clinic
has also kept in mind the future, supporting and pro-
moting young doctors. Today, the members of the CC
Iliescu Cardiology clinic are: Prof. Dr. Carmen Ginghi-
na - head of clinic, Prof. Dr. C Macarie, Assoc. Prof. Dr.
Ion Coman, Assoc. Prof. Bogdan Popescu, Dr. R. Ciu-
din lecturer, Dr. Ioana Stoian lecturer, Adrian Mereuta
lecturer, Dr. Ruxandra Jurcut lecturer, Dr. Andrei Carp
CE, research center in Cardiology. Tis title was gran-
ted by the Ministry of Health. It is the frst clinic in the
country meeting the criteria for such a title (afer a ri-
gorous evaluation of research and didactic activities).
Te clinic runs research programs with partners from
abroad. Due to our active involvement in international
cardiology, the members of this clinic were elected to
international comities, received honorary distinctions
and rewards and were visiting professors in univer-
sities from the US (North Carolina) and England. In
1995 Prof. Apetrei is elected to the Medical Sciences
Academy and since 2006 he is vice-president of this
Academy and Dr. H C of the University of Medicine
from Iasi (2007). In 2009 Prof. Dr. Carmen Ginghina is
elected to the Medical Sciences Academy, fellow of the
American College of cardiology and Prof. Dr. C. Maca-
rie is also elected to the Medical Sciences Academy and
fellow of the American College of Cardiology. Manny
members of the clinic were presidents of the Romani-
an Society of Cardiology: Prof. E. Apetrei (1994-1998),
Prof. C. Macarie (1998-2002), Prof. Carmen Ginghina
(2002-2005). Assoc. Prof. Dr. I. Coman is the elected
president for 2011-2014 (see the book Short History of
the Romanian Society of Cardiology).
In 1996 Dr. C. Macarie become an Asssociate Pro-
fessor position and in 1997 second position of Associa-
te Professor is occupied by Dr. Carmen Ginghina. Both
positions were occupied afer a open competition. In
1997 the clinic had the following confguration: Prof.
Dr. Eduard Apetrei - head of clinic, Assoc. Prof. Dr.
Cezar Macarie, Assoc. Prof. Carmen Ginghina, Dr. Ion
Coman lecturer, Dr. R. Ciudin lecturer, Dr. Ioana Sto-
ian lecturer, Dr. Andrei Carp Assistant Professor, Dr.
Figure 3. 1991 - in the frst line, from right to lef: Prof. C. Carp, Prof. Patri-
cia Come (Harvard, SUA), Conf. E. Apetrei and a group of students. In the
back line: Dr. Carmen Ginghina.
Eduard Apetrei
Vol. 23, No. 4, 2013
820
12. Cardiopatiile ischemice coronariene. Clinica ,dia-
gnostic si tratament. L. Kleinerman (red.), Horten-
sia Cionca, M.Ghita, M. Efraim Editura Medicala
Bucuresti. 1966; 248 pagini
13. Cardiopatiile ischemice coronariene. Clinica, diag-
nostic si tratament. Editia a II a Kleinerman (red.),
Hortensia Cionca, M. Ghita, M. Efraim L. Editura
Medicala Bucuresti. 1973; 381 pagini
14. Miocardiopatiile cornice. Vintila Mihailescu, Lilia-
na Hagi Paraschiv-Dosius, Petronela Vintila.Editu-
ra Medicala Bucuresti 1973
15. Actualitati in diagnosticul si tratamentul bolilor de
inima. V. Cunescu, D. Draghici Editura Medicala
Bucuresti 1974; 228 pagini
16. Actualitati in diagnosticul si tratamentul bolilor de
inima. V. Cunescu, D. Draghici Editura Medicala
17. Mecanofonocardiografa. Eduard Apetrei, E. Viciu
Editura Medicala, Bucuresti, 1977; 164 pagini
18. Terapia intensive in cardiologie. 2 editii Sub redactia
Petronela Vintila Editura Medicala Bucuresti 1979,
1981; 336 pagini
19. Arteriopatii periferice. E. Viciu, Eduard Apetrei.
20. Cardiopatia ischemica. L. Kleinerman (red.), Edu-
ard Apetrei, Hortensia Cionca, Liliana Dosius, Mar-
cel Efraim. Editura Medicala, Bucuresti, 1981; 431
pagini
21. Bolile cardiovasculare. Calauza practicianului. Vin-
tila V. Mihailescu Editura Medicala 1981; 237 pa-
gini
22. Insufcienta cardiaca. Mecanisme. Evaluare. Trata-
ment. Cezar Macarie, Dan-Dominic Ionescu. Edi-
tura Militara. Bucuresti 1982; 310 pagini
23. Indreptar de diagnostic si tratament al bolilor cardi-
ovasculare Cositin Carp (sub red.) Editura Medica-
la Bucuresti 1985; 456 pagini
24. Ecocardiografe. E. Apetrei. ISBN: 973-39 005-1,
25. Actualitati in cardiologie. L. Gherasim. Eduard
Apetrei. ISBN: 973-9397-007. Editura Amaltea Bu-
curesti, 1998; 592 pagini
26. Clasifcari si unele ghiduri practice in bolile cardio-
vasculare. Eduard Apetrei, lleana Arsenescu. ISBN:
973-9394-19-1, Bucurestii - Editura Info-Medica.
Bucuresti, 1999; 180 pagini
27. Boli congenitale, Carmen Ginghina, Eduard Ape-
trei, C. Macarie. ISBN: 973-96286-9-4, Editura
Amaltea, Bucuresti, 2001
28. Clasifcari si unele ghiduri practice in bolile cardio-
vasculare, Eduard Apetrei, lleana Arsenescu. Editia
- Assistant Professor, Monica Rotareasa - Assistant Pro-
fessor, Matei Costel - Assistant Professor, Dr. Cosmin
Calin - Assistant Professor, Carmen Beladan - Assis-
tant Professor, Ioana Savu Ionita - Assistant Professor,
Mona Musteata - Assistant Professor. Tere also a re-
sea r ch center with permanent employees - Dr. Andre-
ea Calin, Dr. Monica Rosca. Prof. Dr. E. Apetrei is still
responsible of doctoral students. Trainings abroad and
in Romania of young cardiologists made possible the
consolidation of a powerful clinic in terms of research,
especially in echocardiography, but not limited to this
feld. Together with the other Cardiology clinics in the
country, the CC Iliescu clinic goes to great lengths to
train students, residents in cardiology and specialists in
the diferent branches of cardiology. Medical research
is also one of the strong points of the CC Iliescu Car-
diology clinic.
ANNEX
Book, treaties, monographies
Written by the members of the Cardiology Clinic
1. De vorba cu studentii. Notiuni de fziologie, fziopa-
tologie, semiologie, patologie si terapeutica cardia ca
editia I-a editii). CC Iliescu Editura Cartea de aur.
2. De vorba cu studentii. Notiuni de fziologie, patolo-
gie si terapeutica cardia ca editia II-a. CC Iliescu
Editura Cartea de aur. Bucuresti 1943; 489 pagini
3. Endocardita lenta. CC Iliescu. Sub red Editura de
stat pentru literatura stiintifca. Bucuresti 1953
4. Electrocardiografa. I. Lobel Editura Medicala Bu-
curesti 1956; 575 pagini
5. Sindromul de ischemie periferica. C.C. Iliescu sub
red Editura Medicala Bucuresti 1956; 457 pagini
6. Stenoza Mitrala. Clinica fziopatologica. Vintila V.
Mihailescu, Elena Malitchi Editura Medicala. Bu-
curesti 1956; 162 pagini
7. Cordul pulmonar cronic. Vintila V. Mihailescu Edi-
tura Medicala Bucuresti 1958; 164 pagini
8. Sindroamele coronariene. C.C. Iliescu, Laurian Ro-
man Editura Medicala Bucuresti 1960; 223 pagini
9. Probleme de patologie cardiovasculara. L. Kleiner-
man; F M. Ghita; Olga Dumitrescu, Sabina Leca
Mi nisterul Sanatatii, ASCAR. Bucuresti 1964); 460
pagini
10. Indreptar de diagnostic si tratament in bolile cardi-
ovasculare. C.C. Iliescu, Elena Malitchi, Dinu Dra-
ghici C.C. Editura Medicala, Bucuresti 1966.
11. Hipertensiunea arteriala. Vintila V. Mihailescu Edi-
tura Medicla Bucuresti 1966; 245 pagini
Vol. 23, No. 4, 2013
821
Eduard Apetrei
44. Cardiologie, cazuri comentate si Ilustrate, vol.IV.
Eduard Apetrei, Carmen Ginghina. Editura Pro
Bucuresti, 2004; 275 pagini.
45. Insufcienta cardiaca - de la studii clinice la ghiduri.
Cezar Macarie, Ovidiu Chioncel. Editura Medicala,
Bucuresti; 2005
46. Esenialul n ecocardiografe. Ginghin C, Popescu
BA, Jurcu R. Editura Medical Antaeus, Bucureti,
2005
47. Hipertensiunea pulmonara in practica de cardio-
logie. Carmen Ginghina. Ed. Academiei Romane,
2006
48. Velocity Vector Imaging technology. A new tool for
myocardial function evaluation - technique and cli-
nical cases. Ruxandra Jurcut. Editura Medicala An-
taeus, Bucuresti, 2007. ISBN: 978-973-88434-6-2
49. Insufcienta cardiaca acuta-abordare practica. Ce-
zar Macarie Ovidiu Chioncel. Editura ErcPress,
Bucuresti, 2008
50. Imagistica la bolnavii cardiaci. Din pagina cartii
la ecranul computerului. Vol III. Sub redactia Car-
men Ginghina. Editura Medicala. Bucuresti, 2008.
ISBN: 978-973-39-0681-0; 95 pagini.
51. Insufcienta cardiaca acuta - Ghid pentru pacienti.
Cezar Macarie, Ovidiu Chioncel. Editura Medicala.
Bucuresti, 2008
52. Enciclopedia Medicala Romaneasca De la origini
pana in prezent. Ursea N., (sub redactia), Angheles-
cu N, Antonescu D. Apetrei E. Editura Universitara
Carol Davila, Bucurest. ISBN: 978-973-708-331-9.
2009; 5 volume
53. Imagistica la bolnavii cardiaci. Din pagina cartii la
ecranul computerului. Vol V. Sub redactia Carmen
Ginghina. Editura Medicala. Bucuresti, 2009
54. Mic tratat de Cardiologie. Carmen Ginghina. Ed.
Academiei Romane, 2010. ISBN: 978-973-27-
1931-2; 894 pagini
la ecranul computerului. Vol V. Sub redactia Car-
ISBN: 978-973-39-0699-5; 124 pagini
56. Societatea Romana de Cardiologie. Scurta istorie. E.
Apetrei. Media Med Publicis. Bucuresti, 2011.
57. Ecocardiografa Doppler. (Tratat nsoit de DVD) .
Popescu BA, Ginghin C. Editura Medical, Bucu-
reti, 2011
ecranul computerului. Vol V. Sub redactia Carmen
Ginghina. Editura Medicala. Bucuresti, 2011. ISBN:
978-973-39-0717-6; 129 pagini. ISBN: 978-973-39-
0717-6; 129 pagini
a II-a, Bucuresti. ISBN: 973-9394-63-9 Editura In-
fo-Medica, Bucuresti, 2001; 210 pagini
29. Cordul diabetic. Carmen Ginghina, Gheorghe S. Ba-
canu, Mirela Marinescu, Dinu Dragomir. Editura
Info Medica Bucuresti 2001. ISBN: 973-9394-57-4
144 pagini
30. Insufcienta cardiaca. Cezar Macarie, Eduard Ape-
trei, Carmen Ginghina. Editura Amaltea, Bucures-
ti, 2001; 211 pagini
31. 111 teste grila comentate pentru rezidentiat. Speci-
alitati medicale si chirurgicale. Ruxandra Ciobanu,
Ilinca Gussi, Ciprian Jurcut, Silviu Stanciu. Ed. Me-
dicala, Bucuresti, 2001
32. Electrocardiografa. Eduard Apetrei, loana Stoian.
Editura Info-Medica, Bucuresti, 2002; 327 pg. Car-
te premiata de Academia Romana (2003)
33. Ecocardiografe in imagini. Eduard Apetrei, B.A.
Popescu CD si volum, Ed. INSEI Print, Bucuresti,
2002
34. Cardiologie (Cazuri comentate si ilustrate), vol.
I. Eduard Apetrei, Carmen Ginghina, C. Macarie.
Editura Info-Medica, Bucuresti, 2002; 167 pagini
35. Indreptar de diagnostic si tratament in Infarctul mi-
ocardic acut. Carmen Ginghina, Mirela Marinescu,
Dinu Dragomir. Ed. Info medica 2002. ISBN: 973-
9394-73-6; 363 pagini
36. Pericardiologia de la diagnostic la tratament. Car-
men Ginghina, Dinu Dragomir, Mirela Marinescu.
Ed. InfoMedica 2002. ISBN: 973-9393-88-4; 283
pagini
37. Tratat de cardiologie. Volumul I. Costin Carp. Edi-
tura Medicala Nationala Bucuresti. 2002. ISBN
9783-8194-65-2; 1161 pagini
38. Tratat de cardiologie. Volumul II. Costin Carp.
Editura Medicala Nationala Bucuresti 2003. ISBN
973-8194-82-2, 1174 pagini
39. Cardiologie (Cazuri comentate si ilustrate), vol. II.
Eduard Apetrei. Editura Stiintifca si Tehnica, Bu-
curesti, 2003; 187 pagini
40. Diagnosticul modern al disectiei de aorta. Ioan Co-
man. Ed. BIC All, 2003. ISBN: 973-571-471-x; 95
pagini
41. Aritmiile cardiace la copil si adultul tanar. Radu
Ciudin, Carmen Ginghina, Ioana Ghiorghiu. Edi-
tura Info medica Bucuresti 2003; ISBN: 973-7912-
16-0; 419 pagini
42. Cardiologie (Cazuri comentate si ilustrate), vol. III.
Eduard Apetrei. Editura Info-Medica, Bucuresti,
2004; 253 pagini
43. Evaluarea ultrasonografca vasculara. Compact
disc. Eduard Apetrei, lleana Arsenescu. Editura IN-
SEI, Bucuresti; 2004
Eduard Apetrei
Vol. 23, No. 4, 2013
822
62. Esenialul n ecocardiografe. Editia a doua, revi-
zuita si adaugita. Ginghin C, Popescu BA, Jurcu
R. Editura Medical Antaeus, Bucureti, 2013; 383
pagini
ecranul computerului. Vol VII. Sub redactia Car-
ISBN: 978-973-39-0749-7; 124 pagini
Tis list does not include chapters written in other
books and monographies. Te list of ISI articles will be
published later.
ISBN: 978-973-39-07 17-6; 129 pagini
ISBN: 978-973-39-0735-0; 142 pagini
61. Cateterismul cardiac pentru clinician. Dan Delea-
nu, Carmen Ginghina. Editura Medicala Antaeus,
Bucuresti, 2012. ISBN: 978-6068470-01-6; 394 pa-
gini. Carte premiata de Academia de Stiinte Medi-
cale (2013)
828
ORIGINAL ARTICLE
Investigation of patients adherence to Angiotensin II Receptor
Blockers drug treatment for hypertensive patients in primary
medical care (I ADHERE)
Daniel Gherasim
1
, Mircea Iurciuc
2
, Cristina Voiculet
3
, Alina Giuca
4
, Virgil Petrescu
5
, Florin Maghiar
6
,
Alexandra Gherghina
7
, Adrian Tase
8
, Carmen Ginghina
1,9
Contact address:
Daniel Gherasim, Clinic of Cardiology, Emergency Institute for Cardio-
vascular Diseases, 258 Fundeni Avenue, 2nd District, Bucharest, Zip code
022328. E-mail: gherasimdanro@yahoo.com
1
Prof.Dr.C.C.Iliescu Emergency Institute for Cardiovascular Diseases,
Bucharest
2
Victor Babes University of Medicine Timisoara
3
Clinical Emergency Hospital Constanta
4
Emergency County Clinical Hospital, Cardiology Center, Craiova
5
Colentina Universitary Hospital, Bucharest
6
University of Medicine Oradea
7
Clinical Emergency Hospital Brasov
8
University of Pitesti, Faculty of Nursing, Emergency County Hospital
Pitesti
9
Carol Davila University of Medicine and Pharmacy, Cardiology Depart-
ment, Bucharest
Abstract: Te aim of the study was to evaluate the compliance with angiotensin II receptor blockers (ARBs) treatment in
hypertensive patients persistent on this medication for at least 6 month and to identify the factors asociated with it. Material
and method Open-label, non-randomized, national, retrospective disease registry, that collected data from 12,538 hyper-
tensive patients in treatment with an ARB for the last 6 months, from 621 study centers of ambulatory clinical practice, ma-
inly cardiological or primary medical care all over the country. Te study evaluated the level of ARBs treatment compliance,
assessed by applying the adapted Medication Adherence Self-Report Inventory questionnaire (MASRI) part I and estimated
the medication possesion rate (MPR). Te MASRI is a questionnaire flled in by patients addresseing the frequency and correct
timing of medication intake. Results Te patients, 45.4% male and 54.3% female, with a mean age of 60.9 years old, were
treated with combination therapy in >80% of cases and the drugs most frequently associated to sartans were diuretics (~57%).
Te mainly associated risk factors were hypercholesterolemia (73,7%) and obesity (59,6%) and the most part of the patients are
coming from urban environment (73,7%). MPR was above 80% value, considered to be the inferior level of adherence to anti-
hypertensive therapy, in 96.6% of the patients on ARB monotherapy and in 96.5% of those with ARB in combinations. None of
the evaluated demographic or medical factors infuenced signifcantly the compliance with ARB treatment. In the subgroup of
patients with ARBs in combinations, urban environment determined signifcantly higher compliance than rural environment
[relative risk (RR) = 1.093, confdence interval (CI) = 1.018 1.173]. Conclusion Our study showed a very good compliance
with ARB treatment in hypertensive patients persistent on ARB treatment for 6 month, in ambulatory practice; MPR> 80% has
been registered in 96.5% of the patients with ARBs treatment, in monotherapy or in combinations.
Keywords: Hypertension, compliance, angiotensin II receptor blockers
Abstract: Obiectivele studiului Evaluarea complianei la tratamentul cu blocani ai receptorilor de angiotensin II (BRA)
la pacienii hipertensivi cu o persisten de cel puin 6 luni pe aceast terapie i, de asemenea, identifcarea factorilor asociai.
Material i metod Registru de boal naional, retrospectiv, nerandomizat n care au fost colectate date de la 12,538 de paci-
eni hipertensivi care urmau tratament cu un BRA de 6 luni, din 621 de centre de consultaie de specialitate n ambulatoriu, n
principal de cardiologie sau de medicin primar, din toat ara. Studiul a evaluat compliana la tratamentul cu BRA, determi-
nat prin aplicarea unui chestionar adaptat de auto-raportare a aderenei la medicaie (MASRI partea I) i estimarea ratei de
posesie a medicaiei (medication possesion rate, MPR). MASRI este un chestionar completat de ctre pacieni care se refer la
frecvena i la corectitudinea administrrii medicaiei. Rezultate Pacienii, 45,4% brbai i 54,3% femei, cu o vrst medie
de 60,9 ani, primeau terapie combinat n mai mult de 80% din cazuri, iar medicamentele cel mai frecvent asociate sartanilor
au fost diureticele (~57%). Principalii factori de risc asociai au fost hipercolesterolemia (73,7%) i obezitatea (59,6%) iar ma-
joritatea pacienilor provenea din mediul urban (73,7%). MPR a fost peste valoarea de 80%, considerat a f limita inferioar
pentru aderena la terapia antihipertensiv, pentru 96,6% dintre pacienii cu BRA n monoterapie i pentru 96,5% pentru cei
cu BRA n terapie combinat. Niciunul dintre factorii demografci sau medicali evaluai nu a infuenat semnifcativ compli-
ana la tratamentul cu BRA. n subgrupul de pacieni cu BRA n cadrul unei terapii combinate, proveniena din mediul urban
Daniel Gherasim et al.
Investigation of patients adherence to Angiotensin II Receptor Blockers
Vol. 23, No. 4, 2013
821
efective in reducing the risk of total cardiovascular
eve nts and specifc events such as stroke, myocardial
in farction and heart failure
10,11
. Despite the availability
of safe and efective antihypertensive agents, hyperten-
sion and its concomitant risk factors remain uncontro-
lled in most patients
12
.
One of the major factor of poor control of hyperten-
sion is nonadherence of the patients to medical treat-
ment. Studies have shown that around 50% of indivi-
duals discontinue antihypertensive medications within
6 to 12 months of their initiation
13
.
Overall, one third of patients used antihypertensive
therapy continuously during the 10 years of follow-up
and one third permanently discontinued therapy
14
.
Nonadherence to medical treatments is an increasin-
gly recognized cause of adverse outcomes and increa-
sed health care costs. Drug compliance is defned as the
extent to which patients follow medical instructions.
Tis term was replaced by adherence which includes
also the responsibility of the caregivers. Adherence has
been defned as the active, voluntary, and collaborati-
ve involvement of the patient in a mutually acceptable
course of behaviour to produce a therapeutic result
15
.
Medication persistence refers to the act of continuing
the treatment for the prescribed duration. It may be de-
fned as the duration of time from initiation to discon-
tinuation of therapy
16
.
Tere are many diferent methods of assessing adhe-
rence to medications. Osterberg et al
17
categorized the-
se methods as either direct or indirect. Direct methods
include directly observed therapy, measurement of the
level of medicine or metabolite or the biological mar-
ker in blood sample. Despite the fact that these direct
me thods are considered to be more robust than indi-
rect methods, they are not practical for routine clinical
use. Indirect methods of adherence assessment include
pa tient questionnaires, self-reports, pill counts, rate of
pre scription reflls, assessment of the patients clinical
response, electronic medication monitors, measure-
ment of physiological markers and patient diaries. Te
most commonly used indirect methods include patient
self-report, pill counts and pharmacy reflls
18
.
Te objective of our study is to evaluate the compli-
ance with ARBs medication of hypertensive patients
INTRODUCTION
Te World health statistics Geneva 2012 report, re-
leased on 16 May 2012, puts the spotlight on the gro-
wing problem of the noncommunicable diseases bur-
den. One in three adults worldwide, according to the
re port, has raised blood pressure a condition that
ca uses around half of all deaths from stroke and heart
di sease
1
. Epidemiological data for Romania are coming
from SEPHAR studies which took place in 2005 and
2011, being initiated with the purpose of estimating
the hypertensions prevalence, treatment and control in
adult population for developing prevention strategies
in hypertension management. In SEPHAR II study hy-
per tension was recorded in 40.4% of cases (798 subjects
from 1975 responders)
2
. Other studies conducted on
selected populations showed a variable HT prevalen-
ce
3,4
.
Te raised levels of blood pressure represent the con-
sequence of a complex interplay of environmental and
genetic factors. Te primary goal of treatment of the
patient with high blood pressure is to achieve the maxi-
mum reduction in the long-term total risk of cardiovas-
cular morbidity and mortality. Tis requires treatment
of all identifed risk factors and the appropriate ma-
nagement of associated clinical conditions, as well as
treatment of the raised blood pressure per se
5
. Te use
of antihypertensive drug therapy has been shown to re-
duce the risk of stroke and coronary heart disease by an
estimated 30-40% and 20%, respectively, in long-term
randomized controlled trials (RCTs)
6
.
Te underlying haemodynamic disorder in the ma-
jority of cases is a rise in peripheral vascular resistance,
so the vasodilatator efect was an important feature for
the strategies developed over time for the treatment of
hypertension
7
. Among the antihypertensive clases, a
special interest is given to the renin-angiotensin system
(RAS) blockers, related to the role of this sistem in the
pathophysiology of hypertension and organ injury
8
.
Angiotensin-converting enzyme inhibitors (ACEIs)
and angiotensin II receptor blockers (ARBs) are widely
used in patients with hypertension, heart failure and
diabetes as well as in other clinical conditions sharing
an increased cardiovascular risk
9
. Individual trials and
meta-analyses showed that both ACEIs and ARBs are
a determinat o complian semnifcativ mai mare comparativ cu cel rural [risc relativ (RR) = 1.093, interval de ncredere (II)
= 1.018 1.173]. Concluzie Studiul nostru a artat o complian foarte bun la tratamentul cu BRA la pacienii hipertensivi
persisteni pe aceast terapie timp de 6 luni, tratai in ambulator; indicele de posesie a medicaiei MPR> 80% a fost nregistrat
la 96,5% dintre pacienii n tratament cu BRA, n monoterapie sau n terapie combinat.
Cuvinte cheie: hipertensiune arterial, complian, blocani de receptor de angiotensin II
Vol. 23, No. 4, 2013
825
already treated for at least 6 month with these drugs.
Another goal is to raise the awereness on the impor-
tance of treatment adherence in chronic patients and to
identify the factors asociated with it.
MATERIALS AND METHODS
I ADHERE is an open-label, non-randomized, natio-
nal (Romania), multicentric, retrospective disease re-
gistry, sponsored by Sanof, that collected data from
12,538 pa tients, in 621 study centers of ambulatory cli-
nical pra ctice, cardiological or primary medical care all
over the country. All patients signed an informed con-
sent for participation and were informed on the study
objec tives.
Te purpose of I ADHERE was to establish the achie-
vement of the prescribed regimen of ARBs (amount of
medication actually taken), based on a questionnaire
flled by patients, in a population persistent on ARBs
treatment for at least 6 months. Te study evaluated the
level of ARBs treatment compliance, assessed by ap-
plying the adapted Medication Adherence Self-Report
Inventory questionnaire (MASRI) part I and estimated
the medication possesion rate (MPR). Te MASRI is a
12-item questionnaire originally developed for use in
Human Immunodefciency Virus (HIV) populations.
Te MASRI addresses the frequency and correct ti m-
ing of medication intake. Its reliability and specifcity
were high using a set of measures such as test-retest co-
n sistency and internal consistency
19
. In our study we
used only the frst adapted section of the questionnaire
re lated to the amount of medication actually taken. (Fi-
gure 1).
Patients included in this study were adults hyperten-
sive patients (according to ESC/ESH guidelines, 2007),
age >18 years, men and women, in treatment with an
ARBs (in either monotherapy or in combination) for
the last 6 months, who accepted to sign the informed
consent. Exclusion criteria were: patients refusal to
sign the informed consent; patients refusal or incapa-
city to complete the MASRI questionnaire; ARB treat-
ment for other indication than hypertension.
Primary objectives were the assessment of adheren-
ce on ARB treatment in hypertensive patients who are
persistent on ARBs treatment for at least 6 months, eva-
luating the level of compliance, in ambulatory practice,
by the use of a MASRI (Medication Adherence Self-
Report Inventory) type auto-evaluation questionnaire
and the estimation of MPR (medication possession
rate) considering that MPR 0.80 is the inferior margin
of adherence to antihypertensive therapy (according
with Siegel D et al.).
We looked also (as secondary objectives) for: fnd-
ing factors associated with adherence (MPR >0.80) to
ARBs given in monotherapy or given in combinations
in a population persistent on this medication for 6 mo-
nths; assessment of standard diagnostic procedures for
hypertension in the ambulatory clinical practice and for
assessment of standard therapy for hypertension in the
ambulatory clinical practice. We collected demogra-
phic data of the patients, and also we noted personal
history of cardiovascular disease and organ damages,
risk factors / comorbidities, standard of diagnostic pro-
cedures for hypertension (type of laboratory exams /
other exploratory investigations recommended) and
pre viously antihypertensive treatment prescribed.
Statistical methods
Te main statistical analysis was descriptive: for the
con tinuous data the mean, median and mode values,
Figure 1. Adapted MASRI questionnaire used in I ADHERE study.
MASRI questionnaire (adapted) frst section:
Did you miss the daily dose of ARB (INN..) yesterday?
Yes No Dont know
Did you miss the daily dose of ARB (INN) the day before yesterday?
Yes No Dont know
Did you miss the daily dose of ARB (INN) 3 days ago?
Yes No Dont know
How many daily doses of ARBs have you missed in the 2 weeks before that?
0 1 2 or more* Dont know
* please approximate the number of missed doses_ _ _ _
When was the last time you missed a daily dose of ARB?
Today Yesterday Earlier this week Last week Less than a month ago More than a month ago Never
Dont know
Please estimate the proportion of total daily dosage of ARBs (INN..) you have taken during the last month?
.% from the total amount of doses
EX: 0% (means you have taken no medication); 50% (means you have taken half your medication);
100% (means you have taken every single dose of medication).
Vol. 23, No. 4, 2013
826
standard deviations and 95% two-tailed confdence
interval (CI) have been calculated and for categorical
data the proportions and 95% CI (two-sample Z-test).
Presuming that 50% of patients have a good treatment
adherence, for estimating the adherence rate with a
precision of 1.5% and assuming a level of alpha error
of 0.05 and a power of 90%, we needed to include at
least 4538 patients. If we also assume an attrition rate
of 25%, then 5672 patients should have been included.
Tis sample size has been amended one month afer
the frst patient was enrolled. For establishing positi-
ve correlation between some factors and drug therapy
adherence, the Odds Ratio (OR) had to be calculated,
the cut-of value for positive correlation being fxed
at 1.5. For the secondary exploratory end-points, the
sample-size estimation had to take into consideration
the frequency of the factors involved as independent
variables in the regression model. For some certain va-
luable factors, these frequencies estimated are low (no
more than 2%). Assuming a cut-of value for OR of 1.5
and also a p-value of 0.05 and a power of 90%, the sam-
ple-size had to be at least of 10,555 patients.
RESULTS
Characteristics of the patients
Data were collected for 12,538 patients out of whom
only 12,483 were eligible according to the inclusion
criteria and were included in the study analysis. 55 pa-
tients have been excluded from the analysis because
they didnt meet the inclusion criteria 13 were not
hypertensive patients (according to ESC/ESH guideli-
nes, 2007), and 42 were not treated with ARBs during
the 6 months preceding the study visit. Te 12,483 eli-
gible patients were diagnosed with arterial hypertensi-
on (according to ESC/ESH guidelines, 2007) and were
treated with sartans 6 months before the enrollment.
45.4% were male and 54.3% were female (for 0.4% data
were missing) and the mean age was 60.9 years. 24.8%
of them were living in rural areas, while 73.7% were co-
ming from urban environment, for 1.5% this data were
missing.
Te mean duration of the arterial hypertension was
6.3 years. Te mean values of blood pressure (BP) regi-
s tered at the study visit were: 153.6 mmHg (sistolic BP),
89.3 mmHg (diastolic BP), (with a maximul value of
280 mmHg for sistolic BP and 160 mmHg for diastolic
BP).
Associated risk factors: 34.4% of the patients were
smokers (for 0.8% data were missing); 73.7% had hyper-
cholesterolemia (HC) (for 2.9% cholesterol was not de-
termined and for 0.6% data were missing), and 52.8%
hypertriglyceridemia (HT) (for 3.7% triglycerides were
not determined and for 0.9% data were missing). 59.6%
of the patients had abdominal obesity, defned as: > 102
cm for male and > 88 cm for female patients (for 1.6%
was not determined, for 1% data were missing); 32.6%
had diabetes mellitus (DM) type 1 or type 2 (for 2.7%
unknown, for 0.9% data were missing) (Figure 2).
Many of the patients had target organ damage: 49.8%
had lef ventricular hypertrophy (ECG diagnosed) with
4.1% not determined (for 1.1% data were missing); 38%
had retinopathy (for 1.7% data were missing). Prote-
inuria (>300 mg/24 hours) was determined for 15.4%
of the patients and it was present in 8.9% of the cases.
Mean value of serum creatinine was 1.07 mg/dl; 8.8%
of patients had chronic renal failure (for 2.4% data were
missing).
Another important aspect was the high frequence
of cardiovascular diseases in hypertensive patients in-
Figure 2. Percentages (%) of patients with associated risk factors: HC hypercholesterolemia; HT hypertriglyceridemia; DM diabetes mellitus.
Vol. 23, No. 4, 2013
82I
cluded in this study. 40.3% of the patients had history
of coronary disease (angina pectoris and/or myocardi-
al infarction), for 0.8% data were missing; 16.8% had
history of cerebrovascular disease (stroke/transient is-
chemic attack), for 1.7 data were missing; 13.9% had
peripheral artery disease (for 9.3% was undetermined
and for 0.9% data were missing), 11% of the patients
had atrial fbrillation with 1.9% not determined and
25% had heart failure (10.3% with reduced ejection
fraction and 14.7% with preserved ejection fraction),
for 1.5% data were missing (Figure 3). Te data regar-
ding previous history of cardiovascular diseases were
based upon the patients medical documents.
Blood pressure measurement was based on specifc
recommendations of the European Society of Hyper-
tension 6; the methods used for BP monitoring in pa-
tients with hypertension are represented in Figure 4,
with the measure of blood presure in the clinic of ce
beeing performed at almost half of the patients.
Te laboratory investigations and the search for sub-
clinical organ damage are presented in Table 1.
The antihypertensive treatment
In the 6 months before the enrollment in the study the
recommended antihypertensive treatment was ARBs in
12,483 patients (100% as per inclusion criteria), ACE-
Is in 1271 patients (10.2%), calcium channel blockers
(CCB) in 3484 patients (27.9%), beta-blockers in 7063
patients (56.6%) and diuretics in 7178 patients (57.5%).
ARBs were recommended as monotherapy in 15.9%
and in combinations in 84.1% of the patients. At the
study visit the treatment recommended was represen-
ted by the following: ARBs in 12,467 patients (99.9%),
ACEIs in 1201 patients (9.6%), CCB in 3537 patients
(28.3%), beta-blockers in 4690 patients (37.6%) and di-
uretics in 7164 patients (57.4%) of the patients.
As a profle, the enrolled patients were hypertensives
mainly comming from urban environment, had abdo-
minal obesity and dyslipidemia, many of them were on
combination therapy and the drugs most frequently
associated to sartans were diuretics.
Te compliance on ARBs treatment was evaluated in
patients treated with ARBs at least 6 months before the
enrollment by using an adapted MASRI (Medication
Adherence Self-Report Inventory) questionnaire secti-
on I (Table 2).
Medication Possession Rate (MPR) was evaluated in
relation with the answers given to the last questions of
the adapted questionnaire: What is the approximate
per centage of the total ARB daily doses that you have
been taking during the last month? T
a
b
l
e

1
.

A
B
I

A
n
k
l
e

B
r
a
c
h
i
a
l

I
n
d
e
x
,

F
B
G

F
a
s
t
i
n
g

B
l
o
o
d

G
l
u
c
o
s
e
,

T
C

T
o
t
a
l

C
h
o
l
e
s
t
e
r
o
l
,

H
D
L
-
C

H
D
L

C
h
o
l
e
s
t
e
r
o
l
,

L
D
L
-
C

-

L
D
L

C
h
o
l
e
s
t
e
r
o
l
,

T
G

T
r
i
g
l
y
c
e
r
i
d
e
m
i
a
.
E
K
G
E
c
h
o
c
a
r
d
i
o
g
r
a
p
h
y
O
p
t
i
c

f
u
n
-
d
u
s

e
x
a
m
C
h
e
s
t

r
a
d
i
-
o
g
r
a
p
h
y
A
B
I
F
B
G
T
C
H
D
L

C
L
D
L

C
T
G
A
l
b
u
m
i
n
u
r
i
a
S
e
r
u
m

c
r
e
a
t
i
n
i
n
e
N
a
t
r
e
m
i
a
K
a
l
e
m
i
a
Y
e
s

n

(
%
)
1
2
1
8
6

(
9
7
.
6
%
)
9
8
2
2

(
7
8
.
7
%
)
9
6
8
1
(
7
7
.
6
%
)
7
8
9
5
(
6
3
.
2
%
)
5
5
3
8

(
4
4
.
4
%
)
1
2
1
8
1

(
9
7
.
6
%
)
1
2
0
9
7

(
9
6
.
9
%
)
1
0
8
9
4

(
8
7
.
3
%
)
1
0
6
7
6

(
8
5
.
5
%
)
1
1
8
9
4

(
9
5
.
3
%
)
6
4
1
1

(
5
1
.
4
%
)
1
1
7
0
8

(
9
3
.
8
%
)
7
4
5
2

(
5
9
.
7
%
)
7
7
5
7

(
6
2
.
1
%
)
N
o

n

(
%
)
2
3
8

(
1
.
9
%
)
2
4
0
6

(
1
9
.
3
%
)
2
5
7
7
(
2
0
.
6
%
)
4
1
2
8

(
3
3
.
1
%
)
6
1
5
8

(
4
9
.
3
%
)
2
2
2

(
1
.
8
%
)
3
0
5

(
2
.
4
%
)
1
3
8
9

(
1
1
.
1
%
)
1
5
7
5

(
1
2
.
6
%
)
5
8
9

(
4
.
7
%
)
5
3
8
3

(
4
3
.
1
%
)
6
0
9

(
4
.
9
%
)
4
4
0
4

(
3
5
.
3
%
)
4
1
1
1

(
3
2
.
9
%
)
M
i
s
s
i
n
g

d
a
t
a

n

(
%
)
5
9

(
0
.
5
%
)
2
5
5

(
2
%
)
2
2
5

(
1
.
8
%
)
4
6
0

(
3
.
7
%
)
7
8
7

(
6
.
3
%
)
8
0

(
0
.
6
%
)
8
1

(
0
.
6
%
)
2
0
0

(
1
.
6
%
)
2
3
2

(
1
.
9
%
)
0
6
8
9

(
5
.
5
%
)
1
6
6

(
1
.
3
%
)
6
2
7

(
5
%
)
6
1
5

(
4
.
9
%
)
Vol. 23, No. 4, 2013
828
According to the answers to this question, in 1912
(96.6%) of the patients who have been recommended
ARB in monotherapy and in 10,136 (96.5%) of those
with ARB in combinations, it has been registered a
MPR above 80%, value considered the inferior level of
ad herence to anti HTN therapy.
DISCUSSION
Hypertension, defned as a systolic blood pressure
(SBP) 140 mmHg and/or a diastolic blood pressure
(DBP) 90 mmHg, is one of the most important pre-
ven table causes of premature death worldwide, contri-
buting to approximately half of all global cardiovascu-
lar disease
5
. In many countries, up to 30% of adults have
hy pertension; cardiovascular disease incidence doubles
for every 10 mmHg increase in DBP or every 20 mmHg
in crease in SBP
20
.
Blood pressure can be reduced either by lifestyle in-
terventions or by pharmacotherapy to obtain the best
outcome for the patient
21
.
Adequate measurement of BP is the most-important
requirement for the diagnosis and treatment of pati-
ents with suspected hypertension. Te use of metho-
dologies such as ambulatory and home BP monitoring
have become powerful tools for defning the real BP
of patients.
An important issue refers to following the physicians
therapy by the patient. Nonadherence to antihyperten-
sive treatment is a common problem in cardiovascular
pre vention and may infuence prognosis.
Data published in 2009 by Mazzaglia et al., on newly
diagnosed hypertensive patients initially free of cardio-
vascular diseases, obtained from 400 Italian primary
care physicians, showed that only high adherence to
Figure 3. Percentages (%) of patients with associated cardiovascular diseases: CAD coronary diseases;CVD - cerebrovascular diseases; PAD peripheral
artery diseases; AF - atrial fbrillation; HF heart failure.
Figure 4. Percentages (%) of patients with BP determined by the following methods: missing data-MD; not determined-ND; self-determination-SD; self-
determination +consulting roomSD+CR; self-determination +consulting room+24h monitoring-SD+CR+M; self-determination+24h monitoring- SD+M;
consulting room- CR; consulting room+24h monitoring- CR+M; 24h monitoring- M.
Vol. 23, No. 4, 2013
829
treatment (proportion of days covered, 80%), signi-
fcantly decreased risk of acute cardiovascular events
22
.
Adherence to prescription, investigated based on a qu-
estionnaire in a female population aged 35-65 years in
Sweden, revealed that age, scheduled check-up, percei-
ved importance of medication, concerns about medi-
cation safety and taking medication for a respiratory
or a cardiovascular disease were signifcantly related to
adherence. Adherence ranged from 15-98% being the
lowest among young women who regarded their me-
dication as unimportant and who had no scheduled
check-up and the highest among elderly women who
regarded their medication as important and who had
a scheduled check-up
23
. Adherence is better when the
pa tient accepts the severity of his/her illness, trusts
the therapist and believes in the efectiveness of the
re commended therapeutic measures. Non-adherence
is, among other factors, negatively associated with the
level of education. Another important factors infuen-
cing adherence include the afordability of the therapy
and the susceptibility to adverse efects of drugs in in-
dividual patients
15
.
ARBs adherence was previously studied evaluating
persistence in newly diagnosed hypertensive patients
who were initiated on irbesartan. Patients on irbesartan
had statistically signifcant higher persistence (of 60.8%
for monotherapy and of 76.8% for either monothera-
py or in combinations), followed by patients who were
initiated on all other ARBs with a persistence rate of
51.3% (74.9% either as monotherapy or in combinati-
on). Diuretics scored lowest with a persistence rate of
34.4% (65.5% either as monotherapy or in combinati-
ons) at 1 year
24
.
Did you miss your daily dose of ARB yesterday? ARB in combination (n=10504) ARB monotherapy (n=1979) Total
No 10,234 97.4% (a) 1930 97.5% (a) 97.4%
Yes 188 1.8% (a) 40 2.0% (a) 1.8%
I dont know 44 0.4% (a) 6 0.3% (a) 0.4%
No answer 38 0.4% 3 0.2% 0.3%

Did you miss to your daily dose of ARB the day before yesterday? ARB in combination ARB monotherapy Total
No 10,261 97.7% (a) 1939 98% (a) 97.7%
Yes 102 1.0% (a) 21 1.1% (a) 1.0%
I dont know 68 0.6% (a) 13 0.7% (a) 0.6%
No answer 73 0.7% 6 0.3% 0.6%

Did you miss your daily dose of ARB three days ago? ARB in combination ARB monotherapy Total
No 10,081 96% (a) 1883 95.1% (b) 95.8%
Yes 144 1.4% (a) 30 1.5% (a) 1.4%
I dont know 204 1.9% (a) 59 3.0% (b) 2.1%
No answer 75 0.7% 7 0.4% 0.7%

How many daily ARB doses have you missed during last 2 weeks? ARB in combination ARB monotherapy Total
No dose 9446 89.9% (a) 1781 90% (a) 89.9%
1 dose 616 5.9% (a) 96 4.9% (a) 5.7%
2 or more doses 114 1.1% (a) 30 1.5% (a) 1.2%
I dont know 225 2.1% (a) 62 3.1% (b) 2.3%
No answer 103 1% 10 0.5% 0.9%

When was the last time when you missed a daily dose of ARB ? ARB in combination ARB monotherapy Total
Today 215 2% (a) 28 1.4% (a) 1.9%
Yesterday 140 1.3% (a) 27 1.4% (a) 1.3%
Tis week 265 2.5% (a) 47 2.4% (a) 2.5%
Last week 617 5.9% (a) 92 4.6% (b) 5.7%
Less than 1 month ago 334 3.2% (a) 54 2.7% (a) 3.1%
More than 1 month ago 511 4.9% (a) 75 3.8% (b) 4.7%
Never 7496 71.4% (a) 1515 76.6% (b) 72.2%
I dont know 832 7.9% (a) 130 6.6% (b) 7.7%
No answer 94 0.9% 11 0.6% 0.8%
Table 2. Adapted MASRI type auto-evaluation questionnaire section I; (a) and (b) denotes a subset of categories which column proporti-
ons differ (a/b) or do not differ (a/a) signicantly from each other at the 0.05 level.
Vol. 23, No. 4, 2013
880
In a more recent study adressing persistence with
antihypertensive treatments for a period of 3 years,
Hasford et al. concluded that persistence difers mar-
kedly among the drug classes (p0.001) but even per-
sistence of the best drug class is not suf cient to provide
an adequate blood pressure control in the population.
Te largest decline in persistence occurs in the frst 3
mo nths of treatment. In our study the patients were al-
ready persistent on ARB treatment for 6 months, aspect
which may explain the high level of compliance.
In Hasford at al. study, persistence with the initi-
ally prescribed antihypertensive treatment was signif-
cantly diferent (p<0.001) and longest for patients who-
se initial prescription was for a free combination based
on ACEIs, followed patients initially receiving a fxed
combination, including ARBs and ARBs monotherapy.
Persistence was shortest with diuretics
25
.
Our study was addressing compliance and show high
compliance rate to ARBs in a population persistent on
this treatment for at least 6 months and also demons-
trate that urban environment, possibly in relation with
the level of education, and history of coronary disease
are positively corelated with adherence to ARBs. None
of the other factors including age, gender, hypertension
duration, history of cerebrovascular diseases, diabetes
mellitus or heart failure infuenced signifcantly the
adherence to ARB treatment in our study.
Te comparison between the answers to adapted
MASRI questionnaire given by the group of patients
with ARBs monotherapy vs. ARBs in combinations
has been performed using Chi-Square Test. Diferences
statistically signifcant between these subgroups have
been identifed for the patients who didnt miss (higher
% in combination group) and those who didnt know
if they missed (higher % in monotherapy group) the
daily dose of ARB 3 days before, for those who didnt
know how many daily ARB doses have missed during
last 2 weeks (higher % in monotherapy group), and for
those for whom the last day when they missed a daily
ARB dose was last week or more than a month before
(higher % in combination group), or never (higher %
in monotherapy group) or who didnt know the answer
(higher % in combination group).
Our study was based on a questionnaire flled in by
patients. An aspect that should be considered is that
phy sicians generally overestimate the level of adheren-
ce to therapy. Poor adherence should be suspected in
those whose blood pressure appears resistant to treat-
ment. Monitoring prescription reflls and pill-counting
are of value when nonadherence is suspected but can
be unreliable in patients who wish to avoid admitting
their failure to adhere to prescribed regimens
26
.
A limitation of this retrospective registry is that the
concept of adherence was separated in two parts per-
sistence being part of the inclusion criteria and compli-
ance part of the primary objective and the purpose of
the registry was to analyse the compliance with ARBs
treatment in an already persistent population. Ano-
ther limitation is that medication adherence appeared
to be higher when measured using self-reported que s-
tionnaires than when measured using electronic mo-
n itoring devices. Tis questionnaires are subject to
measurement bias such as social desirability, recall bias
and response bias
17
. Tere are mixed reports about the
accuracy of self reported adherence, compared with
the Medication Event Monitoring System monitored
adherence. MASRI questionnaire used in our study is
one of the most commonly used and have shown good
validity with Medication Event Monitoring System.
CONCLUSIONS
Our study showed a very good compliance with ARB
treatment in hypertensive patients persistent on ARB
treatment for 6 month, in ambulatory practice. Te le-
vel of Medication Possession Rate (MPR) above 80%,
has been registered in 96.5% of the patients with ARBs
treatment, even in monotherapy or in combinations.
Te following factors potentially associated with
compliance with ARB therapy have been evaluated for
those sub-groups of patients (ARB monotherapy and
in combinations): age (with 50 years as threshold), gen-
der, living environment (urban / rural), hypertension
duration, history of coronary or cerebrovascular disea-
ses, diabetes mellitus and heart failure. None of these
individual factors infuenced signifcantly the compli-
ance with ARB treatment.
In the subgroup of patients with ARBs monothera-
py the potential factors evaluated did not signifcantly
infuence patients compliance with the recommended
treatment. In the subgroup of patients with ARBs in
com binations urban environment determined signif-
cantly higher compliance than rural environment (RR
= 1.093, CI = 1.018-1.173).
Te logistic regression calculation (taking into acc-
ount all these potential factors simultaneously) iden-
tifed that patients living in urban area (p=0.017) and
those with history of coronary disease (p=0.025) have
a signifcantly better treatment compliance with ARB
treatment.
Vol. 23, No. 4, 2013
881
Tis research was funded by Sanof.
Confict of interests:
D.Gherasim: Speaker fees from Novartis and Les Labo-
ratoires Servier for case presentations
M. Iurciuc: None declared.
Cristina Voiculet: Speaker fees from Astra Zeneca for
case presentations
Alina Giuc: Speaker fees from Novartis, Les Labora-
toires Servier and Astra Zeneca LTD for case presen-
tation
V. Petrescu: Speaker fees from Astra Zeneca, Boehrin-
ger-Ingelheim and KRKA for case presentations
F. Maghiar: None declared.
Alexandra Gherghin: Speaker fees from Astra Zene-
ca, Les Laboratoires Servier and Berlin Chemie for case
presentations
A.Tase: Research fees from Les Laboratoires Servier,
Sanof and Novartis
Carmen Ginghin: None declared.
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ORIGINAL ARTICLE
The study of vascular reactivity in the ascending aorta after aortic
coarctation corrective surgery
Ioana Adriana Ghiorghiu, Mdlina Elena Iancu*, Marinela erban, Carmen Ginghin
Contact address:
Ioana Ghiorghiu, MD, Prof Dr C.C. Iliescu Institute of Emergency for
Cardiovascular Diseases, Sos Fundeni No. 258, 022322, Bucharest.
E-mail: ioanagh2001@yahoo.com
Prof. Dr. C.C. Iliescu Emergency Institute for Cardiovascular Diseases,
Bucharest
*
"Regina Maria" Private Healthcare Network
Abstract: Premises Te elastic structure of the aorta permits it to act as a conduct for the cardiovascular system
1
. Its elastic
properties moderate the lef ventricles performance and help regulate the coronary fow. Patients undergoing aortic coarctati-
on (AoCo) surgery sufer from a change in elasticity of the ascending aorta, favoring early atherosclerotic change
2
. Tis change
of the vascular elasticity can be assessed using the elasticity indices: aortic strain, distensibility and stifness. A change in the
aortic elasticity parameters consequently determines hemodynamic changes, as well as alterations to the dimensions of the
ascending aorta in patients who underwent AoCo corrective surgery. Materials and methods 23 patients who underwent
surgery for AoCo were included in the study, with a proper correction, supported by clinical and echocardiographic data. Te
control lot consisted of 20 healthy subjects. Te two lots had a similar structure regarding age and sex. Te vascular reactivity
was assessed by aortic strain, distensibility and stifness measured with TTE according to classic formulas. Results Patients
who underwent AoCo surgery presented modifcations of the vascular reactivity indexes of the ascending aorta, respectively
decreased distensibility capacity (p<0,001), reduced aortic strain (p<0,001), increased aortic stifness (p<0,001) compared to
the control lot. Te dimensions of the ascending aorta are statistically signifcant greater, compared to a control lot consisting
of healthy subjects. Conclusions Assessment of vascular reactivity in the ascending aorta in patients who achieved correc-
tion of Ao Co shows a more rigid ascending aorta with diminished elasticity and distensibility, compared to a control group
of healthy subjects. Te elastic properties were highlighted by the assessment of classical vascular reactivity indices (stifness,
aortic strain and distensibility). Te ascending aorta shows higher dimensions that are likely due to altered vascular reactivity
at this level.
Keywords: Aortic coarctation, vascular reactivity, aortic strain, distensibility, stifness, ascending aorta size
Rezumat: Premize Artera aort are o structur elastic care i confer o funcie de conduct la nivelul aparatului cardiovas-
cular
1
. Datorit proprietilor elastice contribuie la reglarea performanei VS i a fuxului coronarian. Pacienii cu coarctaie de
aort (Co Ao) operat prezint o modifcare a funciei elastice a aortei ascendente care predispune la modifcri aterosclerotice
precoce
2
. Aceast modifcare a elasticitii vasculare poate f evaluat cu indicii de elasticitate: strain aortic, distensibilitate,
rigiditate. Modifcarea parametrilor de elasticitate aortici determin modifcri ale hemodinamicii sanguine la acest nivel dar
i ale dimensiunilor aortei ascendente la pacienii post corecia Co Ao. Material i metod Au fost luai n studiu un numr
de 23 pacieni cu coarctaie de aort operai cu datele clinice i ecocardiografce ale unei corecii bine realizate i un lot con-
trol de 20 subieci sntoi, cele dou loturi avnd o structur asemntoare ca vrsta i sex. Rezultate Pacientii cu Co Ao
operat au avut indici de reactivitate vascular la nivelul aortei ascendente modifcai, respectiv distensibilitate aortic redus
(p<0,001), strain-ul aortic redus (p<0,001), rigiditate aortic crescut (p<0,001) comparativ cu lotul martor. Dimensiunile
aortei ascendente post corecia Co Ao sunt semnifcativ statistic mai mari comparativ cu un lot martor de subieci sntoi.
Concluzii Evaluarea reactivitii vasculare la nivelul aortei ascendente la pacienii la care s-a realizat corecia unei coarctaii
de aort evideniaz o aort ascendent mai rigid, cu elasticitate i distensibilitate diminuate. Aceste proprieti elastice au
fost evideniate prin determinarea indicilor clasici de reactivitate vascular (strain aortic, rigiditate i distensibilitate). Aorta
ascendent prezint dimensiuni crescute care sunt cu mare probabilitate determinate de reactivitatea vascular modifcat de
la acest nivel.
Cuvinte cheie: Coarctaie de aort, reactivitate vascular, strain aortic, distensibilitate, rigiditate, dimensiuni aort ascendent
Vol. 23, No. 4, 2013
Ioana Ghiorghiu et al.

Vascular reactivity after repair of coarctation of the aorta
INTRODUCTION
AoCo is a congenital heart disease benefting from sur-
gical correction since 1944
3
and interventional angio-
plasty since 1982
4
. In this time frame, a large number of
patients survived correction, representing a part of the
grown-up congenital heart disease population. Stu-
dies conducted on these patients have revealed a wide
spectrum of cardiovascular comorbidities, even in ca-
ses with a good anatomical result at the isthmic region.
Studies published in the literature have not succee-
ded in positively identifying the factors leading to post-
correction complications. If the age of correction and
a bicuspid aorta were documented by several studies
6
,
the data for the other parameters (correction method,
the remaining gradient in the itshmic region, the an-
kle-arm index) is contradictory. A new factor consi-
dered of great importance in the development of post-
correction complications is currently investigated - the
ascending aortas vascular reactivity.
Previous studies have shown an early vascular re-
modeling of the ascending aorta
6
and of the vascular
territory preceding the isthmic region. Vascular remo-
deling includes a modifed vascular reactivity and an
increase of intima media thickness at the level of the
great arteries
8,9
. Te studies have revealed a more sti-
fer aorta, with a decreased elasticity, leading to aortic
di latation as the patient ages
6,10
. Tis modifed vascular
reactivity has been identifed even in newly born babies
and infants and it is detectable before the intervention
and remains partially stable, even when the correction
is succesfull
11
. Te change in vascular reactivity seems
to be the determining cause of post corrective surgery
complications
8,9,11,12
. It has been proven that the chan-
ges of vascular reactivity leads to the increase of car-
diovascular risk and early atherosclerosis. Identifying
these problems at the level of the ascending aorta lead
to a new vision of AoCo, which is no longer regarded
as an isolated problem of the aortic isthm, but rather a
ge neralized problem of the precoarctation vascular te-
rri tory
14
.
MATERIALS AND METHODS
Te study of vascular reactivity in the ascending aorta
has been conducted on a lot consisting of 23 patients
treated for AoCo (21 patients with surgical correction
and 2 patients who underwent balloon angioplasty)
(Ta ble 1). Tey were admitted between 2001 and 2007
in Prof. Dr. C.C. Iliescu Emergency Institute for Car-
diovascular Diseases. Te study also had a control lot
of 20 healthy subjects with a similar distribution regar-
d ing sex and age to the ones present in the study lot.
Inclusion criteria:
An interventional or surgical correction for AoCo
Clinical criterion of a successful correction - nor-
mal pulse amplitude at the femoral arteries
Echocardiographic criterion for a good correcti-
on - velocity in the ascending aorta <3 m/s and
the absence of anterograde diastolic fux (diastolic
tail)
Normal blood pressure values with/without anti-
hypertensive drugs
Exclusion criteria:
Signifcant aortic insuf ciency (>III
rd
degree ac-
cor ding to the echocardiographic classifcation
Aortic stenosis
Aortic metallic prosthesis
Arterial hypertension (patients without treatment
or with uncontrolled values under treatment)
Signifcant stenosis (post-corrective gradient >30
mmHg)
Te patients were excluded because we considered
that they present lesions accompanied by signifcant
he modynamic alterations, infuencing the vascular ela-
sti city parameters calculated for the ascending aorta.
Analyzing the male/female ratio we notice a slight
pre ponderance of the male patients. Te BP values
were signifcantly higher in patients who underwent
co rrective surgery for AoCo, compared to healthy sub-
jects (p<0.05 but were within normal limits for all the
pa tients enrolled in the study).
Te parameters parameters for vascular reactivity
of the ascending aorta:
Te following classic aortic elasticity indices were
measured
15
:
Aortic strain = 100 (Ao S - Ao D)/Ao D
Aortic distensibility index = (2(Ao S Ao D)/Ao
D(PP)) (10
-6
cm
2
dyne
-1
)
Aortic stifness index (SI) = ln (SBP/DBP)/ ((Aos
AoD)/AoD)
Te dimensions of the aorta were: AoS - systolic di-
ameter, AoD - diastolic diameter (as measured in 2D
guided M mode, 3 cm above the aortic valve, Ao D
measured at the peak of the R wave, with a simultaneo-
us EKG, Ao S measured at the maximum anterior mo-
vement of the aortic wall) (Figure 1). Te values of the
blood pressure are represented by SBP = Sistolic blood
pressure, DBP = diastolic blood pressure - values mea-
sured at the right arm.
Tere are few papers in the literature studying the
elastic function of the aorta post AoCo corrective sur-
gery, using these parameters
7,11,14
.
Vol. 23, No. 4, 2013
Te echocardiographic examination was performed

with an Aloka Alpha 10 Prosound (Aloka Japan) devi-
ce. Te echocardiographic images were recorded si-
mu l taneously with an EKG signal, with at least 3 sinus
rhy thm cardiac cycles being recorded, using the medi-
an value of the measurements. Te patients were exa-
mined in lef lateral decubitus postion, with a 4MHz
trans ducer.
Te aortic elasticity parameters were determined by
using an echocardiography transducer set for M mode
examination guided by a 2D image (we considered it
necessary to place the M mode perpendicularly on the
long axis of the ascending aorta in order to measure the
maximal diameters)
14
. Te patient was placed in lef la-
teral decubitus and a long parasternal axis section was
performed. Te following parameters were measured
in M mode section, placed 3 cm above the aortic ring,
using the edge to edge technique:
AoS the systolic diameter of the ascending aor-
ta - it is measured at the point of the maximum
anterior movement of the aortic wall
AoD the diastolic diameter of the ascending
aorta - it is measured at the end of the diastole,
co rresponding to the Q wave on the EKG
Te dimensions of the ascending aorta and of the
aortic arch were measured from the suprasternal view,
also from this view were measured the dimensions of
the great vessels. Te dimension of the abdominal aorta
was measured from the subcostal view. Blood pressure
was measured on the right arm, im mediately afer the
beginning of the echocardiographic examination. An
aneroid capsule sphygmomanometer was used, with an
adequately sized cuf for the arms width (the width of
the cuf >2/3 of the diameter of the arm). Te ausculta-
tion method was employed.
Te statistic analysis of the data was performed by
using SPSS sofware, v. 14.0 for Windows. Te data was
presented in percentiles and as median values stan-
dard deviation (SD) for the continuous variables. Te
diferences between the diferent groups median values
were compared by using the t test for independent va-
riables, the Mann Whitney U, or Wilcoxon test. A p
<0.05 was considered to be statistically signifcant and
a p<0.01 was considered highly signifcant.
RESULTS
Diferent measurements of the aorta were performed
at various levels, as well as measurements of the origins
of the large vessels emerging from the ascending aorta:
Te aortic ring
Te aorta at the level of the Valsalva sinuses
Te ascending aorta 3 cm from the aortic ring, in
a parasternal long axis
Te aortic cross (before the origin of the lef com-
mon carotid artery)
Te descending aorta, below the isthmic region
Te abdominal aorta
Te origin of the lef common carotid artery
Te origin of the lef subclavian artery
Te values obtained through 2D measurements were
considered in relation to the corporeal surface. Te me-
dian values obtained were indexed with the corporeal
surface and are presented in Table 2, compared to the
values recorded for the control lot:
Te dimensions of the aorta were signifcantly hig-
her at the level of the aortic ring (11+/-1,5 mm/m
2

Table 1. The characteristics of the study lot
Patients (n=23) Control lot (n=20) p
Age (years) 28,659,98 29,7010,92 0,789
Sex (M/F) 17/6 12/8 0,337
Systolic BP (mmHg) 123,0413,63 114,5013,56 0,034
Diastolic BP (mmHg) 75,2211,63 73,0010,81 0,300
Corporeal surface (m) 1,810,21 1,790,21 0,826
Figure 1. Measuring the aortic dimensions in 2D guided M mode, in order
to calculate the elasticity parameters of the ascending aorta. Te M mode
section is perpendicular to the long axis of the ascending aorta. Te AoS and
the AoD are measured.
Vol. 23, No. 4, 2013

versus 9,9 +/- 0,8 mm/m
2
), the ascending aorta (3 cm
above the aortic ring), (17,3 +/- 5,6 mm/m
2
versus 13,4
+/- 1,8 mm/m
2
) and abdominal aorta(91,99 mm/m
2

versus 7,241,34 mm/m
2
) in patients sufering from
AoCo, compared to the healthy subjects. Te dimensi-
ons measured at the level of the Valsalva sinuses were
also higher, but the p value was not statistically signi-
fcant.
Te values obtained for the aortic cross in patients
who underwent surgery were smaller than the ones ob-
tai ned for the control lot, but without any statistic sig-
nifcance. Higher values (statistically signifcant) were
obtained at the origin of the great vessels (lef subcla-
vian artery, lef common carotid artery), starting from
the aortic cross in patients with surgically corrected
AoCo, compared to the control lot.
Te elasticity indices of the ascending aorta for pa-
tients operated for AoCo were compared to elasticity
indices obtained from the ascending aorta of healthy
subjects. Te results are presented in Table 3.
Te distensibility and aortic strain indices are sta-
tistically signifcant lower in the ascending aorta and
stifness indices are statistically signifcant higher in
patients, compared to the control lot, contouring the
picture of a less elastic, less distenssible, but stifer as-
cending aorta.
Te correlation between the dimensions of the ascen-
ding aorta and aortic elasticity indices
A correlation between the dimensions of the aorta
measured as previously mentioned and the vascular
reactivity indices (calculated by using unanimously ac-
Table 2. The dimensions of the aorta and of the great vessels originating from the aorta
Aortic artery diameters indexed with the
corporeal surface
Patients operated for AoCo Control lot p
Aortic ring (mm/m) 111,5 9,90,8 0,004
Aorta - Valsalva sinuses (mm/m) 18,55,8 151,8 0,01
Ascending aorta (mm/m) 17,35,6 13,41,8 0,003
Aortic cross 10,732,19 11,381,94 0,400
Lef common carotid artery - origin (mm/m) 3,460,67 2,940,35 0,003
Lef subclavian artery origin (mm/m) 5,271,35 4,781,02 0,005
Descending aorta (mm/m) 9,002,06 8,021,29 0,100
Abdominal aorta (mm/m) 9,001,99 7,241,34 0,002
p <0.01 statistically significant
p <0.005 highly statistically significant
Table 3. Vascular reactivity indices
Patients Control lot p
Aortic distensibility (10
-6
cmdyne
-1
)
(Ao dis)
3,972,44 11,445,97 <0,001
Ao strain (%) 9,176,20 23,8511,16 <0,001
Aortic stifness (aortic stifness)
(AoSI)
10,176,17 2,190,89 <0,001
Table 4. The correlation between the dimensions of the ascending aorta and aortic elasticity indices
Aortic distensibility Aortic strain Aortic stifness
Aorta - ring -,492(**) -,477(**) ,630(**)
Aorta - Valsalva sinuses -,607(**) -,585(**) ,704(**)
Ascending aorta -,595(**) -,565(**) ,700(**)
Aortic cross -0,14 -0,11 0,13
Lef common carotid artery origin (mm/m) -,402(**) -,427(**) ,408(**)
Lef subclavian artery origin (mm/m) -0,23 -0,2 0,21
Descending aorta (mm/m) -0,24 -0,24 0,24
Abdominal aorta (mm/m) -0,23 -0,21 0,29
*p <0.05 statistically significant
**p <0.001 highly statistically significant
Vol. 23, No. 4, 2013
cepted formulas - distensibility, aortic strain and aortic

stifness) was done in order to obtain an objective view
of the infuence of the modifed aortic vascular reac-
tivity on the dimensions of the ascending artery. Te
results are presented in Table 4.
Te dimensions of the aorta at level of the aortic
ring, Valsalva sinuses and ascending aorta negatively
correlate with aortic distensibility and aortic strain (a
less distensible aorta is larger at the level of the aortic
ring), but is positively correlated to the aortic stifness
(a more rigid aorta has greater dimensions measured
at the aortic ring). All 3 correlations have p <0.001. A
negative correlation is suggested between the dimensi-
ons of the aorta at the aortic cross and distensibility and
aortic strain. A positive correlation is suggested betwe-
en the afore mentioned dimensions and the aortic sti-
fness, both without statistically signifcant indices. Te
aortic cross was the only segment of the aorta which
had smaller dimensions in patients who underwent
corrective surgery for AoCo, compared to the central
lot, revealing once more a degree of hypoplasia of the
aortic cross in these patients. Te lef common carotid
artery negatively correlates with the distensibility and
aortic strain indices and a positive correlation with the
aortic stifness index, with p <0.001. We can conclude
that the less distensible, more stifer aortic pattern is
maintained in the lef common carotid artery. Te same
types of correlations are present in the descending and
abdominal aorta, as well as in the lef subclavian artery,
without statistically signifcant p values. Moreover, for
these last results, it is important to mention and dis-
cuss the fact that the thoracic descending aorta and the
abdominal aorta represent the aortic territory situated
below the coarctation, with a diferent vascular reacti-
vity. Te lef subclavian artery has its own particularity,
as the main source for collateral circulation. Its dilata-
tion is owed mostly to the increased preoperatory debit
and less to the vascular reactivity changes.
DISCUSSIONS
Previous studies published in the literature have shown
the presence of an early vascular remodeling in the
ascending aorta
7,11,14
and in the precoarctation vascu-
lar territory. Vascular remodeling includes an altered
vascular reactivity and the increase of the intima me-
dia thickness of the endovascular layer of the large
vessels
8,9
. Studies revealed a more stifer aorta, with
de creased elasticity, resulting in a tendency to dilate in
time
10,11
. Tis modifed vascular reactivity was identi-
fed beginning with infants
7
, it is present before the cor-
rection and remains partially unmodifed even when
the corrective surgery was successful
11
. Te changes in
vascular reactivity seem to be the determining cause of
most postsurgery complications
8,9,11,12
.
Vascular reactivity indices have presented the follow-
ing particularities in patients who underwent correcti-
ve surgery for AoCo:
Distensibility (3,972,44 10
-6
cm
2
dyne
-1
in patients
with AoCo versus 11,44 5,72 10
-6
cm
2
dyne
-1
in
healthy subjects) and aortic strain (9,176,2%
in patients with AoCo versus 23,8511,16% in
healthy subjects) registered lower values than
normal, thus the capacity of the ascending aorta
to expand itself and store kinetic energy at the
moment of impact with the blood pumped by the
heart during the systole is low.
Aortic stifness registered increased va lu es (10,17
6,17 in patients with AoCo versus 2,19 0,89
in healthy subjects), characterizing a more stifer
aorta, probably secondary to the particular anato-
mical structure.
Te results of this study show that the vascular re-
activity indices characterizing the elastic nature of the
ascending aorta are modifed even in cases with a good
correction of the isthmic lesion. Te modifcations in
the elastic properties of the ascending aorta change the
hemodynamic behavior at this level and infuences BP,
velocity and the irrigation pattern of two very impor-
tant arterial territories: the carotid and the coronary
systems. Te modifed elasticity parameters in the as-
cending aorta determine an increase of the vascular
resistance in the precoarctational territory. We can
conclude that the afer load of the LV, which is much
higher before the correction, decreases - but does not
return to normal values afer corrective surgery. Tis
might be one of the factors determining the persistence
of increased BP values, despite a good anatomical result
afer the correction of an AoCo
8
.
Considering the vascular reactivity of the arterial
system in patients with corrected AoCo it seems to be
divided in two segments with particular reactivity: the
more rigid, less elastic precoarctation segment and the
post coarctational segment, with a normal vascular re-
activity. Te two segments react diferently during an
efort, determining a dynamic tightening of the isthmic
region, even in cases with a good anatomical correcti-
on
11
. Tis could partially explain the persistence of high
BP values afer corrective surgery, especially during an
efort. On the other hand, constantly increased blood
pressure values can determine the fragmentation of the
Vol. 23, No. 4, 2013

elastin fbers from the media layer and changes in the
intima layer, determining early atherosclerotic lesions.
Hence, increased blood pressure values can be both ca-
use and efect of the modifed vascular reactivity.
Te modifed vascular reactivity has long term con-
sequences on the function of the LV (both the systolic
and diastolic components)
13
and on the irrigation of
the myocardium via the coronary arteries. Tese con-
sequences appear as a result of the modifcation indu-
ced in the blood velocity and in the behavior of the re-
fected wave. Te residual hypertrophy of the LV walls
can be partially explained by the increased stifness and
decreased distensibility
12
.
Histology studies conducted on aortic tissue samples
obtained from the AoCo resection area have revealed
a larger quantity of collagen and a smaller quantity of
smooth muscle fbers in the precoarctation area of the
aorta, than in the area located below the coarctation
16
.
Tese histological modifcations are the basis of the
functional changes previously described and have led
to the conclusion that this arterial malformation is a
generalized arteriopathy of the precoarctational area
and not just an anomaly located in the isthmic region.
Tis global approach of the precoarctational arterial
system could better explain the complications connec-
ted to the arterial wall (aneurysms, early atherosclero-
tic lesions, aortic dissection) and the early age of debut,
compared to the general population.
Te median age of the patients in the lot for which
vascular reactivity was studied was 28.659.98 years.
Tis is an age characterizing a young population, but
with a series of complications connected to the arterial
wall, associating increased intima median thickness of
the carotid, a subclinic marker of atherosclerotic lesi-
ons. Te median age for the diagnosis of vascular re-
activity changes raises the valid question of what is the
age for the onset of these reactivity modifcations. Te-
re are studies conducted on lots of newly-born babies
and infants, sufering from AoCo, pre and post opera-
tory
7
, which have demonstrated that even infants have
preoperatory changes of the vascular reactivity. Tese
modifcations persist in the postoperative period. Te
described modifcations are similar to those described
by the present study, respectively reduced elasticity, re-
duced distensibility and an increased stifness.
Considering the fact that these parameters can be
measured with an echocardiograph which does not
re quire supplementary programs and the validation
through various studies of these indices obtained by
transthoracic echocardiogram (non-invasive method)
we can ask ourselves as cardiologists whether or not
these indices could be determined in series for these
patients, in order to quantify the risk of complications
connected to the arterial wall. Te vascular reactivity
indices (distensibility, strain and stifness) proved to
be useful in long term care of patients sufering from
Marfan syndrome, with a greater capacity of prediction
regarding the risk of dissection and aortic rupture than
the dimensions of the aorta
13
. In patients sufering from
Marfan syndrome it has been demonstrated that aortic
dissection can appear even in patients who do not pre-
sent a signifcant dilatation of the ascending aorta, but
have altered vascular reactivity indices.
Te dimensions of the ascending aorta
Altered elasticity properties of the ascending aorta
modify not only the hemodynamic behavior at this le-
vel, but also the dimensions of the ascending aorta
11,14,17
.
In patients sufering from AoCo the aorta is more di-
lated at the aortic ring (111.5 mm/m
2
corporeal surfa-
ce for patients versus 9.40.8 mm/m
2
corporeal surface
for healthy subjects), Valsalva sinuses (18,55,8 mm/
m corporeal surface for patients versus 151,8 mm/m
2

corporeal surface for healthy subjects) and ascending
aorta 17,35,6 mm/m
2
corporeal surface for patients
versus 13,41,8 mm/m
2
corporeal surface for healthy
subjects). Tese increased dimensions can be the con-
sequence of modifcations in the media layer, which
has a small number of smooth muscle fbers and a lar-
ger number of collagen fbers which sufer a degradati-
on process over time, leading to a progressive dilatation
at this level
11
. Tis takes us to the conclusion that the
aortic dilatation present at the aortic ring and ascen-
ding aorta are secondary to the particular histological
structure of the ascending aorta and not a consequence
of the associated aortic valve lesions.
Te histological basis of the anatomic modifcations
is represented by a particular structure of the ascend-
ing aorta, especially in the aortic media layer, which
contains elastic fbers with a particular structure, with
a reduced capacity of elastic recoil at the moment of
impact with the blood, permitting a gradual plastic de-
formation of the ascending aorta
17
. Te same type of
histological structures of the ascending aorta is descri-
bed in several af ictions: Marfan syndrome, bicuspid
aortic valve, aortic coarctation). Tere are no histologi-
cal and genetic comparative studies for these diseases.
Such studies could have revealed whether or not the
microscopic anatomic structure is identical and if the
determining genetic modifcation is similar. However,
Vol. 23, No. 4, 2013
several studies have succeeded in creating an objective

view of the functional behavior of the ascending aorta,
which is similar in all of these patients
7,11
.
Tis study has identifed statistically signifcant mo-
difcations in the size of the lef common carotid ar-
tery (3.460.67 mm/m
2
corporeal surface for patients
versus 2.940.35 mm/m
2
corporeal surface for healthy
subjects) and lef subclavian artery (5.271.35 mm/m
2

corporeal surface for patients versus 4.281.02 mm/
m
2
corporeal surface for healthy subjects). In the case
of the lef subclavian artery the dilatation at the point
of origin can be explained by the fact that it is the so-
urce of the collateral circulation and its dilatation is a
characteristic of AoCo. However, the persistence of this
dilatation afer the correction of the lesion can only be
partially explained in this manner. Tis dilatation is
most likely owed to the particular anatomical structure
of the precoarctational arteries. Te origin of the lef
common carotid artery is more dilated in patients than
in the control lot, further supporting the idea that the
precoarctational arteries have a particular anatomical
structure, favoring a progressive dilatation of the vessel
at this level, despite a successful correction.
CONCLUSIONS
Te evaluation of the elastic properties of the ascen-
ding aorta has shown a more stifer (aortic stifer in pa-
tients 10.176.17 versus 2.190.89 in healthy subjects,
p <0.001), less distensible (distensibility in patients
3.972.44 10
-6
cm
2
dyne
-1
versus 11.445.92 10
-6
cm
2
dy-
ne
-1
in healthy subjects, p <0,001) aorta, with a dimi-
nished elasticity (aortic strain in patients 9.176.20%
versus 23.8511.16% in healthy subjects, p <0.001) af-
ter the correction of the AoCo.
An increase in the dimensions of the ascending aor-
ta appears secondary to the changes in the vascular re-
activity.
Te evaluation of the ascending aortas elastic pro-
perties by the determination of vascular reactivity re-
presents the transition to the direct functional evaluati-
on of the ascending aorta.
By determining both the dimensions of the ascend-
ing aorta, as well as the vascular reactivity indices, this
study represents a complex evaluation, both morpho-
logical, as well as functional of the ascending aorta in
patients who have previously underwent corrective
sur gery for an isthmic AoCo.
Confict of interest: none declared.
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889
REVIEWS
Almanac 2013: acute coronary syndromes*
Pascal Meier
1,2
, Alexandra J Lansky
1
, Andreas Baumbach
3
Received 12 July 2013. Accepted 24 July 2013
Contact address:
Pascal Meier, MD
YaleUCL Cardiovascular Research Programme, Te Heart Hospital,
University College London Hospitals UCLH, UCLH16-18 Westmoreland
Street, London W1G 8PH, UK; pascalmeier74@gmail.com
Abstract: Unstable coronary artery plaque is the most common underlying cause of acute coronary syndromes (ACS) and
can manifest as unstable angina, non-ST segment elevation infarction (NSTE-ACS), and ST elevation myocardial infarction
(STEMI), but can also manifest as sudden cardiac arrest due to ischaemia induced tachyarrhythmias. ACS mortality has decre-
ased signicantly over the last few years, especially from the more extreme manifestations of ACS, STEMI, and cardiac arrest.
Tis trend is likely to continue based on recent therapeutic progress which includes novel antiplatelet agents such as prasugrel,
ticagrelor, and cangrelor.
INTRODUCTION
In the USA every year nearly 1.2 million patients are
hos pitalized for acute coronary syndrome (ACS)
1
.
How ever, the proportion of ACS with ST elevation
myo cardial infarction (STEMI) appears to be decli-
ning
2,3
. We can only speculate upon the reasons: po-
tential explanations include the reduction in smoking,
the age structure of the population (STEMI is more
common in middle age while non-ST segment eleva-
tion (NSTE-ACS) occurs more in the elderly), and
broa der use of statin therapy. Over the last few years
there has been a signicant improvement in outcomes
afer STEMI in regard to mortality, cardiogenic shock,
and heart failure1. Similar trends have been seen for
other manifestations of ACS, such as sudden cardiac
arrest (SCA)
4,5
. Astonishingly, the clinical outcomes for
NSTE-ACS now appear to be worse than for STEMI.
However, such gures are misleading, and short term
(in-hospital) outcome is still better for NSTE-ACS than
for STEMI, while the longer term mortality rate is hi-
gher for NSTE-ACS, but this is probably inuenced by
the diferent age and risk structure of the STEMI and
NSTE-ACS populations: NSTE-ACS patients are gene-
rally older and ofen have multivessel (MV) coronary
artery disease (CAD).
ST ELEVATION MYOCARDIAL INFARCTION
A major reason for the improved outcomes for STEMI
over the last decades has been the increasing availabi-
lity of primary percutaneous coronary intervention
(PCI) services, which all try to continuously improve
their performance (door-to-balloon time). Initiati-
ves include telemetric transmission of ECGs from the
ambulance services, and training of ambulance staf
in ECG interpretation. More important than door-to-
balloon time is of course the overall symptom onset
to balloon time. Patients have become much better in-
formed about symptoms of heart attacks, and many
ambulance services transfer patients with a suspected
STEMI directly to a primary PCI service rather than
going to the nearest hospital.
PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Not only has the rate of primary PCI increased over the
years, but progress in device technologies and adjunc-
tive pharmacology has also improved the procedural
success rate for example, the availability of stents and
second generation drug eluting stents, thrombus aspi-
ration devices, and safer and more efective periproce-
dural anticoagulation/antiplatelet treatments. Trom-
bus aspiration has been shown to improve outcomes
in smaller randomized trials and is currently recom-
mended by European and American PCI guidelines.
However, its efect should probably not be overrated.
A recent large scale randomized trial in 452 patients,
INFUSE-AMI (Intracoronary Abciximab and Aspirati-
on Trombectomy in Patients with Large Anterior Myo-
cardial Infarction) did not demonstrate an efect of ma-
1
Division of Cardiology, Yale Medical School, New Haven, Connecticut,
USA
2
YaleUCL Cardiovascular Research Programme, Te Heart Hospital,
University College London Hospitals UCLH, London, UK
3
Division of Cardiology, Bristol Heart Institute, Bristol, UK
* To cite: Meier P, Lansky AJ, Baumbach A. Heart Published Online First:
doi:10.1136/heartjnl- 2013-304649
Pascal Meier et al.
Almanac 2013: acute coronary syndromes
Vol. 23, No. 4, 2013
810
nual thrombus aspiration on infarct size when used in
conjunction with bivalirudin (and intracoronary abci-
ximab)
6,7
. Intravenous glycoprotein (Gp) IIb/IIIa inhi-
bitors have an immediate and potent platelet inhibitory
efect and certainly improve thrombus resolution; they
may reduce infarct size
6
while their efect on clinical
out comes is somewhat more debatable. Bivalirudin, a
direct thrombin inhibitor, which has anticoagulant and
probably also antiplatelet efects (via suppression of
thro mbin dependent platelet activation
8
), can be used
as an alternative to heparin and Gp IIb/IIIa inhibi-
tors, and has shown reduced bleeding and even redu-
ced mortality in the HORIZON-AMI trial (Heparin
plus a glycoprotein IIb/IIIa Inhibitor versus Bivalirudin
Monotherapy and Paclitaxel-Eluting Stents versus Bare-
Metal Stents in Acute Myocardial Infarction)
6
. Bleeding
reduction has become a key aim in primary PCI beca-
use of the well documented (but less well understood)
association with increased mortality (Table 1).
Transradial versus transfemoral access
Another rather elegant option used increasingly, which
may reduce bleeding, involves the transradial approach
instead of the traditional transfemoral access
9
. An in-
creasing wealth of data indicate that this reduces blee-
ding in general; some data even suggest that it reduces
mortality when used for primary PCI, but the latter
efect is debatable10,11. A recent meta-analysis of nine
studies involving 2977 patients with STEMI demons-
trated an impressive nearly 50% reduction in mortality
for the transradial approach (OR 0.53, 95% CI 0.33 to
0.84; p=0.008)
10
. While the authors concluded that the
transradial approach should be preferred in STEMI pa-
tients, an accompanying editorial highlighted some
limitations of these data
11
. Some data indicate a nega-
tive impact of transradial PCI. Baklanov et al
12
showed
a longer median door-to-balloon time with transra-
dial PCI. Another retrospective comparison by Cafri
et al
13
, however, showed similar door-to-balloon time
irrespective of the access route. Even in elderly people,
where there is more advanced atherosclerosis, the ra-
dial access does not seem to delay reperfusion as it does
not lead to any increase in the door-to-balloon time
14
.
Tere have also been concerns that transradial access
may increase the risk of neurological complications
com pared to transfemoral access. However, in a retros-
pective analysis of the British Cardiovascular Interven-
tion Society database conducted between January 2006
and December 2010, Ratib et al
15
have shown that there
is no signicant association between the use of radial
access and the occurrence of neurological complicati-
ons.
Overall, transradial PCI is certainly a promising te-
chnique when used by experienced operators. Howe-
ver, despite its benets, its use is highly variable across
countries. In France and Japan it is the predominant
access route
11
. In the UK, its use increased nearly four-
fold from 17.2% in 2006 to 57% in 2011
16
. Te USA has
the lowest rate of radial access adoption
for PCI worldwide (only one in six PCIs)
17
. Even
here, there has been an increase in use of radial access.
In the rst quarter of 2007, 1.2% of PCIs were by the
transradial approach; this increased to 16.1% in the
third quarter of 2012. Tere is little doubt that the in-
creasing use of transradial PCI has led to a reduction in
access site complications
12,16,17,18
.
While some data indicate that the transradial route
may reduce mortality in STEMI patients, this has not
been demonstrated in NSTE-ACS. In the RIVAL (Ra-
Table 1. Bleeding avoidance strategies
9
Strategy Comments
Radial instead of femoral
access
Reduces access site bleeding risk (and potentially also mortality in high risk groups)
Bivalirudin Bivalirudin superior to heparin and glycoprotein IIb/IIIa inhibitors, reduces bleeding (and reduces mortality in STEMI
patients)
Fluoroscopy guided punctu-
re for femoral access
High (or low) puncture to be avoided. Te femoral head has a consistent relationship with the common femoral artery,
and localization using fuoroscopy is a useful landmark. However, randomized studies failed to show a clinical beneft but
were underpowered
Fewer vascular complications with this approach in randomized trials
Ultrasound guided puncture
for femoral access
1347
Vascular closure devices Controversial study results. Increasing evidence pointing towards a positive efect of vascular closure devices, especially if
used with bivalirudin
Individualized bleeding risk
assessment
Individualized risk assessment and adjustment of clinical practice using risk models, for example, NCDR CathPCI blee-
ding risk model (bivalirudin, radial access, etc)
NCDR, National Cardiovascular Database Registry; PCI, percutaneous coronary interventions; STEMI, ST elevation myocardial infarction.
Vol. 23, No. 4, 2013
811
Pascal Meier et al.
dial vs Femoral Access for Coronary Intervention) trial,
currently the largest randomized trial on this topic,
there was no diference in major clinical outcomes in
NSTE-ACS patients
19
. In a cohort of high risk NSTE-
ACS patients enrolled in the EARLY-ACS trial (Early
Gly coprotein IIb/IIIa Inhibition in non-ST-Segment Ele-
vation Acute Coronary Syndrome), there were no sig-
n i cant diferences in either bleeding or ischaemic
out comes whether radial or femoral access was used
20
.
A recent consensus statement by the European Soci-
ety of Cardiology (ESC) states that a default radial ap-
proach is feasible in routine practice in both stable and
unstable patients
21
. Te ESC recommends performing
transradial PCI in STEMI patients only afer the ope-
rator has become familiar with this approach in stable
patients and in diagnostic procedures.
Culprit lesion PCI
Culprit lesion only treatment versus a complete revas-
cu larization approach remains the subject of some
debate. One could argue either way: a complete revas-
cularization strategy may improve overall myocardial
perfusion in the critical initial phase; but on the other
hand, we know that major adverse complications are
increased during acute PCI, and this also may have an
impact on the outcome following treatment of non-
acute, non- culprit lesions. A randomized study of 214
patients showed that angioplasty of the culprit vessel
only was associated with higher rates of adverse events
(50.0%) during a mean follow up of 2.5 years than MV
PCI, regardless of simultaneous complete revasculari-
zation (23.1%) or a staged complete revascularization
(20.0%)
22
. A recent report of the Ibaraki Cardiovascular
Assessment Study registry of Japan showed signicantly
higher mortality with PCI of a non-culprit lesion in
the same setting as the culprit lesion than with PCI of
only the culprit lesion
23
. In contrast, results based of
the American College of Cardiology National Cardio-
vascular Database Registry (NCDR-CathPCI) showed
similar morbidity and mortality rates with either single
vessel or MV PCI
24
. While these data were conicting,
most studies were non-randomized and need to be in-
terpreted with caution. A large meta-analysis of 18 ran-
domized controlled trials (RCTs), including the above
mentioned RCT, involved 40 280 patients and showed
that staged PCI was associated with lower short and
long term mortality compared to culprit vessel PCI and
MV PCI
25
. Terefore, current guidelines discourage the
performance of multivessel PCI for STEMI and suggest
that non-culprit lesions should be staged
26,27
. However,
if STEMI patients present in cardiogenic shock or afer
an SCA, they should be considered for complete revas-
cularization in one sitting.
The time effect
Te current ESC guidelines recommend that STEMI
patients should be immediately transported within 2 h
of onset of symptoms to a PCI-capable center without
delay
28
. In clinical practice, it is extremely difcult to
achieve this goal of symptom onset-to-balloon time
29
.
System delays have been shown to be associated with
mortality at a median follow-up of 3.4 years in STEMI
patients treated with primary PCI
30
. In a more recent
study, shorter symptom onset-to-balloon time predic-
ted lower mortality in the long term
31
. A longer treat-
ment delay was seen in females, patients living in a ru-
Figure 1. Change in short and intermediate term mortality afer ST elevation myocardial infarction. Standardised 30 day and 31365 day mortality afer rst
hospitalization for myocardial infarction among men and women between 1984 and 2008 in Denmark33. Reprinted with permission from BMJ Publishing
Group.
Pascal Meier et al.
Vol. 23, No. 4, 2013
812
ral area >22 km from hospital, and when patients were
admitted to the emergency department of the hospital
instead of direct emergency medical services (EMS)
transportation. Researchers suggest that a more gene-
ralised use of ambulance/EMS would reduce treatment
delays and associated mortality.
Optimal duration of monitoring/hospital stay
Te duration of hospital stay has decreased dramati-
cally over the years, which has a major impact on health
care expenditure and on patient quality of life. Current
practice is widely variable across countries and centres,
but it is unclear whether early hospital discharges are
safe
32
. It is very reassuring that, despite the continuous
reduction in hospital stay, outcomes have signicantly
improved (Figure 1).
Two new studies have demonstrated that dischar-
ging low risk STEMI patients within 2 days following
primary PCI is safe and feasible
34,35
. Over 40% of the
STEMI patients in one of the studies met early dischar-
ge criteria
34
. An early discharge could lower healthcare
costs considerably.
Based on the literature, we propose the following cri-
teria to dene low risk patients for early discharge:
1. Age <70 years
2. Short pain to reperfusion interval (<4 h)
3. Uncomplicated primary PCI with good result
(TIMI (Trombolysis in Myocardial Infarction) 3
ow and prompt complete ST elevation resoluti-
on)
4. Lef ventricular ejection fraction >45% without
symptoms of heart failure
5. No signicant arrhythmias during the rst 24 h
6. Socially supported, collaborative/compliant pati-
ent.
NON-ST ELEVATION ACS
Risk prediction
Tere is a great need for proper risk prediction in ACS
patients for clinical decision making, especially with
regard to coronary angiography. Tere are several risk
prediction models in use. Te Global Registry of Acute
Coronary Events (GRACE) is among the most com-
monly used scores. Recently, a mini-GRACE (MG) risk
score has been developed which excludes creatinine
and Killip class from the original eight-factor GRACE
risk model. Te adjusted mini-GRACE (AMG) risk
score includes prescription of a loop diuretic during
admission in place of Killip class and creatinine con-
centration. Both risk scores showed good accuracy in
the Myocardial Ischemia National Audit Project (MI-
NAP), with the AMG risk score performing somewhat
better than the MG risk score
36
.
Laboratory markers may further help with this risk
stratication. Te maximal troponin value in patients
presenting with NSTE-ACS has been shown to be an
independent predictor of in-hospital morbidity and
mortality
37
. Other predictive markers include interleu-
kin 10, myeloperoxidase, and placental growth factor
38
.
Role and timing of PCI in NSTE-ACS
For intermediate to high risk patients, there is strong
evidence supporting routine angiography rather than
conservative management. However, the optimal time
for coronary angiography is not clear. Tough an early
invasive approach seems favorable, studies testing the
timing efect used varying time points for early and
delayed angiography. In very high risk patients such
as those with refractory angina, severe heart failure, life
threatening ventricular arrhythmias or haemodynamic
instability or an evolving myocardial infarction (MI),
an urgent invasive approach is indicated. For patients
not belonging to this high risk category, the optimal
timing is not clear. Tere is no clear benet with re-
gard to hard clinical end points for an early invasive
strategy within 24 h, but an increasing number of cen-
ters undertake an early invasive strategy within 24 h for
intermediate to high risk patients. Such an approach is
probably reasonable, as an earlier approach certainly
helps to reduce hospital stay. Factors such as diabe-
tes, renal function, lef ventricular function, recurrent
symptoms, and previous revascularization should be
considered along with the TIMI or GRACE score.
Intravascular imaging
Intravascular imaging guided PCI is a concept that
evolved when devices such as intravascular ultrasound
(IVUS) and more recently optical coherence tomogra-
phy (OCT) became available. Tere are two diferent
modes of use, either for the pre-PCI assessment in or-
der to better understand the coronary plaque (stable or
unstable plaque, diameter and length, thrombus bur-
den, etc), or for post-PCI assessment of stent expan-
sion and apposition. Te advantages are obvious; in
contrast to angiography as an eyeballing tool, which
allows measurement of luminal diameters in a few ort-
hogonal views, coronary IVUS provides a tomographic
view. Furthermore, the resolution is much better than
for angiography.
Te rst concept, pre-PCI assessment of lesions has
been tested in the multicenter PROSPECT (Providing
Regional Observations to Study Predictors of Events
Vol. 23, No. 4, 2013
818
Pascal Meier et al.
clopidogrel is the most commonly used agent for this
purpose at the moment. However, the problems with
this treatment are the rather long delay until maximal
platelet inhibition is reached and the high rate of poor
responders
46
. One approach that has been tested re-
peatedly is triple antiplatelet therapy using cilostazol.
Even though results of this approach have indicated
some benet, it is rarely used
47,48
. One reason for this is
probably the development of newer generation P2Y12
receptor blockers such as prasugrel, ticagrelor, and can-
grelor. Tey block the binding of ADP to the platelet re-
ceptor P2Y12, thereby inhibiting platelet aggregation.
Naturally, we would expect that stronger antiplatelet
inhibition comes with an increased bleeding risk. Many
patients therefore receive proton pump inhibitors
(PPI). However, the data do not completely following
this logic.
Prasugrel: Te TRITON-TIMI 38 trial was a head-
to-head comparison between aspirin and prasugrel
versus aspirin plus clopidogrel in 13 608 moderate to
high risk ACS patients under-going PCI. In most ca-
ses, the study drug was given afer coronary angiogra-
phy. At 15 months follow-up, MACE (cardiovascular
death, non-fatal MI, or non-fatal stroke) was reduced
with pra sugrel (9.9% vs 12.1%; HR 0.81, 95% CI 0.73
to 0.90) Tis composite end point was mainly driven
by a reduction in non-fatal MI. Major bleeding was
some what increased with prasugrel (2.4% vs 1.8%; HR
1.32, 95% CI to 1.68). Bleeding was mainly increased
in those with a history of stroke or transient ischemic
attack, age 75 years or a bodyweight 60 kg. Te TRI-
LOGY ACS trial tested prasugrel versus clopidogrel
with NSTE-ACS not undergoing PCI. Tere was no
statistically signicant diference in MACE rate (13.9%
vs 16.0%; HR 0.91, 95% CI 0.79 to 1.05).
Ticagrelor: In contrast to clopidogrel and prasugrel,
ticagrelor binds reversibly to the P2Y12 platelet recep-
tor. Tis agent was tested in the PLATO trial (18 624
patients) in patients with ACS, and also those who did
not undergo PCI but had medical therapy. Treatment
was started early, at a median of 5 h afer hospital ad-
mission. Tis study showed a reduced risk for MACE
(dened as cardiovascular death, MI, or stroke) in the
ticagrelor arm (9.8% vs 11.7%, HR 0.84, 95% CI 0.77
to 0.92), and there was also a reduced risk for car dio-
vascular mortality as a single end point. Overall, the-
re was no signicant diference in the rates of major
bleeding between the ticagrelor and clopidogrel groups
(11.6% vs 11.2%, respectively). However, there was a
in the Coronary Tree) study
39
. Tis study showed that
IVUS can be used to dene characteristics of vulne-
rable plaques. Te highest risk phenotypes associated
with non-culprit major adverse cardiac events (MACE)
in cluded thin-cap broatheromas, plaque burden
>70%, and minimal lumen area <4.0 mm. However,
these data are not sufcient to advocate using IVUS de-
rived plaque characteristics to decide whether a lesion
needs to be treated
40
.
While IVUS is based on ultrasound, OCT is based
on light, which has a much shorter wavelength, and
therefore achieves 10-fold better spatial resolution
com pared to IVUS
41
.Tis allows better denition of
the thin brous caps and the circumferential extent of
the necrotic cores. It helps detect other microstructural
features such as cholesterol crystals, thrombus, calcium
deposits, brous plaques, and lipid-rich plaques
42
. OCT
can visualize features not seen by IVUS such as intimal
aps and defects in the intima, disruptions in the me-
dia, and stent strut apposition.
A Japanese study that analyzed the culprit lesion in
AMI patients found that the incidence of plaque ruptu-
re observed by OCT was signicantly higher than that
observed by both angioscopy and IVUS
43
. OCT was
also superior in detecting brous cap erosion and thin
cap broatheroma, and OCT could also estimate the
brous cap thickness.
However, the depth of imaging penetration is limi-
ted to only a few millimeters with this new technique
44
.
So, it is unable to image the adventitia and assess the
plaque burden. Terefore, Alfonso et al
45
had the idea
of a combined use of OCT and IVUS in patients with
stent thrombosis. Since image length was shorter with
OCT, they suggested overlapping OCT runs to cir-
cumvent the problem. Te challenge of OCT is that it
requires a eld clear of blood for imaging.
Because OCT has superior resolution to IVUS, it
clearly recognizes stent struts on heavily calcied are-
as which are difcult to identify with IVUS. Post-in-
tervention OCT also produces a sharper image of the
neointimal-thrombus boundary and provides a reliable
diagnosis of in-stent restenosis or neoatherosclerosis.
In current practice, OCT and IVUS seem to comple-
ment each other with their respective advantages and
disadvantages. However, we have to be aware that data
on clinical outcomes are limited and that these tech-
niques add to procedural costs.
Antiplatelet therapy
Aspirin is still the basis of every antiplatelet therapy.
However, dual antiplatelet therapy of aspirin and a
P2Y12 receptor blocker is clearly more efective and
Pascal Meier et al.
Vol. 23, No. 4, 2013
811
(OHCA)). Survival for OHCA patients has been poor
for several decades, averaging <10% to hospital dis-
charge, and may be even lower, particularly in remote
areas. However, in recent years survival has increased,
especially in metropolitan areas. Te London Ambu-
lance Service observed an increase in survival rates
from 12% to 32% between 2007 and 2012
5
.
We can only speculate about the reasons for this im-
provement since few single interventions have really
proven to be efective
54
. It is therefore more likely that it
is the combination of multiple efective treatments that
is responsible for the observed improvements in sur-
vival. Early chest compressions and early debrillation
are the undisputed game changers
55
. It is likely that the
availability of public automatic debrillators, debrilla-
tors of the EMS and public awareness, and an increa-
sing number of lay people trained in chest compressi-
on, played major roles
56
.
However, other factors such as therapeutic hypother-
mia and immediate angiography to dene and potenti-
ally treat the underlying cause are important as well
57,58
.
An observational study of 9971 patients with OHCA
of suspected cardiac cause were assessed regarding the
hospital they were referred to. Tose treated at hos-
pitals with 24 h cardiac interventional services had a
better survival (OR 1.40, 95% CI 1.12 to 1.74; p=0.003).
Current guidelines recommend immediate angio-
graphy in patients afer successful resuscitation for an
OHCA (return of a spontaneous circulation) in case of
ST elevations in the post-resuscitation ECG. However,
the accuracy of post-resuscitation ECGs is unclear and
there are grounds for recommending early angiogra-
phy in all patients over 35-40 years, regardless of the
ECG, if there is no obvious non-cardiac cause.
Cardiac rehabilitation after ACS
While it seems intuitive that cardiac rehabilitation pro-
grams are benecial by providing careful follow-up,
supervised physical activity and guidance on lifestyle
modication, clinical data on its efect are controver-
sial. Very recently, cardiac rehabilitation for ACS has
been challenged again by the multicenter RCT of com-
prehensive cardiac rehabilitation in patients following
acute MI (RAMIT: Rehabilitation Afer Myocardial
Infarction Trial)
59
. In this study, cardiac rehabilitation
in patients afer an AMI had no efect on mortality or
morbidity, cardiac medication, risk factors or lifestyle
modication. However, we have to be aware that the
RAMIT trial was small and if we look at the evidence
more comprehensively, by pooling all available RCTs
as done by a Cochrane review (combining 47 studies),
higher risk of non-coronary artery bypass surgery re-
lated major bleeding (4.5% vs 3.8%).
Cangrelor: In contrast to these drugs, cangrelor is
administered intravenously. It has been tested against
placebo and against clopidogrel. Te CHAMPION-
PLATFORM trial (placebo control) was stopped ear-
ly because an interim analysis showed disappointing
re sults. Te CHAMPION-PCI trial (clopidogrel as a
comparator) failed to show a signicant benet as well.
Te most recent and largest study, the CHAMPION-
PHOENIX trial, compared cangrelor against pre-loa-
ding with 300-600 mg of clopidogrel. Tis study not
only included ACS but also patients with stable CAD.
It found a reduced risk for ischemic events (death, MI,
ischemia-driven revascularization or stent thrombosis)
over the rst 48 h without any increase in major ble-
eding risk
49
. Its role in clinical practice in the context
of having ticagrelor and prasugrel available is not cle-
ar yet, and it has never been compared against these
agents.
With additional and more potent antiplatelet the-
rapies now available, the challenge is to decide which
agent to use and when. Currently, the decision is usu-
ally based on clinical and risk factors; pharmacogene-
tics may also play a role in guiding therapies in the fu-
ture
50
.
Gastrointestinal (GI) bleeding is one of the more
common risks of strong antiplatelet therapy. Terefore,
PPI are ofen prescribed as well. A recent study found,
interestingly, that lower GI bleeding is more common
than upper GI bleeding in patients on PPI
51
. Further-
more, the impact of PPI on the clopidogrel efect has
been a matter of controversy for some time. Laboratory
studies have suggested a reduced antiplatelet efect if
PPI are used. However, studies looking at clinical end
points have shown conicting results. A recent syste-
matic review provides a very good overview, including
33 studies, and concludes that clinical data are highly
conicting but that even newer, better designed studies
do not show evidence of a relevant adverse efect of
PPI in patients on clopidogrel regarding clinical out-
comes
52
.
SUDDEN CARDIAC ARREST
SCA is a less common but ofen fatal presentation of
ACS
53
. While there are other reasons for SCA, especi-
ally in younger patients, the most common cause for
tachyarrhythmic cardiac arrests in patients over 40 is
myocardial ischemia
4,37
. Most of these cardiac arrests
occur out of hospital (out-of-hospital cardiac arrest
Vol. 23, No. 4, 2013
815
Pascal Meier et al.
Competing interests: None.
Provenance and peer review Commissioned; internally
peer reviewed.
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lity
60
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61
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62
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. Tose
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for baseline diferences in smoking status the doseres-
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Tough cardiac rehabilitation as currently provided
in many countries may not be efective in reducing
hard clinical end points, it still helps provide informa-
tion, advice, and reassurance and helps in long term
secondary prevention
65
.
CONCLUSIONS
Te treatment options for ACS have improved signi-
cantly over the past few years, contributing to notable
improvements in outcomes. Tis is especially the case
for STEMI, while long term mortality afer an NSTE-
ACS is still considerable. Te very recent introduction
of third generation antiplatelet therapies (prasugrel,
ticagrelor) and the most recent intravenous form, can-
grelor, are likely to continue to improve clinical outco-
mes afer ACS. Tese more potent agents can increase
bleeding risks, and considering the association betwe-
en bleeding and outcomes, periprocedural bleeding
avoidance strategies are important. Tey may include
radial access angiography; ultrasound guided femoral
access, and the use of bivalirudin.
Contributors: PM drafed the manuscript. AB, AJL and
AB revised the manuscript critically for intellectual
content. All three authors contributed signicantly to
this paper and have approved the nal version.
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REVIEWS
Almanac 2013: heart failure*
Andrew L Clark
Received 31 July 2013. Accepted 4 August 2013
Contact address:
Professor Andrew L Clark, Academic Cardiology, Hull York Medical
School, Castle Hill Hospital, Castle Road, Cottingham HU165JQ, UK;
a.l.clark@hull.ac.uk
EPIDEMIOLOGY, THE NATIONAL AUDIT AND
GUIDELINES
Te National Heart Failure Audit continues to be an
invaluable resource for understanding how acute heart
failure is managed in England and Wales. Te most re-
cent report
1
describes just over 37 000 hospitalizations.
As in previous publications, fewer than half the pati-
ents were managed in cardiology wards, yet those who
were had a better outcome; half were referred at dis-
charge to cardiologists for follow-up and they, too, had
a better outcome. An innovation in the audit this time
was the publication of hospital level analysis. It would
be invidious to pick out names, but it is very striking
how variable are the rates of such basic items as the
use of echocardiography, availability of a cardiologist
to manage the patients and the rate of prescription of
di ferent drugs.
Studies show that, during long-term follow-up, pa-
tients managed by heart failure specialists including
heart failure nurses are more likely to be treated with
the appropriate medication in the appropriate dose,
have lower (re-)admission rates to hospital and a better
prog nosis
2
. Tere is reasonable evidence that there are
better outcomes if part of the multidisciplinary inter-
vention is made in the home
3
. Tere is strong eviden-
ce that specialist clinics reduce the risk of readmission
with heart failure immediately afer an index admissi-
on
4
.
Also available to the clinician are the heart failure
guidelines from the National Institute for Health and
Care Excellence (NICE)
5,6
and the associated quality
standards
7
. Te NICE standards make it clear what
NHS services across England and Wales should be stri-
ving towards. Combined with the hospital level analysis
from the audit, the quality standards should give clini-
cal teams the ammunition they need when discussing
their heart failure service with management teams in
both primary and secondary care.
However, it is becoming ever clearer that the systems
used for managing heart failure at present are unlikely
to be adequate in future: a study from the USA
8
predicts
that the costs of managing heart failure will more than
double by 2030, mainly due to the ageing of the popu-
lation. Te capacity of the health service to accommo-
date the increasing numbers is not innite. Part of the
solution will surely have to be a change towards greater
efciency of use of limited resources, but reducing the
risk of developing heart failure will also be a major con-
tributor. Of some relief to many doctors, cofee appears
to ofer some protection
9
!
Te latest guidelines from the European Society of
Cardiology were published in 2012, merging the man-
agement of acute and chronic heart failure
10
. Tey
continue to emphasize the central role of natriuretic
peptide testing for diagnosis which is still not uni-
versally available in the UK but a key part of the NICE
recommendations. Te guidelines emphasize that mi-
neralocorticoid receptor antagonists should now be
considered to be part of standard therapy for anyone
with symptomatic heart failure and should be used in
preference to angiotensin receptor blockers as add-on
therapy ACE inhibitors and blockers.
ACUTE HEART FAILURE
For many years the focus of heart failure research has
been on patients with chronic stable heart failure. Te-
re has been little new for acute heart failure for many
years. Recruiting patients with acute heart failure is
difcult: they present acutely, ofen in the middle of the
night, and are ofen extremely unwell. However, clini-
cal trials are now reporting which are starting to chal-
lenge the standard management of acute heart failure.
Common precipitants of an admission to hospital
with heart failure include intercurrent illness, an ische-
mic event or an arrhythmia. Lists of precipitants ofen
quote environment without specifying further what
* To cite: Clark AL. Heart. Published Online First: doi:10.1136/
heartjnl-2013-304761
Vol. 23, No. 4, 2013
Andrew L Clark
Almanac 2013: heart failure
that might mean; but now we have some hard eviden-
ce. In a meta-analysis, Shah and colleagues
11
found very
strong relations between the risk of both hospitalizati-
on for heart failure and death and many environmental
pollutants including carbon monoxide, sulfur dioxide,
nitrogen dioxide and particulate matter. Tere is a clear
public health interest in reducing environmental pollu-
tion, and we can now see the economic consequences
of pollution in terms of heart failure admissions.
Fluid management
Data from the national audit suggest that around half
of patients admitted to hospital with heart failure have
moderate or severe uid retention. Traditional mana-
gement has been by uid restriction (ofen with salt
restriction), but there is remarkably little evidence to
show that this treatment is efective. In a small but in-
triguing study, Aliti et al
12
randomized 75 patients to
a radical uid-restricted (800 mL/day) and sodium-re-
stricted (800 mg/day) regime versus no such restricti-
on. Tere was no efect of the restricted diet on clinical
outcomes (particularly weight loss and readmission
rates at 30 days), but the uid restriction led to greater
thirst. While this is certainly not denitive evidence,
it does challenge standard practice and should lead to
larger trials.
Te standard therapy for uid retention is intra-ve-
nous diuretic use, ofen using infusions over several
days. It might be possible to use ultraltration to re-
move uid more rapidly, and an early trial of 200 pa-
tients suggested that ultraltration might reduce the
need for emergency attendances with heart failure up
to 3 months afer discharge compared with standard
therapy
13
. In CARRESS-HF, however, the efects of
ultraltration in 188 patients with the combination of
uid retention due to heart failure and worsening renal
failure were studied. Te primary endpoint was creati-
nine and weight loss at 96 h. Perhaps surprisingly, renal
function deteriorated more in the ultraltration group
than with standard therapy. Tere was no diference
between the groups in either mortality or 90-day read-
mission rate.
It is difcult to know how to interpret these data.
Te patients in CARESS-HF difered from those in
UNLOAD, being at much higher risk because of their
renal failure at baseline. Despite the patients at trial en-
try having persistent congestion and worsening renal
function (mean creatinine at trial entry 180 mol/L),
those randomized to standard therapy lost over 4 kg in
weight with no change in creatinine at 96 h. Tose ran-
domized to ultraltration had a similar weight loss. It
may simply be that the rise in creatinine of around 20
mol/L with ultraltration represented hemoconcen-
tration rather than reecting any signicant change
in renal function. Ultraltration holds out the hope of
more rapid removal of uid for patients with heart fa-
ilure (the median length of stay for uid retention re-
mains around 11 days), but its precise role has still not
been dened.
Relaxin
Tere has been much excitement about serelaxin, hu-
man recombinant relaxin-2. Relaxin is mainly known
for its efect in pregnancy, but it causes arterial vaso-
dilation with little efect on venodilation. A small dose-
nding trial suggested that it might lead to more rapid
relief of breathlessness in patients with acute heart fai-
lure, with a suggestion that it might improve outcome
14
.
In the RELAX-AHF trial
15
, 1161 patients with acute
heart failure were randomised to receive 48 h infusions
of placebo or serelaxin. Te serelaxin-treated patients
had a modest improvement in their breathlessness, but
only in one of the two scales used. More interestingly,
though, there was a reduction in mortality at 6 months
in the serelaxin group compared with placebo.
How this will translate into clinical practice is not at
all clear. Although the Food and Drug Administration
in the USA has given serelaxin Breakthrough Tera-
py designation
16
, suggesting that they believe serelaxin
re presents a substantial improvement over currently
available therapies, the data from RELAX-AHF are not
convincing. Tere were only a small number of events,
serelaxin appeared to have no efect on other events,
and the comparator limb of the trial was placebo (and
not another vasodilator such as a nitrate). Nevertheless,
if the results are conrmed in further trials, serelaxin
may represent the rst major step forward in treating
acute heart failure in many years.
Neprilysin inhibition
LCZ696 is the rst in a new class of drugs termed
ARNIsthat is, a combined angiotensin II receptor
antagonist (valsartan) with a neprilysin inhibitor. Ne-
prilysin is the enzyme responsible for the breakdown
of natriuretic peptides, so its blockade increases the
amount of natriuretic peptide in the circulation. In the
PARAMOUNT trial
17
, 301 patients with heart failure
and a normal ejection fraction were randomized to re-
ceive the combined inhibitor or valsartan alone. Tose
receiving LCZ696 had a greater decline in N-terminal
prohormone of brain natriuretic peptide at 12 weeks
(an efect lost by 36 weeks), and there was greater im-
Andrew L Clark
Vol. 23, No. 4, 2013
provement in symptoms. Te positive results will pro-

bably trigger a large outcome study, although there will
be problems in knowing what the comparator to LCZ
might be
18
.
Levosimendan
Te REVIVE studies testing the efects of levosimendan
in patients with acute heart failure have nally been
published, around 8 years afer they were rst presen-
ted
19
. Levosimendan is a calcium sensitizing drug it
has inotropic and vasodilator efects. Tere was much
initial enthusiasm over its possible role in acute heart
failure and, in REVIVE, there was a greater likelihood
of clinical improvement with levosimendan. Howe-
ver, there was an increased risk of death, albeit non-
signicant, in the levosimendan group.
Te delay in publication highlights a very important
issue in clinical trials namely, that neutral or negati-
ve trials might go unreported. Levosimendan has been
widely available in Europe, but its potentially deleterio-
us efects may not be recognized by those using it. To-
se designing and running clinical trials have a moral
obligation to publish their data: patients have, afer all,
agreed to take part in clinical trials on the basis that the
results may benet others
20
.
CHRONIC HEART FAILURE
Ivabradine
Te SHIFT study
21
suggested that the addition of iva-
bradine, which slows the heart rate by inhibiting sinus
node depolarisation, improves outcomes in patients
with heart failure due to lef ventricular systolic dys-
function, in sinus rhythm and with a heart rate 70/
min. Te benet seen was largely a reduction in hospi-
talisation for heart failure, but a post hoc analysis sug-
gested that there may be a survival benet for patients
with a resting heart rate 75/min
22
.
A single technology assessment of ivabradine by
NICE
23,24
recommends ivabradine as an adjunct for pa-
tients with a resting heart rate 75/min who are already
on standard therapy (including appropriate blocker at
the maximally tolerated dose), but goes on to suggest
that ivabradine should only be started by a heart fai-
lure specialist. Te need for a specialist goes some way
to addressing the major concern that ivabradine mi-
ght come to be seen as an acceptable alternative to
blockers when the evidence that blockers improve
survival is overwhelming.
Te ivabradine discussion highlights the potential
importance of heart rate reduction as a therapeutic tar-
get. A challenging reinterpretation of the data from the
DIG trial suggests that digoxin in patients with heart
failure in sinus rhythm had a similar reduction in the
endpoint used in the SHIFT study (namely, cardiovas-
cular death or hospitalization for heart failure) as iva-
bradine, with the efect being a reduction in hospitali-
zation rather than an increase in survival
25
. Although
digoxin is very variably used nowadays, it may be that
we should be revisiting its use as heart rate-reducing
agent.
Aliskiren
Inhibition of the renin-angiotensin-aldosterone system
(RAAS) has been the cornerstone of heart failure ma-
nagement for decades but, although the outlines of the
system are well known, the full ramications of the
RAAS are still being uncovered. For example, angio-
tensin II (Ang II) can be broken down by ACE2 to yield
Ang17, which itself has biological activity
26
. Tere are
many potential targets for treatment becoming avail-
able. One potential target has been the initial step in
the cascade inhibition of the enzymatic activity of renin
itself.
Aliskiren is a direct renin inhibitor. Early work su-
ggested that it might have a more profound efect on
su ppressing natriuretic peptide production than stan-
dard therapy
27
, and its ability to avoid any escape from
ACE inhibition makes it an attractive agent. However,
two trials have cast doubt on its efectiveness. In the
ALTITUDE trial
28
, 8561 patients with diabetes, chro-
nic kidney disease, cardiovascular disease or both were
randomized to receive aliskiren or placebo in addition
to standard therapy. Te trial was stopped early afer
an interim efcacy analysis, and there was a suggesti-
on (although not statistically signicant) that aliskiren
might be harmful. In the ASTRONAUT study
29,30
, 1639
patients were randomized to aliskiren or placebo aro-
und 5 days afer an index heart failure admission, again
in addition to standard therapy. Tere was no efect on
the main outcome measures of cardiovascular death or
rehospitalization with heart failure at 6 and 12 months,
but a denite signal that aliskiren might be deleterious
in patients with diabetes.
Te ATMOSPHERE study
31
is rather diferent. It is a
study of patients with chronic heart failure due to lef
ventricular systolic dysfunction and a raised natriure-
tic peptide level. Patients are randomized to aliskiren,
enalapril or both. Fewer patients have diabetes (around
a third), and renal function is considerably less im-
paired in patients in the ATMOSPHERE trial than in
those in the ALTITUDE study
32
. Te results of the AT-
MOSPHERE trial should give a much more profound
Vol. 23, No. 4, 2013
Andrew L Clark
understanding of the possible role of aliskiren: it is su-
rely possible that it might have a role as an alternative to
conventional RAAS blockade rather than as an add-on.
Aldosterone antagonists
Te problem of heart failure with a normal ejection
fraction (HeFNEF) remains tricky. It has proved a di-
fcult entity to dene clinically despite its apparent
freq uency in epidemiological studies, and no clinical
trial has yet shown any convincing benet from any
treat ment strategy. Another disappointment is spiro-
nolactone. In patients with heart failure due to lef
ven tricular systolic dysfunction, there is no doubt that
mineralocorticoid antagonists help improve cardiac
function, symptoms and survival
33
. Mineralocorticoid
antagonists might be thought to be particularly likely
to work in HeFNEF through their antibrotic pro-
perties. However, in the Aldo-DHF study conducted
in 422 patients with HeFNEF, spironolactone had no
efect on exercise capacity, symptoms or quality of life
34
.
Te mean N-terminal prohormone of brain natriuretic
peptide level in the patients included in the study was
only 158 ng/L, suggesting that yet again a trial of HeF-
NEF has included patients who really do not have heart
failure or, if they do, they are patients with an intrinsi-
cally good prognosis.
DEVICE THERAPY AND MONITORING
Remote monitoring
Tere has been a great deal of enthusiasm for telemo-
nitoring, particularly among commissioners who see it
as a way of reducing admissions to hospital among pa-
tients with chronic disease. Te role of remote monito-
ring for patients with heart failure has been much deba-
ted. Although early studies suggested that there might
be a major benet, more recent trials have been much
less positive, perhaps because the background standard
of care against which telemonitoring is being compared
has improved.
It might be that targeted intensive monitoring during
periods of high risk, such as immediately afer hospital
discharge, makes the best use of remote monitoring. In
a meta-analysis of trials involving over 6000 patients,
Pandor et al
35
found that remote monitoring following
an admission with heart failure was associated with im-
proved survival, particularly where usual care was less
good.
Debrillators
It is commonly thought that having discharges from an
implantable cardioverter-debrillator (ICD), whether
appropriate or inappropriate, is associated with an
adverse prognosis in patients with heart failure
36
. Te
commonest reason for an inappropriate shock is atrial
brillation with a rapid ventricular response; additio-
nally, it is becoming increasingly apparent that antita-
chycardia pacing may treat ventricular tachycardia wi-
thout a shock being necessary. Te MADIT-RIT trial
37

reported that programming techniques that both in-
crease antitachycardia pacing and delay ICD discharges
reduce the risk of inappropriate discharge. Tere was a
reduction in all-cause mortality of around a half in the
advanced programming group.
Intriguingly, in a cohort study of 1698 patients,
Deyell et al
38
found no association between inappropri-
ate ICD shock and an adverse outcome. In contrast, an
appropriate shock was associated with a HR of 3.11
for the combined endpoint of death and transplantati-
on. Te reasons for the discrepancy are not clear: it may
be related to the fact that the patients in Deyell et als
cohort were less severely symptomatic and were more
likely to be on blocker therapy. However, regardless
of the prognostic implications, by reducing inappropri-
ate shocks, advanced programming of ICDs improves
patients quality of life by reducing the risk of a very
unpleasant ICD discharge.
Cardiac resynchronisation therapy
Te other major device for heart failure is, of course,
the cardiac synchronization therapy (CRT) pacema-
ker. Although it has been proved to increase life expec-
tancy in patients with heart failure due to lef ventricu-
lar systolic dysfunction, sinus rhythm and lef bundle
branch block, controversies remain. Many are convin-
ced that patients in atrial brillation or other forms of
conduction defect might benet, although there is no
evidence from randomized trials to support these be-
liefs
39,40
. A particular recurring theme is the concept of
response: around a third of patients are said not to res-
pond to CRT based on either their symptom status or
some echocardiographic index of lef ventricular func-
tion. Te subtext is that there might be some patients
with conventional indications for CRT who perhaps
should be denied the treatment, and others with no in-
dication who might benet based on some measure of
so-called dyssynchrony preoperatively.
As Witte points out
41
, deactivating a CRT device in
a supposed non-responder results in hemodynamic
wor sening
42
. Dening response in terms of symptoma-
tic change, or worse, a surrogate measure such as lef
ven tri cular volume, is doomed to fail we cannot
know what would otherwise have happened to the pa-
Andrew L Clark
Vol. 23, No. 4, 2013
waiting lists are at high risk of sudden death, and in a

retrospective observational study of over 1000 patients
listed for potential cardiac transplantation, Frlich et
al found a marked survival benet for patients recei-
ving an ICD for primary prevention independent of
the etio logy of heart failure only around one-third
of the patients had ischemic heart disease
50
. Te efect
was very much less marked for patients receiving an
ICD for secondary prevention. Maybe ICDs should be
considered more widely in patients on a transplant wai-
ting list.
Some cells from myocardial biopsy samples cluster
together to form cardiospheres which can potentially
diferentiate into many cell types. In a very small study
to demonstrate safety, patients treated with intracoro-
nary cardiosphere-derived cells (CDCs) following
myo cardial infarction had smaller volumes of scar and
lar ger volumes of viable heart mass than those recei-
ving standard care
51
. CDCs join a long list of potential
sou rces of stem cells, none of which has really borne
fruit despite enormous enthusiasm.
peer reviewed.
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A fascinating new device for patients with chronic
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tially be combined with existing devices
46
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chronic heart failure commonly have an imbalance be-
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47
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48
.
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brillators should be used. Te UK guidelines on referral
for heart transplantation
49
address the issue of use of
implantable debrillators in terms of NICE guidance,
and point out that we do not have much information
to guide the management of those without ischemic
heart disease. However, patients on cardiac transplant
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851
REVIEWS
Almanac 2013: cardiac arrhythmias and pacingan editorial
overview of selected research that has driven recent advances in
clinical cardiology*
Reginald Liew
1,2
Received 5 July 2013. Revised 16 July 2013. Accepted 18 July 2013
Contact address:
Reginald Liew, MD,
Gleneagles Hospital, 6A Napier Road, Singapore 258500, Singapore
E-mail: reginald.liew@duke-nus.edu.sg
Abstract: Important advances have been made in the past few years in the elds of clinical cardiac electrophysiology and
pa cing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial
brillation (AF), which has transpired into improved methods of detection, risk stratication, and treatments. Te introduc-
tion of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate
to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symp-
tomatic AF. Another area of intense research in the eld of cardiac arrhythmias and pacing is in the use of cardiac resynchro-
nization therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark rando-
mized controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves
symptoms, many subsequent studies have been performed to further rene the selection of patients for CRT and determine
the clinical characteristics associated with a favorable response. Te eld of sudden cardiac death and implantable cardiover-
ter debrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on
improved methods for patient selection, risk stratication, and management. Tis review covers the major recent advances in
these areas related to cardiac arrhythmias and pacing.
ATRIAL FIBRILLATION
Epidemiology of atrial brillation
A number of large scale epidemiological studies using
registry databases and prospective cohort data have
reported novel associations between atrial brillation
(AF) and other non-traditional risk factors for AF. Te-
se include an increased risk of incident AF in patients
with high glycosylated hemoglobin (HbA1c) and poor
glycemic control
1
, coeliac disease
2
, rheumatoid arthri-
tis
3
and psoriasis
4
, use of non-aspirin, non-steroidal
anti-inammatory drugs (NSAIDs)
5
, and increased
height
6
. Another interesting association is the nding
from a substudy of 260 patients with chronic AF from
the SAFETY trial (Standard versus Atrial Fibrillation
Specic Management Study) that mild cognitive impai-
r ment is highly prevalent among older, high risk pa-
tients hospitalized with AF
7
. In another substudy of
the Cardiovascular Health Study, investigators found
that higher base-line circulating concentrations of to-
tal long chain n-3 polyunsaturated fatty acids (PUFA)
were associated with a lower risk of incident AF
8
.
Other interesting recent epidemiological studies on
AF include the association of incident AF with an in-
creased risk of developing end stage renal disease in pa-
tients with chronic kidney disease
9
, and a community
based study of 3220 patients which showed that new
AF in patients with no history of AF before a myocardi-
al infarction increased mortality in patients with myo-
cardial infarction
10
. In a large Swedish registry study of
100 802 patients with AF, Friberg et al
11
found that is-
chemic strokes were more common in women than in
men, supporting the notion that female gender should
be taken into consideration when making decisions
about anticoagulation treatment. Furthermore, among
older patients admitted with recently diagnosed AF, the
risk of stroke appears to be greater in women than in
men, regardless of warfarin use
12
, and among healthy
women new onset AF was found to be independently
1
Duke-NUS Graduate Medical School, Singapore, Singapore
2
Gleneagles Hospital, Singapore, Singapore
* To cite: Liew R. Heart. Published Online First: doi:10.1136/
heartjnl-2013-304592
Vol. 23, No. 4, 2013
855
Reginald Liew
Almanac 2013: cardiac arrhythmias and pacing
associated with all cause cardiovascular and non-car-
dio vascular mortality
13
.
Medical management of AF
Data from the RealiseAF study, an international, ob-
servational, cross-sectional survey of patients with any
history of AF in the previous year, suggested that pati-
ents in which their AF was controlled (dened as si-
nus rhythm or AF with a resting heart rate 80 beats/
min) had a better quality of life and fewer symptoms
than those whose AF was uncontrolled
14
. Nonetheless,
even patients with controlled AF experienced frequent
symptoms, functional impairment, altered quality of
life and cardiovascular events-hence the importance of
ongoing eforts to develop novel and better treatments
for AF. Te RECORDAF (Registry on Cardiac Rhythm
Disorders Assessing the Control of Atrial Fibrillation) re-
gistry was a worldwide, prospective observational sur-
vey of AF management in an unselected, community
based cohort over a 12 months period
15
. Te investiga-
tors found that in 5171 patients whose data were avai-
lable, therapeutic success (driven by control of AF) was
achieved in 54% overall (rhythm control 60% vs rate
control 47%). Te choice of rate or rhythm strategy did
not afect clinical outcomes (which were driven mainly
by hospitalizations for arrhythmia and other cardiovas-
cular causes), although the choice of rhythm control re-
duced the likelihood of AF progression.
Te RACE (Rate Control Efcacy in Permanent Atri-
al Fibrillation) II trial was the rst formal assessment of
alternative rate control goals in AF and demonstrated
for the rst time that a lenient rate control strategy
(target resting heart rate <110 beats/min) was non-
inferior to a strict rate control strategy (target resting
heart rate <80 beats/ min and heart rate during mode-
rate exercise <110 beats/min)
16
. Two subsequent sub-
studies of the RACE II trial showed that the stringency
of rate control had no signicant efect on the quality
of life in patients with permanent AF
17
and that leni-
ent rate control did not have an adverse efect on atrial
and ventricular remodeling compared with strict rate
control (although female gender was independently
associated with signicant adverse cardiac remode-
ling)
18
. In another sub-study looking at cardiovascular
outcomes in subjects from the original AFFIRM trial
(Atrial Fibrillation Follow-Up Investigation of Rhythm
Management), investigators found that the composite
outcome of mortality or cardiovascular hospital stays
was better in rate compared with rhythm control stra-
tegies (using amiodarone or sotalol)
19
. Non-cardiovas-
cular death and intensive care unit hospital stay were
more frequent in patients on amiodarone, and time to
cardiovascular hospital stay was shorter. In a prospec-
tive, randomized, open label trial of pharmacological
cardioversion in patients with persistent AF, Yamase et
al compared amiodarone with bepridil in 40 consecuti-
ve subjects
20
. Te investigators found that bepridil was
superior to amiodarone in achieving sinus conversion
(85% vs 35%; p<0.05) and maintaining sinus rhythm af-
ter an average follow-up of 14.7 months (75% vs 50%).
Te issue of whether PUFA have any benecial efects
on AF remains a topical one. A large meta-analysis of
10 randomized controlled trials involving 1955 patients
found that PUFA supplementation had no signicant
efect on AF prevention
21
. In the FORWARD trial (Ran-
domized Trial to Assess Efcacy of PUFA for the Mainte-
nance of Sinus Rhythm in Persistent Atrial Fibrillation),
586 outpatient participants with conrmed symptoma-
tic paroxysmal AF who required cardioversion or had
at least two episodes of AF in the preceding 6 months
were randomly assigned to receive placebo or PUFA
(1 g/day) for 12 months
22
. Te investigators found
that PUFA supplementation did not reduce the recur-
rence of AF or have any benecial efects on the other
prespecied end points (all cause mortality, non-fatal
stroke, non-fatal acute myocardial infarction, systemic
embolism or heart failure). In a large placebo contro-
lled, randomized clinical trial involving 1516 patients
in 28 centres, perioperative supplementation of PUFA,
although well tolerated, was not shown to reduce the
risk of postoperative AF
23
. In contrast, another rando-
mized, double blind, placebo controlled trial involving
199 patients who received either PUFA (2 g/day) or
placebo for 4 weeks before direct current (DC) cardi-
oversion found that patients who received PUFA were
more likely to be in sinus rhythm at 1 year follow-up
compared with control patients
24
.
Monitoring and assessment of AF
Te detection of paroxysmal AF can be difcult with
current methods and technology; hence ongoing eforts
are being made to improve methods for detection and
diagnosis. Te association between subclinical AF and
cryptogenic stroke has gained increasing prominence
with more careful monitoring of patients using invasive
and non-invasive methods. In a nice study of 2580 pa-
tients aged 65 years or older with a pacemaker or de-
brillator recently implanted and no history of AF, in-
vestigators detected subclinical atrial tachyarrhythmia
in 261 patients (10.1%)
25
. Over a mean follow-up of
2.5 years, patients with subclinical atrial tachyarrhyth-
mias were found to have an increased risk of clinical
Reginald Liew
Vol. 23, No. 4, 2013
856
AF and of ischaemic stroke or systemic embolism (HR
2.49, 95% CI 1.28 to 4.85; p=0.007). In patients who
do not have pacemakers or debrillators who present
with cryptogenic stroke, longer term ambulatory ECG
monitoring using external or implantable devices may
be worth considering to help conrm a diagnosis of
subclinical AF
26,27
. In a study of 100 patients being scre-
ened for AF, investigators compared the efectiveness of
using 7-day triggered ECG monitoring with 7-day con-
tinuous Holter ECG monitoring for detection of AF
28
.
An arrhythmia was recorded in 42 subjects (42%) with
continuous ECG recordings versus 37 subjects (32%)
with triggered monitoring (p=0.56). Te sensitivity of
triggered ECG monitoring was found to be lower than
that of continuous ECG monitoring, mainly due to a
shorter efective monitoring duration, although quali-
tative triggered ECG analysis was less time consuming
than continuous ECG analysis. In another larger study
of 647 patients with implantable continuous moni-
toring devices, intermittent rhythm monitoring was
found to be signicantly inferior to continuous moni-
toring for the detection of AF and was not able to iden-
tify AF recurrence in a great proportion of patients at
risk
29
. In an interesting study investigating the use of N-
terminal pro B-type natriuretic peptide (NT-proBNP)
values to estimate the recency of AF onset and safety of
cardioversion, investigators separated 86 patients pre-
senting with presumed recent onset AF into two groups
(43 in each group), based on NTproBNP concentrati-
ons above and below a cut-of value, and subjected all
subjects to transoesophageal echocardiography
30
. NT-
proBNP concentrations below the cut-of value were
found to be the most powerful predictor of the presen-
ce of thrombus, suggesting that a short term increase in
NT-proBNP afer AF onset might be useful in assessing
the recency of onset of the AF episode, if unknown, and
might be potentially used to help determine the safety
of cardioversion.
Catheter ablation of AF
Although antiarrhythmic drugs (AADs) and catheter
ablation are the main treatment options available to
maintain sinus rhythm in symptomatic patients with
AF, many clinicians and patients still opt for an initi-
al conservative strategy and consider catheter ablati-
on only afer one or more AADs have been tried and
found to be inefective. Te question of whether ca-
theter ablation of AF is an efective initial therapy for
paroxysmal AF was addressed in a small randomized
study in which 294 patients (with no history of AAD
use) were randomly assigned to an initial strategy with
radiofrequency catheter ablation or therapy with a class
1c or III AAD
31
. Te investigators found no signi-
cant diference between the ablation and drug therapy
groups in the cumulative burden of AF (90
th
centile of
arrhythmia burden 13% and 19%, respectively; p=0.10)
in the initial 18 months. However, at 24 months, AF
burden was signicantly lower in the ablation group
compared with the drug therapy group (9% vs 18%;
p=0.007) and more patients in the ablation group were
free from symptomatic AF (93% vs 84%; p=0.01). In
the drug therapy group, 54 patients (36%) subsequently
underwent ablation.
In another small randomized study of AF ablation in
patients with persistent AF, advanced heart failure and
severe lef ventricular (LV) systolic dysfunction, Mac-
Donald et al
32
found that catheter ablation was success-
ful at restoring sinus rhythm in 50% of patients, althou-
gh the procedure was associated with a signicant
complication rate of 15%. In addition, catheter abla-
tion did not improve LV ejection fraction (LVEF) (as
measured using cardiovascular magnetic resonance)
or other secondary outcomes, calling into question the
risk/benet ratio of performing AF ablation in patients
with persistent AF and LV dysfunction. An internatio-
nal multicentre registry study of 1273 patients under-
going AF ablation suggested that maintenance of sinus
rhythm through catheter ablation was associated with a
lower risk of stroke and death compared with a control
group consisting of medically treated patients with AF
in the Euro Heart Survey
33
.
Several studies have recently been reported which
increase our understanding of the factors associated
with success or failure following AF ablation. Te im-
portance of pulmonary vein (PV) isolation was further
reinforced by Miyazaki et al
34
who reported long term
clinic outcomes of 83.6% (480 out of 574 patients) with
a mean follow-up of 2714 months using an extensive
PV isolation approach in patients with both paroxys-
mal and persistent AF
34
. Late recurrences (dened as
612 months following the initial AF ablation proce-
dure) was associated with PV reconnection in all pa-
tients, while very late recurrences (>12 months afer
the procedure) were associated with non-PV triggers
in 85.7% of cases. Te added benet of performing
additional linear ablation lines afer PV isolation on
improving outcomes following AF ablation has been
further questioned in a prospective, randomized
study of 156 patients with paroxysmal AF who were
randomly assigned to undergo PV isolation only, PV
isolation and a roof line, or PV isolation, roof line and
Vol. 23, No. 4, 2013
85I
Reginald Liew
a posterior inferior line
35
. Te investigators found no
improvement in clinical outcome in the patients who
received the additional lines while, unsurprisingly, the
addition of the linear ablations signicantly prolonged
procedure times. A number of investigators have found
that many factors are predictive of or adversely related
to outcome following AF ablation in addition to well
established factors, such as type of AF (paroxysmal or
persistent), lef atrial size, and presence of LV dysfunc-
tion. Tese novel factors include cardiac related factors,
such as atrial electromechanical interval on pulse wave
Doppler imaging
36
and lef atrial brosis as assessed by
measuring echocardiograph derived calibrated integra-
ted backscatter
37
, pericardial fat
38
, plasma biomarkers
(such as plasma B-type natriuretic peptide values
39
),
renal dysfunction
40
, and the metabolic syndrome
41
.
Interestingly, the presence of dissociated PV potenti-
als, ofen used as a marker of successful PV isolation,
was not found to predict AF recurrence in a study of
89 consecutive patients over a mean follow-up of 218
months
42
. In a small randomized controlled study of
161 patients, a 3 month course of colchicine (0.5 mg
twice daily) was found to decrease early AF recurren-
ce afer PV isolation, probably due to a reduction in
inammatory mediators, including interleukin 6 (IL-6)
and C reactive protein (CRP)
43
. Colchicine (1.0 mg twi-
ce daily initially followed by a maintenance dose of 0.5
mg twice daily for 1 month) was also found to reduce
the incidence of post-operative AF and decrease in-ho-
spital stay in a multicentre, double blind, randomized
trial of 336 patients
44
. In an interesting small randomi-
zed study of PV isolation with and without concomitant
renal artery denervation in 27 patients with refractory
symptomatic AF and resistant hypertension, Pokusha-
lov et al showed that renal artery denervation reduced
systolic and diastolic blood pressure and reduced the
recurrence of AF during 1 year follow-up
45
.
Another area of research in the eld of AF ablati-
on has been on the factors associated with increased
complications from the procedure. Using data from the
California State Inpatient Database, Shah et al found
that among 4156 patients who underwent an initial
AF ablation procedure, 5% had periprocedural com-
plications (most commonly vascular) and 9% were
readmitted within 30 days
46
. Factors associated with a
higher risk of complications and/or 30-day readmissi-
on following an AF ablation were older age, female sex,
prior AF hospitalizations, and recent hospital proce-
dure experience. In another retrospective study of 565
patients, both the CHADS
2
and CHA
2
DS
2
-VASc scores
were found to be useful predictors of adverse events
following AF ablation
47
.
Te rst randomized clinical trial comparing the
efcacy and safety of catheter ablation of AF with sur-
gical ablation involved 124 patients with drug refrac-
tory AF
48
. Te investigators found that the primary
end point (freedom from lef atrial arrhythmia >30 s
without AADs afer 12 months) was 36.5% for the ca-
theter ablation group and 65.6% for the surgical group
(p=0.0022), but patients in the surgical group experien-
ced signicantly greater adverse efects (driven mainly
by procedural complications) compared to the cathe-
ter ablation group. Pison et al reported relatively high
1 year success rates (93% for paroxysmal AF and 90%
for persistent AF) with a combined transvenous endo-
cardial and thorascopic epicardial approach for a single
AF ablation procedure in a small cohort of 26 patients
with AF
49
.
Strategies to decrease thromboembolism
Te use of novel oral anticoagulants to decrease the risk
of stroke and systemic thromboembolism in patients
with AF has gained increasing use and acceptance over
the past several years following the publication of a
number of landmark multicentre, randomized clinical
trials comparing their efcacy with conventional vita-
min K antagonists
50-53
. A meta-analysis of 12 studies
totaling 54 875 patients showed a signicant reducti-
on of intracranial hemorrhage with these novel anti-
coagulants compared with vitamin K antagonists, and
a trend toward reduced major bleeding
54
. Tese novel
oral anticoagulants may also have a role in patients
undergoing DC cardioversion. A sub-study of patients
with AF who underwent cardioversion in the RE-LY
(Randomized Evaluation of Long-Term Anticoagulation
Terapy) trial showed that dabigatran (at two doses of
110 and 150 mg twice daily) is a reasonable alternative
to warfarin, with low frequencies of stroke and major
bleeding within 30 days of cardioversion
55
.
Tese novel oral anticoagulants may also have a role
to play in the periprocedural anticoagulation of patients
undergoing radiofrequency ablation for AF. Several re-
gistry and observational studies have suggested that
dabigatran is as safe as periprocedural warfarin in pa-
tients undergoing AF ablation
56-58
, although one study
suggested an increased risk of bleeding and thrombo-
embolic complications with dabigatran compared with
warfarin
59
. A prospective randomized controlled trial is
required to denitively address the issue as to whether
these novel oral anticoagulants can be used in place of
warfarin for periprocedural anticoagulation in patients
Reginald Liew
Vol. 23, No. 4, 2013
858
decreased the risk of heart failure events in relatively
asymptomatic patients with a low ejection fraction
and wide QRS complexes
66
, a number of subsequent
analyses have provided further interesting information.
Tis includes data on the benets of CRT in reducing
the risk of recurring heart failure events
67
and atrial ar-
rhythmias
68
, identication of additional factors that are
associated with improved response to CRT
69,70
and with
a super-response (dened by patients in the top quar-
tile of LVEF change)
71
, factors associated with greatest
improvement in quality of life
72
, and information on
optimal lead positioning of the LV lead
73,74
.
In a prospective, randomized controlled study to
address whether ventricular dysynchrony on echocar-
diography predicted response to CRT, Diab et al found
that the presence of echocardiographic dysynchrony
identied patients who derived the most improvement
from CRT, although patients without dysynchrony also
showed more benet and less deterioration with CRT
than without. Te authors concluded that the latter
group of patients should not be denied CRT
75
. CRT ap-
peared to produce some benets in patients with heart
failure and a normal QRS duration, with patients expe-
riencing an improvement in symptoms, exercise capa-
city and quality of life, although there was no diferen-
ce in total or cardiovascular mortality in patients who
received CRT compared with those receiving optimal
pharmacological management
76
. Among patients with
heart failure and prolonged QRS duration who recei-
ved a CRT device, those with a lef bundle branch block
(LBBB) morphology derived greater benet (lower risk
of ventricular arrhythmias and death and improved
echocardiographic parameters) compared with pati-
ents who had a non-LBBB QRS pattern (right bundle
branch block (RBBB) or intraventricular conduction
disturbances)
77
.
Te issue of whether CRT in patients undergoing
atrioventricular (AV) junction ablation for permanent
AF was superior to conventional RV pacing in reducing
heart failure events was addressed in a prospective, ran-
domized, multicentre study involving 186 patients
78
.
Over a median follow-up of 20 months (IQR 11-24
months) fewer patients in the CRT group (11%) expe-
rienced primary end point events (death from heart fa-
ilure, hospitalization due to heart failure or worsening
heart failure) compared with patients in the RV group
(26%; CRT vs RV group: sub-hazard ratio (SHR) 0.37,
95% CI 0.18 to 0.73; p=0.005). Total mortality was si-
milar in both groups. In a follow-up analysis looking at
the predictors of clinical improvement afer the ablate
undergoing AF ablation. Economic evaluation of these
novel oral anticoagulants suggest that they may be cost
efective as a rst line treatment for the prevention of
stroke and systemic embolism
60
, especially in patients
at high risk of hemorrhage or stroke, unless inter- na-
tional normalized ratio (INR) control with warfarin is
already excellent
61
.
Another strategy to decrease thromboembolic
e vents in patients with AF that is gaining favor invol-
ves the use of mechanical lef atrial appendage (LAA)
occ lu sion devices. In a systematic review of 14 studies,
im p la n tation of LAA occlusion devices in patients with
AF was successful in 93% of cases, with periprocedural
mor tality and stroke rates of 1.1% and 0.6%, respecti-
vely; the overall incidence of stroke among all studies
was 1.4% per annum
62
. A substudy of the PROTECT AF
(Percutaneous Closure of the LAA versus Warfarin Te-
rapy for Prevention of Stroke in Patients with AF) study
repo rted that 32% of implanted patients had some de-
gree of peridevice ow at 12 months on transoesopha-
geal echo cardiography, although this did not appear to
be associated with an increased risk of thromboembo-
lism com pared to patients with no peridevice ow who
disco n tinued warfarin
63
. A systematic review aimed at
determining which subgroups of patients would benet
most from LAA closure devices looked at the location
of atrial thrombi in patients with AF in a total of 34 stu-
dies
64
. Te investigators concluded that patients with
non-valvular AF may derive greater benet from LAA
closure devices 56% of patients with valvular AF had
atrial thrombi located outside the LAA, 22% in mixed
cohorts and 11% in non-valvular AF patients.
CARDIAC RESYNCHRONISATION THERAPY AND
PACING
Cardiac resynchronization therapy
Recent research in the area of cardiac resynchronizati-
on therapy (CRT) has looked at the long term efects of
CRT pacing on LV and right ventricular (RV) function
and further into which sub-groups of patients may de-
rive greatest benet from CRT pacing. A favorable RV
functional response to CRT appears to be associated
with improved survival in patients with CRT devices,
and RV function was found to be an independent pre-
dictor of long term outcome afer CRT insertion in a
study of 848 CRT recipients
65
. Following the landmark
MADIT-CRT (Multicenter Automatic Debrillator Im-
plantation Trial-Cardiac Resynchronization Terapy)
study, which demonstrated that CRT combined with
implantable cardioverter debrillator (ICD, CRT-D)
Vol. 23, No. 4, 2013
859
Reginald Liew
ents have a long history of recurrent syncope and may
benet from cardiac pacing, although in a small series
of 18 patients (followed up for up to 14 years), no pa-
tient had permanent AV block
86
. Te prognosis among
healthy individuals admitted with their rst episode of
syncope was studied in a Danish nationwide registry
involving 37 017 patients with syncope and 185 085
age and sex matched controls
87
. Patients who were ad-
mitted with syncope had signicantly increased all ca-
use mortality, cardiovascular hospitalization, recurrent
syncope and stroke event rates and were more likely to
have a pacemaker or ICD inserted later.
CIED related infection
CIED infection is recognized as a signicant cause of
morbidity, mortality, and increased healthcare costs.
Te clinical characteristics, outcome, and health care
implications of CIED related infections and endocar-
ditis was analyzed in a prospective cohort study using
data from the International Collaboration on Endocar-
ditis-Prospective Cohort Study (ICE-PCE) involving
61 centres in 28 countries
88
. CIED infection was dia-
gnosed in 177 out of 2760 patients (6.4%). In-hospital
and 1 year mortality rates were 14.7% (95% CI 9.8% to
20.8%) and 23.2% (95% CI 17.2% to 30.1%), respecti-
vely. Te rate of concomitant valve infection was high
(found in 66 patients, 37.3%, 95% CI 30.2% to 44.9%)
and early device removal was associated with impro-
ved survival at 1 year. In an attempt to assess the long
term outcomes and predictors of mortality in patients
treated according to current recommendations for
CIED infection, Deharo et al conducted a two-group
matched cohort study of 197 cases of CIED infection
89
.
Long term mortality rates were similar between cases
and matched controls (14.3% vs 11.0% at 1 year and
35.4% vs 27.0% at 5 years, respectively; both p=NS). In-
dependent predictors of long term mortality were older
age, CRT, thrombocytopenia, and renal insufciency.
In another study examining whether the timing of the
most recent CIED procedure inuenced the clinical
presentation and outcome of lead associated endocar-
ditis (LAE), investigators found that early LAE presen-
ted with signs and symptoms of local pocket infection,
whereas a remote source of bacteremia was present in
38% of late LAE but only 8% of early LAE
90
. In-hospital
mortality was low (early 7%; late 6%).
and pace strategy, more patients in the CRT group res-
ponded to treatment (83% vs 63% in the RV group)
79
.
CRT mode and echo-optimized CRT were found to be
the only independent protective factors against non-
response (HR=0.24, 95% CI 0.10 to 0.58, p=0.001 and
HR=0.22, 95% CI 0.07 to 0.77, p=0.018, respectively).
In the PACE (Pacing to Avoid Cardiac Enlargement) tri-
al, RV pacing in patients with bradycardia and preser-
ved LVEF was associated with adverse LV remodelling
and deterioration of systolic function at the second
year, which was prevented by biventricular pacing
80
.
Heart block and pacemakers
Te long term survival of older patients (average age
75 9 years) with Mobitz I second degree AV blo-
ck was examined in a retrospective cohort study of
299 pa tients
81
. Te investigators found that 141 pa-
tients (47%) had a cardiac implantable electronic de-
vice (CIED) inserted during the follow-up period, of
which 17 were ICDs. Patients with a CIED had grea-
ter cardiac co morbidity than those without a CIED,
although CIED implantation was associated with a 46%
reduc tion in mortality (HR 0.54, 95% CI 0.35 to 0.82;
p=0.004). In another observational study of the impact
of the ventricular pacing site on LV function in chil-
dren with AV block, van Geldrop et al found that LV
fractional shortening was signicantly higher with LV
pacing than with RV pacing
82
.
Further research on the topic of whether cardiac
pacing is benecial in patients with neurally mediated
syncope suggests that dual chamber pacing may be use-
ful in patients with severe asystolic forms. In the ran-
domized multicentre ISSUE-3 trial (Tird International
Study on Syncope of Uncertain Etiology) patients with
syncope due to documented asystole on an implantable
loop recorder were randomly assigned to dual cham-
ber pacing with rate drop response or to sensing only
83
.
Tose assigned to dual chamber pacing had fewer
syncopal episodes during follow-up (32% absolute
and 57% relative reduction in syncope). A positive test
with intravenous adenosine 50-triphosphate (ATP) has
been shown to correlate with a subset of patients with
neurally mediated syncope
84
. A randomized, multicen-
tre trial of the potential benet of the ATP test in el-
derly patients (mean age 75.97.7 years) with syncope
of unknown origin reported that active dual chamber
pacing in those with a positive ATP test reduced synco-
pe recurrence risk by 75% (95% CI 44% to 88%)
85
. Long
term outcome data on a distinct form of AV block,
paroxysmal AV block, which cannot be explained by
currently known mechanisms, suggest that these pati-
Reginald Liew
Vol. 23, No. 4, 2013
860
city (African Americans having a higher risk) as well as
traditional risk factors
96
.
More intense research has been conducted in a va-
riety of settings on the early repolarization syndrome
(ERS) since landmark studies showed a link with idi-
opathic ventricular brillation and sudden death
97,98
.
Tese include studies on ERS on cardiac arrest survi-
vors with preserved ejection fraction
99
, in families with
sudden arrhythmic death syndrome
100
and other fami-
lies with an early repolarization pattern on the ECG
101
,
and in Asian populations
102
. However, there is still
some controversy over the exact clinical signicance of
these ECG ndings and what the implications are
103,104
.
Te genetics of inherited cardiac conditions and
how specic genotypes can lead to clinical manifesta-
tions of disease, afect SCD risk or guide management
continues to attract intense interest
105-108
. Results from
the DARE (Drug-induced Arrhythmia Risk Evaluation)
study, in which 167 single nucleotide polymorphisms
spanning the NOS1AP gene, were evaluated in 58 Cau-
casian patients who had experienced drug induced QT
prolongation and 87 Caucasian controls, demonstra-
ted that common variations in the NOS1AP gene were
associated with a signicant increase in drug induced
long QT syndrome
109
. Tis may have clinical implicati-
ons for future pharmacogenomics testing in patients at
risk of drug induced long QT syndrome and safer pre-
scribing. In another study assessing whether non-car-
diovascular hERG (human Ether go-go-Related Gene)
channel blockers are associated with an increased risk
of SCD in the general population, investigators com-
pared 1424 cases of SCD with 14 443 controls
110
. Use
of hERG channel blockers was found to be associated
with an increased risk of SCD and drugs with a high
hERG channel inhibiting capacity had a higher risk of
SCD than those with a low hERG channel inhibiting
capacity.
Implantable cardioverter debrillators
Te clinical parameters associated with death befo-
re appropriate ICD therapy in patients with ischemic
heart disease who had an ICD inserted for primary
prevention were assessed in a retrospective cohort
study of 900 patients
111
. Te investigators found that
New York Heart Association (NYHA) functional class
III, advanced age, diabetes mellitus, LVEF 25%, and
a history of smoking were signicant independent pre-
dictors of death without appropriate ICD therapy, and
suggested that this information may facilitate a more
patient tailored risk estimation. Another risk score for
predicting acute procedural complications or death af-
VENTRICULAR ARRHYTHMIAS AND SUDDEN CARDIAC
DEATH
Epidemiology of sudden cardiac death
Sudden death is a frequent and well recognized risk
in patients following myocardial infarction. In a study
analyzing data from 1067 patients from VALIANT
(Valsartan in Acute Myocardial Infarction Trial) who
had sudden death, investigators found that a high pro-
portion of the deaths occurred at home, although in-
hospital events were more common early on
91
. Patients
who were asleep were more likely to have unwitnessed
events. Although sudden cardiac death (SCD) and co-
ronary artery disease (CAD) have many risk factors in
common, certain clinical and electrocardiographic
parameters may be useful to help separate out the two
risks. For example, in a study of 18 497 participants
from the ARIC (Atherosclerosis Risk in Communities)
study and the Cardiovascular Health Study, Soliman
et al found that afer adjusting for common CAD risk
factors, hypertension, increased heart rate, QTc prolon-
gation, and abnormally inverted T waves were found
to be stronger predictors of high SCD risk
92
. In com-
parison, elevated ST segment height (measured at both
the J point and 60 ms afer the J point) was found to be
more predictive of high incident CAD risk.
More research has also been performed on SCD in
other sub-groups. In a prospective, national survey of
sports related sudden death performed in France from
2005 to 2010, involving subjects 10-75 years of age,
investigators found that the overall burden of sudden
death was 4.6 per million population per year, with 6%
of cases occurring in young competitive athletes and
more than 90% of cases occurring in the context of re-
creational sports
93
. Bystander cardiopulmonary resus-
citation (CPR) and initial use of cardiac debrillation
were the strongest independent predictors for survival
to hospital discharge, although bystander CPR was
only initiated in one third of cases. In a retrospective
autopsy study of 902 young adults (mean age 3811
years) who had sufered non-traumatic sudden death,
the cause of sudden death was attributed to a cardi-
ac condition in 715 (79.3%) and unexplained in 187
(20.7%)
94
. In another nationwide study on the inciden-
ce of SCD in persons aged 1-35 years, 7% of all deaths
were attributed to SCD
95
. Te incidence of SCD in the
young, estimated to be 2.8% per 100 000 person-years,
was higher than previously reported. Risk factors for
SCD in post-menopausal women may include more
novel parameters, such as higher pulse, higher waist-
to-hip ratio, elevated white blood cell count, and ethni-
Vol. 23, No. 4, 2013
861
Reginald Liew
ventricle) with LVEF >30% had a similar risk to those
with LVEF 30%, while in patients with LVEF 30%,
minimal or no scarring was associated with low risk,
similar to those with LVEF >30%.
Te use of intracardiac ICD parameters to assess risk
has also received further attention. In a prospective,
multicentre study of 63 ICD patients, T wave alternans
and non-alternans variability (TWA/V) was found to
be signicantly greater before ventricular tachycardia/
ventricular brillation (VT/VF) episodes than during
baseline rhythm
117
. Te investigators suggested that
continuous measurements of TWA/V from the intra-
cardiac ICD electrograms may be a useful parameter to
detect impending VT/VF and allow the device to initi-
ate pacing therapies to prevent the ventricular arrhyth-
mias from occurring. In contrast, an early analysis of
a prospective, single centre study on the use of ICD
based ischemia monitoring on clinical care and pati-
ent management reported that this parameter was not
clinically useful and actually increased the number of
unscheduled outpatient visits in patients with this fea-
ture on their ICD compared with patients with ICDs
without this capability
118
.
Reports on the complications and negative aspects
of ICDs include problems associated with the Sprint
Fidelis ICD leads
119-121
and potential psychological im-
pact and phobic anxiety among ICD recipients
122
. In a
study of 3253 patients from 117 Italian centres who un-
derwent de novo implantation of a CRT-D device, in-
vestigators found that device related events were more
frequent in patients who received CRT-D devices com-
pared with those who received ICDs only (single or
dual chamber), although these events were not associ-
ated with a worse clinical outcome
123
. In a multicentre,
longitudinal cohort study of 104 049 patients receiving
single and dual chamber ICDs, dual chamber devi-
ce implantation was more common, but was associa-
ted with increased peri-procedural complications and
in-hospital mortality compared with single chamber
ICDs
124
. A retrospective, single centre cohort study of
334 hypertrophic cardiomyopathy patients with ICDs
reported that this group of patients had signicant car-
diovascular mortality and were exposed to frequent in-
appropriate shocks and implant complications
125
. Ad-
verse ICD related events (inappropriate shocks and/or
implant complications) were seen in 101 patients (30%;
8.6% per year), and patients with CRT-D were more li-
kely to develop implant complications than those with
single chamber ICDs and had a higher 5-year cardio-
vascular mortality rate.
ter ICD implantation using 10 readily available variables
from 268 701 ICD implants was developed to provide
useful information in guiding physicians on patient se-
lection and determining the intensity of post-implant
care required
112
. A risk score aimed at predicting the
long term (8 years) benet of primary prevention ICD
implantation was applied to 11 981 patients from the
MADIT-II trial
113
. Te investigators found that patients
with low and intermediate risk (0 or 1-2 risk factors,
respectively) benetted more from ICD implantation,
compared with patients with high risk (3 risk factors)
who had multiple comorbidities, in which there was no
signicant diference in 8 years survival between ICD
and non-ICD recipients.
Another risk score for the prediction of mortality
in Medicare beneciaries receiving ICD implantation
for primary prevention was developed from a cohort
of 17 991 patients and validated in a cohort of 27 893
patients
114
. Over a median follow-up of 4 years, 6741
(37.5%) patients in the development cohort and 8595
(30.8%) patients in the validation cohort died. Seven cli-
nically relevant predictors of mortality were identied
and used to develop a model for determining those pa-
tients at highest risk for death afer ICD implantation.
Future selection of ICD recipients for primary preven-
tion ICDs may therefore be rened and more perso-
nalized to the individual patients risk/ benet prole
with the use of such models, rather than being based
predominantly on LVEF, as is recommended by current
guidelines.
Other investigations, such as cardiac magnetic re-
sonance (CMR) imaging to identify and characterize
myocardial scar, may be a useful addition to future risk
stratication of patients for primary prevention ICD
implantation. Te ability of scar characteristics assessed
on CMR to predict ventricular arrhythmias was evalua-
ted in a study of 55 patients with ischemic cardiomyo-
pathy who received an ICD for primary prevention and
in whom CMR with late gadolinium enhancement had
been performed before ICD implantation
115
. All CMR
derived scar tissue characteristics were found to be pre-
dictive for the occurrence of ventricular arrhythmias,
supporting the potential use of this imaging modality
to help rene risk stratication of patients and improve
selection for ICD implantation. Tis nding was furt-
her supported by a prospective study of 137 patients
evaluated with CMR before ICD implantation for pri-
mary prevention
116
. Myocardial scarring on CMR was
found to be an independent predictor of adverse outco-
mes. Patients with signicant scarring (>5% of the lef
Reginald Liew
Vol. 23, No. 4, 2013
862
those that occurred at home (34% vs 12%, respectively;
adjusted OR 2.49, 95% CI 1.03 to 5.99; p=0.04)
136
. Ho-
spital characteristics associated with improved pati-
ent outcomes following OHCA were analyzed from the
Victorian Ambulance Cardiac Arrest Registry of 9971
patients over an 8 year period
137
. Outcome following
OHCA was found to be signicantly improved in ho-
spitals with 24 h cardiac interventional services (OR
1.40, 95% CI 1.12 to 1.74; p=0.003) and patient recep-
tion between 08.00 and 17.00 h (OR 1.34, 95% CI 1.10
to 1.64; p=0.004). OHCA in children was assessed in
a prospective, population based study of victims yo-
unger than 21 years of age
138
. Te incidence of pedia-
tric OHCA was 9.0 per 100 000 pediatric person-years
(95% CI 7.8 to 10.3), whereas the incidence of pedia-
tric OHCA from cardiac causes was 3.2 (95% CI 2.5 to
3.9). Te authors concluded that OHCA accounts for a
signicant proportion of pediatric mortality, although
the vast majority of OHCA survivors have a neurologi-
cally intact outcome.
Studies on the optimal sequence of CPR measures to
use in OHCA patients have reported varying results. In
a meta-analysis of four randomized controlled clinical
trials enrolling 1503 subjects with OHCA, no signicant
diference was found between chest compression rst
versus debrillation rst in the rate of return of spon-
taneous circulation, survival to hospital discharge or
favorable neurologic outcomes, although subgroup
analyses suggested that chest compression rst may be
benecial for cardiac arrests with a prolonged response
time
139
. In a more recent, nationwide, population ba-
sed observational study involving OHCA patients in
Japan who had a witnessed arrest and received shocks
with public access AED, compression only CPR was
found to be associated with a signicantly higher rate
of survival at 1 month and more favorable neurological
outcomes compared with conventional CPR measures
(chest compression and rescue breathing)
140
. However,
for children and younger people who have OHCA from
non-cardiac causes, and in people in whom there was a
delay in starting CPR, other studies have suggested that
conventional CPR is associated with better outcomes
than chest compression only CPR
141,142
.
CONCLUSIONS
Important progress has been made over the past few
years in our understanding of basic and clinical cardiac
electrophysiology which have advanced and improved
the management of patients with heart rhythm disor-
ders. Multiple studies have demonstrated an associa-
Strategies to reduce ICD complications and inappro-
priate shocks include using special diagnostic ICD al-
gorithms to identify potential lead problems early
126
,
and changes in ICD programming with a prolonged
delay in therapy for tachyarrhythmias of 200 beats/
min or higher, as demonstrated in the MADIT-RIT
(MADIT-Reduction in Inappropriate Terapy) trial
127
.
Increasing clinical experience is also being gained in
the use of subcutaneous ICDs
128,129
, which holds great
potential in reducing some types of ICD related com-
plications, although an initial learning curve needs to
be overcome rst. Real world data of ICD implantation
and use show that patients treated by very low volume
operators (physicians who implanted 1 ICDs per year)
were more likely to die or experience cardiac compli-
cations compared with operators who frequently
performed ICD implantation
130
. Another strategy to
reduce ICD complications is to improve the selecti-
on process of those patients who would truly benet
from these devices. In an observational outcome study
of consecutive subjects referred to a regional inherited
cardiac conditions clinic because of a relative who had
sudden unexpected death, the number of ICDs inser-
ted as a result of specialist assessment was found to be
very small (2%)
131
.
Out-of-hospital cardiac arrest
Survival from out-of-hospital cardiac arrest (OHCA)
appears to have increased over the past several years,
probably as a result of better pre-hospital care (early
recognition, more efective CPR, faster emergency ser-
vices response) and advances in the hospital manage-
ment of patients following OHCA
132,133
. Data from the
London Ambulance Services cardiac arrest registry
from 2007 to 2012 showed an improvement in OHCA
survival over the 5 year study period
134
. In an obser-
vational Swedish registry study of 7187 patients with
OHCA over an 18 year period, bystander CPR was
found to increase from 46% to 73% (95% CI for OR
1.060 to 10.081 per year), early survival increase from
28% to 45% (95% CI 1.044 to 1.065), and survival to
1 month increase from 12% to 23% (95% CI 1.058 to
1.086)
135
. Strong predictors of early and late survival
were a short interval from collapse to debrillation,
bystander CPR, female gender, and place of collapse.
A large prospective cohort study of OHCA in North
American adults involving 12 930 subjects (2042 occur-
ring in a public place and 9564 at home) also found that
the rate of survival to hospital discharge was better for
arrests in public settings with automated external de-
brillators (AEDs) applied by bystanders compared to
Vol. 23, No. 4, 2013
868
Reginald Liew
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JAMA 2011;305:20807.
14. Steg PG, Alam S, Chiang CE, et al. Symptoms, functional status and
quality of life in patients with controlled and uncontrolled atrial
brillation: data from the RealiseAF cross-sectional international re-
gistry. Heart 2012;98:195201.
15. Camm AJ, Breithardt G+, Crijns H, et al. Real-life observations of
clinical outcomes with rhythm- and rate-control therapies for atri-
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58:493501.
16. Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient versus strict
rate control in patients with atrial brillation. N Engl J Med 2010;
362:136373.
17. Groenveld HF, Crijns HJGM, Van den Berg MP, et al. Te efect of rate
control on quality of life in patients with permanent atrial brillation:
data from the RACE II (Rate Control Efcacy in Permanent Atrial
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18. Smit MD, Crijns HJGM, Tijssen JGP, et al. Efect of lenient ver-
sus strict rate control on cardiac remodeling in patients with atrial
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19. Saksena S, Slee A, Waldo AL, et al. Cardiovascular outcomes in the
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20. Yamase M, Nakazato Y, Daida H. Efectiveness of amiodarone versus
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21. Liu T, Korantzopoulos P, Shehata M, et al. Prevention of atrial
brillation with omega-3 fatty acids: a meta-analysis of randomised
clinical trials. Heart 2011;97:103440.
22. Macchia A, Grancelli H, Varini S, et al. Omega-3 fatty acids for the
prevention of recurrent symptomatic atrial brillation: results of the
FORWARD (Randomized Trial to Assess Efcacy of PUFA for the
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23. Mozafarian D, Marchioli R, Macchia A, et al. Fish oil and postope-
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24. Nodari S, Triggiani M, Campia U, et al. n-3 Polyunsaturated fatty
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cal cardioversion: a prospective, randomized study. Circulation 2011;
124:11006.
25. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial brillation
and the risk of stroke. N Engl J Med 2012;366:1209.
26. Ritter MA, Kochhauser S, Duning T, et al. Occult atrial brillation
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tion between AF and various systemic conditions and
novel risk factors. Tese studies highlight the impor-
tance and complexity of this complex arrhythmia and
further support the notion that AF is a systemic con-
dition. Although many of these associations have not
been shown to play a causal role, they may nonetheless
prove useful clinically in future risk stratication scores
for the diagnosis or treatment of AF. More research is
still needed to increase our understanding of the un-
derlying mechanisms responsible for the development
and progression of AF and which patient subgroups
will benet most from specic treatments or the dife-
rent options for anticoagulation.
Te eld of CRT and pacing has also progressed ra-
pidly over the past few years with a lot of interest in the
optimal clinical parameters for selection of patients,
prediction of response, and adverse remodeling . Simi-
larly, as our understanding of the substrate responsi-
ble for ventricular arrhythmias and SCD improves, the
selection of suitable candidates for ICD therapy is be-
coming more rened. Research into the complications
associated with implantable cardiac devices, such as
device infection and inappropriate shocks from ICDs,
remains important as indications for device implanta-
tion continue to expand and more and more patients
with existing devices undergo device replacement
procedures.
peer reviewed.
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86I
REVIEWS
Fostering Diffusion of Scientific Contents of National Societies
Cardiovascular Journals: The New ESC Search Engine
Fernando Alfonso
1,2
, Lino Gonalves
3
, Fausto Pinto
1
, Adam Timmis
1
, Hugo Ector
1
,Giuseppe Ambrosio
1
,
Panos Vardas
1
, On behalf of the Editors' Network European Society of Cardiology Task Force
Author Affiliations
Editors Network Members (Editors-in-Chiefs of National Society Cardiovascular Journals):
BYLINE NOT YET FINALISED
Eduard Apetrei (Editor-in-Chief, Romanian Journal of Cardiology),
Michael Aschermann (Editor-in-Chief, Cor et Vasa),
Leonardo Bolognese (Editor-in-Chief, Giornale Italiano Di Cardiologia),
Mirza Dilic (Editor-in-Chief, Medical Journal),
Istvan Edes (Editor-in-Chief, Cardiologia Hungarica),
Krzysztof J. Filipiak (Editor-in-Chief, Kardiologia Polska),
Faig Guliyev (Editor-in-Chief, Azerbaijan Cardiology Journal),
Habib Haouala (Editor-in-Chief, Cardiologie Tunisienne),
Magda Heras (Editor-in-Chief, Revista Espaola de Cardiologa).
Mahmoud Mohamed Hassanein (Editor-in-Chief, Egyptian Heart Journal),
Kurt Huber (Editor-in-Chief, Journal fr Kardiologie),
Mario Ivanusa (Editor-in-Chief, Cardiologia Croatica),
Germanas Marinskis (Editor-in-Chief, Seminars in Cardiovascular Medicine),
Izet Masic (Editor-in-Chief, Medical Archives),
Miodrag Ostojic (Editor-in-Chief, Heart and Blood Vessels),
Dimitar Raev (Editor-in-Chief, Bulgarian Cardiology),
Mamanti Rogava (Editor-in-Chief, Cardiology and Internal Medicine XXI),
Olaf Rdevand (Editor-in-Chief, Hjerteforum),
Vedat Sansoy (Editor-in-Chief, Archives of the Turkish Society of Cardiology),
Valentin A. Shumakov (Editor-in-Chief, Ukrainian Journal of Cardiology),
and Tomas F. Lscher (Editor-in-Chief, Kardiovaskulre Medizin)
Contact address:
Fernando Alfonso MD ESC Editors Network Task Force Chair. Interven-
tional Cardiology. Cardiovascular Institute. Clnico San Carlos University
Hospital. IdISSC. Plaza Cristo Rey. Madrid. 28040. Spain.
E-mail: falf@hotmail.com
Abstract: European Society of Cardiology (ESC) National Society Cardiovascular Journals (NSCJ) are high-quality biome-
dical journals focused on cardiovascular diseases. Te Editors Network of the ESC devises editorial initiatives aimed at im-
proving the scientifc quality and difusion of NSCJ. In this article we will discuss on the importance of the Internet, electronic
editions and open access strategies on scientifc publishing. Finally, we will propose a new editorial initiative based on a novel
electronic tool on the ESC web-page that may further help to increase the dissemination of contents and visibility of NSCJ.
Keywords: biomedical journal, editors network, open access, Internet, electronic editions
1
Nucleus Members Editors Network of the European Society of Cardio-
logy
2
ESC Editors Network Task Force Chair
3
ESC Search Engine Task Force Chair
Fernando Alfonso et al.
The New ESC Search Engine
Vol. 23, No. 4, 2013
868
European Society of Cardiology (ESC) National Society
Cardiovascular Journals (NSCJ) are high-quality bio-
medical journals devoted to publish original research
and also educative material on cardiovascular disea-
ses
1-3
. Tese journals of cially belong to the correspon-
ding ESC national societies. However, many of them
have achieved major international recognition, are in-
cluded in most important bibliometric databases and
have gained major scientifc impact
1-5
. Some NSCJ ofer
full-text English content and are freely available from
ele ctronic editions. NSCJ, however, are largely hetero-
geneous and some of them are only published in local
languages with a limited visibility
1-3
.
Te main goal of biomedical journals is to publi-
sh high quality scientifc information. To achieve this
goal, journals should compete for the best research ge-
nerated in their feld being the prestige of the journal
the main driver to attract original contributions
1-3
. In
turn, journals prestige is based upon credibility, difu-
sion and scientifc impact
6
. To ensure that the scientifc
process is fully respected journals relay in the peer re-
view system. Tis process not only allows the Editors
to select the best possible material for publication but
also ensure the readers that the quality of the informa-
tion follows the highest scientifc standards. Actually,
the process signifcantly improves the fnal quality of
manuscripts eventually published. Once the article is
defnitively accepted for publication the Journal should
guarantee its expedited publication and widespread di-
fusion among the scientifc community
1-3
.
Te Editors Network of the ESC provides a unique
platform to devise editorial initiatives aimed to impro-
ve the scientifc quality and to facilitate difusion of
con tents from NSCJ
1-5
. Herein we will discuss on the
importance of the Internet and electronic editions on
scientifc publishing. We will also review the growing
relevance of open access strategies. Last but not least,
we will propose a new initiative based on a novel elec-
tronic tool that may further help to increase the difu-
sion, dissemination and overall visibility of NSCJ. Tis
tool, located at the ESC web site, should foster colla-
boration among the diferent NSCJ and also broaden
exposure from diverse scientifc sites and ESC of cial
journals. Hopefully, this will help to further expand the
scientifc impact of European cardiovascular research.
Electronic Editions and the Internet: A paradigm shift
in Scientic Publishing:
Sharing the results of late breaking research through
peer-reviewed journals remains the mainstay of the
sci entifc process and the progress in science
1-3
. Te
success of research requires articles to be read, spre-
ad, discussed and cited among interested investigators.
Terefore, in the fast moving and globalized world of
science, journals should ensure the maximal accessibi-
lity and difusion of their articles
1-3
. Indeed, most pu-
blications have already moved into a new online era
where the emphasis is placed on the Internet and in
electronic editions
1-3
. Just a few years ago scholars did
all their reading from paper journal issues obtained as
personal copies circulating inside their organizations,
or by retrieving the issues from library archives
7
. Today
the predominating reading mode is to download a di-
gital copy and either read it directly of the screen or as
a printout
7
. Currently, readers and investigators readily
retrieve articles with just a click on their home or of ce
computers
7
.
Interestingly, the Internet not only impacts resear-
ch but also clinical practice. Nowadays, physicians are
freq uently approached and challenged by patients who
had downloaded medical information from the inter-
net. Ofen they face either unnecessarily worried pati-
ents or patients with unrealistic expectations. Although
some patients are confused others are over-informed
and demand in-depth explanations regarding their
diag nosis, management and prognosis. Patient-orien-
ted information should be provided from the scienti-
fc societies to address these demands. Terefore, even
everyday clinical practice should accommodate the so-
cio-cultural change induced by the Internet.
Access to medical information has been revolutio-
ni zed by electronic editions. Likewise, bibliometric
data bases are also evolving. MEDLINE, the ISI Web
of Sci ence and more recently Scopus ofer compre-
hensive online information on medical literature
8-11
. In
addition, Google Scholar is increasingly used by many
investigators
8-11
. Scopus and specially Google Scholar
obtain data from a larger data sources including widely
diverse scientifc items (not only ISI publications) and
therefore ofer a slightly diferent perspective of the f-
eld. Interestingly, Google scholar is free and diferent
studies suggest that it provides accurate search and data
analyses that difer little from those obtained from clas-
sical bibliometric sources
8-11
.
Traditionally, the most commonly used source of bi-
bliometric data is the Tomson ISI Web of Knowledge,
in particular the Science Citation Index and the Jour-
nal Citation Reports, which provide the yearly Jour-
nal Impact Factors. Recently, other indicators such as
SCImago SJR or the Eigenfactor are emerging as alter-
native indices of a journals quality
8-11
. Tese consider
not only the number but also the quality or relevance
Vol. 23, No. 4, 2013
869
of the citations received by a given paper. Quantitati-
ve publication metrics (research output) and citations
analyses (scientifc infuence) are key determinants of
the scientifc success of individual investigators and in-
stitutions because the publish or perish dictum still
prevails in most academic settings
8-11
. In this scenario,
the electronic editions and accessibility on the Internet
certainly play a critical role. Nowadays, once a paper
is electronically published on a journal website, the
information can propagate rapidly in the community
and extremely high downloads could be the results of
mechanisms such as the Matthew efect (richer get
richer)
12
. Indeed, the relationship between the number
of citations acquired by an article has been explored in
relation to the number of downloads
13
. Hit counts on
a journal website for an article during the week afer
the online publication predict the number of citations
of that article in subsequent years
14
. Of note, Uniform
Resource Locators (URLs), are being increasingly used
in scientifc publications
15
. Citation of URLs provide
the possibility of calculating an objective electronic im-
pact factor (eIF) to measure their impact on scientifc
research
15
. However, the stability of URLs remains a
matter of concern and this should be guaranteed by the
responsible organization because URLs are vulnerable
to technical problems and may become inaccessible in
a time-dependant manner
15
.
Notably, the Internet ofers a new window to scien-
ce and provides new insights on access and use of re-
search16. Currently web-usage-data may be analyzed
in depth to outline a map of knowledge. According
to Butler et al
16
when readers click from one page to
another while looking through online scientifc jour-
nals, they generate a chain of connections between
links they think belong together. Tese clickstream
eve nts may be analyzed to map such connections and
to provide a snapshot of interconnections between dis-
ci plines.
Usage maps reveal how ofen users looking at an
article in journal A moved on to an article in journal
B during a browser session. By aggregating all these
complex relationships using network-visualization al-
gorithms, maps can be generated based on the distan-
ces between journals and disciplines
16
. Te structure
of these maps is quite similar to those created using
citation data: a network of clusters in diferent felds
within which journals have strong connections with
one another but fewer links to other clusters. Interes-
tingly, journals in the humanities and social sciences
fgure much more prominently in these maps than in
citation-based maps
16
. Another key diference between
citation- and usage-based maps is that the former only
refect citations by researchers who publish, but ignore
the impact of papers on the medical community who
read and apply the literature in medical practice but
who rarely publish. Citation data may undervalue pa-
pers written in practitioner-based felds that are widely
read but not cited proportionally
16
. Moreover, usage
maps are more up-to-date than citation ones because
of the inherent delay in publication therefore providing
a diferent time-slice of the scientifc process. Accor-
dingly, both usage and citation data each provide com-
plementary information on the impact of papers and
journals on the scientifc community
16
.
Electronic editions provide unique publishing pos-
sibilities and open new venues in scientifc communi-
cation1-3. For instance, they ofer a fexible layout and
structure for articles, new formats and the possibility
of including additional documentation attached to the
paper as media enhancements (videos, etc). Important
sections as methods and additional data can be now
presented as supplementary material without additio-
nal costs. Electronic managing systems facilitate both
the processes of peer-review and publishing
1-3
. Open
peer-review and even post-publication readers com-
ments may be uploaded on the journal website facilita-
ting interactivity and a more transparent and dynamic
scientifc process. Finally, statistics on electronic papers
(downloads and citation metrics) are ofered to the in-
terest of readers and researchers
17
.
Publicly available data is advocated as a means to
further promote transparency in research and a more
open science
18-20
. Online editions allow the publicati-
on of longer papers free from the economic burden of
print charges. Posting the complete anonymized raw
data set has been advocated
in this regard
18-20
. Te raw data can be used to con-
frm original results by independent analyses but also
to explore related or new hypotheses, particularly when
combined with other publicly available data sets. From
an ethical perspective it appears unacceptable that whi-
le patients are willing to share data about themselves
with investigators and sponsors these may be unwilling
to share the trial data with others. Data sharing has
been already successful among genomic investigators.
However, this strategy may cause concerns including
inappropriate analyses, data dredging and drawing
inappropriate conclusions
18-20
. Te International Com-
mittee of Medical Journals Editors has developed guide-
lines for the preparation of raw clinical data for Publi-
Vol. 23, No. 4, 2013
8I0
cation
18
. Interestingly, this practice has been associated
with a 69% increase in citations, independently of jour-
nal impact factor, date of publication, and author coun-
try of origin
20
. Te correlation between publicly avai-
lable data and increased literature impact may further
motivate investigators to share their detailed research
data.
On the other hand, the Web 2.0 is also been increa-
singly used in the medical feld
21-25
. RSS feeds, podcasts,
personal publishing platforms (blogs), social networks
(like Twitter and Facebook), and social media are pro-
posed as innovative tools for the education and update
of clinicians. Tey allow physicians to distribute, share
and comment medical information
21-25
. However, the
scientifc community is less than eager to regard them
as equivalent to the traditional models of information
dissemination on peer-reviewed medical journals. In
this regard, some have proposed that platforms of post-
publication peer-review may provide the required safe
guard in this new setting
22
. In addition, intuitive brow-
sing of Journals content on smartphones and the iPad,
is being provided by a growing number of publications
(including the European Heart Journal)
24
to enhance
difusion of contents
21
. Furthermore, some Web 2.0
technologies facilitate collaborative data collection
for clinical trials
23
. Google Docs, for instance, is freely
available and allows multiple users to enter patient data
into electronic case report forms of multicenter trials
through mobile devices
23
.
Finally, we should keep in mind that English repre-
sents the lingua franca of science. Tis is important
and eforts should be made within the ESC to pre-
vent tower-of-Babel phenomena in the digital era
1-3
.
However, this may create major problems and unique
challenges for non-English-speaking investigators and
countries
26
. Actually, some NSCJ only publish in their
mother tongue and therefore they are not readily acces-
sible to the international scientifc community. Some
NSCJ have decided to publish their articles in both nati-
ve language and English, to address healthcare professi-
onals and international scholars, respectively. Dif cult
concepts are easier to remember in the mother tongue.
Interestingly, Public Library of Science journals encou-
rage non-English-speaking authors to provide a versi-
on of their article in its original language as supporting
material
27
. Science should not be considered an ivory
tower separated from the rest of society but rather im-
bedded on it to facilitate its cultural assimilation
27
.
Some Editorial Perspectives on Open Access
Initiatives:
Te Internet and the electronic editions set the bases
for Open Access (OA) initiatives
28,29
. Te two main
cha racteristics of OA publications are: 1) all published
con tents are freely accessible through the Internet, and
2) readers are given copyright permission as long as
authors and publishers receive the adequate attributi-
on
28
. In turn, this model requires two major changes
from the traditional subscription based- model. First,
OA shifs the fnancing of publication from readers
(subscriptions fees by individuals or universities) to
authors and investigators (through the corresponding
funding organization or academic institutions) by
mean of articles processing fees
28
. Second, the copyri-
ght is not longer used to prevent but rather to stimula-
te re-publication. Subscription-based journals usually
require authors to transfer the copyright to the journal
to be empowered to restrict access to paying customers
and threat with infringement lawsuits to competing
publications. Major subscription-based journals are f-
nanced by individuals or medical societies but mainly
by bundled e-license agreements between publishers
and universities or librarians
28,29
. Electronic individual
articles can also be accessed on a pay-per-view basis.
Readers are charged one way or the other in the tra-
ditional way whereas authors and investigators are
charged in the OA model
28,29
. Some commercial publi-
shers charge authors a publication fee to substitute for
subscription revenue while signifcantly limiting reuse.
Tis initiatives, however, should not be considered real
OA. Some traditional publishers have recently open to
hybrid initiatives where authors are allowed (afer
paying a fee) to make individual articles OA
28,29
.
In the early 90s, pioneer OA journals were founded
by individual investigators based on voluntary work
and usually were hosted in individual or university ser-
vers
29
. Tereafer, many established journals made their
articles OA when they implemented their digital editi-
ons in parallel with print editions. Tis was especially
the case for of cial journals from medical societies and
in non-English speaking countries in an attempt to in-
crease their readership and impact
30
. In the last decade,
new, formal, OA journals fourished using article pro-
cessing charges to fnance publications
29
. Interestingly,
some major publishers (BioMed Central, Public Library
of Science) became specialized in OA
29
. OA has to ma-
jor pathways: 1) Gold OA (via direct publishing) and
2) Green OA (traditional publication in subscription-
based journals with parallel openly posting on the Web
Vol. 23, No. 4, 2013
8I1
nifcantly more downloads and reached a broader au-
dience within the frst year. However, in this particular
study, OA were cited no more frequently, nor earlier,
than subscription-access articles within 3 years. It was
suggested that the process of social stratifcation, acc-
ounting for a concentration of scientifc authors at as
mall number of elite research universities with excel-
lent access to the scientifc literature, might help to ex-
plain this apparent paradox
39
. Moreover, this controlled
study suggests that real benefciaries of OA publishing
may notbe the research community but rather commu-
nities of medical practice that consume, but rarely con-
tribute to, the corpus of literature
39
.
As discussed, currently, embargoes are imposed by
publishers for economic reasons. Tis may be a signif-
cant barrier to access in biomedical sciences. As previ-
ously emphasized, it has been suggested that users fa-
vor electronic access and ofen eschew articles that are
not available electronically
40
. In a shy attempt to tackle
these problems many journals ofer now free access to
all articles 6 months afer publication and welcome the
publication of articles as OA afer a fee is paid by the
authors.
However, research funding bodies are becoming in-
creasingly sensible to this ethical issue. Many would ar-
gue that it is unethical to use the research grants from
government (peoples money) and not allow the sci-
entifc community to have free access to the results of
the study. To address such issues, the Berlin declara tion
suggested the establishment of OA repositories. Every
investigator who has received public grants should sub-
mit the full text of the paper published from his study
to PubMed Central and also ensure self archiving at the
corresponding university or research institution. Obvi-
ously, OA journals provide an attractive solution to the
problem of restricted access to results of publicly fun-
ded research
41
.
Most countries and founding bodies are currently
taking further actions to ensure OA for publicly fun-
ded research
41-43
. Researches are compelled to make
their work publicly available in repositories (green
road) within 12 month of publication. Others bodies
even suggest that authors should make their work free
by the publisher upfront (gold road). Clearly, research
budgets should be re-allocated with this aim although
the logistics required and the implications of this chan-
ge remain a matter of ongoing debate. On July 2012,
a new OA policy was announced from the European
Union that recommended OA policies for all the mem-
ber states
31,41-43
. Hopefully, this will represent a para-
the fnal manuscript). Green open access is delivered
by repositories whereas gold open access is delivered
by journals (31). Licences range from any kind of reuse
providing proper attribution is made (CC-BY) to those
that limit commercial use (CC-BY-NC)
31
.
Te health of the free-access author-pay model may
be demonstrated by data showing the steady growing
of papers published in OA journals (20% per year) and
also in the number of OA journals (15% per year), ei-
ther as new journals or traditional journals switching
to this model
32
. Currently 30% of all peer-review jour-
nals in the world are open access
31
.
OA benefts science by accelerating dissemination
and uptake of research fndings. A major advantage of
OA is that readers can use any Web-based research tool
to access and review the literature
28
. Tese articles are
quickly recognized and their results are readily picked
up and discussed by peers
33
. As already mentioned,
there are two main modalities of open access: open
access journals and self-archiving. Interestingly, some
studies suggest
33
that articles immediately published as
OA on the journal site (gold route) have higher impact
than self-archived or otherwise openly accessible OA
articles (green route).
Overall OA initiatives increase difusion of contents,
citations and eventually the impact factor of the corres-
ponding journals
33-35
. Early studies 10 on MEDLINE as
full text on the net also boosts their impact factor
37
.
Tis bias is explained by the tendency to peruse what
is more readily available
37
. OA initiatives also appear
to increase the impact factor
33-35
. However, some argue
that this efect may confound between open and elec-
tronic access. Nevertheless, recent reports, suggest that
in most developed countries journals articles receive an
increase in citations when they come online freely but
experience an additional jump when they frst come
online through commercial sources
35
. Tis efect ap-
pears to be reversed in poor countries where freeaccess
articles are much more likely to be cited
35
. All together
these fndings suggest that free Internet access widens
the circle of those who read and make use of scientifc
research. In addition, this OA impact advantage does
not appear to be a quality bias from authors self-se-
lecting what to make OA, because some studies suggest
that this advance persists afer adjusting for many other
potential confounders related to the editorial and re-
search quality
38
.
Interestingly, a randomized trial on OA publishing
analyzed the efects of free access on article downloads
and citations
39
. Articles placed in the OA received sig-
Vol. 23, No. 4, 2013
8I2
is also presented (guideline, abstract, slide presentati-
on, scientifc report, news, clinical case, or a web docu-
ment). Te document origin can also be easily identi-
fed at a glance through a small institutional logo which
can also be found inside the results page, just below the
icon showing the type of document. Also important to
know is the document availability. A padlock symbol
is displayed when a document is behind a login so that
you can still see that the resource exists, meaning that
its access is for members only. Tis tool also allows to
refne the search by using flters located on the toolbar
located on the lef. With this toolbar you can flter the
type of document you are looking for (only slides for
example). It is also possible to flter only results from
a given time period. During a congress, when a lot of
content is published daily, you may flter for whats new
since yesterday, or you can flter only the results where
a person is cited. Related terms are proposed by the en-
gine from the keywords entered in your request to pro-
pose other related topics which could be of interest. If
you search the same term on a regular basis, you could
be interested in using the RSS feed functionality. We
may show any search result page as an RSS feed whi-
ch you may subscribe to, and get regular updates about
whats new in this feld.
Time has come to involve the National Societies
Journals!
Tis project is already in its adulthood and time has
come now to enter into a second phase of development
and involve also the NSCJ. Te ESC Board chaired by
Michel Komajda decided to support the development of
this project. Te ESC Editors club gave also an enthusi-
astic response and decided to contact those NSCJ that
are already published in an electronic format and that
are published in English. Some of them have already a
signifcant Impact Factor. Te goal of this second phase
of the project is to increase the visibility of the NSCJ
and as a consequence to increase their reading and
their level of reference in other international journals.
Moreover, the excellent research that is performed at
the National level in many countries in Europe will be-
come more visible worldwide.
Tis new tool is already available and you will be able
to get, afer typing the keywords you can get two re-
sults: one from the ESC documents, and a second one
from the NSCJ. It will be possible for the user to see
both in parallel and easily move from one result to the
other with a simple click.
Te frst NSCJ have been added to the search re-
sults and can now be easily identifed and selected. Te
digm shif in scientifc publishing and will herald a new
era of academic discovery.
The ESC Search Engine:
In the last decade the amount of documents and edu-
cational materials available inside the ESC websites
family increased exponentially. Tis situation was na-
turally associated with increasing dif culties for the
user to fnd the information they need. It became qui-
te obvious that a more comprehensive search solution
was necessary. Tis is the reason why the ESC decided
to provide a better search experience for the ESC site
visitors
44
. Te ESC search engine uses semantic analysis
to provide the best results from the typed keywords
45
.
Tis search engine project has four goals. First, to pro-
vide a single entry point to multiple data sources. In
fact, from a single entry point, the user will be able to
explore ESC rich database of slides, scientifc reports,
guidelines, abstracts, clinical cases, news, and articles
from the ESC Journals. Second, to propose a tool whi-
ch can treat requests expressed in natural language, in
a very user-friendly way. Tird, to locate content that
would be dif cult to fnd or access otherwise, therefore
saving a lot of precious time. Finally, to allow visitors
to fnd contents by topic or person in an intuitive way.
In 2008, the ESC Board chaired by Roberto Ferrari,
decided to support the development of a semantic sear-
ch engine that would be able to search for information
inside the ESC Central website and all the six Asso-
ciations websites, as well (EHRA, EAE, EAPCI, HFA,
EACPR, ACCA). Tis idea was based on the previously
reported need of providing to the user a quick and easy
way of getting the information needed from hundreds
of thousands of documents available in all these websi-
tes. Moreover, this engine is also looking into the ESC
journals family were it is possible to get results from
more than 30 000 papers! Not surprisingly, this tool
was a major success, being already the second most vi-
sited page of the ESC website, with 49,853 page views,
in October and November of 2012
46
. With the help of
this search engine it is now extremely easy to get the
information you need by just typing the key words on
the top right hand side of the screen, inside the www.
escardio.org landing page (Figure 1). Te result is a list
of documents addressing that specifc topic, and it is up
to the user to select the ones they want (Figure 2).
Inside this results page you can get a lot of informa-
tion and functionalities. Within the document preview
you can see how the document looks like (Figure 2).
Te relevance score assigned to this document is also
displayed by the search engine. Te type of document
Vol. 23, No. 4, 2013
8I8
Figure 1. ESC website landing page. Te search engine box is located on the top right hand side of the screen (arrow).
Figure 2. Results page with relevant information about the documents found. On the right, there is a toolbar with a fltering system to refne the search.
Vol. 23, No. 4, 2013
8I1
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gueredo J, Guarda E, Gutirrez Sotelo O, Guzmn L, Len Galindo
J, Mario Lombana B, Mrquez MF, Moreno Martnez FL, Navarro
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frst fve journals are: Revista Espaola de Cardiologa,
Heart and Blood Vessels, Journal of the Cardiology So-
ciety of Serbia, Hellenic Journal of Cardiology, Egypti-
an Heart Journal, and Romanian Journal of Cardiology.
An arrangement has been made with the Brazilian So-
ciety of Cardiology and its website should soon include
our Search Engine. Tis is an interesting way to raise
awareness about this very useful tool and allow the Bra-
zilian cardiologists to have better access to our scienti-
fc resources.
Tere is no doubt in our mind that by providing this
tool the bonds between the ESC central and the Nati-
onal Societies will be strengthen even further and that
European Cardiovascular Science will become more vi-
sible and easily accessible from any place in the world.
Acknowledgements: We are grateful for the support
and assistance of Iris Chapuis, Isabelle Collin and Mu-
riel Mioulet from the ESC National Cardiac Societies
Relations Department at the Heart House.
Confict of Interest: No conficts of interest in relation
to this work were disclosed
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34.
CASE PRESENTATION
Surprising awakening of a sleeping heart
Alina Scridon
1,2
, Rzvan Constantin erban
2
, Ayman Elkahlout
3
, Mihaela Opri
2
, Dan Dobreanu
1,2
Contact address:
Mihaela Opri, MD, PhD
Department of Cardiology, Emergency Institute for Cardiovascular Dis-
eases and Transplantation Trgu Mure, 50, Gheorghe Marinescu Street,
540136, Trgu Mure, Romania
E-mail: m_opris2000@yahoo.com
Abstract: Coronary artery disease is the most frequent cause of heart failure. Accumulating evidence indicate that patients
with ischemic cardiomyopathy may beneft from successful coronary revascularization in addition to optimal medical treat-
ment. We report a notable case of very early, highly successful response to percutaneous coronary revascularization in a pati-
ent with long history of coronary artery disease and severe myocardial hibernation. In patients with lef ventricular dysfunc-
tion due to chronic coronary artery disease and high probability of viable myocardium, prompt coronary revascularization
should be considered.
Keywords: hibernating myocardium, coronary artery disease, revascularization
Rezumat: Boala coronarian reprezint cea mai frecvent cauz de insufcien cardiac. Rezultatele studiilor clinice indic
faptul c revascularizarea coronarian efcient la pacienii cu cardiomiopatie ischemic poate aduce benefcii suplimentare
tratamentului medical optimal. Lucrarea de fa prezint un caz particular de rspuns extrem de favorabil i foarte precoce la
terapia de revascularizare coronarian percutan la un pacient cu istoric ndelungat de boal coronarian i hibernare miocar-
dic sever. La pacienii cu disfuncie ventricular stng secundar afectrii coronariene cronice i la care exist o probabili-
tate mare de miocard viabil, revascularizarea coronarian prompt ar trebui luat n considerare.
Cuvinte cheie: hibernare miocardic, boal coronarian, revascularizare
INTRODUCTION
In more than two thirds of cases, heart failure emana-
tes from cardiac damage due to chronic coronary ar-
tery disease
1
. Lef ventricular (LV) dysfunction due to
chronic myocardial ischemia has long been considered
an irreversible process. Te identifcation of two new
en tities, myocardial stunning and myocardial hiberna-
tion, suggests however that this is not necessarily true
2
.
Myo cardial stunning develops in relation with acute
transient ischemia, whilst myocardial hibernation ari-
ses from chronically reduced coronary blood fow
3
.
More importantly, both settings imply the presence of
viable myocardium. Accumulating evidence indicate
that patients with ischemic cardiomyopathy may be-
neft from successful coronary revascularization, dis-
pla ying improved myocardial function, symptoms, and
prognosis, due to functional improvement of the hy-
po perfused, but viable myocardium
2,4,5
. However, the
time-course and the extent of functional recovery afer
co ro nary revascularization seem to be highly depen-
dent on the duration of myocardial hibernation
6
.
We report a notable case of very early, highly succe-
ssful response to percutaneous coronary revasculariza-
tion in a patient with a long history of coronary artery
disease and severe myocardial hibernation.
CASE REPORT
A 56-year-old Caucasian male presented for evaluati-
on of New York Heart Association (NYHA) class III
heart failure symptoms. At age 45 years, in the absen-
ce of any prior symptoms or known cardiac pathology,
he was admitted to hospital for a large anterior myo-
cardial infarction. His risk factors included grade II
arterial hypertension, dyslipidemia, and grade II obe-
sity. Emergency coronary angiography performed 5
hours afer the onset of symptoms revealed proximal
subocclusion of the lef anterior descending (LAD) ar-
tery with TIMI I fow. No other signifcant coronary
lesions were observed at that time. He underwent pri-
mary percutaneous coronary intervention with bare
metal stent implantation of the LAD, with favorable
post-procedural evolution. At discharge, the patient
1
Department of Physiology, University of Medicine and Pharmacy of
Trgu Mure, Romania
2
Department of Cardiology, Emergency Institute for Cardiovascular Dis-
eases and Transplantation Trgu Mure, Romania
3
Laboratory of Cardiac Catheterization, Emergency Institute for Cardio-
vascular Diseases and Transplantation Trgu Mure, Romania
Vol. 23, No. 4, 2013
Alina Scridon et al.

Coronary revascularization in myocardial hibernation
was completely asymptomatic. Te ECG revealed per-
sistent ST-segment elevation in leads V2-5, pathologi-
cal Q waves in V1-3 leads, and negative T waves in lead
V6. Echocardiographic assessment showed normal LV
function (LV ejection fraction of 60%), with moderate
hypokinesia of the apical third of the interventricular
septum, and of the anterior and lateral LV walls. He was
discharged on double antiplatelet therapy, beta-blocker,
angiotensin converting enzyme inhibitor and statin.
Te patient did well for 8 years, when he was read-
mitted for chest pain and heart failure symptoms at
moderate exertion. He admitted having abandoned
his treatment 6 years earlier. Te ECG displayed a per-
sistent pattern (Figure 1). Echocardiography revealed
50% LV ejection fraction, hypertrophied and slightly
dilated LV (LV end-diastolic diameter 57 mm), akine-
sia of the apex and of the apical third of the interven-
tricular septum, hypokinesia of the apical third of the
anterior and lateral walls and of the middle third of the
interventricular septum, and mild aortic and mitral
valve regurgitation. Coronary angiography was per-
formed, revealing no restenosis in the proximal LAD
stent, a 30% stenosis followed by severe stenosis of the
mid segment of the circumfex artery (ACx), and 30%
stenosis in the proximal segment of the right coronary
artery (RCA) (Figure 2A, B). Successful coronary an-
gioplasty of the ACx with bare metal stent implantation
was performed (Figure 2C). Te patient was dischar-
ged free from angina, on double antiplatelet therapy,
beta-blocker, angiotensin conversion enzyme inhibitor,
statin, and calcium channel blocker.
Tree years later, the patient was readmitted with
one month history of dyspnea and fatigue at mild exer-
tion. Again, the patient admitted having abandoned his
treatment one year earlier. Physical examination revea-
led rales on pulmonary auscultation, and mild systolic
Figure 1. ECG tracing depicting ST-segment elevation in leads V2-5, pathological Q waves in V1-3 leads, and negative T waves in lead V6.
Figure 2. Coronary angiograms. (A) Right-anterior-oblique caudal view showing severe stenosis of the mid segment of the circumfex artery (ACx) (arrow).
(B) Lef-anterior-oblique cranial view showing 30% stenosis in the proximal segment of the right coronary artery (arrow). (C) Right-anterior-oblique caudal
view showing the fnal angiographic outcome of coronary angioplasty of the ACx with bare metal stent implantation (arrow).
Vol. 23, No. 4, 2013
and diastolic murmurs on the mitral and aortic points,

respectively. ECG fndings were similar to the previous
tracings. Compared to the prior examination, echo-
cardiography revealed severely impaired LV systolic
function (LV ejection fraction 27%) with preserved LV
walls thickness (Figure 3A), and the presence of an api-
Figure 3. Echocardiographic images. (A) M-mode of the lef ventricle (LV) in lef parasternal short axis view demonstrating hypertrophied and slightly dilated
LV, and severely impaired LV systolic function (LV ejection fraction 27%). (B) B-mode in apical view showing the presence of an apical LV thrombus (arrow).
Figure 4. Coronary angiograms. (A) Right-anterior-oblique cranial view showing severe stenosis of the frst diagonal artery (arrow). (B) Right-anterior-oblique
caudal view showing severe stenosis of the circumfex artery (ACx) proximal to the stent (arrow). (C) Lef-anterior-oblique cranial view showing severe steno-
sis of the frst segment of the right coronary artery (RCA) (arrow). (D) Right-anterior-oblique caudal view showing the fnal angiographic outcome of coronary
angioplasty of the ACx with bare metal stent implantation (arrow). (E) Lef-anterior-oblique cranial view showing the fnal angiographic outcome of coronary
angioplasty of the RCA with bare metal stent implantation (arrow).
Vol. 23, No. 4, 2013

cal LV thrombus (Figure 3B), for which the patient was
started on anticoagulation. Coronarographic examina-
tion revealed 90% stenoses of the frst diagonal (Figure
4A), of the ACx proximal to the stent (Figure 4B), and
of the frst segment of the RCA (Figure 4C). Percuta-
neous transluminal angioplasty and primary stenting
of the 90% stenoses of the ACx (Figure 4D) and RCA
(Figure 4E) with bare metal stents was performed, with
successful procedural outcome. Tree days afer the
procedure, echocardiographic examination revealed
sig ni fcant recovery of LV systolic function, with >60%
ba sal (Figure 5) and 45% global ejection fraction. Te
pa tients symptoms were relieved, and he was dischar-
ged on oral anticoagulation with vitamin K antagonists,
dual antiplatelet therapy, beta-blocker, angiotensin
con verting enzyme inhibitor, calcium channel blocker,
low-dose loop diuretic, statin, and gastric protection.
At 6-months follow-up, the patient continued to do
well, with no further chest pain or dyspnea on exertion.
Echocardiographic fndings were similar to pre-discha-
r ge results, showing 45% LV ejection fraction and no
intra-ventricular thrombosis.
DISCUSSION
Heart failure afects 1% to 3% of the general popula-
tion, associating 5-year mortality rates as high as 75%
following a frst hospital admission
7
. Although optimal
pharmacological therapy signifcantly reduces morta-
lity among heart failure patients, this population conti-
nues to display high mortality rates
8
.
More than two thirds of heart failure cases are rela-
ted to chronic coronary artery disease
1
. Until recently,
LV dysfunction in these patients has been considered
an irreversible process. However, in the past decades,
myocardial hibernation, which can be demonstrated
in up to one third of patients with chronic coronary
arte ry disease and impaired LV function
9
, has been re-
cog nized as an aggravating factor for LV dysfunction
in this population
2
. Unlike tissue necrosis, myocardial
hi bernation implies the presence of hypoperfused but
viable myocardium
10
, and, more importantly, appears
to be partially or even completely reversible upon sur-
gical or percutaneous coronary revascularization
3
. Tis
observation could explain the signifcantly higher sur-
vival rates associated with the use of revascularization
strategies in addition to optimal pharmacological stra-
tegies
11
. Indeed, accumulating evidence indicate that
patients with heart failure due to chronically reduced
coronary blood fow may beneft from coronary revas-
cularization through improved myocardial function,
symptoms, and prognosis
2,4,5
. Furthermore, beneft
from revascularization may also be attributable to de-
creased propensity to ventricular arrhythmias and re-
duction of subsequent ischemic events due to restored
coronary blood fow
12,13
.
Diferentiation between LV dysfunction caused by
myo cardial necrosis and scar tissue formation versus
myocardial hibernation may thus have important clini-
cal consequences
14
. In our patient, preserved thickness
of LV walls despite severely impaired ejection fraction,
indicating preserved myocardial viability
15
, prompted
us to perform coronary angiography and stent angio-
plasty of signifcant coronary lesions. Given that the
time-course and the extent of functional recovery af-
Figure 5. M-mode echocardiographic image of the lef ventricle (LV) in lef parasternal long axis view demonstrating signifcant recovery of LV systolic func-
tion post-coronary angioplasty, with >60% basal LV ejection fraction.
Vol. 23, No. 4, 2013
4. Beller GA. More evidence for the survival beneft of coronary revas-
cularization versus medical therapy in patients with ischemic cardi-
omyopathy and hibernating myocardium. Circ Cardiovasc Imaging,
2013; 6(3): 355-7.
5. Henderson RA, Timmis AD. Almanac 2011: stable coronary artery
disease. An editorial overview of selected research that has driven re-
cent advances in clinical cardiology. Romanian Journal of Cardiology,
2012; 22(1): 15-25.
6. Rahimtoola SH, La Canna G, Ferrari R. Hibernating myocardium:
another piece of the puzzle falls into place. J Am Coll Cardiol, 2006;
47: 978-80.
7. McMurray JJV, Stewart S. Te burden of heart failure. Eur Heart J
Suppl, 2002; 4: D50-8.
8. Khand A, Gemmel I, Clark AL et al. Is the prognosis of heart failure
improving? J Am Coll Cardiol, 2000; 36: 2284-6.
9. Elssser A, Schlepper M, Klvekorn WP et al. Hibernating myocar-
dium: an incomplete adaptation to ischemia. Circulation, 1997; 96:
2920-31.
10. Lupacu L, Popescu BA, Ginghin C. Viabilitatea miocardic di-
agnostic i implicaii terapeutice. Revista Romn de Cardiologie,
2010; 25(4): 248-53.
11. Di Carli MF, Hachamovitch R. New technology for noninvasive eva-
luation of coronary artery disease. Circulation, 2007; 115: 1464-80.
12. Canty JM Jr, Suzuki G, Banas MD et al. Hibernating myocardium:
chronically adapted to ischemia but vulnerable to sudden death. Circ
Res, 2004; 94: 1142-9.
13. Wissner E, Mookadam F. Tirty-four years of hibernating myocar-
dium: a case report. J Nucl Cardiol, 2007; 14(5): 745-9.
14. Buckley O, Di Carli M. Predicting beneft from revascularization in
patients with ischemic heart failure: imaging of myocardial ischemia
and viability. Circulation, 2011; 123(4): 444-50.
15. Cwajg J, Cwajg E, Nagueh SF et al. End-diastolic wall thickness as
predictor of recovery of function in myocardial hibernation. Relati-
on to rest-redistribution Tl-201 tomography and dobutamine stress
echocardiography. J Am Coll Cardiol, 2000; 35: 1152-61.
16. Sharaf A, Kassaian SE, Sharif AY et al. Signifcant improvement in
severely stunned lef ventricle afer percutaneous coronary interven-
tion. J Teh Univ Heart Ctr 3, 2008; 173-5.
17. Bax JJ, Visser FC, Poldermans D et al. Time course of functional reco-
very of stunned and hibernating segments afer surgical revasculari-
zation. Circulation, 2001; 104(12 Suppl 1): I314-8.
18. Schinkel AF, Poldermans D, Vanoverschelde JL et al. Incidence of re-
covery of contractile function following revascularization in patients
with ischemic lef ventricular dysfunction. Am J Cardiol, 2004; 93(1):
14-7.
ter coronary revascularization seem to be highly de-
pendent on the duration of the hibernating status
6
, the
short history of heart failure symptoms in our patient
could explain the very early signifcant recovery of
myo cardial function afer successful coronary revascu-
la rization.
Cases of signifcant early recovery following percuta-
neous coronary revascularization have already been re-
ported. However, this usually happens in patients with
stunned myocardium and LV dysfunction following
acute coronary events
16
, whilst in patients with hiber-
nating myocardium recovery usually takes longer
17
.
Furthermore, early recovery of myocardial function
upon percutaneous coronary revascularization in pati-
ents with hibernating myocardium is usually less im-
portant and occurs in patients with less severe LV im-
pairment
18
.
CONCLUSIONS
Tis case report illustrates a very early, highly success-
ful response to revascularization in a patient with a long
history of coronary artery disease and severe myocar-
dial hibernation. In patients with LV dysfunction due
to chronic coronary artery disease and high probability
of viable myocardium, prompt coronary revasculariza-
tion should be considered.
Conficts of interests: none declared.
References
1. Gheorghiade M, Sopko G, De Luca L et al. Navigating the crossroads
of coronary artery disease and heart failure. Circulation, 2006; 114:
1202-13.
2. Camici PG, Rimoldi OE. Te contribution of hibernation to heart fa-
ilure. Ann Med, 2004; 36: 440-447.
3. Rahimtoola SH. Te hibernating myocardium. Am Heart J, 1989; 117:
211-21.
CASE PRESENTATION
Endovascular treatment in a case of transplant
renal artery stenosis
Adrian Buca
1
, Cristina Buca
2
, Costel Matei
1
, Cristina Chirion
2
, Marian Croitoru
1
Contact address:
Adrian Bucsa, MD, Prof. Dr. C. C. Iliescu Emergency Institute for
Cardiovascular Diseases, Bucharest
E-mail: abucsa@yahoo.com
CASE PRESENTATION
We present the case of a 45-year-old female patient ad-
mitted for increases in the values of the blood pressure
and of the serum creatinine during the last four weeks.
Te patient underwent a renal transplantation fourteen
weeks ago. She was diagnosed with chronic renal failu-
re when she was 33-year-old and afer several years of
conservative treatment she entered in the hemodialysis
program. Afer four months she received a kidney from
her brother. Te post-transplantation outcome was
favourable and she was discharged 3 weeks afer the
surgery with a serum creatinine of 1.6 mg/dl and with
normal blood pressure with only minimal medication
(metoprolol 50 mg bid). At 10 weeks post-transplant
there was a progressive increase in the blood pressure
values to about 170/100 mm Hg and a gradual increase
in the serum creatinine to 2.2 mg /dl and subsequently
to 3.7 mg/dl. Te investigations conducted by the ne-
phrologist included among other tests, a Doppler ultra-
sonography of the renal graf. Tis examination show-
ed turbulent fow proximal to the arterial anastomosis
with a maximum velocity of 180 cm/s; the blood fow at
the level of the interlobar arteries had a slow ascending
slope and the resistance index (RI) at this level was 0.5.
Tese parameters are strong indicators for a high-grade
stenosis in the transplant renal artery
1
. Te patient was
sent to the department of interventional cardiology for
confrmation of the diagnosis and invasive treatment
with angioplasty and stenting.
Te physical exmination was not remarkable and the
routine electrocardiogram and echocardiogram show-
ed no abnormalities. Te lab data indicated mild ane-
mia (Hb=11.2 g/dl) and thrombocytopenia (131.000/
mm
3
) and a serum creatinine of 3.4 mg/dl. Te trans-
planted kidney was, in this case, placed in the right iliac
fossa, the renal artery was connected end-to-end to the
internal iliac artery of the recipient and the renal vein
was connected end-to-side to the external iliac vein;
the ureter was anastomosed with the bladder. Te pa-
tient was premedicated with 250 mg aspirin and 300
mg clopidogrel the day before the intervention. Te ar-
terial approach was made by inserting a 6F sheath in
the lef femoral artery. Afer that, a diagnostic catheter
JR 4.0 was advanced in cross-over into the right com-
mon iliac artery and subsequently in the right inter-
nal iliac artery. Manual injection of contrast medium
confrmed the presence of 90% stenosis at the presu-
med site of surgical anastomosis with the graf artery
(Figure 1). Angioplasty of the lesion was decided and
performed by the direct implantation of a Herculink
Elite renal stent, 5.5/18 mm, expanded at 11 atm. Te
angiographic result was very good (Figure 2). Te post-
procedural outcome was complicated by the formation
of a pseudo-aneurysm at the puncture site, which was
resolved by manual compression. Te blood pressure
normalised whithin 48 hours and a Doppler ultraso-
nography performed in ffh day afer the procedure
showed a normal fow in the interlobar arteries with
an RI of 0.63. Te serum creatinine values dropped in
the frst 48 hours at 2.2 mg/dl but afer that rose aga-
in to 3.8 mg/dl in the seventh day, decreasing again at
2.1 mg/dl at 14 days and 1.6 mg/dl at one month afer
the stent implantation. Tis evolution, with initial de-
crease followed by gradual increase and return to nor-
mal was interpreted as an episode of contrast induced
nephropathy. It is known that the renal grafs may be
particularly sensitive to ischemia and this can amplify
the efects of other injuries, like the contrast media ad-
ministration
2
. Also, the calcineurin inhibitor that the
patient took as an immunosuppresive agent can have a
deleterious efect on the allograf function.
1
Prof. Dr. C. C. Iliescu Emergency Institute for Cardiovascular Diseases,
Bucharest
2
Fundeni Clinical Institute, Bucharest
A. Bucsa et al.
Endovascular treatment in a case of transplant renal artery stenosis
Vol. 23, No. 4, 2013
Te patient was discharged with double antiplatelet

me dication (aspirin 100 mg and clopidogrel 75 mg),
statin, beta-blocker and, of course, the post-transplant
me dication. Te follow-up was made at 1, 3, 6 and 12
months. Te values of the serum creatinine and the
blood pressure were stable and a Doppler examination
performed at six months showed an RI of 0.7 and a ma-
ximum velocity of 103 cm/s. At six months the as pirin
was discontinued due to the fear of gastric bleeding
that may have occur. At 12 months there was a discussi-
on between the cardiologist and the nephrologist about
the oportunity of continuing colpidogrel administrati-
on and the decision was to continue this medication for
the next 12 months.We dont expect to have any further
problems with the stent because, as in all bare metal
stent cases, the restenosis can occur only in the frst 6
months afer implantation.
DISCUSSION
Tere are several causes of impaired blood fow to the
renal allograf. Te lesions situated in the iliac artery,
proximal to the anastomosis, are ofen of atherosclero-
tic origin while those found in the allografs artery are
ofen due to progressive stenosis at the surgical anasto-
mosis site. Transplant renal artery stenosis is more of-
ten found in the recipients of living donor kidneys (as is
the case of our patient) than in those of deceased donor
grafs
3
. Te explanation is the diference in the surgical
technique for the arterial anastomosis. In living donor
transplants the end of the donor renal artery is connec-
ted directly to the side of the recipients internal iliac
artery, while in deceased donor transplants, a patch of
donor aorta connected to grafs artery is sewn to the
recipients iliac artery. Tis latter surgical technique
(which, obviously can not be used in living donor
transplants) is less likely to cause stenosis at the origin
of the transplant renal artery
4
.
Table 1
4
summarizes the clinical presentations of the
transplant artery stenosis. Of note, the presence of the
bruits or murmurs in the area of the transplanted kid-
ney can be misleading and is not necessarily an indi-
cator for a vascular stenosis. Te Doppler examination
for the diagnosis must be performed by experienced
operators because of unusual anatomic features and ul-
trasound angles found in the pelvic area in this kind of
situations. Magnetic resonance arteriography can also
be used as a diagnostic tool but it is reported to have
a high rate of false positive results
5
. Te treatment of
choice is the angioplasty with stenting but surgical cor-
rection might be needed in case of repeated restenosis.
Te experience of our department of invasive car-
dio logy in this feld consists in three case of angioplas-
Figure 1. 90% stenosis of the renal transplant artery (arrow). Figure 2. Result afer stent implantation.
Table 1. Common clinical features of transplant recipients with
renal artery stenosis
Symptoms/signs
De novo hypertension any time posttransplant
Unexplained worsening of blood pressure control
Volume retention
Worsening renal graf function
Worsening renal graf function afer angiotensin II inhibition
Bruits over the allograf
Vol. 23, No. 4, 2013
A. Bucsa et al.
Endovascular treatment in a case of transplant renal artery stenosis
ty and stenting and one with balloon angioplasty only.
Te case we presented here is the most recent of all four.
In all cases the angiographic results were good and the
clinical improvement was evident and stable in time.
SUMMARY
Te increase in number of renal transplants in the re-
cent years led to the appearance of a less known patho-
logy until now: the transplant renal artery stenosis.
Te clinical features that are usually worsening hyper-
tension and deterioration of the grafs function with
rise in the serum creatinines values. Te cause is ofen
a progressive stenosis at the site of the arterial anasto-
mosis and the diagnosis is generally made by Doppler
ultrasound examination. Te endovascular treatment
consisting in angioplasty with stenting leads to good
results both immediately and in long-term, and can
save the transplanted kidney. Te renal grafs function
can be transiently impaired due to the combined efect
of ischemia, iodinated contrast media administration
and other drugs that may interfere.
References
1. Baxter GM. Ultrasound of renal transplantation. Clin Radiol 2001; 56:
802-818.
2. Napoli V, Pinto S, Bargellini I, et al. Duplex doppler sonography of
trans plant renal artery stenosis before and afer renal stenting. Eur
Radiol 2002; 12:796-803.
3. Curtis JJ. Hypertension and kidney transplantation. Am J Kidney Dis
1986; 7:181-196.
4. FG Cosio, SC Textor. Hypertension afer transplantation. In Weir RM,
Medical management of kidney transplantation,Ed. Lippincott Willi-
ams& Wilkins, 2005.
5. Loubeyre P, Cahen R, Grozel F, et al. Transplant renal artery stenosis.
Transplantation 1996; 62:446-450.
Complex cardiac malformation in a young pregnant woman
Oana Nstase
1
, Roxana Enache
2
, Bogdan A. Popescu
1,2
, Carmen Ginghin
1,2
, Ruxandra Jurcu
1,2
Contact address:
Ruxandra Jurcu, University of Medicine and Pharmacy Carol Davila,
Prof Dr C.C. Iliescu Institute of Emergency for Cardiovascular Diseases,
Sos Fundeni No. 258, 022322 Bucharest. E-mail rjurcut@gmail.com
T
his is the case of a 29 years-old, pregnant woman
who presented in our center for cardiologic evalu-
ation at 28 weeks of pregnancy, being known since in-
fancy with a complex cardiac malformation. Te pati-
ent was asymptomatic until two weeks before presenta-
tion, when she started to describe dyspnea at important
eforts, coincidental with progression of pregnancy.
At transthoracic echocardiography signifcant lef
ventricular hypertrophy (concentric wall thickness of
16 mm) was found, which appeared secondary to severe
aortic stenosis. Te continuous wave Doppler analysis
of transaortic fow (Figure 1), showed a peak velocity
of 4.7 m/s and a mean gradient of 56 mm Hg. Tere
was subvalvular obstruction realized by an incomplete
dia phragm (Figure 2). Te orifce area at the level of the
diaphragm was estimated by 3D transthoracic echocar-
diography planimetry at 1.8 cm
2
(Figure 3). Te patient
had associated valvular stenosis probably secondary to
jet-lesion, estimated by planimetry as moderate (aortic
valve area of 1.4 cm
2
) (Figure 4) and mild aortic re-
gurgitation. An interventricular basal septal aneurysm
with a small lef to right shunt was also seen (Figure 5).
Tere was persistent ductus arteriosus with lef-right
shunt seen both from the parasternal short axis view
and from the suprasternal view (Figure 6 and Figure
7). Te suprasternal view revealed the coexistence of
aortic coarctation with a peak Doppler gradient of 31
mmHg, indicating mild obstruction (Figure 8).
Patients with subvalvular aortic stenosis may tolerate
pregnancy well as long as they remain relatively asy m-
ptomatic and have a normal BP response during exer-
cise
1
. Obstetric complications may be increased in pa-
tients with severe AS (hypertension-related disorders,
pre mature labour)
1
. Regular follow-up during preg-
nancy is required by an experienced team. In severe AS,
monthly or bimonthly cardiac evaluations including
echo cardiography are advised to determine symptom
status, progression of stenosis, or other complications.
In severe aortic stenosis, particularly with symptoms
during the second half of pregnancy, caesarean deli-
very should be preferred with endotracheal intubation
and general anesthesia. Te patient had an uneventful
preg nancy evolution and gave birth to a healthy baby at
38-weeks of pregnancy by caesarean section.
1
Prof. Dr. C.C. Iliescu Institute of Emergency for Cardiovascular Dis-
eases
2
University of Medicine and Pharmacy Carol Davila, Bucharest
Figure 1. Transthoracic echocardiography, apical fve chamber view, con-
tinuous wave Doppler examination of transaortic fow: peak fow velocity
of 4.7 m/s.
Figure 2. Tree-dimensional transthoracic echocardiography parasternal
long axis view focus on lef ventricular outfow tract: the subaortic valve
dia phragm (white arrow). LV = lef ventricle, LA = lef atrium, RV = right
ventricle, Ao = aorta
RV
LV
LA
Ao
Vol. 23, No. 4, 2013
Oana Nastase et al.

Figure 3. Tree-dimensional transthoracic echocardiography apical fve-
chamber view, reconstruction of the lef ventricular outfow tract, view from
the lef ventricle. A circular diaphragm (white arrow) can be seen in lef ven-
tricular outfow tract, creating a stenosis with ananatomical aria at 1.8 cm
2
.
Figure 4. Tree-dimensional transthoracic echocardiography focus on the
aortic valve: moderate valvular aortic stenosis planimetric anatomic area
of 1.4 cm
2
.
Figure 5. Transthoracic echocardiography, apical fve chamber view, focus on aortic valve: interventricular septum basal aneurysm with a small lef-right shunt
(white arrow) at this level seen at color Doppler.
Figure 6. Transthoracic echocardiography, short axis view at great vessels (A) and suprasternal view (B), color Doppler examination: patent ductus arteriosus
with a diameter of 5 mm (white arrow).
A B
Oana Nastase et al.
Vol. 23, No. 4, 2013

References
1. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C et al. ESC Co-
m mittee for Practice Guidelines. ESC Guidelines on the management
of cardiovascular diseases during pregnancy: the Task Force on the
Management of Cardiovascular Diseases during Pregnancy of the Eu-
ropean Society of Cardiology. Eur Heart J. 2011; 32(24):3147-97
Figure 7. Transthoracic echocardiography, parasternal short axis view, continuous wave Doppler examination of the patent ductus arteriosus shows continu-
ous fow with maximal aorto-pulmonary gradient of 100 mmHg.
Figure 8. Transthoracic echocardiography, suprasternal view: aortic coarctation seen in 2D (A),with a peak systolic gradientof 31 mmHg at continuous wave
Doppler examination (B).
A B
Aortic arch
Descending
aorta
Aortic
coarctation
Ultrasound imaging of a bilateral carotid body paraganglioma
Roxana Oana Darabont
Contact address:
Roxana Oana Darabont, MD, PhD, Cardiology Department of University
Emergency Hospital Bucharest, Splaiul Independentei Street, no. 169,
050098 Bucharest, Romania; fax: +40 21 3180576; phone: + 40 723 441 315.
e-mail: rdarabont@yahoo.com;
P
aragangliomas are rare tumors that grow from cells
of the peripheral nervous system, which derive
from the embryonic neural crest cel
1,2
. Te head and
neck represent the most common topography of these
tumors. At this level they originate mainly from carotid
body (carotid bi fur cation), with other possible locati-
ons on vagal body, in the middle ear, and larynx. Te
carotid body paragangliomas (CBPs) are highly vascu-
larized lesions, therefore one formerly name used for
them was glomus tu mors. Another ancient denomi-
nation chemodectoma was indicating their possi-
ble chemoreceptor function
3
.
CBPs are usually benign, non-secreting, slow grow-
ing tumors
4,5
. About 60% of them did not exhibit grow-
th in follow-up. Some reports are indicating that 4.2
years is the average double time for this tumors
6
. CBPs
can be found at any age, but the usual age for onset is
between the third and six de ca de of life (mean age 55
years)
7,8
and is slightly more fre q u ent in women
8
. As
a whole, carotid body tumors are b ilateral in 10% of
cases
9
.
Te true incidence of CBPs is still unknown as long
as many cases remain undiagnosed and the disease is
very rare, but it is estimated to 0.012%
10
.
Keywords: carotid body paraganglioma, ultrasound,
color Doppler ultrasound
We are presenting the case of 30 years old male with
asymptomatic bilateral swelling of the neck which is
the usual presentation in 60-70% of CBP
11
. During the
clinical exam we found a palpable mass on each side of
the neck, in front of the sternocleidomastoidian mus-
cle, being more easier moved horizontally rather than
vertically (the Fontaines sign)
12
.
In other cases a pulsating mass can be detected at
palpation. Very rarely a carotid bruit can be heard, due
to an important compression induced by the tumor on
the carotid arteries. Large CBP may be associated with
dysfunction of the vagal nerve or cranial nerves IX, XI,
and XII, with Horners syndrome or defcits of the fa-
cial nerve
13
.
Te usual diagnostic methods for this pathology are:
B-mode and Doppler ultrasound, angio-CT, angio-
MRI, 111 In-OctreoScan and digital subtraction angio-
graphy. Depending on carotid arteries involvement
CBPs can be of three categories, according to Shamblin
clas sifcation: class I splaying of the carotid bifurca-
tion with little attachment to the carotid vessels, class
II partial surrounding of the internal and external ca-
ro tid arteries, Class III complete surrounding of the
carotid vessels
14
.
A relatively recent evaluation proved a sensitivity of
92% and a specifcity of 100% for the B-mode combi-
ned with color Doppler ultrasound in the detection
of carotid paragangliomas compared with CT/MRI.
However, the diference in maximum diameter of the
lesions measured at ultrasound versus CT/MRI was
signifcant (p=0.008), ranging between 5 mm and +
16 mm (mean diference 2.26.0)
15
.
1
University of Medicine and Pharmacy Carol Davila Cardiology De-
partment of University Emergency Hospital Bucharest
Figure 1. B-mode ultrasound imaging of the right-sided carotid paragangli-
oma. Te tumor is oval, well-defned, inhomogeneous, hypoechoic. Cranio-
caudal diameter has 21.5 mm and tranversal diameter has 28.3 mm.
Ultrasound imaging of carotid paraganglioma
Vol. 23, No. 4, 2013
In our case the diagnostic of carotid body tumor was

frstly established at ultrasound exam. An oval, well-
defned, inomogenous, hypoechoic and hypervascula-
rized structure was observed at carotid bifurcation on
the right side of the neck (Figure 1 and 2) and on the
lef side as well (Figure 3 and 4). Figure 4 is indicating a
CBP of Shamblin class III, with complete surrounding
of the carotid arteries. In Figure 5 it is illustrated the
attachement of CBP on the entire proximal wall of the
lef internal carotid artery in longitudinal view. Figu-
re 6 is emphasizing that the fow is still normal in lef
internal carotid artery despite the adjacent invasion of
the tumor.
Afer three years of follow-up the patient did not
pro ceed to surgical correction of the bilateral CBP ta-
king into account that the tumors are asymptomatic,
Figure 2. Color Doppler ultrasound of the vascularized right-sided carotid
para ganglioma.
Figure 3. B-mode ultrasound imaging of the lef-sided carotid paragangli o-
ma with Shamblin class III characteristics splaying of the carotid bifurca-
tion and complete surroundings of the carotid arteries. Cranio-caudal dia-
meter has 21.9 mm and transversal diameter has 34.8 mm. L-ECA = lef
external carotid artery; L-ICA = lef internal carotid artery.
Figure 4. Color Doppler ultrasound of the hypervascularised lef-sided caro-
tid paraganglioma.
Figure 5. B-mode ultrasound imaging of the lef sided paraganglioma atta-
ched to the proximal wall of the lef internal carotid artery in longitudinal
view. L-ICA=lef internal carotid artery.
Figure 6. Color and spectral Doppler ultrasound of the lef internal carotid
artery indicating normal fow at this level; L-ICA = lef internal carotid ar-
tery.
Vol. 23, No. 4, 2013

Ultrasound imaging of carotid paraganglioma
with very slow grow and the risk of intervention is sig-
ni fcantly high.
References
1. Najibi S, Terramani TT, Brinkman W et al. Carotid body tumors., J.
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2. Paal E, Chung EM, Head and neck pathology Radiology classics:
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3. Martin TP. What we call them: the nomenclature of head and neck
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4. Myssiorek D, Ferlito A, Silver CE et al. Screening for familial paragan-
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ment proposal, Cancer, 2000; 88: 2811-2816.
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tumor: case report and literature review, Journal of Geriatric Cardio-
logy, 2013; 10: 116-118.
9. Pacheco-Ojeda L. Malignant carotid body tumors: report of three ca-
ses. Ann. Otol. Rhinol. Laryngol., 2001; 110: 36-40.
10. Grotemeyer D, Loghmanieh SM, Pourhassan S et al. Dignity of ca-
rotid body tumors. Review of the literature and clinical experiences.
Chirurg, 2009; 80: 854-863.
11. Patetsios B, Gable DR, Garrett WV et al. Management of carotid body
paragangliomas and review of a 30-year experience, Ann. Vasc. Surg.,
2002; 16: 331-338.
12. Boedeker CC, Ridder GJ, Schipper J. Paragangliomas of the head and
neck: diagnosis and treatment, Fam. Cancer, 2005; 4: 55-59
13. Ofergeld C, Brase C, Yaremchuk S. et al. Head and neck paragan-
gliomas: clinical and molecular genetic classifcation, Clinics, 2012;
67(S1): 19-28.
14. Shamblin WR, ReMine WH, Sheps SG et al. Carotid body tumor
(chemodectoma). Clinico-pathologic analysis of ninety cases, Am. J.
Surg., 1971; 122: 732-739.
15. Dematt S, Di Sarra D, Schiavi F et al. Role of ultrasound and color
Doppler imaging in the detection of carotid paragangliomas, J. Ultra-
sound, 2012; 15: 158-163.
UPDATES IN CARDIOLOGY
O comparaie direct a rezultatelor precoce i
tardive dup trei tipuri diferite de revascularizare
carotidi an i chirurgie cardiac
Prevalena leziunilor carotidiene severe la pacienii cu
indicaie de chirurgie cardiac este ntre 6-12%, dar
mana gementul optim al acestor pacieni este controver-
sat n lipsa unor trialuri clinice randomizate. Exist n
practica curent trei abordri: endarterectomie caroti-
dian urmat de chirurgie cardiac (staged CEA-OHS),
endarterectomie carotidian concomitent cu chirur-
gia cardiac (combined CEA-OHS) i angioplastie ca-
rotidian cu implantare de stent urmat de chirurgie
cardiac (staged CAS-OHS).
Autorii i propun s compare rezultatele celor trei
procedee. Studiul s-a desfurat n perioada 1997-2009
i au fost nrolai 350 de pacieni supui unei intervenii
de revascularizare carotidian naintea sau concomi-
tent cu o intervenie chirurgical cardiac (ntr-un in-
terval de maxim 90 de zile), urmrii o perioad medie
de 3-7 ani. n funcie de procedura aleas, pacienii au
fost mprii n trei grupuri: staged CEA-OHS (45),
combined CEA-OHS (195), staged CAS-OHS (110).
Endpointul primar a fost unul compozit incluznd
mortalitatea de orice cauz, accidentul vascular cere-
bral (AVC) i infarctul miocardic (IM).
Rezultatele au artat c la nrolare, prevalena bolii
carotidiene simptomatice i a stenozei/ocluziei caroti-
diene contralaterale a fost similar n cele trei grupuri,
dar n grupul supus staged CAS-OHS a fost o pre-
valen mai mare a antecedentelor de AVC (p=0,03),
de re vascularizare carotidian i a interveniilor chirur-
gi cale cardiace mai complexe. Pentru interveniile n
dou etape, analiza complex a artat importana inter-
valului interprocedural. Astfel, n acest interval, staged
CEA-OHS a fost asociat cu un risc semnifcativ mai
mare de IM. Rezultatele arat c nu a existat o diferen
semnifcativ n endpointul compozit pe termen scurt
ntre staged CAS-OHS i combined CEA-OHS, dar sta-
ged CAS-OHS a avut un risc mai mare de IM n inter-
valul interprocedural, iar combined CEA-OHS a avut
un risc mai mare de AVC perioperator. Pe termen lung
(>12 luni) staged CAS-OHS a avut un risc semnifcativ
mai mic de evenimente compozite comparativ att cu
staged CEA-OHS (adjusted hazard ratio: 0,33; 95% CI:
0,15- 0,77; p=0,01) ct i cu combined CEA-OHS (ad-
justed hazard ratio:0,35; 95% CI: 0,18-0,70; p=0,003).
Staged CEA-OHS a avut riscul cel mai mare att preco-
ce ct i tardiv.
n concluzie, autorii subliniaz c staged CAS-OHS
i combined CEA-OHS prezint riscuri similare de de-
ces, AVC i IM pe termen scurt, ambele find mai bune
dect staged CEA-OHS. Cu toate acestea, dup un an,
re zultatele sunt semnifcativ mai favorabile pentru sta-
ged CAS-OHS. Un argument n favoarea combined
CEA-OHS ar putea f urgena necesitii revasculariz-
rii coronariene, avnd n vedere intervalul de 3-4 spt-
mni necesar de dubl antiagregare dup CAS, nain-
tea OHS. Astfel, autorii consider staged CAS-OHS de
prim intenie dac este acceptabil ideea temporizrii
OHS cu 3-4 sptmni.
Mehdi H. Shishehbor et al. A Direct Comparison of
Early and Late Outcomes With Tree Approaches to Ca-
rotid Revascularizaton and Open Heart Surgery. J Am
Coll Cardiol 2013; 62:1948-56. (ACM).
Rezerva contractil a ventriculului drept la pacienii
cu HTP sever evaluare i semnicaie prognostic
Comparativ cu numrul mare de studii privind eva-
luarea rezervei contractile a ventriculului stng, pen-
tru ventriculul drept nu exist metode recunoscute de
evaluare. Plecnd de la prezumia intuitiv c exist o
relaie ntre creterea la efort a presiunii sistolice din
artera pulmonar (PAPS) i funcia VD, autorii i pro-
pun s analizeze creterea PAPS la efort ca un indicator
de rezerv contractil a VD la pacienii cu HTP sever
i insufcien cardiac dreapt.
Studiul citat a fost prospectiv i a inclus 124 de pa-
cieni diagnosticai invaziv cu HTP arterial sau HTP
cronic tromboembolic i cu disfuncie sistolic de
VD n ciuda tratamentului optim, ce au fost urmrii
pe o perioad medie de 31,8 ani. Pacienii au efectuat
ecocardiografe de stres i testul cardiopulmonar i, n
funcie de creterea PAPS la efort peste valoarea de 30
mmHg au fost mprii n dou grupuri: cu/fr cre-
terea PAPS cu peste 30 mmHg, aproximativ egale (58,
respectiv 66 de pacieni). Din cei 124 de pacieni, 104
aveau HTP arterial i 20 HTP cronic tromboembo-
lic inoperabil. Rezultatele au artat c la nrolare nu
au existat diferene semnifcative ntre cele dou gru-
puri privind medicaia, parametrii hemodinamici de
repaus msurai prin cateterism (PAP medie crescu-
t, rezistena vascular pulmonar mare, indicele car-
diac sczut) sau parametrii ecocardiografci (aria VD
crescut, TAPSE sczut, etc.). La efort, creterea PAPS
cu mai puin de 30 mmHg s-a asociat cu valori sem-
nifcativ mai mici pentru distana parcurs la testul de
Vol. 23, No. 4, 2013
Updates in cardiology
internai n 26 de spitale din China n perioada august
2009 i mai 2013 pentru AVC ischemic acut, netrom-
bolizat, debutat n primele 48 de ore, i cu valori mari
ale TA. Au fost alei n mod aleatoriu 2038 de pacieni
care au primit tratament hipotensor, cu obiectivul de
a reduce TA cu 10% pn la 25% n primele 24 de ore
dup randomizare, obinerea unei TA <140/90 mm Hg
n primele 7 zile i meninerea acestor valori pe par-
cursul spitalizrii. Ceilali 2033 de pacieni crora li s-a
oprit medicaia antihipertensiv au reprezentat lotul de
control. End-pointurile primare stabilite au fost: rata
mortalitii i dizabilitatea major (defnit ca scorul
Scalei Rankin modifcate 3) la 14 zile sau la externare.
n primele 24 de ore de la randomizare, TA sistolic
medie a fost redus de la 166.7 mm Hg la 144.7 mm
Hg (-12.7%) n grupul pacienilor care au primit tra-
tament hipotensor i de la 165.6 mm Hg la 152.9 mm
Hg (-7.2%) n grupul control (diferena 5.5% [95%CI,
4.9 la 6.1%]; diferena absolut, 9.1 mm Hg [95%
CI, 10.2 la 8.1]; p <0.001). La 7 zile de la randomi-
zare, TA sistolic medie n grupul celor cu tratament
hipotensor a fost 137.3 mm Hg, iar n grupul control
146.5 mm Hg (diferena, 9.3 mm Hg [95%CI, 10.1 la
8.4]; p <0.001).
Endpointul primar nu a fost diferit semnifcativ sta-
tistic ntre cele dou grupuri la 14 zile sau la externare
(683 de evenimente adverse n grupul cu tratamentul
hipotensor vs. 681 n grupul control; OR 1.00 [95%CI,
0.88 - 1.14]; p=98). Nici dup 3 luni de urmrire a
pacienilor rata mortalitii i dizabilitatea major nu
au fost semnifcativ diferite n cele dou grupuri (500
de evenimente adverse n grupul cu tratamentul hipo-
tensor vs. 502 n grupul control; OR 0.99 [95%CI, 0.86
- 1.15]; p=93).
n concluzie, acesta este primul studiu clinic rando-
mizat cu sufcient putere statistic pentru a testa efec-
tul scderii imediate a valorilor TA asupra ratei mor-
talitii i dizabilitii majore la pacienii cu AVC ische-
mic acut. Rezultatele studiului au demonstrat c admi-
nistrarea imediat a medicamentelor hipotensoare la
aceast categorie de pacieni nu amelioreaz semnif-
cativ prognosticul acestora la 14 zile sau la externare.
He J, Zhang Y, Xu T, Zhao Q, Wang D, Chen CS,
Tong W, Liu C, Xu T, Ju Z, Peng Y, Peng H, Li Q, Geng
D, Zhang J, Li D, Zhang F, Guo L, Sun Y, Wang X, Cui Y,
Li y, Ma D, Yang G, Gao Y, Yuan X, Bazzano LA, Chen J.
Efects of Immediate Blood Pressure Reduction on Death
and Major Disability in Patients With Acute Ischemic
Stroke. Te CATIS Randomized Clinical Trial. JAMA.
Published online on November 17, 2013. doi:10.1001/
jama.2013.282543. (AM)
mers de 6 minute, pentru consumul maxim de O
2
/kg i
pentru ratele de supravieuire la 1-, 3-, i 4 ani. La tes-
tul cardiopulmonar, valoarea cutof pentru consumul
maxim de VO
2
care a submprit pacienii a fost de
11,4 ml/min/kg, pacienii cu consum VO
2
peste aceast
valoare au avut rate de supravieuire semnifcativ mai
bune dect cei sub aceast valoare. La analiza univari-
at, parametrii predictivi pentru supravieuire au fost:
testul de mers de 6 minute, consumul maxim VO2
per se i indexat la greutate, PAPS maxim i creterea
PAPS. La analiza multivariat, creterea PAPS la efort
i consumul maxim VO
2
/kg s-au dovedit a f predic-
tori independeni de prognostic (HR, 2,56 pentru con-
sumul maxim O
2
/kg i 2,84 pentru creterea PAPS la
efort).
Concluzia studiului a fost c creterea PAPS la efort
are o mare relevan clinic i prognostic la pacienii
cu HTP i poate sugera prezena rezervei contracti-
le a VD subliniind rolul potenial al ecocardiografei
Doppler de stres n evaluarea prognostic a pacienilor
cu HTP. Corelnd aceste rezultate cu confrmarea re-
cent a faptului c funcia sistolic a VD este un pre-
dictor prognostic mai puternic dect rezistena vascu-
lar pulmonar, se contureaz rolul posibil superior al
evalurii rezervei contractile a VD fa de parametrii
hemodinamici de repaus (msurai ecocardiografc) n
urmrirea i managementul terapeutic al pacienilor cu
HTP.
Ekkehard Grunig et al. Assessment and Prognostic
Relevance of Right Ventricular Contractile Reserve in Pa-
tients With Severe Pulmonary Hypertension. Circulation
2013;128:2005-2015. (ACM).
Efectele reducerii imediate ale tensiunii arteriale
asupra decesului i dizabilitii majore la pacienii
cu accident vascular cerebral ischemic acut
Studiul clinic randomizat CATIS
Accidentul vascular cerebral (AVC) este a doua cauz
de deces i prima cauz de dizabilitate important pe
termen lung din lume. Studiile clinice au demonstrat c
reducerea tensiunii arteriale (TA) scade riscul de AVC
la pacienii hipertensivi i normotensivi cu istoric de
AVC sau accident ischemic tranzitor. Dei benefciile
tratamentului hipotensor pentru prevenia primar i
secundar a AVC-ului sunt cunoscute, efectele reduce-
rii imediate a valorilor TA la pacienii cu AVC ischemic
acut nu sunt nc bine stabilite.
Astfel, autorii acestui studiu clinic randomizat au
avut ca obiectiv evaluarea efectului scderii imediate
a valorilor TA la pacienii cu AVC ischemic acut, ur-
mrind rata mortalitii i dizabilitatea major la 14
zile sau la externare. Au fost inclui 4071 de pacieni
Vol. 23, No. 4, 2013
Repararea valvular mitral versus nlocuirea

valvular n regurgitarea mitral ischemic sever
Regurgitarea mitral ischemic, consecin a remode-
lrii ventriculare stngi (VS) post infarct miocardic, se
aso ciaz cu un risc substanial de deces. Tratamentul
chi rurgical al acesteia difer considerabil de cel al re-
gur gitrii mitrale degenerative, organice. Ghidurile ac-
tuale recomand intervenie chirurgical pacienilor cu
re gurgitare mitral ischemic sever care sunt simpto-
matici n ciuda tratamentului maximal medicamentos,
ns evidenele n ceea ce privete repararea versus n-
locuirea valvular sunt limitate.
n acest studiu au fost inclui 251 de pacieni diag-
nos ticai cu regurgitare mitral ischemic sever. Ace-
tia au fost supui interveniei chirurgicale, find ran-
do mizai fe pentru efectuarea reparrii valvulare, fe
pentru nlocuirea acesteia cu prezervarea cordajelor,
sco pul find evaluarea efcacitii i siguranei acestor
dou tehnici. End-pointul primar a fost reprezentat de
gradul de reversibilitate a remodelrii VS, evaluat prin
volumul telesistolic ventricular stng indexat (VTSVSI)
la 12 luni. End-pointurile secundare au fost reprezenta-
te de rata mortalitii i evenimentelor adverse cardia-
ce sau cerebrovasculare. Din punct de vedere statistic,
pen tru a evalua VTSVSI s-a utilizat testul Wilcoxon
rank-sum.
La 12 luni, VTSVSI mediu n cadrul supravieuitorilor
a fost de 54.625.0 ml/m
2
n grupul pacienilor cu repa-
rare valvular (G1) i 60.731.5 ml/m
2
n grupul celor
cu nlocuire valvular (G2) (modifcarea medie fa de
momentul iniial, 6.6 ml/m
2
i 6.8 ml/m
2
, respectiv).
Rata deceselor a fost de 14.3% n grupul G1 i 17.6%
n G2 (reparare valvular - HR 0.79; 95% intervalul de
confden, 0.42-1.47; p = 0.45). Nu a fost o diferen
semnifcativ ntre cele 2 grupuri n ceea ce privete
VTSVSI dup ajustare pentru deces (scor z 1.33; p =
0.18). Rata recurenei regurgitrii mitrale moderate sau
severe la 12 luni a fost semnifcativ statistic mai mare
n grupul G1 fa de G2 (32.6% vs. 2.3%, p <0.001). Nu
s-a constat o diferen semnifcativ ntre cele 2 grupuri
n ceea ce privete rata evenimentelor adverse cardiace
sau cerebrovasculare, statusul funcional sau calitatea
vieii la 12 luni.
n concluzie, nu a fost observat o diferen semni-
fcativ statistic n ceea ce privete remodelarea VS sau
supravieuirea la 12 luni la pacienii la care s-a efectuat
nlocuire valvular, comparativ cu repararea valvular.
nlocuirea valvei mitrale a conferit o corecie mai du-
rabil a regurgitrii mitrale ischemice, ns nu au fost
observate diferene n ceea ce privete prognosticul cli-
nic al pacienilor din cele dou grupuri studiate. Re-
zu l tatele acestui studiu contrazic multe dintre datele
pu blicate n literatur anterior pe acest subiect, i anu -
me c repararea valvular mitral confer avantaje in-
clu znd o rat mai mic a mortalitii perioperatorii, o
ame liorare a funciei ventriculare stngi i o mai mare
rat a supravieuirii pe termen lung. Continuarea ur-
mrii pe termen lung a acestor pacieni este necesa r
pentru con frmarea rezultatelor acestui studiu, putnd
de aseme nea ajuta la identifcarea predictorilor de recu-
ren a regurgitrii mitrale i permind astfel o selecie
mai adecvat a pacienilor.
Acker MA, Parides MK, Perrault L, Moskowitz A,
Gelijns A, Voisine P, Smith P, Hung J, Blackstone E,
Puskas J, Argenziano M, Gammie J, Mack M, Asche-
im D, Bagiella E, Moquete E, Ferguson B, Horvath K,
Geller N, Miller M, Woo J, DAlessandro D, Ailawadi
G, Dagenais F, Gardner T, OGara P, Michler R, Kron I.
Mitral-Valve Repair versus Replacement for Severe Ische-
mic Mitral Regurgitation. N Engl J Med November 18,
2013; at NEJM.org; DOI: 10.1056/NEJMoa1312808 (AM)
Studiul CORAL: Angioplastia i terapia
medicamentoas n stenoza aterosclerotic de
arter renal
Rezultatele studiilor de screening indic o prevalen
a stenozelor aterosclerotice de arter renal de pn
la 7% n rndul persoanelor cu vrsta peste 65 de ani.
Ste nozele aterosclerotice de la nivelul arterelor rena-
le pot conduce la hipertensiune arterial, nefropatie
ischemic i la complicaii multiple pe termen lung.
Benefciile angioplastiei de arter renal n prevenia
evenimentelor adverse majore renale i cardiovasculare
sunt incerte. Exist pn n prezent trei trialuri clinice
randomizate n care angioplastia de arter renal nu a
prezentat benefcii n ceea ce privete valorile tensiunii
arteriale i alte dou trialuri clinice randomizate care
nu au demonstrat un benefciu al stentrii n ceea ce
privete ameliorarea funciei renale.
Trialul CORAL (Te Cardiovascular Outcomes in Re-
nal Atherosclerotic Lesions) a avut ca scop evaluarea in-
fuenei angioplastiei de arter renal asupra incidenei
evenimentelor clinice adverse cardiovasculare i renale.
S-a efectuat un studiu multicentric, randomizat, con-
trolat, pe un numr de 947 de pacieni care prezentau
stenoze aterosclerotice la nivelul arterelor renale i care
asociau hipertensiune arterial sistolic n ciuda tera-
piei cu dou sau mai multe medicamente antihiper-
tensive (valori de 155 mmHg sau peste), boal renal
cronic (RFG prin MDRD sub 60 ml/min/1.73 m
2
) sau
ambele. Stenoza sever de arter renal a fost defnit
Vol. 23, No. 4, 2013
stentare 0.94; IC 95%, 0.76 la 1.17; p = 0.58). Nu s-au
nregistrat diferene semnifcative ntre cele dou gru-
puri nici n ceea ce privete ratele componentelor indi-
viduale ale end point-ului compozit sau ale mortalitii
de orice cauz. Valoarea tensiunii arteriale sistolice a
nregistrat o reducere n ambele grupuri (cu 15.625.8
mm Hg n grupul cu tratament medical i cu 16.621.2
mm Hg n grupul cu angioplastie i tratament medi-
cal). S-a observat o reducere uor mai mare, semnif-
cativ statistic, a tensiunii arteriale sistolice n favoarea
grupului la care s-a efectuat stentarea (2.3 mm Hg; IC
95%, 4.4 la 0.2; p = 0.03), dar aceasta nu s-a asociat
cu o reducere a evenimentelor clinice.
Concluzia acestui studiu a fost aceea c stentarea
arterelor renale, asociat terapiei medicale complexe i
multifactoriale, nu a prezentat un benefciu semnifca-
tiv n ceea ce privete prevenia evenimentelor clinice
fa de terapia medical izolat.
Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and
Medical Terapy for Atherosclerotic Renal-Artery Steno-
sis. N Engl J Med 2013. DOI: 10.1056/NEJMoa1310753
(AP)
Trialul TTM (Targeted Temperature Management):
temperatura int dup stop cardiac, 33 grade versus
36 grade Celsius
Pacienii care nu i-au recptat starea de contien,
dup un stop cardiac resuscitat n afara spitalului, se
af la risc crescut de deces, iar deteriorarea neurologi-
c ulterioar este frecvent la cei care supravieuiesc.
Exis t dou trialuri clinice, efectuate la supravieuitorii
afai n stare de incontien dup un stop cardiac re-
suscitat (presupus a f de cauz cardiac i cu apariia
unei tulburri de ritm ce a necesitat defbrilare), care au
comparat efectele hipotermiei terapeutice (ntre 32 i 34
grade Celsius timp de 12-24 de ore) cu efectele terapiei
standard. Aceste trialuri au demonstrat c hipotermia
terapeutic se asociaz cu o mbuntire semnifcati-
v a funciei neurologice i a supravieuirii. n prezent,
in ducerea hipotermiei terapeutice este recomandat
de ghidurile internaionale, ns dovezile n acest sens
sunt limitate iar valoarea temperaturii int asociat cu
cel mai bun prognostic este nc necunoscut.
Trialului TTM (Targeted Temperature Management)
este un studiu randomizat desfurat pe 939 de pacieni
selectai din 36 de uniti de terapie intensiv din Euro-
pa i Australia, n care s-au comparat rezultatele hipo-
termiei terapeutice induse la o valoare de 33 versus 36
grade Celsius. Au fost selectai pacieni cu vrsta peste
18 ani, afai n stare de incontien (scor Glasgow mai
mic de 8) dup moarte subit, presupus a f de cauz
angiografc ca stenoz de cel puin 80% dar mai mic de
100% din diametrul arterei, sau ca stenoz de cel puin
60% dar mai mic de 80% din diametrul arterei i cu un
gradient presional de cel puin 20 mmHg.
Pacienii au fost randomizai pentru management
prin terapie medical plus stentare la nivelul arterei re-
nale (467 de pacieni, ulterior doar 459 inclui n anali-
za statistic) sau doar management prin terapie medi-
cal (480 pacieni, ulterior doar 472 inclui n analiza
statistic).
n ceea ce privete medicaia administrat, toi parti-
cipanii au primit terapie antiagregant plachetar, me-
dicaie pentru controlul valorilor tensionale, glicemiei
i pentru tratarea dislipidemiei. n absena contraindi-
caiilor, s-au administrat candesartan cu sau fr hi-
droclorotiazid i agentul care conine combinaia fx
de amlodipin cu atorvastatin, dozele find ajustate n
funcie de valorile tensionale i de proflul lipidic. Pen-
tru valorile tensionale, inta a fost o valoare sub 140/
90 mmHg la pacienii fr afeciuni coexistente i de
sub 130/80 mmHg la pacienii cu diabet sau cu boal
renal cronic, medicaia find ajustat pn la atinge-
rea intelor.
n ceea ce privete angioplastia, s-au folosit stenturi
Palmaz Genesis stent, iar la unii pacieni, la aprecie-
rea medicului, s-a efectuat predilatare. Au fost stentate
toate stenozele mai mari sau egale de 60%. La pacienii
cu stenoze multiple, s-a efectuat stentarea multipl n
cadrul aceleiai proceduri sau la intervale de 2-4 sp-
tamni. A fost plasat i un dispozitiv de protecie pen-
tru embolie distal de tip Angioguard, iniial la toi
pacienii, ulterior folosirea acestuia a fost lsat la apre-
cierea medicului.
Participanii au fost urmrii pe o perioad medie de
43 de luni pentru producerea de evenimente adver se
cardiovasculare i renale. Endpoint-ul primar a fost un
compozit al decesului de cauz cardiovascular sau re-
nal, infarctului de miocard, accidentului vascular ce-
rebral, spitalizrilor pentru insufcien cardiac con-
gestiv, insufcienei renale progresive sau al nevoii de
terapie de substituie a funciei renale. End point-urile
secundare au fost reprezentate de componentele indi-
viduale ale end point-ului primar i de mortalitatea de
orice cauz.
La fnalul studiului s-a constatat c rata end point-
ului compozit nu a prezentat diferene semnifcative
ntre grupul pacienilor la care s-a efectuat stentarea
de arter renal plus administrare de terapie medical
i grupul pacienilor care au primit doar terapie medi-
cal (35.1% i respectiv 35.8%; rata hazardului pentru
Vol. 23, No. 4, 2013
Algoritm de diagnostic n cardiomiopatii - o punte de

legtur ntre fenotipul clinic i diagnosticul nal.
Cardiomiopatiile, sunt un subiect deocamdata greu
de stpnit, att din cauza varietii i variabilitii,
ct i a limitelor tehnice. Clasifcarea cardiomiopatii-
lor din 2008 (conform ESC), mparte cardiomiopatii-
le n funcie de fenotipul morfologic i funcional n:
cardiomiopatia hipertrofc, cardiomiopatia dilatativ,
cardiomiopatia aritmogen de ventricul drept, cardio-
miopatia restrictiv si cardiomiopatii neclasifcate, care
la rndul lor sunt mprite n funcie de modalitatea
de transmitere n familiale/genetice i non-familiale/
non-genetice.
Acest articol ne propune o abordare de ansamblu a
pacientului cu aceast patologie. Clinicianul ncercnd
s obina informaii pe baza tuturor instumentelor care
i sunt la ndemn. Astfel c nc de la intrarea n cabi-
net o anamnez amnunit ne poate aduce informaii
preioase, ncepnd cu sexul, vrsta, istoricul personal
i familial. Pe baza istoricului familial se poate contura
modalitatea de transmitere a bolii (ex: boala Fabry are
transmitere de la mama la fu- X lincata).
O examinare fzic atent ne poate aduce o sumede-
nie de indicii" (stegulee roii cum le place autorilor
s spun) ex: lentigo n sindromul LEOPARD, sin-
drom de canal carpian n amiloidoz. Cnd examinm
un pacient cu cardiomiopatie trebuie s avem mereu
n minte faptul c, de obicei, acestea apar n contextul
unor boli multisitemice; prin urmare clinicianul ar tre-
bui s aib un index crescut de suspiciune i astfel s
identifce expresiile fenotipice n alte organe ale acestor
boli pentru a avea un diagnostic fnal ct mai fdel i ct
mai precoce; cunoscndu-se faptul c de regul acestea
preced manifestrile fenotipice cardiace (ex: distrofile
musculare- asociere frecvent ntlnit aceti pacieni
necesitnd o abordare multidisciplinar, incluznd un
specialist neurolog).
n urmtoarele etape de diagnostic, indiciile se adun
i astfel se contureaz ncet-ncet diagnosticul. Electro-
cardiograma ne poate da de exemplu informaii legate
de afectarea membrilor din familie, la care unica ma-
ni festare poate f vizibil doar electric (ex: unde T gi-
gante, negative n cardiomiopatia hipertrofc) sau des-
pre o afectare subclinic a pacientului (ex: microvol taj
n amiloidoz, pattern de pseudoinfarct n cardiomio-
patia dilatativ).
Urmeaz examenele de laborator pe care autorii le-
au mprit n dou categorii, de prim nivel (care se fac
tuturor pacienilor ex: CK, proteinuria, funcia hepa-
tic i renal sau analize care sunt destinate pacienilor
cardiac, resuscitat n afara spitalului, indiferent de
rit mul cardiac prezent la debut. Durata de inducere a
hipo termiei terapeutice a fost de 36 de ore, s-au folo-
sit metode de suprafa sau intravasculare de inducere
a hipotermiei, pacienii au fost sedai pe toat aceast
perioad. Pacienii au fost urmrii apoi pe o perioad
de 180 de zile dup inducerea hipotermiei. S-a evaluat
mor talitatea global, ca rezultat fnal al studiului, iar ca
re zultate secundare defcitul neurologic si mortalitatea
de cauz neurologic la 180 zile, evaluate prin scala
CPS (Cerebral Performance Category) i scala Rankin
modifcat.
La fnalul studiului, din grupul celor la care s-a in-
dus hipotermia la 33 grade, 50% din pacieni (235 din
473 de pacieni) au decedat, n comparaie cu 48% din
grupul pacienilor cu hipotermie la 36 grade (225 din
466 de pacieni) (rata hazardului de 1.06 pentru tem-
peratura de 33 grade, 95% IC, 0.89 la 1.28; p 0.51). La
180 de zile, 54% din pacienii cu hipotermie la 33 grade
au decedat sau au prezentat defcit neurologic conform
scalei CPC, n comparaie cu 52% din pacienii cu hi-
potermie la 36 grade (rata de risc 1.02; IC 95%, 0.88 la
1.16; p 0.78). Defcitul neurologic la 180 de zile evaluat
prin scala Rankin modifcat a fost similar, rata find de
52% pentru ambele grupuri (rata de risc 1.01; IC 95%;
0.89 la 1.14; p 0.87). Efecte adverse majore ale hipoter-
miei s-au nregistrat la 93% din pacienii afai n gru-
pul de 33 grade i la 90% din cei afai n grupul de 36
grade (rata riscului 1.03; IC 95% CI, 1.00 la 1.08; p =
0.09). Hipopotasemia a fost mai frecvent n grupul de
33 grade Celsius (19%, vs. 13%; p 0.02).
Prin urmare, nu s-au nregistrat diferene semnifca-
tive ntre cele dou grupuri n ceea ce privete mortali-
tatea global i nici n ceea ce privete mortalitatea de
cauz neurologic la 180 zile sau defcitul neurologic la
180 de zile. Hipotermia terapeutic indus la 33 grade
Celsius nu s-a dovedit a se asocia semnifcativ cu efecte
adverse majore mai importante sau mai frecvente fa
de hipotermia la 36 grade Celsius, dar nu a prezentat
nici benefcii semnifcative statistic.
Concluzia acestui studiu a fost aceea c la supravie-
uitorii incontieni dup un stop cardiac resuscitat n
afara spitalului inducerea hipotermiei terapeutice la va-
loarea de 33 grade Celsius nu aduce benefcii suplimen-
tare fa de hipotermia la 36 grade.
Nielsen N, Wetterslev J, Cronberg T, et al. et al. Tar-
geted Temperature Management at 33C versus 36C af-
ter Cardiac Arrest. N Engl J Med 2013. DOI: 10.1056/
NEJMoa1310519 (AP).
Vol. 23, No. 4, 2013
ar are un rol limitat n diagnosticul cardiomiopatiilor,
se folosesc radiotrasori specifci n funcie de tipul de
cardiomiopatie suspicionat.
n privina investigaiilor invazive, dei biopsia mi-
ocardic este standardul de aur pentru unele tipuri de
cardiomiopatie (ex: sarcoidoz, amiloidoz, miocar-
dit) biopsia extracardiac este mai frecvent folosit,
avnd n vedere impactul mai puin marcat asupra pa-
cientului (ex: biopsie esut gras i rectal n amiloidoz).
Concluzii: autorii ne propun un algoritm de diag-
nostic al cardiomiopatiilor, n care medicul este ncura-
jat s se foloseasc de toate instrumentele pe care le de-
ine, ncepnd cu simul vizual pn la investigaii in-
vazive cum este biopsia endomiocardic, pentru obi-
nerea de indicii diagnostice care s il ajute la contu-
rarea unui diagnostic ct mai corect i astfel pacientul
s benefcieze de un tratament intit. De asemenea se
accentueaz importana abordrii multidisciplinare a
acestor pacieni, tiindu-se c de obicei cardiomiopatii-
le apar n contextul unor boli multisistemice.
(Diagnostic work-up in cardiomyopathies: bridging
the gap between clinical phenotypes and fnal diagnosis.
A position statement from the ESC Working Group on
Myocardial and Pericardial Diseases. European Heart
Journal (2013) 34, 14481458 doi:10.1093/eurheartj/
ehs397) (SP)
Rubric realizat de Alina Crciun Mirescu, Anca
Mateescu, Anca Popar, Polixenia Stanciu sub coordo-
narea lui Bogdan. A. Popescu.
care ne sugereaz o anumit patologie ex: sideremia
i feritina n hemocromatoz) i de nivel doi (care se
fac doar atunci cnd suspicionm un tip specifc de car-
diomiopatie- ex: alfa galactozidaza cnd suspicionm
boala Fabry; enzima de conversie a angiotensinei cnd
suspicionm sarcoidoza).
Testarea genetic a acestor pacieni este unul dintre
benefciile inovaiilor din ultimii ani, n acest articol f-
ind mai puin amnunit, avnd n vedere publicarea
n 2010 a unui articol de ctre aceeai autori, care dez-
bate pe larg consilierea i testarea genetic a pacienilor
cu cardiomiopatii.
Ecocardiografa este o investigaie extrem de im-
portant i plin de indicii. Un bun cunosctor poa-
te uor s integreze informaiile oferite de aceasta i s
contureze deja diagnosticul (ex: dac la un pacient cu
cardiomiopatie hipertrofc se evideniaz ngroarea
valvelor atrioventriculare i a septului interatrial iar
aspectul miocardului este strlucitor se poate suspi-
ciona amiloidoza; sau la un pacient cu cardiomiopatie
dilatativ i tulburare de cinetic parietala care nu res-
pect distribuia coronarian putem suspiciona mio-
cardita).
Dintre investigaiile imagistice, Rezonana Magneti-
c Cardiac are un rol aparte, deoarece caracterizeaz
structura esutului miocardic pe baza timpilor de rela-
xare (ex: T2 scurt n hemocromatoz) i a modalitii
de captare a contrastului (ex: captare subendocardic
n amiloidoz; captare la nivelul septului interventricu-
lar i muchii papilari n sarcoidoz). Imagistica nucle-
NATIONAL AND INTERNATIONAL CARDIOLOGY AGENDA 2014

EVENIMENTE SRC 2014
LUNA DENUMIREA MANIFESTRII DATA LOCAIA
Februarie
CAZURI CLINICE DIFICILE N INSUFICIENA CARDIAC
Directori de curs: Prof. Dr. C. Macarie, Prof. Dr. D. Vinereanu, Dr. O. Chioncel
21 februarie Timioara
CARDIOCOAG
Directori de curs: Prof. Dr. D. Vinereanu, Prof. Dr. D. Lighezan
22 februarie Timioara
DIAGNOSTICUL I TRATAMENTUL ACTUAL AL SINDROAMELOR
CORONARIENE ACUTE
Directori de curs: Prof. Dr. D. Dimulescu, Conf. Dr. S. Blnescu
28 februarie Bucureti
Martie
CARDIOEFORT (efortul fzic i bolile cardiovasculare)
Directori de curs: Conf. Dr. F. Mitu, Dr. D. Gherasim
7 martie Iai
LIPID SCHOOL GHIDUL DISLIPIDEMII 2012 (LIPS PLUS Sindroame
Coronariene ACUTE)
Directori de curs: Prof.Dr. D. Gai, Prof. Dr. D. Vinereanu
14 martie Tg. Mure
HIPERTENSIUNEA ARTERIAL S ANALIZM GHIDURILE
Directori de curs: Prof. Dr. M. Cintez, Prof. Dr. C. Arsenescu Georgescu
14 martie Iai
SOLUII TERAPEUTICE N INFARCTUL MIOCARDIC ACUT DE LA
TEORIE LA PRACTIC - CAZURI CLINICE N DIRECT
Directori de curs: Dr. D. Deleanu, Dr. A. Iancu, Dr. M. Croitoru
15 martie Bucureti
ELOGIU
Director de curs: Prof. Dr. Eduard Apetrei
21 martie Constana
PARTICULARITI ALE BOLILOR CARDIOVASCULARE LA VRSTNIC
(CARDIOSEN)
Directori de curs: Conf. Dr. F. Mitu, Conf. Dr. D. Pop, Dr. D. Gherasim
21 martie Cluj-Napoca
CAZURI CLINICE DIFICILE N CARDIOLOGIA DE URGEN
Directori de curs: Conf. Dr. C. Pop, Dr. G. Tatu Chioiu, Conf. Dr. A. Petri
21 martie Oradea
IMAGISTICA N VALVULOPATII
Directori de curs: Conf. Dr. B. A. Popescu, Conf. Dr. A. Ilieiu
21 martie Craiova
REDRISC (REDucerea RISCului Rezidual)
Directori de curs: Prof. Dr. C. Arsenescu Georgescu, Prof. Dr. G. A. Dan,
Prof. Dr. D. Vinereanu
21 martie Timioara
Aprilie
ACTUALITI N ARITMOLOGIE (ARCA 3)
Directori de curs: Dr. R. Vtescu, Prof. Dr. D. Dobreanu, Prof. Dr. G. A. Dan
11 aprilie Iai
CARDIOEFORT (Efortul fzic i bolile cardiovasculare)
Directori de curs: Conf. Dr. F. Mitu, Dr. D. Gherasim
11 aprilie Sibiu
REDRISC (REDucerea RISCului Rezidual)
Directori de curs: Prof. Dr.Ctlina Arsenescu Georgescu, Prof. Dr.G.A.Dan, Prof.
Dr.D.Vinereanu
11 aprilie Constana
CONFERINA NAIONAL DE ATEROTROMBOZ
Moderatori: Prof. Dr. E. Apetrei, Prof. Dr. C. Popa
11 aprilie Bucureti
Mai
CONFERINA NAIONAL A GRUPURILOR DE LUCRU 8-9 mai Sibiu
THE XIX WORLD CONGRESS OF ECHOCARDIOGRAPHY AND ALLIED
TECHNIQUES
10-11 mai Sibiu
PARTICULARITI ALE BOLILOR CARDIOVASCULARE LA VRSTNIC
(CARDIOSEN)
23 mai Tg. Mure
HIPERTENSIUNEA ARTERIAL S ANALIZM GHIDURILE
Directorde curs: Prof. Dr. M. Cintez
30 mai Tg. Jiu
Iunie
CAZURI CLINICE DIFICILE N INSUFICIENA CARDIAC
Directori de curs: Prof. Dr. C. Macarie, Prof. Dr. D. Vinereanu, Dr. O. Chioncel
13 iunie Constana
ELOGIU
Directori de curs: Prof. Dr. E. Apetrei
20 iunie Piatra Neam
EXPERT MEETING CARDIODIAB 26-28 iunie Poiana Brasov
Vol. 23, No. 4, 2013

Agenda
Septembrie
LIPID SCHOOL GHIDUL DISLIPIDEMII 2012 (LIPS PLUS Sindroame
Coronariene Acute)
Directori de curs: Prof. Dr. D. Gai, Prof. Dr. D. Vinereanu
12 sepembrie Suceava
ACTUALITI N ARITMOLOGIE (ARCA 3)
Directori de curs: Dr. R. Vtescu, Prof. Dr. D. Dobreanu, Prof. Dr. G. A. Dan
12 septembrie Tg. Mures
Octombrie
CONGRESUL NAIONAL DE CARDIOLOGIE 2-4 octombrie Sinaia
THE 9
TH
EUROPEAN ECHOCARDIOGRAPHY COURSE ON
CONGENITAL HEART DISEASE
15-18
octombrie
Timioara
PARTICULARITI ALE BOLILOR CARDIOVASCULARE LA
VRSTNIC (CARDIOSEN)
17 octombrie Covasna
CAZURI CLINICE DIFICILE N CARDIOLOGIA DE URGEN
Directori de curs: Conf. Dr. C. Pop, Dr. G. Tatu Chioiu, Conf. Dr. A. Petri
24 octombrie Braov
SOLUII TERAPEUTICE N INFARCTUL MIOCARDIC ACUT DE LA
TEORIE LA PRACTIC - CAZURI CLINICE N DIRECT
Directori de curs: Dr. D. Deleanu, Dr. A. Iancu, Dr. M. Croitoru
24 octombrie Cluj-Napoca
DIAGNOSTICUL I TRATAMENTUL ACTUAL AL SINDROAMELOR
CORONARIENE ACUTE
Directori de curs: Prof. Dr. D. Dimulescu, Conf. Dr. S. Blnescu
31 octombrie Sibiu
Noiembrie
IMAGISTICA N VALVULOPATII
Directori de curs: Conf. Dr. A. Ilieiu, Conf. Dr. B. A. Popescu
14 noiembrie Galai
CARDIOCOAG
Directori de curs: Prof. Dr. D. Vinereanu, Prof. Dr. D. Lighezan
22 noiembrie Sibiu
CARDIOLOGY EVENTS IN THE WORLD
MONTH NAME OF THE EVENT DATE PLACE
January
ACCA webinar on Acute Heart Failure
09 January - 09
January 2014
Online
XXIV European Days, Annual Meeting of the French Society of
Cardiology
15 January - 18
January 2014
Paris, France
33
rd
Annual Scientifc Meeting of the Belgian Society of Cardiology
30 January - 31
January 2014
Brussels,
Belgium
ESC Webinar on Catheter Ablation for Atrial Fibrillation: Ready for
prime time?
30 January - 30
January 2014
Online
February
Advanced Invasive Cardiac Electrophysiology (Course)
13 February
- 15 February
2014
Sophia
Antipolis,
France
2
nd
Edition of the Resistant Hypertension Course
20 February
- 22 February
2014
Berlin,
Germany
17
th
International Congress in Advances in Cardiac Ultrasound
24 February
- 27 February
2014
Davos,
Switzerland
Stent for Life Forum 2014
27 February -
01 March 2014
Prague,
Czech Republic
March EHRA Cardiac Pacing, ICD and Cardiac Resynchronisation Course
17 March - 19
March 2014
Vienna,
Austria
April
EuroHeartCare 2014
04 April - 05
April 2014
Stavanger,
Norway
Fifh European Course on Adult Congenital Disease
10 April - 11
April 2014
Amsterdam,
Netherlands

Agenda
Vol. 23, No. 4, 2013
April
Fifh European meeting on Adult Congenital Heart Disease
10 April - 11
April 2014
Amsterdam,
Netherlands
EuroHeartCare 2014
04 Apr 2014 -
05 Apr 2014
Stavanger,
Norway
May
EuroPRevent 2014
08 May - 10
May 2014
Amsterdam,
Netherlands
EuroCMR (Cardiovascular Magnetic Resonance) 2014
15 May - 17
May 2014
Vienna,
Austria
Heart Failure 2014
17 May - 20
May 2014
Athens, Greece
World Congress on Acute Heart Failure
17 May - 20
May 2014
Athens,
Greece
EuroPCR 2014
20 May - 23
May 2014
Paris,
France
June
2
nd
Annual meeting on New Trends in Cardiovascular Drug Terapy
30 May - 01
June 2014
Rome,
Italy
Joint Meeting of the European Society of Hypertension (ESH) and
International Society of Hypertension (ISH)
June 13 - 16,
2014
Athens, Greece
CARDIOSTIM-EHRA EUROPACE 2014
18 June - 21
June 2014
Nice, France
July Frontiers in CardioVascular Biology 2014
04 July - 06
July 2014
Barcelona,
Spain
September
ESC Congress 2014
30 Aug 2014 -
03 Sep 2014
Barcelona,
Spain
EuroTrombosis Summit 2014
28 September
- 30 September
2014
Paris, France
October
Acute Cardiovascular Care 2014
18 October
- 20 October
2014
Geneva,
Switzerland
Te 11
th
Meeting of the ESC Working Group on Myocardial and
Pericardial Disease
22 October
- 24 October
2014
Tel Aviv, Israel
REVIEWERS 2013
Thanks to our reviewers for 2013
Eduard Apetrei (5)
Ion Bruckner (1)
erban B l nescu (1)
Radu C plneanu (1)
Carmen Ginghin (5)
Gabriel Tatu-Ghi oiu (1)
Andre Keren (1)
Florin Mih l an (1)
Tiberiu Nanea (1)
Ion intoiu (1)
Dumitru Zdenghea (1)
INSTRUCIUNI PENTRU AUTORI

Informaii generale
Romanian Journal of Cardiology public articole originale din domeniul fziologiei i patologiei cardiovasculare
sub forma studiilor clinice, de laborator, experimentale, epidemiologice etc. Autorii vor respecta principiile eticii i
adevrului tiinifc n realizarea studiului, obinerea datelor i prezentarea rezultatelor.
Pentru publicare, articolele vor f trimise ntr-un exemplar, mpreun cu toate fierele pentru text (n format MS
Word) i imaginile pe CD. Formatul manuscrisului este de tip A4, scris la dou rnduri, cu caractere Times New
Roman 12.
Articolele vor f redactate n limba englez. Cele trimise n limba romn vor f traduse de redacie n limba
englez (contra cost).
Fiecare manuscris trebuie s fe nsoit de o scrisoare de intenie a autorilor, semnat n original, care s afrme
c articolul nu a mai fost trimis simultan niciunei alte publicaii i nu a mai fost publicat n alt revist ntr-o form
substanial similar. Responsabilitatea asupra coninutului articolului aparine n ntregime autorilor.
Articolele vor f semnate de toi autorii. Toi autorii vor semna o declaraie privind confictul de interese i
contribuia avut la elaborarea lucrrii. Primul autor are obligaia de a colecta declaraiile de la toi co-autorii.
Pregtirea manuscrisului
Titlu: Pe pagina de titlu se va scrie titlul articolului n limba englez i romn, numele complet al autorilor,
gradul academic, aflierea acestora, adresa de coresponden, precum i un titlu scurt n limba englez (ntre 3-6
cuvinte) pentru paginile urmtoare ale articolului, i cuvintele cheie ale articolului. Vor f precizate sursele de f-
nanare ale lucrrii (acolo unde este cazul).
Rezumatul: Rezumatul, n limba englez i romn, va cuprinde cel mult 200 de cuvinte. Va f alctuit din ur-
mtoarele subtitluri: obiectivele studiului, metodologia folosit, rezultate i concluziile studiului.
Textul manuscrisului: Textul manuscrisului nu va depi 12 pagini pentru studiile originale sau referatele gene-
rale i 5 pagini pentru prezentrile de caz. Prescurtrile vor f defnite la prima lor folosire. Pentru denumirile me-
dicamentelor sau ale altor substane folosite n studiile prezentate vor f utilizate denumirile comune internaionale.
Aparatele utilizate n studii vor f prezentate cu denumirea comercial, cu indicarea productorului. Eventualele
mulumiri pentru colaborare vor f inserate la sfritul textului.
Bibliografa: Bibliografa se va nota cu cifre arabe n ordinea cresctoare a apariiei n text, unde vor f notate
superscript. Referinele bibliografce vor cuprinde numele autorilor, titlul complet al articolului, revista, anul apa-
riiei, volumul, paginile. Prescurtarea numelui revistei se va face dup cea folosit n Index Medicus.
Recomandm introducerea referinelor bibliografce actuale. Se recomand citarea referinelor bibliografce
romneti, iar n cazul n care autorii au mai publicat n Romanian Journal of Cardiology, citarea acestor publicaii.
Ex: Ridker PM, Rifai N, Pfefer M et al. Elevation of TNF-a and increased risk of recurrent coronary events af er
myocardial infarction. Circulation, 2000; 101: 2149-53 [pentru articole din reviste] Madahi J. Myocardial perfusion
imaging for the detection and evaluation of coronary artery disease.In Cardiac Imaging: A Companion to Braunwalds
Heart Disease, Second edition. Eds: DJ Skorton, HR Schelbert, GL Wolf et al. WB Saunders, London, 1996, 193-203
[capitole n cri]
Figurile: Calitatea fgurilor trebuie s fe excelent pentru a permite reproducerea corect. Ele nu vor f inserate
n interiorul textului manuscrisului, ci vor f prezentate separat. n format electronic vor f trimise separat ca fiere
imagine (JPG, TIFF etc.). Fiecare fgur va f nsoit de o legend n care vor f explicate, n mod concis, principale-
le date referitoare la respectiva fgur si eventualele prescurtari. Figurile vor f numerotate cu cifre arabe n ordinea
apariiei lor n text. n text va f precizat ntre paranteze rotunde numrul fgurii la care se face referire (Ex: Fig.
3). Dac este cazul, n parantez va f precizat sursa bibliografc a fgurii i, n acest caz, utilizarea fgurii trebuie
fcut cu avizul de copyright. Prezentarea sursei bibliografce va f urmat de cifra corespunztoare din bibliografe.
Figurile color vor f publicate contra cost.
Tabelele: Tabelele vor f numerotate cu cifre arabe n ordinea apariiei n text i vor f nsoite de titlul concis al
tabelului i eventualele explicaii. Vor f precizate prescurtrile utilizate n tabel. Dac este cazul, n parantez va f
precizat sursa bibliografc a tabelului i avizul de copyright.
Vol. 23, No. 4, 2013
Instructions for authors

Textele trimise pentru a f publicate vor f referate de ctre 2 refereni fr cunoaterea autorilor. Recomandrile
referenilor sunt comunicate autorilor pentru refacerea articolului. Dac articolul este aprobat pentru publicare, va f
transmis data publicrii. Refuzul publicrii va f motivat i comunicat n scris autorilor. Manuscrisele nepublicate nu
se returneaz autorilor.
Manuscrisele i suportul lor electronic (CD) vor f trimise prin pot sau e-mail la urmtoarea adres:
n atenia dlui Prof. Dr. Eduard Apetrei, redactor-ef
Institutul de Urgen pentru Boli Cardiovasculare Prof. Dr. C. C. Iliescu, os. Fundeni, nr. 258, 022328,
Bucureti, Romnia.
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E-mail: eapetrei@gmail.com, mihaela_salagean@yahoo.com
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Premiu
Vol. 23, No. 4, 2013
ROMANIAN JOURNAL OF CARDIOLOGY

acord, n acest an,
un premiu pentru cel mai bun articol original din anul 2013
(prim-autori sub 40 de ani).

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ISSN: 1583-2996

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