|



 
 |

 
` Mean pulmonary artery pressure of 8 to 20
mmHg at rest is normal
` mean pulmonary artery pressure of 21 to 24
mmHg at rest has uncertain clinical implications
 |  
| 
` Jefined as a mean pulmonary artery pressure >
25 mmHg at rest

` Previous accepted definitions (no longer valid):

` a mean pulmonary artery pressure > 30 mmHg
with exercise (measured by right heart
catheterization)
` a systolic pulmonary artery pressure > 40 mmHg
 ^
 
` 5 groups (WHO)
` Previously
` Primary PHT
` Secondary PHT
` 1. Pulmonary arterial hypertension (PAH)
` 1.1. Idiopathic PAH
` 1.2. Heritable
` 1.3. Jrug
Jrug-- and toxin-
toxin-induced
` 1.4. Ass with
with^onn Tissue diseases, HIV, Portal hypertension, ^ongenital heart diseases, Schistosomiasis, ^hronic hemolytic anemia
` 1.5 Persistent pulmonary hypertension of the newborn
` 1Ȩ. Pulmonary veno-
veno-occlusive disease (PVOJ) and/or pulmonary capillary
hemangiomatosis (P^H)

` 2. Pulmonary hypertension owing to left heart disease

` 2.1. Systolic dysfunction
` 2.2. Jiastolic dysfunction
` 2.3. Valvular disease

` 3. Pulmonary hypertension owing to lung diseases and/or hypoxia

` 3.1. ^hronic obstructive pulmonary disease
` 3.2. Interstitial lung disease
` 3.3. Other pulmonary diseases with mixed restrictive and obstructive pattern
` 3.4. Sleep-
Sleep-disordered breathing
` 3.5. Alveolar hypoventilation disorders
` 3.6. ^hronic exposure to high altitude
` 3.7. Jevelopmental abnormalities

` 4. ^hronic thromboembolic pulmonary hypertension (^TEPH)

` 5. Pulmonary hypertension with unclear multifactorial mechanisms

` 5.1. Hematologic disorders: myeloproliferative disorders, splenectomy
` 5.2. Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis: lymphangioleiomyomatosis, neurofibromatosis, vasc
vasculitis
ulitis
` 5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
` 5.4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis
 è| è|
` ÷Idiopathic pulmonary arterial hypertension
(IPAH) IPAH exists when an underlying
cause of the PAH cannot be identified. It is
usually sporadic, with only 6 to 10 percent of
patients having hereditary disease.
 |
 

` Vasoconstriction
` Remodelling: smooth muscle cell and
endothelial cell proliferation, vascular wall
inflammation
` ^hronic vascular thrombosis
 ^

 
` Initially - exertional dyspnea, lethargy, and fatigue,
fatigue,
which are due to an inability to increase cardiac output
with exercise

` As the PH progresses and right ventricular failure

develops - exertional chest pain (ie,
(ie, angina), exertional
syncope, and peripheral edema
 ^

 
` Angina is due to subendocardial hypoperfusion caused
by increased right ventricular wall stress and
myocardial oxygen demand.
` Angina is occasionally caused by dynamic
compression of the left main coronary artery by an
artery; this risk is greatest for
enlarged pulmonary artery;
patients with a pulmonary artery trunk at least 40 mm
in diameter.
` Passive hepatic congestion - anorexia and abdominal
pain in the right upper quadrant.
 ^

 
` Less common symptoms of PH - cough, hemoptysis,
and hoarseness (ie, Ortner's syndrome) due to
compression of the left RLNby a dilated main
pulmonary artery
` Features of the causative condition in non Idiopathic
Pulmonary Hypertension
 u
 
u 
 

 



 
` ^
 è- Patients with pulmonary hypertension but without resulting limitations of
^
 è-
physical activity. 
 
  undue
undue fatigue or
dyspnea, chest pain, or heart syncope.

` ^
 èè- Patients with pulmonary hypertension resulting in slight limitation of

^
 èè-
physical activity. They are comfortable at rest. 
 

 
  
 
 


` ^
 èèè- Patients with pulmonary hypertension resulting in marked limitation of

^
 èèè-
physical activity. They are comfortable at rest. Î 
 

     
 
 
.

 
 
.

` ^
 è -- Patients with pulmonary hypertension resulting in inability to carry on any
physical activity without symptoms. These patients manifest signs of right heart failure.
J
  
  .

  . Jiscomfort is increased by
physical activity.
 ^

 
` Initial physical finding of PH loud P2
` P2 may become palpable.
` The S2 narrowly split or single in patients with
PH and preserved right ventricular function.
` Splitting of S2 widens as the right ventricle fails
or if right bundle branch block develops.
` systolic ejection murmur
` In more severe disease, a diastolic pulmonic
regurgitation murmur
` Right ventricular hypertrophy is characterized by
` a prominent A wave in the jugular venous pulse,
` a right-
right-sided fourth heart sound,
` and either a left parasternal heave or a downward
subxiphoid thrust.
` Right ventricular failure
` elevated jugular venous pressure,
` a right ventricular third heart sound,

` a high-
high-pitched tricuspid regurgitant murmur
accompanied by a prominent V wave in the jugular
venous pulse.
` hepatomegaly, a pulsatile liver, peripheral edema,
ascites, and pleural effusion may exist
 J  
` ^onfirm PAH
` Find underlying cause ( if any)
 ^

` Enlargement of the central pulmonary arteries
with attenuation of the peripheral vessels 
Pruning & Oligemia
` Right ventricular enlargement (diminished
retrosternal space) and right atrial dilatation
(prominent right heart border) may also be seen
` Features of ILJ
 ·^
` F/O right ventricular hypertrophy or strain
` right axis deviation,
` an R wave/S wave ratio >1 >1 in lead V1
V1,
` incomplete or complete RBB

` increased P wave amplitude in lead II (P pulmonale)

due to right atrial enlargement

` E^G changes cannot determine disease severity or

prognosis
 JJ! 
JJ!  

` ü Posterior wall myocardial infarction

` ü Wolff
Wolff--Parkinson-
Parkinson-White syndrome

` ü Hypertrophic cardiomyopathy (septal hypertrophy)

` ü Early transition (counterclockwise rotation)

` ü Normal variant
` marked right axis deviation, tall R wave in V1
V1 (as part of a qR
complex), delayed precordial transition zone with prominent S
waves in leads V5
V5 and V6
V6, inverted T waves and ST depression
in V1
V1 to V
V33 consistent with right ventricular "strain", and peaked
P waves in lead II consistent with concomitant right atrial
enlargement.
 ·

` estimate the pulmonary artery systolic pressure
and
` to assess right ventricular size, thickness, and
function

` right atrial size, left ventricular systolic and

diastolic function, and valve function
 · 


 

 
` Joppler ultrasound to estimate the pulmonary artery systolic
pressure.

` The maximum tricuspid regurgitant jet velocity is recorded and

the pulmonary artery systolic pressure (PASP) is then calculated:

PASP = (4 x TRV squared) + RAP

` Joppler echocardiography is limited when an adequate tricuspid

regurgitant jet cannot be identified
` PH is likely if the PASP is >50
>50 and the TRV is >3
>3.4

` PH is unlikely if the PASP is ”36

”36,, the TRV is ”2
”2.8, and
there are no other suggestive findings

` PH is possible with other combinations of findings

 
  


 

` paradoxical bulging of the septum into the left
ventricle during systole
` hypertrophy of the right ventricular free wall
and trabeculae
` As the right ventricle fails, there is dilation and
hypokinesis, septal flattening, right atrial
dilation, and tricuspid regurgitation
 |
 "  
#||
` Overestimation and underestimation of pulmonary arterial
pressure
` limited when an adequate tricuspid regurgitant jet cannot
be identified
` Inaccurate when tricuspid regurgitant jet is over-
over-
interpreted

olow threshold needed to evaluate patients with suspected

pulmonary hypertension via right heart catheterization
however doppler assessment is more sensitive than clinical
parameters
 |
  
` identify and characterize underlying lung disease
that may be contributing to PH. An obstructive
pattern is suggestive of ^OPJ, while restrictive
disease suggests interstitial lung disease,
neuromuscular weakness, or chest wall disease.
` usually severe interstitial lung disease (with lung
volumes below 50 percent of predicted) or
obstructive lung disease that produces PH.
 |
  
` PH should not be attributed to lung disease if
the PFTs are only mildly abnormal
 $
` Nocturnal oxyhemoglobin desaturation can be
identified by overnight oximetry. It is common
in patients with PH and may prompt
supplemental oxygen therapy during sleep
` Nocturnal oxyhemoglobin desaturation not
diagnostic of sleep breathing disorders
 |
 

` gold standard diagnostic test for sleep related
breathing disorders,
 % 
` A normal V/Q scan accurately excludes chronic
thromboembolic disease with a sensitivity of 96
to 97 percent and a specificity of 90 to 95
percent

` If V/Q scan suggests chronic thromboembolic

disease exists, pulmonary angiography is
necessary to confirm & define the extent of
disease
 ÿ
  
` HIV serology to screen for HIV-
HIV-associated PH

` Liver function tests to screen for

portopulmonary hypertension

` Antinuclear antibody (ANA), rheumatoid factor

(RF), and antineutrophil cytoplasmic antibody
(AN^A) titers to screen for PH due to the
connective tissue diseases
 ·$  
` six-minute walk test (6
six- (6MWT) or
` cardio pulmonary exercise testing with gas exchange measurements,
echocardiography, and/or right heart catheterization

` Screens for alternative causes of the patient's symptoms.

` Jetects exercised-
exercised-induced PH, which may be an intermediate stage that exists
between normal and resting PH

` Jetermines the patient's World Health Organization (WHO) functional class

which guides therapy

` Establishes a baseline from which the response to therapy can be measured.

 
` necessary - confirm PH and determine severity

` confirmed if the MPAP > 25 mmHg at rest

` presence/severity of a congenital or acquired L  R shunt can be

` Helpful in distinguishing patients who have group 2 PH (PH due

to left heart disease, such as systolic dysfunction, diastolic
dysfunction, or valvular heart disease)  however false positive in
PHT  need independent Left heart catheterzation
 J  
` ^onfirm PAH
` Find underlying cause ( if any)
 
` PRIMARY THERAPY Primary therapy
refers to treatment that is directed at the
underlying cause of the PH

` AJVAN^EJ THERAPY Advanced

therapy is directed at the PH itself, rather than
the underlying cause of the PH
 
#$
` Jiuretic
` treat fluid retention
` caution to avoid decreased cardiac output

` Oxygen
` may benefit patients with PH and either resting,
exercise--induced, or nocturnal hypoxemia
exercise
` Anticoagulant
` warfarin, with a therapeutic goal INR of approximately
2
` SScl & telangectasia ?
` digoxin therapy
` ^OPJ and biventricular failure
` supraventricular tachycardias associated with right ventricular
dysfunction
` Exercise training 
` Improves mean six-
six-minute walk distance. The improved
distances exceed those described for all types of advanced
therapy. Exercise training improved the WHO functional
class and peak oxygen consumption
` does not improve haemodynamic parmeters
` skeletal muscle training
 |

` There are no effective primary therapies for most types
of group 1 PAH. As a result, advanced therapy is often
needed
` Primary therapy for group 2 PH consists of treatment
of the underlying heart disease
` Primary therapy for group 3 PH consists of treatment
of the underlying cause of hypoxemia and correction of
the hypoxemia with supplemental oxygen
` Oxygen is the only modality with proven mortality benefit in
some patients with group 3 PH - The Nocturnal Oxygen
Therapy Trial (NOTT)
 |

` Anticoagulation is primary medical therapy for
patients with group 4 PH.
` Surgical thromboendarterectomy is primary
surgical therapy for selected patients with
thromboembolic obstruction of the proximal
pulmonary arteries in group 4 PH
` Primary therapy is directed at the underlying
cause in group 4 PH.
 

` Includes treatment with prostanoids such as
epoprostenol, endothelin receptor antagonists,
phosphodiesterase 5 inhibitors such as sildenafil,
or certain calcium channel blockers (eg, a
dihydropyridine or Jiltiazem)
` considered for patients who have evidence of
persistent PH and a World Health Organization
(WHO) functional class II, III, or IV despite
adequate primary therapy
 


` Group 1 PAH often needed in group 1 PAH because

there are no effective primary therapies.

` Group 2 PH There are a few situations in which

advanced therapy may be considered for group 2 PH
(eg, patients with persistent PH due to mitral stenosis
who have undergone mitral valve replacement).
` However, for most patients with group 2 PH, advanced
therapy should be avoided - harmful.
` Group 3 PH Advanced therapy is not
approved & decided only on a case by case basis
where PHT is disproportionate to the
underlying disease
` ü Group 4 PH Advanced therapy can be
considered for patients with group 4 PH who
remain WHO functional class III or IV even
after anticoagulation or hromboendarterectomy.
` Group 5 PH Small studies have addressed the role
of advanced therapy for patients with PH related to
sarcoidosis

` Patients with portopulmonary hypertension are rarely

vasoreactive and are at increased risk for adverse
sequelae from pure vasodilator therapy. Therefore,
neither vasoreactivity testing nor calcium channel
blocker therapy is indicated in this group
 è

` undergo an invasive hemodynamic assessment
prior to the initiation
` patients with group 1 PAH also undergo a
vasoreactivity test with intravenous adenosine,
intravenous epoprostenol, or inhaled nitric oxide
 ^
 

&
` Some patients who are vasoreactive and receive
^^B therapy with a dihydropyridine or
diltiazem can achieve prolonged survival,
sustained functional improvement, and
hemodynamic improvement
 | 
` Prostanoid formulations used to treat PH include
intravenous epoprostenol (prostacyclin), intravenous
treprostinil, subcutaneous treprostinil, inhaled
treprostinil, and inhaled iloprost
` Intravenous epoprostenol is the advanced therapy that
has been best studied. It improves hemodynamic
parameters, functional capacity, and survival in patients
with IPAH
` Treprostinil improves hemodynamic parameters,
symptoms, exercise capacity, and survival in patients
with group 1 PAH. It has not been evaluated in patients
with other types of PH
 ·

 
` The endothelin receptor antagonists improved exercise
capacity, dyspnea, and hemodynamic measures
(pulmonary artery pressure, pulmonary vascular
resistance, and cardiac index)
` Bosentan Bosentan (Tracleer), a nonselective
endothelin receptor antagonist , improves
hemodynamics and exercise capacity in patients with
group 1 PAH and delays clinical worsening. The
mortality of bosentan-
bosentan-treated IPAH patients appears
favorable compared to historical controls
 ÿ· ·
ÿ· · 



` 213 patients with severe group 1 PAH were
randomly assigned to receive bosentan (6262..5 mg)
or placebo twice daily for four weeks, followed
by either of two doses of bosentan (125
(125 or 250
mg) twice daily for a minimum of 12 weeks [60 [60].].
Bosentan improved symptoms, the six-six-minute
walking distance, and the WHO functional class
 
  ·


 
` Ambrisentan (Letaris) and sitaxsentan (Thelin)
are selective type A endothelin-
endothelin-1 receptor
antagonists that are administered orally. The
evidence (eg, the ARIES-
ARIES-1 and ARIES-
ARIES-2 trials)
suggests that ambrisentan and
sitaxsentan improve exercise tolerance, WHO
functional class, hemodynamics, and quality of
life in patients with PAH.
 |J· 
 
` Sildenafil improves pulmonary hemodynamics and
exercise capacity in patients with group 1 PAH. Its
effect on mortality has not been adequately evaluated

` Tadalafil also appears to improve outcomes in patients

with group 1 PAH, Tadalafil (40
(40 mg) significantly
increased the six-
six-minute walk distance and the time to
clinical worsening, while decreasing the incidence of
clinical worsening and improving health related quality
of life
 ^ 

` It has been proposed that combining
pharmacologic agents with different mechanisms
of action may produce an additive effect or may
induce the same effect at lower doses of each
agent
` Sildenafil plus epoprostenol The addition of
sildenafil to long-
long-term epoprostenol therapy
improves clinical outcomes.
` Sildenafil plus bosentan The benefits of adding
sildenafil to bosentan therapy are more certain
among patients with IPAH
 èη|#'
` ^reation of a right-
right-to
to--left shunt by atrial septostomy
has been performed in some patients with syncope or
severe right heart failure in an attempt to increase
systemic blood flow by bypassing the pulmonary
vascular obstruction
` The right-
right-to
to--left shunting and consequent arterial
desaturation that follow the procedure are offset in
some patients by increased cardiac output and
augmentation of systemic oxygen delivery
 èη|#'
` difficult to predict which patients will benefit and which will deteriorate.

` ^an be considered in refractory severe PAH and right heart failure, despite
aggressive advanced therapy and maximal diuretic therapy.

` ^onsider in patients who have signs of impaired systemic blood flow (such as
syncope) due to reduced left heart filling.

` Patients with the most advanced PAH appear more likely to die or get worse
with atrial septostomy This includes patients with
` markedly elevated mean right atrial pressure (eg, greater than 20 mmHg),
` extremely low cardiac output,
` resting arterial oxyhemoglobin saturation less than 80 percent.
` In addition, older age and impaired renal function were associated with early
adverse outcomes in one series
 (|Î(è(
` Transplantation has been performed in patients
with idiopathic pulmonary arterial hypertension
(IPAH) and is considered by some to be the
final effective treatment for selected patients
with IPAH. Bilateral lung or heart-
heart-lung
transplantation is the procedure of choice
&