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Cardiac rehabilitation in patients with ST-segment elevation myocardial

infarction: Can its failure be predicted?

Article  in  Therapeutic Advances in Cardiovascular Disease · May 2017

DOI: 10.1177/1753944717706845

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TAK0010.1177/1753944717706845Therapeutic Advances in Cardiovascular DiseaseI. Robert et al.

Therapeutic Advances in Cardiovascular Disease Original Research

Cardiac rehabilitation in patients with

Ther Adv Cardiovasc Dis

2017, Vol. 11(7) 177­–184

ST-segment elevation myocardial DOI: 10.1177/

https://doi.org/10.1177/1753944717706845
https://doi.org/10.1177/1753944717706845
1753944717706845

infarction: can its failure be predicted?

© The Author(s), 2017.
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Robert Irzmański, Joanna Kapusta, Agnieszka Obrębska-Stefaniak,

Beata Urzędowicz and Jan Kowalski

Abstract
Background: The prognosis in patients after acute coronary syndromes (ACS) is significantly
burdened by coexisting anaemia, leukocytosis and low glomerular filtration rate (GFR).
Hyperglycaemia in the early stages of ACS is a strong predictor of death and heart failure in non-
diabetic subjects. This study aimed to evaluate the effect of hyperglycaemia, anaemia, leukocytosis,
thrombocytopaenia and decreased GFR on the risk of the failure of cardiac rehabilitation (phase II at
the hospital) in post-ST-segment elevation myocardial infarction (STEMI) patients.
Methods: The study included 136 post-STEMI patients, 96 men and 40 women, aged 60.1 ±
11.8 years, admitted for cardiac rehabilitation (phase II) to the Department of Internal Medicine
and Cardiac Rehabilitation, WAM University Hospital in Lodz, Poland. On admission fasting
blood cell count was performed and serum glucose and creatinine level was determined (GFR
assessment). The following results were considered abnormal: glucose ⩾ 100 mg/dl, GFR
< 60 ml/min/1, 73 m², red blood cells (RBCs) < 4 × 106/μl, white blood cells (WBCs) > 10 ×
103/μl; platelets (PLTs) < 150 × 10³/ml. In all patients an exercise test was performed twice,
before and after the completion of the second stage of rehabilitation, to assess its effects.
Results: Based on logistic regression analysis and the results of an individual odds ratio
(OR) of the tested parameters, their prognostic impact was determined on the risk of failure
of cardiac rehabilitation. This risk has been defined on the basis of the patient’s inability to
tolerate workload increment >5 Watt in spite of the applied program of cardiac rehabilitation.
As a result of building a logistic regression model, the most statistically significant risk factors
were selected, on the basis of which cardiac rehabilitation failure index was determined.
leukocytosis and reduced GFR determined most significantly the risk of failure of cardiac
rehabilitation (respectively OR = 6.42 and OR = 3.29, p = 0.007). These parameters were
subsequently utilized to construct a rehabilitation failure index. Correspondence to:
Joanna Kapusta
Conclusions: Peripheral blood cell count and GFR are important in assessing the Department of Internal
prognosis of cardiac rehabilitation effects. leukocytosis and decreased GFR determine to Medicine and Cardiac
Rehabilitation, Medical
the highest degree the risk of cardiac rehabilitation failure. Cardiac rehabilitation failure University of Lodz,
Kościuszki 4, Lodz 90-419,
index may be useful in classifying patients into an appropriate model of rehabilitation. Poland
These findings support our earlier reports. joanna.kapusta@vp.pl
Robert Irzmański
Agnieszka Obrębska-
Stefaniak
Keywords: acute coronary syndrome, cardiac rehabilitation, leucocytosis, glomerular filtration Beata Urzędowicz
rate Department of Internal
Medicine and Cardiac
Rehabilitation, Medical
Received: 17 December 2016; revised manuscript accepted: 5 April 2017
University of Lodz, Poland
Jan Kowalski
Department of Internal
Medicine and Cardiac
Introduction often in the course of cessation of blood flow Rehabilitation, Medical
University of Lodz, Poland
ST-segment elevation myocardial infarction through the coronary artery due to its occlusion. University of Social
(STEMI) is a clinical syndrome developing most This causes myocardial necrosis in the area Science, Lodz, Poland

http://tac.sagepub.com 177
Therapeutic Advances in Cardiovascular Disease 11(7)
of   coronary vasculature, which is manifested by
an increase in the concentration of biomarkers in
blood and persistent ST-segment elevation on the
electrocardiogram (ECG).1
Coronary angiography in these patients usually
reveals occlusion of infarct-related artery (respon-
sible for the occurrence of myocardial infarction)
and simultaneously defines invasive treatment
options (percutaneous coronary intervention [PCI]
or coronary artery bypass grafting [CABG]).
Via application of different methods, the risk for
death and cardiovascular complications is assessed
in all patients. The risk is estimated on the basis of
the rate of increase and duration of elevated level
of troponin, GRACE score, presence of diabetes,
renal failure (glomerular filtration rate (GFR)
<60 ml/min/1.73 m²) and impaired left ventricu-
lar function (LVEF < 40%).2–4
The presence of hyperglycaemia in acute STEMI
has been linked to worse in-hospital prognosis
and the presence of inflammation (leukocyte
count measured on admission) in these patients
was associated with higher mortality during hos-
pitalization. Furthermore, concomitant presence
of hyperglycaemia and leukocytosis was associ-
ated with a higher in-hospital death or cardio-
genic shock.3 Other studies however, have
demonstrated that thrombocytopaenia and anae-
mia are predictors of in-hospital mortality in
patients with STEMI that are undergoing endo-
vascular interventions.5–7
Patients with STEMI who are in a stable condi-
tion, and have no recurrence of myocardial ischae-
mia, serious arrhythmias and increasing symptoms
of heart failure, should start rehabilitation within
12–24 hours after PCI or CABG (stage I of car-
diac rehabilitation).8
Patients who are 3–4 weeks post-STEMI undergo
comprehensive inpatient cardiac rehabilitation in
cardiac rehabilitation wards. In Poland, Omission
of stage II cardiac rehabilitation is considered a
medical malpractice that results in the patient’s
deprivation of treatment. According to research,
such treatment leads to the reduction of morbid-
ity and mortality in patients after myocardial
infarction (secondary prevention).9
The basis of an ECG stress test, which is per-
formed on a treadmill or cyclo-ergometer, serves
to qualify patients for the appropriate model of
178 http://tac.sagepub.com
stage II cardiac rehabilitation. The initial exercise
test, as well as the result of the medical and physi-
otherapeutic examination, are taken into account
before determining the exercise program, its
duration, the applied loads and the intensity.8
Moreover, prior to the start of cardiac rehabilita-
tion it is necessary to determine the patients’ risk
factors for cardiac events. The risk stratification of
cardiac events includes the results of physical
examination, medical history as well as the results
of additional tests. LVEF, the presence of complex
ventricular arrhythmia at rest and during exercise,
myocardial ischaemia, exercise capacity based on
stress test, haemodynamic response to exercise are
all evaluated. The clinical data taken into account
comprises the course of myocardial infarction,
uncomplicated or complicated by shock, heart fail-
ure and recurrent ischaemia after invasive treat-
ment.10 There are no simple methods of assessment
on the basis of which one could predict the risk of
failure of cardiac rehabilitation.
As such, the aim of our study was to attempt
assessing cardiac rehabilitation failure in patients
after STEMI, using an index of our own design.
Materials and methods
The study included 136 post-STEMI patients, 96
men and 40 women, aged 60.1 ± 11.8 years,
admitted for cardiac inpatient rehabilitation (after
a period of approximately 3 weeks from the time
of STEMI) to the Department of Internal
Medicine and Cardiac Rehabilitation, Medical
University in Lodz (Poland).
On admission, a fasting blood sample (5 ml) was
collected from the basilic vein in the morning in
order to determine blood cell count and glucose
and creatinine levels. The determination of cre-
atinine levels was necessary to calculate GFR
from Modification of Diet in Renal Disease
(MDRD) formula:11
GFR (ml / min /1.73 m2 = 186.3
_1.154
× creatinine level ( mg/dl )
_ 0.203
× age × 0.742 ( if woman ) and
× 1.21 ( if the patient is black )
Red blood cells (RBCs), white blood cells (WBCs)
and platelets (PLTs) were measured in the com-
plete blood count. The following results were

Table 1.  Values of the studied peripheral blood
parameters.
Variable Mean Standard deviation
Age 60.98 11.89
Days after ACS 25.21 5.21
Gluc (mg/dl) 105.93 45.43
RBC (ml/mm3) 4.26 0.49
WBC (× 109/l) 7.75 3.52
CREA (mg/dl) 0.98 0.34
PLT (thous.) 256.16 87.80
eGFR (ml/ 83.19 24.59
min/1.77 m2)
ACS, acute coronary syndrome; CREA, creatinine; eGFR,
estimated glomerular filtration rate; Gluc, glucose; PLT,
platelet; RBC, red blood cell; thous, thousand; WBC,
white blood cell
considered abnormal: fasting glucose ⩾ 100 mg/dl,
GFR < 60 ml/min/1.73 m²; RBCs < 4 × 106/μl;
WBCs > 10 × 103/μl; PLTs < 150 × 103/μl.
The values of the studied peripheral blood param-
eters presented in this work, from our patients,
are shown in Table 1.
Submaximal exercise test (achievement 70–85%
of the maximum age heart rate, with the formula
220 − age) was performed on a treadmill ITAM
using the diagnostic workstation SCHILLER
CARDIOVIT CS-200 with software from
Schiller Poland. Submaximal exercise test was
carried out according to a standard or modified
Bruce protocol. The criteria for interruption of
the stress test was: reaching the limit of your
heart rate, chest pain, severe muscle pain or very
severe tiredness, feeling faint, shortness of
breath, difficulty breathing, sudden pallor or
cyanosis, impaired balance, ECG abnormalities
(ST-segment depression < 2 mm, ST-segment
elevation > 2 mm, the occurrence branch block
or AV block II° and III°, arrhythmias worsening
during exercise), no increase in heart rate
despite an increase in load or a rapid increase in
heart rate at a low load, no increase in blood
pressure during exercise or pressure drop during
the test, and the patient’s refusal or failure to
cooperate with the patient. Submaximal exer-
cise test allowed the evaluation of the haemody-
namic response to exercise, assessment of
current functional status and qualification of
patients for appropriate models of the second
stage of cardiac rehabilitation.12–14
http://tac.sagepub.com 179
R Irzmański, J Kapusta et al.
Interval training performed using a central
monitoring system Ergoline ERS with cyclo-
ergometers Ergoselect, with the possibility of load
control, heart rate, blood pressure and analysis of
the electrographic curve record was the basic line
of rehabilitation. Training sessions were held five
times a week in the morning. Individually matched
breathing, relaxation, isometric (of small muscle
groups) exercises and general rehabilitation gym-
nastics performed twice a day complement inter-
val training. After completion of rehabilitation
(15 training units) the exercise test was performed
again to assess its effects. The patient’s inability
to tolerate workload increment >5 Watt was con-
sidered a failure.
The limitation of the study was the patient’s
refusal to participate in cardiac rehabilitation sta-
tionary second stage, advanced heart failure pre-
vents the taking of physical effort on the ergometer,
rest pain behind the sternum confirmed the result
of an ECG, shortness of breath at rest, cardiac
arrhythmias worsening during exercise, acute
infectious diseases, aortic dissection, aortic steno-
sis significant degree, age over 89 years.
The study was approved by the Bioethics
Committee at the Medical University of Lodz,
Poland No. RNN/813/13/KB, and written
informed consent was obtained from all
patients.
Statistical analysis
The results were subjected to statistical analysis
using Statistica software (version 10) (Statsoft,
Poland). To determine the risk factors for failure
of cardiac rehabilitation in patients with STEMI
a logistic regression model was used with the esti-
mation of the (unit) odds ratio (OR). A p < 0.05
was considered statistically significant.
To build a logistic regression model, the five
independent variables (WBCs, RBCs, PLTs,
fasting glucose, GFR) that met the following two
criteria were selected:
(1) Statistical significance of the established
model was at the level p < 0.05 with a
preference of a model of higher level of
significance.
(2) Obtaining of the highest value of the unit
OR of the tested blood parameter (inde-
pendent variable) in the established
model.
Therapeutic Advances in Cardiovascular Disease 11(7)
Figure 1a-d.  Models of logic regression expressing OR.
Glc, glucose; GFR, glomerular filtration rate; OR, odds ratio; PLT, platelet; RBC, red blood cell; WBC, white blood cell
Results
Based on logistic regression analysis and the
results of individual OR of the tested parameters,
their prognostic impact was determined on the
risk of failure of cardiac rehabilitation.
This risk has been defined on the basis of the
patient’s inability to tolerate workload increment
>5 Watt in spite of the applied program of car-
diac rehabilitation. Designing a model of logistic
regression in accordance with the assumptions of
statistical analysis resulted in four models which
met criterion 1 (Figures 1a-d).
Models of logistic regression expressing OR are
presented in Figures 1a-d.
The fourth model (Figure 1 d) demonstrating the
highest statistically significant unit values of
odds   (for WBCs and GFR) best fulfilled criterion
2. Leukocytosis (WBCs > 10 × 103/μl) and
decreased GRF (GFR < 60 ml/min/1.73 m²)
determined most significantly the risk of failure of
cardiac rehabilitation (Figure 1 d) (respectively
OR = 6.42 and OR = 3.29, p = 0.007). Thus,
they were used to construct cardiac rehabilitation
failure index with the values ranging from 0 to 2.
180 http://tac.sagepub.com
0, corresponding to the situation of the
absence of any of them.
1, corresponds to the situation of the occur-
rence of leukocytosis or reduced GFR in
patients with STEMI and is associated with
4.35-fold increased risk of cardiac rehabili-
tation failure (Figure 2).
2, corresponds to the case of simultaneous
occurrence of both parameters (and
decreased GFR) and is associated with
18.92-fold increased risk of cardiac reha-
bilitation failure (Figure 2).
Discussion
The role of biomarkers in predicting increased
morbidity and mortality in patients post-myocar-
dial infarction has been supported by a number
studies over the years.
The biomarker copeptin has recently gotten a lot of
attention in MI research. The LAMP (Leicester
Acute Myocardial Infarction Peptide) study dem-
onstrated the presence of persistently elevated levels
of copeptin following acute coronary syndrome
(ACS) in patients who died or were readmitted
with heart failure. Moreover, they found high

Figure 5.  Multiple risk of cardiac rehabilitation failure.
concentrations of copeptin in patients who died in
long-term follow up post-ACS.15 Furthermore,
in a 60-day observation, they determined that
the concentrations of copeptin and NT-proBNP
are independent risk factors for death and heart fail-
ure in patients with ACS.15 This suggests the utility
of these biomarkers in risk stratification of patients
after myocardial infarction.16 In a 6-month follow
up, the LAMP II study demonstrated that copeptin
is a significant predictor of death [hazard ratio (HR)
= 5.98, 95% confidence interval (CI): 3.75–9.53, p
< 0.0005].17 The study also indicated that the deter-
mination of copeptin in combination with the
GRACE score increased the risk stratification. The
CHOPIN (Copeptin Helps in the Early Detection
of Patients with Acute Myocardial Infarction) study
however, demonstrated that elevated levels of
copeptin and troponin I were predictors of death
within a period of 180 days.18 It seems that the
copeptin determination in blood can be very helpful
in the accurate assessment of prognosis in patients
with ACS, however, there are restrictions on the use
of copeptin assays due to their cost and the need for
specialized equipment.
A lot of attention has also been paid to the impor-
tance of determining basic and low-cost blood tests
for the assessment of cardiovascular risk in patients
with STEMI. For example, a study by Malmberg
et  al. (2005) demonstrated that hyperglycaemia is
an independent predictor of mortality in patients
after ACS (DIGAMI 2:20% per 3 mmol/l glucose
levels above the normal range).19
Furthermore, Wang and colleagues showed that
even mild thrombocytopaenia was associated with a
two-fold higher risk of in-hospital mortality in patients
with ACS (OR = 2.01, 95% CI (confidence interval),
1.69–2.38).5 In a further study, a 2-year follow up in
STEMI patients with thrombocy-topaenia reported
a higher incidence of adverse cardiovascular events:
http://tac.sagepub.com 181
R Irzmański, J Kapusta et al.
death, recurrent myocardial infarction, need for
repeated PCI and stroke.6 In conclusion, the authors
pose the hypothesis that thrombocytopaenia in
patients with STEMI can be a useful and quickly
accessible indicator of adverse clinical events, espe-
cially within a short period of time.
Salizbury and colleagues found that the presence
of anaemia in patients hospitalized with acute
myocardial infarction is associated with in-hospi-
tal mortality. According to the authors both mod-
erate and severe anaemia were independently
associated with short-term adverse prognosis.7
The results indicated that patients with ACS and
accompanying anaemia were at higher risk of
death and cardiovascular complications.20,21
Further research also demonstrated that renal dys-
function is a strong independent predictor of long-
term mortality in patients with ACS.4,22 Long-term
mortality was found to increase exponentially with
the decrease of the glomerular filtration.
The findings of the above cited studies prompted
us to try answering the question of whether such
simple and yet cheap tests could be useful as
prognostic indicators of the failure of cardiac
rehabilitation conducted in hospital conditions in
patients with STEMI.
All patients eligible for cardiac rehabilitation
reported to the clinic after a period of approxi-
mately 3 weeks from the time of STEMI and PCI
was performed in the infarct-related artery. On
admission to hospital, fasting blood was drawn to
determine the serum level of creatinine, glucose,
leukocytosis erythrocytes and PLTs. GFR was
calculated from MDRD formula. Thus, there
was a difference in time (approximately 3 weeks)
between the determinations of blood parameters
Therapeutic Advances in Cardiovascular Disease 11(7)
in patients with acute STEMI and those that
were made after admission to hospital for cardiac
rehabilitation. At this point, we questioned
whether this difference in time would affect the
results of our research. At present, there is no
literature evaluating the prognostic impact of
tested blood parameters several weeks after the
onset of STEMI on cardiovascular risk.
Furthermore, there is currently no data evaluat-
ing the prognostic value of the tested blood
parameters in relation to the results of cardiac
rehabilitation. In this regard, this is the first study
which attempts to assess the prognostic value of
basic laboratory blood tests in predicting the risk
of failure of in-hospital cardiac rehabilitation.
Moreover, this assessment was not performed in
patients with acute STEMI but after a period of
approximately 3 weeks, that is after admission to
the department for in-hospital cardiac rehabilita-
tion. We demonstrated the utility of these tests in
predicting the risk of failure of cardiac rehabilita-
tion in post-STEMI patients, as well as the use-
fulness of their determination several weeks after
its occurrence during the period of regression of
many acute metabolic, hormonal and other dis-
ease-related disorders.
Based on logistic regression analysis and the
results of individual OR of the tested parameters,
we determined their prognostic impact on the risk
of failure of the undertaken cardiac rehabilitation
in post-STEMI patients. This risk was defined on
the basis of the patient’s inability to tolerate work-
load increment >5 Watt between the initial and
final exercise test performed on completion of the
cardiac rehabilitation (15 training units).
As a result of building a logistic regression
model, the most statistically significant risk fac-
tors were selected, on the basis of which cardiac
rehabilitation failure index was determined
(Figures 1, 2, 3 and 4). It appeared that leukocy-
tosis (>10 × 103/µl) and reduced GFR (<60 ml/
min/1.73 m²) determined most significantly the
risk of failure of cardiac rehabilitation. The
occurrence of leukocytosis or reduced GFR
value was associated with 4.35-fold increased
risk of cardiac rehabilitation failure (Figure 5).
In the case of simultaneous occurrence of both
these parameters however, the risk of cardiac
rehabilitation failure in post-STEMI patients
increased almost 19-fold (Figure 5).
The results of the study indicate the advantage of
determining the fasting level of glucose, GFR,
182 http://tac.sagepub.com
leukocyte erythrocyte and PLT count in patients
in the acute phase of STEMI. This is associated
with the ability to assess cardiovascular risk in
these patients using simple blood tests.
Currently, a large role in predicting risk of death is
attributed to the concentration of glucose indicated
at an early stage of the disease, but fasting glucose
in comparison with the values obtained immedi-
ately after admission to hospital.23 Hyperglycaemia
on admission to hospital, and especially its occur-
rence and persistence in the course of hospitaliza-
tion, militate in favour of a particularly poor
prognosis in patients with ACS.24,25 It should be
added that hyperglycaemia acute phase in the
course of ACS can occur not only in people with
previously diagnosed diabetes but also in those
with normal glucose tolerance or pre-diabetes.26
Furthermore, with increasing concentrations of
HbA1c there is an increase in annual and long term
mortality regardless of the glucose concentration
on admission to hospital.27
Terlecki and colleagues showed that inflamma-
tion assessed with the value of leukocyte count on
admission to hospital was more pronounced in
patients with STEMI who died during hospitali-
zation compared with patients who survived.3
This observation was related to all examined
patients and to subgroups with and without dia-
betes. The authors demonstrated that the con-
comitant presence of both acute hyperglycaemia
and more severe inflammation (assessed with the
leukocyte count) in patients with STEMI was
found to be an independent predictor of poor in-
hospital outcomes.3
On the other hand, Wi and colleagues demon-
strated that patients with acute myocardial
infarction treated with PCI who developed
contrast-induced acute kidney injury had worse
short- and long-term prognosis compared to
patients who did not develop this complica-
tion.28 Furthermore, the authors showed that
as many as 45.9% of patients with that injury
presented persistent (>1 month) renal dys-
function, which should be treated as an addi-
tional negative prognostic factor. In the 2-year
follow up, the death rate and hospitalization
due to cardiovascular causes was higher in this
group of patients compared with patients with-
out reduced GFR.28
Finally, the CHARM study (Candesartan in
Heart Failure: Assessment of Reduction in

Mortality and Morbidity) evaluated the effect of
renal failure expressed by reduced GFR (<60 ml/
min/1.73 m²) on all-cause mortality, cardiovascu-
lar mortality and cardiovascular hospital admis-
sions. Renal failure proved to be an important
factor increasing both the risk of cardiovascular
death and hospitalization for cardiac causes. The
risk was consistently higher with increasing renal
dysfunction.29 This supports the fact that
decreased renal function is an independent pre-
dictor of cardiovascular risk, which increases pro-
portionally to the increase of renal failure.
The results of our study demonstrate the impor-
tance of determining leukocytosis and GFR during
the assessment of the risk of cardiac rehabilitation
failure. Thus, these findings could provide guid-
ance to physicians and physiotherapists in qualify-
ing post-STEMI patients to the appropriate model
of rehabilitation.
Furthermore, these results support our previous
study in which additional parameters were
assessed, to predict the results of in-hospital car-
diac rehabilitation (phase II) of post-STEMI
patients (stage II).30
In conclusion, leukocytosis and reduced GFR
could be predictors of failure of cardiac rehabili-
tation and we believe that the assessment of the
above criteria could be beneficial for the design of
individual programs of cardiac rehabilitation for
patients with STEMI.
Funding
This research received no specific grant from any
funding agency in the public, commercial, or not-
for-profit sectors.
Conflict of interest statement
The authors declare that there is no conflict of
interest.
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