Download Effects of Bisoprolol and Carvedilol on Left Ventricular Remodeling

International Journal of BioMedicine
4(4) (Suppl 1) (2014) S34-S37
INTERNATIONAL
JOURNAL
OF BIOMEDICINE
Effects of Bisoprolol and Carvedilol on Left Ventricular Remodeling
in Patients with Chronic Heart Failure
T. A. Alieva¹; D.K. Avezov, PhD¹; U.K. Kamilova, PhD, ScD*²
¹Tashkent Medical Academy
²The Republican Specialized Scientific - Practical Medical Center
of Therapy and Medical Rehabilitation
Tashkent, Uzbekistan
Abstract
The purpose of the present research was to study the types of left ventricular (LV) remodeling in post-MI patients with
chronic heart failure (CHF) and assess the impact of bisoprolol and carvedilol on LV remodeling.
Material and Methods: The study included 217 post-MI patients with CHF between the ages of 38 and 60 (mean age
50.6±6.8 yrs) who were treated at the cardiology department of Tashkent Medical Academy. NYHA functional class (FC) of CHF
was determined by the 6-minute walk test (6MWT). All the patients were divided into two groups. Group 1 consisted of 107 postMI patients with FC I-III, who received bisoprolol on the background of basic therapy during 6 months; Group 2 consisted of 110
post-MI patients with FC I-III, who received carvedilol on the background of basic therapy during 6 months. The mean daily dose
of bisoprolol was 10 mg, and carvedilol. 25-50 mg. All patients underwent clinical examination, ECG, and echocardiography.
Result: Reverse remodeling and improvement in left ventricular function was observed in both groups, with a slight
advantage in the bisoprolol group. There was a decrease in the number of patients with prognostically unfavorable types of
remodeling (eccentric and concentric LVH) and restoration of normal LV geometry.
Keywords: chronic heart failure; left ventricular remodeling, bisoprolol; carvedilol.
Introduction
Chronic heart failure (CHF) is still the most common,
severe and prognostically unfavorable outcome of many
diseases of the cardiovascular system [1]. The outcome of
CHF remains very serious regardless of its etiology [2-4]. In
post-MI patients, according to the Framingham study, CHF
developed within 5 years, and the risk of its development in
patients with left ventricular (LV) dilatation was significantly
higher than in patients with normal LV cavity size [5]. A
combination of the lesions with early and late mechanical
and neurohormonal effects contribute to the LV restructuring
and the post-MI remodeling in post-MI patients. In post-MI
patients, the LV remodeling process is caused by the death
*Corresponding author: Umida K. Kamilova, PhD, ScD.
The Republican Specialized Scientific - Practical Medical Centre of
Therapy and Medical Rehabilitation; Tashkent, Uzbekistan. E-mail:
[email protected]
of a large number of cardiomyocytes and continues after
the cessation of the damaging effect of ischemia. The loss
of part of a functioning myocardium is accompanied by a
complex of structural changes involving both the damaged
and undamaged areas of the myocardium. This process is
adaptive in its nature, aimed at maintaining a normal cardiac
output and adequate myocardial stress. These changes in the
structure and geometry of the heart chambers, referred to as
“adaptive remodeling of the heart,” often precede the clinical
manifestations of heart failure. However, it is known that
heart failure develops in the future in a significant proportion
of post-MI patients. The cause of this complication is that the
remodeling process becomes maladaptive in character with
progressive dilatation of the LV, an alteration of its geometry,
and final fall of the pumping function [6-8].
Use of beta-blockers opened a new era in treatment
of CHF patients [9,10]. Many studies, including long-term
multicenter studies, determined that this drug group has
a positive impact on the clinical course, the quality of life,
T. A. Alieva et al / International Journal of BioMedicine 4(4) (Suppl 1) (2014) S34-S37
and the prognosis of post-MI patients and patients with heart
failure [11,12]. Despite numerous clinical and experimental
studies on the remodeling processes, questions about the
timing and types of LV remodeling in patients with different
functional classes remain a matter of debate. Data on the close
relationship between the episodes of myocardial ischemia
and impaired myocardial relaxation, which is one of the most
important pathogenetic mechanisms of diastolic dysfunction
and LV remodeling, are the subject of special attention. The
purpose of our work was to study the types of LV remodeling in
post-MI patients with CHF and assess the impact of bisoprolol
and carvedilol on LV remodeling.
Materials and Methods
The study included 217 post-MI patients with CHF
between the ages of 38 and 60 (mean age 50.6±6.8 yrs),
who were treated at the cardiology department of Tashkent
Medical Academy. NYHA functional class (FC) of CHF
was determined by the 6-minute walk test (6MWT) and the
Russian scale of evaluation of the clinical condition of the
patients (V.Yu. Mareev, 2000). All the patients were divided
into two groups. Group 1 consisted of 107 post-MI patients
with FC I-III, who received bisoprolol, β1-selective betablocker, on the background of basic therapy during 6 months;
Group 2 consisted of 110 post-MI patients with FC I-III,
who received carvedilol, nonselective beta-blocker with α1-,
β1- and β2- blocking properties, on the background of basic
therapy during 6 months. The mean daily dose of bisoprolol
given to Group 1 patients was 10 mg; the mean daily dose of
carvedilol in Group 2 patients ranged from 25 to 50 mg.
The standard therapy includes spironolactone, ACE
inhibitors, antiplatelet agents. The control group comprised
20 healthy, age-matched, randomly selected male persons.
Exclusion criteria were diabetes, atrial fibrillation, COPD,
asthma, and acute stroke. Echocardiography was performed
using the ultrasound system Toshiba SSH – YO(60)A (Japan).
Standard views and techniques in M - and B - modes were
used according to guidelines of the American Society of
Echocardiography [13]. Measurement of end-diastolic and
end-systolic LV volumes (EDV and ESV of LV) was carried
out using the modified Simpson’s method in the apical
2-wire and 4-chamber view. Left ventricular dimension
and left ventricular relative wall thickness (LVRWT) were
measured by echocardiography in M-mode according to the
recommendations of theAmerican Society of Echocardiography
[14]. Then, using the standard formula, stroke volume (SV)
and left ventricular ejection fraction (LVEF) were calculated.
LV mass and LVMI (LV mass standardized by body surface
area) were measured by M-mode echocardiography with the
use of the Devereux formula [15,16]. Finally, end-diastolic
and end-systolic sphericity index (EDSI and ESSI), as well
as meridional end-systolic wall stress (mESS) were measured.
LV diastolic function was evaluated by pulsed Doppler
echocardiography. Maximum velocities E and A, E/A, and the
isovolumic relaxation time (IVRT) were measured.
The study was approved by the Republican Specialized
Scientific - Practical Medical Centre of Therapy and Medical
S35
Rehabilitation. Written informed consent was obtained from
each patient.
Statistical analysis was performed using ECXEL 6.0 for
Windows-95. For data with normal distribution, inter-group
comparisons were performed using Student’s t-test. The mean
(M) and standard deviation (SD) were calculated. A probability
value of P<0.05 was considered statistically significant.
Results
In patients with CHF FC-I, normal values of LVEF were
revealed. By increasing the degree of CHF, LVEF progressively
decrease, so in patients with FC-II, LVEF was 20.1% (P
<0.001) less than in patients with FC-I; furthermore, EDV
and ESV were also slightly higher than in patients with FC-I.
Despite the increase in intramyocardial tension and dilation of
the heart chambers, stroke volume was within normal values.
With an increase in CHF FC, LVMI and wall thickness tended
to increase, but without statistical significance. In patients
with FC-II, mESS was higher by 26.9% (P<0.01) than in
patients with FC-I; this was probably due to the increase in
LV intramyocardial tension. EDSI and ESSI had a tendency
to increase in patients with FC-II. Development of CHF FCIII was accompanied by even more pronounced structural
changes of LV. In patients with CF-III compared to patients
with FC-I, EDD, EDV, and ESD were 16.6% (P<0.001),
37.9% (P<0.001), and 36.8% (P<0.001) greater, respectively,
and ESV increased more than 2-fold. Myocardial contractility
was characterized by a decrease in LVEF by 37.2% (P<0.001)
compared to the control group. Also noted was an increase
in the longitudinal dimensions in diastole by 1.3% in patients
with CHF FC-I. These changes were accompanied by an
increase in EDSI and ESSI by 11.7% and 15.9% (P<0.001),
respectively. An increase in intramyocardial tension in systole
by 5.1%, compared to the level in the end-systolic period, was
characterized by a significant increase in mESS by 38.1% (P
<0.02) compared to that in patients with CHF FC-I.
Pathological changes in LV myocardium after MI
resulted in the development of the spherical LV shape. LV
remodeling in post-MI patients is accompanied with changes
of muscle mass; there is LV dilatation with increases in EDD
and ESD. Wall thickening in the intact myocardium without
changes in LV geometry and LVMI occurred in 15% of
patients, which corresponded to the presence of concentric left
ventricular remodeling (CLVR). Concentric left ventricular
hypertrophy (CLVH) was observed in 52%, and signs of
eccentric left ventricular hypertrophy (ELVH) were observed
in 33% of patients.
CLVH was found in 21.3% of patients with FC-I and
in 50.8% of patients with FC-II. ELVH was found in 58.3%
of patients with FC-III. A diastolic variant of heart failure
occurred in 76.4% of patients with CLVR and 82% of patients
with CLVH, and only in 43.6% of patients with ELVH. In
ELVH, systolic and mixed variants of heart failure occurred
equally often (48.6 and 45.9%, respectively).
In patients with CLVH, LVEF was not significantly
decreased; at the same time, E decreased by 27.7% (P<0.05)
and A by 17.4% (P<0.05) compared to the control group. In
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T. A. Alieva et al / International Journal of BioMedicine 4(4) (Suppl 1) (2014) S34-S37
patients with ELVH, E decreased by 37.0% (P<0.05), A by
12.5% (P<0.05), and LVEF by 40.8% compared to the control
group. In patients with CLVR, E decreased by 26.0% (p<0.05),
A by 18.7% (P<0.05), and LVEF by 21.4% compared to the
control group (Table 1).
Table 1.
Types of LV remodeling and parameters of LV systolic and diastolic
function
Parameters Control group
CLVR
CLVH
ELVH
Е, cm/sec
75.9±9.8
56.2±11.1*
54.9±13.8* 47.8±14.9*
А, cm/sec
63.1±11.4
51.3±12.5*
52.1±12.9* 55.2±11.9*
Е/А
1.2±0.18
1.10±0.14*
1.05±0.17*
LVEF, %
66.8±8.8
56.0±15.2*
57.8±13.1* 44.4±13.5*
LVRWT
0.42±0.05
0.46±0.026* 0.48±0.023*0 0.34±0.018*
0.87±0.12
*- P<0.05 vs control group
Our results showed that diastolic heart failure, an
isolated systolic variant, and a mixed variant of heart failure
occurred in 63.3%, 3.8%, and 32.9% of cases, respectively, in
post-MI patients with CHF FC I-III. The maximum decrease
in diastolic relaxation occurred in patients with ELVH, which
was accompanied by the most significant decrease in LVEF.
In patients with CLVH and CLVR, LV diastolic filling was
reduced while velocity of circumferential fiber shortening was
maintained and, as a consequence, LVEF at rest was reduced.
Analysis of the dynamics of the LV geometric
parameters during long-term therapy with bisoprolol and
carvedilol revealed the characteristic features for the observed
groups. In post-MI patients with FC-I after 6 months’ therapy
with bisoprolol and carvedilol, we found a significant decrease
in EDD by 9% and 12.2% (P<0.001), EDV by 18.9% and
26% (P<0.01), ESD by 11.1% and 17.5% (P<0.001), and
ESV by 30.1% and 36.3% (P<0.005), respectively, compared
to baseline data. Although baseline LVEF was within normal
values in these patients, by the end of treatment this parameter
had significantly increased by 12% for bisoprolol and 14.5%
(P<0.001) for carvedilol. In post-MI patients with FC-II after
6 months’ therapy with bisoprolol and carvedilol, we observed
a significant decrease in EDD by 9% and 10.5% (P<0.001),
respectively, and in ESD by 7% and 15.9% (P<0.001),
respectively. These decreases were accompanied by an
increase in LVEF by 11.8% and 14.8%, respectively.
In post-MI patients with FC-III after 6 months’ therapy
with bisoprolol, we found a significant decrease in EDD and
ESD by 11.1% and 15.4% (P<0.001), EDV and ESV by 26.2%
and 35.8% (P<0.001), respectively, compared to baseline data.
These decreases were accompanied by an increase in LVEF
by 23.1%. In post-MI patients with FC-III after 6 months’
therapy with carvedilol, we revealed a significant decrease
in EDD and EDV by 12.9% and 27.6% (P<0.001), ESD and
ESV by 17.6% and 38.3% (P<0.001), respectively, compared
to baseline data. These decreases were accompanied by an
increase in LVEF by 17.3%.
Therapy with bisoprolol and carvedilol for 6 months had
a positive impact on LV remodeling. In the group receiving
bisoprolol, a statistically significant decrease in LVMI was
noted, improving LV systolic function, which resulted in a
significant increase in LVEF in patients with ELVH. The
type of cardiac remodeling had also undergone significant
changes: at baseline, CLVH was predominant (52.3%), and
ELVH accounted for 35%. At the end of observation, we noted
a decrease in the proportion of patients with CLVT and ELVH;
normal LV geometry was determined in 40.1% of patients. By
the end of the observation in patients with baseline CLVH
(n=56), CLVR and normal LV geometry was observed in 16
patients, ELVH in 4 patients, and CLVH in 36 patients; in
patients with baseline ELVH (n=38), CLVR and normal LV
geometry was observed in 10 patients, CLVH in 4 patients,
and ELVH in 24 patients.
In the group receiving carvedilol, it was also noted a
decrease in LVMI and statistically significant increase in
LVEF in patients with ELVH. The type of cardiac remodeling
had also undergone significant changes: at baseline, CLVH
was predominant (55%), and ELVH accounted for 33.6%. At
the end of observation, we noted a decrease in the proportion
of patients with CLVT and ELVH; normal LV geometry was
determined in 33.1% of patients. By the end of the observation
in patients with baseline CLVH (n=61), CLVR and normal LV
geometry was observed in 10 patients, ELVH in 8 patients, and
CLVH in 43 patients; in patients with baseline ELVH (n=37),
CLVR and CLVH was observed in 8 patients and ELVH in 29
patients.
Conclusion
Thus, reverse remodeling and improvement in left
ventricular function was observed in both groups, with a slight
advantage in the bisoprolol group. There was a decrease in the
number of patients with prognostically unfavorable types of
remodeling (eccentric and concentric LVH) and restoration of
normal LV geometry.
Competing interests
The authors declare that they have no competing interests.
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