European Journal of Heart Failure 3 Ž2001.
403᎐406
Review
Cardiomyoplasty for treatment of heart failure
Edimar Alcides BocchiU
˜ Paulo Uni¨ ersity Medical School, Sao
Heart Institute, Sao
Received 7 April 1999; received in revised form 3 November 1999; accepted 23 November 1999
1. Introduction
Heart failure is a complex syndrome characterized
by a wide spectrum of clinical manifestations; multi-
ple etiologies can lead to heart failure with many
pathophysiological mechanisms w1,2x.
Successful treatment of heart failure is challenging
in view of the complexity of the syndrome. Multiple
drugs may improve, but do not stop progression of the
disease. Surgical procedures have been proposed for
the treatment of heart failure, as an additional proce-
dure for progressive heart failure after drug therapy
has failed w3,4x. Heart transplantation is the treatment
of choice for severe heart failure. However, its appli-
cation is limited by donor shortage and selection
criterion for heart transplantation. Other procedures
have been proposed including cardiomyoplasty, par-
tial left ventriculectomy, mitral valve surgery, and
ventricular synchronization with pacemaker.
2. Cardiomyoplasty — technical procedure
The left latissimus dorsi muscle has been most
commonly used in cardiomyoplasty. In summary, the
latissimus dorsi muscle is wrapped around the left
ventricle to contract in cardiac systole w5x. Electrical
stimulation of the muscle with implanted electrodes is
initiated approximately 2 weeks after the surgical
procedure. Skeletal muscle fast fatigable type II fibers
may be transformed into fatigue resistant type I fibers,
after 6᎐8 weeks of chronic electrical stimulation. The
U ments and associated to partial replacement by fatty
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addition of sequential electrical pulses leads to sum-
mation of skeletal muscle twitches, increasing the
duration and force of contraction. The skeletal mus-
cle may be paced synchronously to every cardiac beat
in variable modes from 1:1 to 1:2 or to be turned off
during sleep. An epimyocardial sensing lead is placed
over either the left or the right ventricle and con-
nected to the cardiomyostimulator placed in an ab-
dominal subcutaneous or submuscular pocket. A pe-
riod of 8 weeks is required to ‘train’ the muscle and a
so-called vascular delay period of 2 weeks, which is
the time between muscle mobilization and recovery of
distal muscle blood supply from a single vascular
pedicle. Only patients in a stable clinical condition
can reasonably be put forward for cardiomyolasty as
sicker patients are unlikely to tolerate this prolonged
preliminary period. Factors related to surgery such as
the acute and chronic electrical stimulation, and the
surgical manipulation with ischemia to distal mobilized
muscle could damage the latissimus dorsi muscle, with
atrophy jeopardizing a successful outcome after dy-
namic cardiomyoplasty w6x. Expressive increment of
creatinokynase enzyme levels with prognostic values
that may occur in the immediate post-operative pe-
riod after the cardiomyoplasty is evidence for surgical
skeletal muscle flap ischemia and lesion w7x. The
skeletal muscle flap ischemia may lead to partial or
total suppression of the muscle flap contraction re-
sponse to electrical stimulation. The preservation of
the latissimus dorsi muscle may be important in the
success of dynamic cardiomyoplasty w8x. Also, the
muscle fiber type transformation in humans may not
be as complete as that observed in animal experi-
tissue and fibrosis w9x.
404 E.A. Bocchi r European Journal of Heart Failure 3 (2001) 403᎐406
3. Potential mechanisms of action of cardiomyoplasty
Experimental and clinical studies have postulated
that dynamic cardiomyoplasty may work as an active
as well as a passive support of the damaged my-
ocardium. The effects include, direct synchronized
cardiac systolic assistance, reduction of left ventricu-
lar stress, change in left ventricular geometry, active
or passive support, prevention of progressive ventricu-
lar dilation, partial replacement of the heart muscle,
reduction of myocardial oxygen consumption, or an
increase in blood flow to ischemic myocardium
w10᎐15x. Improvement in the pressure᎐volume rela-
tionship with a better contractile state of the com-
bined ventricular myocardium and wrapped latissimus
dorsi muscle has been documented w7x. These effects
could reverse some mechanisms of the remodeling
process in heart failure. However, beneficial effects of
cardiomyoplasty on other complex pathophysiological
mechanisms such as increased neurohormonal activ-
ity, abnormal baroreflexrchimioreflex, pro-inflamma-
tory process, endothelial dysfunction, hypertrophy,
apoptosis, mitral or tricuspid regurgitation, atrial and
ventricular arrhythmias, right ventricular function, and
oxidative stress have not been well studied or de-
scribed.
4. Selection criteria
Patients with chronic systolic congestive heart fail-
ure due to ischemic or idiopathic dilated cardiomy-
opathy in persistent New York Heart Association
functional class III are candidates for cardiomy-
oplasty. Additional indices to support the indication
are recurrent hospitalizations, peak oxygen consump-
tion during exercise testing - 16 mlrkg per min, left
ventricular ejection fraction - 30% ŽMUGA., cardiac
index - 2.5 lrmin per m2 at rest, high left ventricular
filling pressure, and stable condition on medical ther-
apy enough to withstand a waiting time of 2᎐3 months
before effective skeletal muscle flap adaptation or to
survive the operation. Also, patients with left ventric-
ular tumor or aneurysms are candidates for dynamic
cardiomyoplasty.
5. Contraindications
Patients are not accepted for cardiomyoplasty in
the presence of: intravenous inotropic drug support;
hemodynamic or clinical instability or both; N.Y.H.A.
functional class IV; severe valvular dysfunction; ar-
rhythmia not controlled by medical therapy; resuscita-
tion or sustained ventricular tachycardic episodes;
major enlargement of left ventricle with left ventricu-
lar end diastolic diameter by echo ) 5 cmrm2 ; cha-
gasic cardiomyopathy; poor lung function with forced
vital capacity - 55% of predicted value; drug or
alcohol abuse; chronic atrial fibrillation; older age;
syncope; irreversible excessive elevation of pulmonary
vascular resistance; severe pulmonary hypertension;
peak oxygen consumption - 10 mlrkg per min;
thrombus in left ventricle; myocarditis; muscle dis-
ease; coexistent systemic illness with poor mid-term
prognosis; morbid obesity; non-compliance with treat-
ment; coexisting disease with high surgical risk or
cardiac cachexia.
6. Risks of surgery
The post-operative intra-hospital mortality rate is
between 0 and 23%. Medtronic worldwide experience
demonstrates in-hospital mortality of 17% w16,17x. The
most important factors associated with high immedi-
ate mortality are New York Functional Class IV, left
ventricular ejection fraction - 10% ŽMUGA., and
peak oxygen consumption during maximal exercise
- 10 mlrkg per min. In the C-Smart study hospital
mortality was 4%. The causes of in-hospital deaths
are mainly related to primary ventricular failure, ar-
rhythmias and surgical procedure w18x. Isolated car-
diomyoplasty carries a mortality rate of up to 10%;
however, it is associated with a mortality of between
20 and 30% when combined with coronary artery
bypass, valvular surgery or other procedure.
7. Clinical effects of cardiomyoplasty
Several centers have combined cardiomyoplasty with
aneurysmectomy, coronary artery bypass grafting, and
valve replacement or repair, making improvement
from the cardiomyoplasty procedure itself difficult to
evaluate. Most previous trials of cardiomyoplasty have
not compared in a randomized fashion the results of
the operation with standard medical therapy for heart
failure or cardiac transplantation. Non-randomized
data suggest that cardiomyoplasty may improve func-
tional class and quality of life, reducing the need for
drug therapy. In the Medtronic Multicenter trial car-
diomyoplasty improved the functional class in most
patients w12x. Improvement in quality of life after
cardiomyoplasty has been observed for daily activities,
social activities, quality of interaction, and mental
health. In addition, cardiomyoplasty improved physi-
cal activity, sleep pattern, food pattern, perception
and expectations about the treatment.
Modest effects on left ventricular ejection fraction
have been consistently reported in most clinical stud-
ies w19᎐21x. Regional left ventricular function im-
 E.A. Bocchi r European Journal of Heart Failure 3 (2001) 403᎐406
proved in anterolateral, apical, diaphragmatic and
posterobasal regions w18x. It was observed that car-
diomyoplasty may improve left ventricular diastolic
function, reducing chamber stiffness and significantly
decreasing Doppler ErA ratio w7,22x. Hemodynamical
benefits are less consistent. Improvement in stroke
volume and stroke work indices was observed, with a
reduction in pulmonary pressures w23,24x. Improve-
ment in stroke volume of between 20 and 30% was
observed using stimulated and non-stimulated beats
w25x.
Cardiomyoplasty may improve peak oxygen exercise
consumption and total exercise time in patients with a
maximal exercise capacity of less than 14 mlrkg per
min w26x. Evidence of the beneficial hemodynamic
effects of cardiomyoplasty, with an increase in cardiac
output and a reduction in pulmonary pressures has
been documented at peak treadmill exercise test in
patients with dilated cardiomyopathy w27x.
The absence of completed randomized trials pre-
cludes conclusions about the influence of cardiomyo-
plasty on long-term survival in patients with heart
failure. In a historical comparison of survival after
cardiomyoplasty, heart transplantation or medical
treatment, improved survival was observed after car-
diomyoplasty compared with medical treatment, how-
ever, the survival rate was worse than that for heart
transplantation w28x. The overall survival rates for
cardiomyoplasty at 1 and 2 years range from 72 to
78%, and from 57 to 60%, respectively w12,29x. The
late mortality is 5.5% each year and at 5 years the
survival rate is approximately 40%. The causes of late
mortality are mainly progressive heart failure and
sudden death. Heart failure can be associated with
many other factors such as progression of the underly-
ing disease, evidence of skeletal muscle ischemia in
the immediate post-operative period, late degenera-
tion of the chronic stimulated latissimus muscle, and
presence of precipitating causes of decompensation.
Despite initial beneficial effects after cardiomyo-
plasty, fatty degeneration of the latissimus dorsi mus-
cle and fibrous connective tissue replacement associ-
ated with progression of congestive heart failure was
observed in patients on late follow-up w30x. Cardiomy-
oplasty does not modify atrial and ventricular ar-
rhythmias. The risk of sudden death remains after
cardiomyoplasty, even in patients with improved left
ventricular function w31x. However, for patients in
whom the cardiomyoplasty has failed, cardiac trans-
plantation can be performed safely and successfully
w32x. Recently, the first randomized study ŽC-SMART.
comparing cardiomyoplasty with medical treatment,
which planned to recruit 400 patients, was interrupted
due to difficulty in recruiting patients w33x. Analysis of
data from 51 patients who underwent cardiomyoplasty
compared with 52 patients on medical treatment, de-
405
monstrated an improvement in a 6-min walk test
distance, N.Y.H.A. functional class and some parame-
ters of quality of life ŽMinnesota Living with Heart
Failure. in the cardiomyoplasty group. There was no
observed difference in survival Ž86% for cardiomyo-
plasty and 84% for medical treatment at 6 months.,
peak VO 2 or in left ventricular ejection fraction im-
provement.
8. Limitations for cardiomyoplasty
Based on the selection criteria of candidates for
cardiomyoplasty, the procedure may potentially bene-
fit just a small percentage of patients with heart
failure. Post-operative ischemia, the progression of
underlying disease, and the reported fatty degenera-
tion of the muscle and fibrous connective tissue re-
placement are all obstacles to long-term clinical bene-
fits of cardiomyoplasty. The persistent risk of sudden
death is a challenge to improve survival after car-
diomyoplasty.
9. Future perspectives and directions
The main focus of research efforts to overcome the
limitations of cardiomyoplasty should concentrate on
the following: concomitant use of cardioverterrde-
fibrillators and pacemakers, preservation of the latis-
simus dorsi muscle during surgery, improvement in
surgical technique with less invasive procedures and
reduction in the duration of surgery Žmini-invasive
techniques ., the use of growth factors to enhance
muscle vascularization, identification of stimulation
protocols to optimize cardiac performance and pre-
serve chronically the flap muscle and consequently
changes in restricted criteria selection for a
widespread indication. In addition, more basic science
studies are required to improve clinical application of
cardomyoplasty.
10. Conclusion
In humans, heart failure is a complex syndrome
with multiple clinical manifestations and pathophysio-
logical mechanisms. Many different etiologies may
lead to heart failure. Despite all basic research and
various clinical investigations, the role of cardiomyo-
plasty in the treatment of heart failure remains un-
clear. The challenge for clinical application of car-
diomyoplasty is that it is a major surgical procedure
and the benefits obtained are limited. Based on avail-
able results of small clinical trials and of an inter-
rupted randomized trial, cardiomyoplasty seems to be
406 E.A. Bocchi r European Journal of Heart Failure 3 (2001) 403᎐406
a procedure for patients with moderately symptomatic
heart failure. Randomized trials should provide an-
swers to the question.
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