Ischemic cardiomyopathy:
therapeutic value of a metabolic approach
P. Sabouret
Pitié-Salpétrière Hospital, Paris
Correspondence: Dr P. Sabouret, Department of Cardiology, Hôpital
Pitié-Salpétrière, Boulevard de l’Hôpital, Paris Cedex 13, 75651
France
Heart failure is a major cause of morbidity and
mortality worldwide.[1-3] Indeed, congestive heart failure (CHF)
affects between 1 and 4% of the total population.[4,5] Despite
many advances in the management of heart failure and coronary
heart disease (CHD), which represents the major cause of CHF,
the prevalence and incidence of left ventricular dysfunction are
increasing dramatically leading to a heavy burden on healthcare
systems.[6,7] The increasing prevalence of CHF is the consequence
of the aging of the population, the increasing prevalence of CHD,
and the reduced age-adjusted mortality of patients with CHD. Better
knowledge of the mechanisms which lead to cardiac diastolic or
systolic dysfunction has also highlighted the need for reevaluation
of the relationship between heart failure and ischemic heart disease
(IHD), especially in terms of potential therapeutic improvements.
Ischemic heart disease represents the leading cause of mortality
worldwide today. This disease is expected to become the world’s
primary cause of disease burden (which represents aggregate mortality
and morbidity) in 2020, despite considerable progress in prevention
and treatment over the past 20 years. IHD is currently the main
cause of heart failure, which remains an increasing major clinical
and health problem. CHF is associated with poor functional capacity,
decreased quality of life, and increased risk of morbidity and
mortality, with a common mortality rate in excess of 40% within
2 years of initial diagnosis.[8-11]
The ischemic cause of CHF increases the risk of death;[12] this
enhances the importance of an improved therapeutic approach to
ischemic cardiomyopathy.
Evolution in the understanding of ischemic
left ventricular dysfunction
In past decades, it was thought that CHF associated with chronic
coronary artery disease (CAD) was irreversible and amenable to
early medical treatment with hemodynamic agents, such as ACE inhibitors,
b-blockers, spironolactone, diuretics, and digoxin if necessary.
This concept has been proven inaccurate, because of the progress
in cardiac imaging techniques, which has shown that ischemic left
ventricular dysfunction is not always irreversible. The improved
myocardial function in some patients after bypass graft or with
dobutamine led Rahimtoola to propose the concept of hibernating
myocardium.[13] In patients with chronic CAD, hibernation means
that left ventricular function seems chronically impaired but
is in fact reversible by reperfusion. Clinical syndromes associated
with hibernation include stable and unstable angina, myocardial
infarction, and documented left ventricular dysfunction with or
without cardiac failure. The hibernating myocardium retains its
inotropic responsiveness, in contrast to irreversibly damaged
muscle. It can be identified by resting and stress echocardiography,
thallium scintigraphy, and positron emission tomography (PET).
The development of PET has permitted better exploration of hibernating
myocardium and opened up a new controversial issue (Figures 1
and 2).
| Figure 1. FDG scan from a patient with viable
hibernating myocardium. |
 |
| Figure 2. FDG scan from a patient with nonviable
scar tissue. |
 |
In fact, the initial definition of hibernation
implied a myocardial dysfunction due to a significant reduction
in coronary blood flow. PET studies, which currently represent
the most accurate method of measuring blood flow, have highlighted
the evidence that blood flow in hibernating segments is not necessarily
reduced to an extent that can account alone for the degree of
dysfunction. These findings suggest a metabolic adaptation of
myocardial cells, which has been postulated by recent studies.
These studies found that the hibernating myocardium is not metabolically
anaerobic after a short time, and that an uncoupling of substrate
(glucose and fatty acid) uptake and mechanical function happens.[14] In consequence, the glucose oxidation is reduced, leading to an
uncoupling between glycolysis and glucose oxidation which results
in deleterious effects. The demonstration of significant reversibility
of the degree of left ventricular dysfunction, i.e. hibernation,
offers the patients the chance to benefit from revascularization,
both symptomatically and prognostically.
Considering the potential gain to be derived from revascularization,
there is the temptation to perform such aggressive procedures
in all patients with a hibernating left ventricle. However, numerous
problems have not yet been resolved. It is not known how much
viable myocardium is required for revascularization to confer
a clinical benefit, or to what extent the interventional strategies
result in sustained symptomatic and functional improvement, as
well as prognostic benefits compared with optimal medical management.
In fact, the conventional drugs used in congestive heart failure,
including ACE inhibitors, diuretics, digitalic glycosides, and
vasodilators, improve either symptoms and/or prognosis, but the
role of these drugs in the specific field of hibernating myocardium
has not been evaluated.
Furthermore, hibernating myocardium is the consequence of a progressive
metabolic adaptation, which clearly emphasizes the need for therapeutic
metabolic modulation in the patient’s favor.
Therapeutic value of a metabolic approach
in left ventricular
dysfunction
Some promising experimental and clinical studies have been conducted
with trimetazidine (Vastarel 20), the first metabolic agent to
be quoted in the European Guidelines, demonstrating initial promising
results in the field of ischemic cardiomyopathy. In fact, this
drug has a number of potentially useful cytoprotective features,
by limiting intracellular acidosis and sodium and calcium overload,
allowing preservation of contractile function and limitation of
cytolysis and membrane damage caused by oxygen free radicals.
In animal studies, the original and specific mechanism of trimetazidine
causes an increase of 33% in the recovery of cardiac work and
a 24% increase in cardiac efficiency in early reperfusion compared
with control rat hearts.[15] The clinical studies tend to confirm
these benefits: Brottier et al. reported symptomatic and functional
improvement, with an increase in left ventricular ejection fraction
(EF) in a small cohort of coronary patients with severe left ventricular
dysfunction.[16]
In 1997, Birand et al. found a significant improvement of EF with
trimetazidine, compared with placebo, in 51 patients with CAD
after percutaneous transluminal coronary angioplasty (PTCA).[17]
More recently, trimetazidine was found to be effective in improving
resting left ventricular function and wall motion score index
in a randomized, double-blind study, compared with placebo (Figure
3).[18]
 Figure
3. Trimetazidine significantly reduced wall motion score index
both at rest and during DET.
A further study has been recently performed to evaluate the activity
of trimetazidine in hibernating myocardium (Figures 1 and 2).[19]
This double-blind, randomized, placebo-controlled study concluded
that there was a significant improvement in wall motion score
index both at rest and at peak infusion, without change in the
hemodynamic parameters (Figure 4).
 Figure
4. Trimetazidine decreases WMSI at rest and at stress in patients
with hibernating myocardium.
Improved cellular function during ischemia could
explain the beneficial effects of trimetazidine on resting and
dobutamine-induced myocardial ischemic dysfunction. Preserving
mitochondrial function and energy metabolism from chronic oxygen
deprivation may reduce ischemic left ventricular dysfunction.
As these effects occur in the absence of detectable changes in
systemic and coronary hemodynamics, the effects of trimetazidine
on ischemic myocardium are likely to rely on direct cytoprotection.
CONCLUSION
Hibernation is a form of prolonged contractile dysfunction associated
with ongoing blood flow in patients with CAD. This newly discovered
phenomenon concept is often present in ischemic cardiomyopathy,
the main cause of CHF. Stress echocardiography and myocardial
tomoscintigraphy represent the most accurate techniques to assess
myocardial viability in case of ischemic cardiomyopathy. Trimetazidine,
a new metabolic antiischemic agent, has triggered initial promising
results in this area.
Further studies are needed for a better understanding of the hibernating
myocardium, to evaluate and compare the benefit of anti-ischemic
agents in this spectrum, in order to improve the morbidity and
the mortality of numerous patients with ischemic CHF.
REFERENCES
Comment in:
Effect of enalapril on survival in patients
with reduced left ventricular ejection fractions and
congestive heart failure. The SOLVD Investigators.
BACKGROUND. Patients with congestive heart failure have a high
mortality rate and are also hospitalized frequently. We
studied the effect of an angiotensin-converting-enzyme
inhibitor, enalapril, on mortality and hospitalization in
patients with chronic heart failure and ejection fractions
less than or equal to 0.35. METHODS. Patients receiving
conventional treatment for heart failure were randomly
assigned to receive either placebo (n = 1284) or enalapril (n
= 1285) at doses of 2.5 to 20 mg per day in a double-bind
trial. Approximately 90 percent of the patients were in New
York Heart Association functional classes II and III. The
follow-up averaged 41.4 months. RESULTS. There were 510 deaths
in the placebo group (39.7 percent), as compared with 452 in
the enalapril group (35.2 percent) (reduction in risk, 16
percent; 95 percent confidence interval, 5 to 26 percent; P =
0.0036). Although reductions in mortality were observed in
several categories of cardiac deaths, the largest reduction
occurred among the deaths attributed to progressive heart
failure (251 in the placebo group vs. 209 in the enalapril
group; reduction in risk, 22 percent; 95 percent confidence
interval, 6 to 35 percent). There was little apparent effect
of treatment on deaths classified as due to arrhythmia without
pump failure. Fewer patients died or were hospitalized for
worsening heart failure (736 in the placebo group and 613 in
the enalapril group; risk reduction, 26 percent; 95 percent
confidence interval, 18 to 34 percent; P less than 0.0001).
CONCLUSIONS. The addition of enalapril to conventional therapy
significantly reduced mortality and hospitalizations for heart
failure in patients with chronic congestive heart failure and
reduced ejection fractions.
Publication Types:
- Clinical Trial
- Multicenter Study
- Randomized Controlled Trial
PMID: 2057034 [PubMed - indexed for MEDLINE]-
Effects of enalapril on mortality in severe
congestive heart failure. Results of the Cooperative North
Scandinavian Enalapril Survival Study (CONSENSUS). The
CONSENSUS Trial Study Group.
To evaluate the influence of the angiotensin-converting-enzyme
inhibitor enalapril (2.5 to 40 mg per day) on the prognosis of
severe congestive heart failure (New York Heart Association
[NYHA] functional class IV), we randomly assigned 253 patients
in a double-blind study to receive either placebo (n = 126) or
enalapril (n = 127). Conventional treatment for heart failure,
including the use of other vasodilators, was continued in both
groups. Follow-up averaged 188 days (range, 1 day to 20
months). The crude mortality at the end of six months (primary
end point) was 26 percent in the enalapril group and 44
percent in the placebo group--a reduction of 40 percent (P =
0.002). Mortality was reduced by 31 percent at one year (P =
0.001). By the end of the study, there had been 68 deaths in
the placebo group and 50 in the enalapril group--a reduction
of 27 percent (P = 0.003). The entire reduction in total
mortality was found to be among patients with progressive
heart failure (a reduction of 50 percent), whereas no
difference was seen in the incidence of sudden cardiac death.
A significant improvement in NYHA classification was observed
in the enalapril group, together with a reduction in heart
size and a reduced requirement for other medication for heart
failure. The overall withdrawal rate was similar in both
groups, but hypotension requiring withdrawal occurred in seven
patients in the enalapril group and in no patients in the
placebo group. After the initial dose of enalapril was reduced
to 2.5 mg daily in high-risk patients, this side effect was
less frequent. We conclude that the addition of enalapril to
conventional therapy in patients with severe congestive heart
failure can reduce mortality and improve symptoms. The
beneficial effect on mortality is due to a reduction in death
from the progression of heart failure.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 2883575 [PubMed - indexed for MEDLINE]
3. Applefed MM. Chronic congestive heart failure: where have
we been? Where are we heading? Am J Med 1986; 80: 73–77.
Comment in:
Echocardiography in chronic heart failure
in the community.
Wheeldon NM, MacDonald TM, Flucker CJ, McKendrick AD,
McDevitt DG, Struthers AD.
Department of Clinical Pharmacology, Ninewells Hospital and
Medical School, Dundee.
A total of 128 patients from a single practice population who
were receiving loop diuretics for treatment of presumptive
cardiac failure were identified from prescribing data captured
by the Medicines Monitoring Unit. A subgroup of 78 patients
underwent echocardiography to determine the prevalence of true
left ventricular systolic dysfunction in this population and
the validity of the diagnosis of cardiac failure in primary
care. A further 50 patients were studied to assess the
workload generated by these patients for both primary health
care and hospital services. The estimated prevalence of left
ventricular systolic dysfunction was 0.84%, whereas 1.6% of
the population received loop diuretics for this indication. A
false-positive diagnosis occurred in 47% and was more likely
in females (73%) than males (37%). Of all consultations 79%
were seen by GPs, 14% as hospital out-patients and 7% as
in-patients. Within the hospital general physicians have most
contact with these patients. In summary chronic heart failure
is common within the community, although the false-positive
rate for diagnosis of this condition is high. GPs and general
physicians treat the majority of these patients and should
therefore receive continuing education regarding recent
advances in this area. Echocardiography should be performed
early in the management of all patients suspected of having
cardiac failure.
PMID: 8438044 [PubMed - indexed for MEDLINE]-
-
Symptomatic and asymptomatic
left-ventricular systolic dysfunction in an urban population.
McDonagh TA, Morrison CE, Lawrence A, Ford I,
Tunstall-Pedoe H, McMurray JJ, Dargie HJ.
Department of Cardiology, Western Infirmary, Glasgow, UK.
BACKGROUND: In most previous epidemiological studies on the
prevalence of chronic heart failure (CHF) the disorder has
been defined on clinical criteria. In a cross-sectional survey
of 2000 men and women aged 25-74, randomly sampled from one
geographical area, we assessed left-ventricular systolic
function by echocardiography. METHODS: 1640 (83%) of those
invited took part. They completed a questionnaire on current
medication, history, and symptoms of breathlessness. Blood
pressure was measured and electrocardiography (ECG) and
echocardiography were done. Left-ventricular ejection fraction
was measurable in 1467 (89.5%) participants by the biplane
Simpson's rate method. FINDINGS: The mean left-ventricular
ejection fraction was 47.3%. The prevalence of definite
left-ventricular systolic dysfunction (defined as a
left-ventricular ejection fraction < or = 30%) was 2.9%
overall (43 participants); it increased with age and was
higher in men than in women (4.0 vs 2.0%). The
left-ventricular systolic dysfunction was symptomatic in 1.5%
of participants and asymptomatic in 1.4%, 83% of participants
with left-ventricular systolic dysfunction had evidence of
ischaemic heart disease (IHD) from history or ECG criteria
compared with 21% of those without this abnormality (p <
0.001). Hypertension was also more common in those with
left-ventricular systolic dysfunction (72 vs 38%, p <
0.001), but there was no difference between those with and
without left-ventricular systolic dysfunction in the rate of
hypertension without IHD. INTERPRETATION: Left-ventricular
systolic dysfunction was at least twice as common as
symptomatic heart failure defined by clinical criteria. The
main risk factors are IHD and hypertension in the presence of
IHD; screening of such high-risk groups for left-ventricular
systolic dysfunction should be considered.
PMID: 9310600 [PubMed - indexed for MEDLINE]
-
The epidemiology of heart failure: the
Framingham Study.
Ho KK, Pinsky JL, Kannel WB, Levy D.
Charles A. Dana Research Institute, Boston, Massachusetts.
Congestive heart failure has become an increasingly frequent
reason for hospital admission during the last 2 decades and
clearly represents a major health problem. Data from the
Framingham Heart Study indicate that the incidence of
congestive heart failure increases with age and is higher in
men than in women. Hypertension and coronary heart disease are
the two most common conditions predating its onset. Diabetes
mellitus and electrocardiographic left ventricular hypertrophy
are also associated with an increased risk of heart failure.
During the 1980s, the annual age-adjusted incidence of
congestive heart failure among persons aged > or = 45 years
was 7.2 cases/1,000 in men and 4.7 cases/1,000 in women,
whereas the age-adjusted prevalence of overt heart failure was
24/1,000 in men and 25/1,000 in women. Despite improved
treatments for ischemic heart disease and hypertension, the
age-adjusted incidence of heart failure has declined by only
11%/calendar decade in men and by 17%/calendar decade in women
during a 40-year period of observation. In addition,
congestive heart failure remains highly lethal, with a median
survival time of 1.7 years in men and 3.2 years in women and a
5-year survival rate of 25% in men and 38% in women.
PMID: 8376698 [PubMed - indexed for MEDLINE]
7. Mc Murray J, Hart W, Rhodes G. An evaluation of the cost of
heart failure to the National Health Service in the UK. Br J Med
Econ 1993; 285: 99–110.
Quality of life in early heart failure. The
study of men born in 1913.
Eriksson H, Svardsudd K, Larsson B, Welin L, Ohlson LO,
Tibblin G, Wilhelmsen L.
Department of Medicine, Ostra Hospital, Sweden.
To see whether well-being and quality-of-life are affected in
congestive heart failure (CHF), a number of health variables,
self-assessed and objectively measured, were estimated among
67-year-old men sampled from the general population of
Gothenburg, Sweden. Based on history, physical examination and
drug treatment, 407 men were studied and grouped into 4 stages
of CHF, ranging from no signs or symptoms of CHF to advanced
CHF. Men with CHF had more of other cardiovascular disease
manifestations, utilized more health care, and reported less
well-being and a higher rate of self-assessed disability than
men with no CHF. These quality-of-life changes were found not
only in the overt cases but also in early CHF. Regardless of
CHF stage, quality-of-life seemed more affected in men on drug
treatment, compared with those not treated.
PMID: 3222587 [PubMed - indexed for MEDLINE]-
Comment in:
Survival after the onset of congestive
heart failure in Framingham Heart Study subjects.
Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D.
Cardiovascular Division, Charles A. Dana Research Institute,
Boston, MA.
BACKGROUND. Relatively limited epidemiological data are
available regarding the prognosis of congestive heart failure
(CHF) and temporal changes in survival after its onset in a
population-based setting. METHODS AND RESULTS. Proportional
hazards models were used to evaluate the effects of selected
clinical variables on survival after the onset of CHF among
652 members of the Framingham Heart Study (51% men; mean age,
70.0 +/- 10.8 years) who developed CHF between 1948 and 1988.
Subjects were older at the diagnosis of heart failure in the
later decades of this study (mean age at heart failure
diagnosis, 57.3 +/- 7.6 years in the 1950s, 65.9 +/- 7.9 years
in the 1960s, 71.6 +/- 9.4 years in the 1970s, and 76.4 +/-
10.0 years in the 1980s; p < 0.001). Median survival after
the onset of heart failure was 1.7 years in men and 3.2 years
in women. Overall, 1-year and 5-year survival rates were 57%
and 25% in men and 64% and 38% in women, respectively.
Survival was better in women than in men (age-adjusted hazards
ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality
increased with advancing age in both sexes (hazards ratio for
men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio
for women, 1.61 per decade of age; 95% CI, 1.37-1.90).
Adjusting for age, there was no significant temporal change in
the prognosis of CHF during the 40 years of observation
(hazards ratio for men for mortality, 1.08 per calendar
decade; 95% CI, 0.92-1.27; hazards ratio for women for
mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26).
CONCLUSIONS. CHF remains highly lethal, with better prognosis
in women and in younger individuals. Advances in the treatment
of hypertension, myocardial ischemia, and valvular heart
disease during the four decades of observation did not
translate into appreciable improvements in overall survival
after the onset of CHF in this large, unselected population.
PMID: 8319323 [PubMed - indexed for MEDLINE]-
Natural history and patterns of current
practice in heart failure. The Studies of Left Ventricular
Dysfunction (SOLVD) Investigators.
Bourassa MG, Gurne O, Bangdiwala SI, Ghali JK, Young JB,
Rousseau M, Johnstone DE, Yusuf S.
Montreal Heart Institute, Montreal, Quebec, Canada.
A total of 6,273 consecutive relatively unselected patients
with heart failure or left ventricular dysfunction, or both
(mean age 62 +/- 12 years, mean ejection fraction 31 +/- 9%),
were enrolled in the Studies of Left Ventricular Dysfunction
(SOLVD) Registry over a period of 14 months. All patients were
followed up for vital status and hospital admissions at 1
year. Ischemic heart disease was the underlying cause of
failure or dysfunction in approximately 70% of patients,
whereas hypertensive heart disease was considered to be
primarily involved in only 7%. There were striking differences
in the etiology of heart failure among blacks and whites: 73%
of whites had an ischemic etiology of failure versus only 36%
of blacks; 32% of blacks had a hypertensive condition versus
only 4% of whites. The total 1-year mortality rate was 18%;
19% of patients had hospital admissions for heart failure and
27% either died or had a hospital admission for congestive
heart failure during the 1st year of follow-up. Factors
related to 1-year mortality or hospital admission for
congestive heart failure included age, ejection fraction,
diabetes mellitus, atrial fibrillation and female gender.
There was no difference in mortality associated with
congestive heart failure among blacks and whites, but hospital
admissions for heart failure were more frequent in blacks.
Digitalis and diuretic agents were the drugs most often used
in these patients, who were often taking many medications in
relation to severity of congestive heart failure symptoms and
ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Types:
PMID: 8376685 [PubMed - indexed for MEDLINE]
11. Rich MW, Beckam V, Wittenberg C, Leven CL, Freedland KE, Carney
RM. A multidisciplinary intervention to prevent readmission of
elderly patients with congestive heart failure. N Engl J Med 1995;
333: 1190–1195.
Comment in:
Insights into the contemporary epidemiology
and outpatient management of congestive heart failure.
McAlister FA, Teo KK, Taher M, Montague TJ, Humen D, Cheung
L, Kiaii M, Yim R, Armstrong PW.
Division of General Internal Medicine, University of Alberta,
Edmonton, Canada.
OBJECTIVES: To evaluate the epidemiology, prognosis, and
patterns of practice in patients with chronic congestive heart
failure (CHF) treated and followed at a specialized clinic.
METHODS: Prospective cohort study of consecutive patients
referred to and followed up in a specialized heart failure
clinic between September 1989 and March 1996. RESULTS: Of the
628 patients referred, 566 were confirmed to have CHF. Mean
duration of follow-up was 518 +/- 490 days (range 1 to 2192
days). Vital status was available for 99.3% of patients. Mean
age at enrollment was 66 years, 68% were men, 67% had an
ischemic cause of heart disease, and 78% had systolic
dysfunction. Patients with preserved systolic function were
older, more often female, had higher mean systolic blood
pressures, and a lower prevalence of ischemic heart disease,
ventricular arrhythmias, or impaired renal function when
compared with those with systolic dysfunction (all P
</=.001). Although there was a significant negative trend
in survival with decreasing ejection fraction (P =. 03), the
survival experience of those with CHF and preserved systolic
function did not significantly differ from those with systolic
failure (P =.25). Multiple logistic regression analysis showed
increased mortality risk was associated with increasing age,
New York Heart Association class IV, ischemic cause of
disease, elevated serum creatinine level, use of diuretics,
and systolic dysfunction, whereas use of beta-blockers was
associated with reduced risk. CONCLUSIONS: Our data suggest
that a specialized outpatient clinic can improve practice
patterns in patients with CHF. The high mortality risk in CHF
with preserved systolic function suggests the need to find
efficacious (and effective) therapies for this condition.
PMID: 10385769 [PubMed - indexed for MEDLINE]-
Comment in:
The hibernating myocardium.
Rahimtoola SH.
Department of Medicine, University of Southern California
School of Medicine.
The hibernating myocardium refers to resting LV dysfunction
due to reduced coronary blood flow that can be partially or
completely reversed by myocardial revascularization and/or by
reducing myocardial oxygen demand. It is different from the
stunned myocardium. Methods for its detection are not yet
perfect. Hibernating myocardium has been demonstrated to be
present in several clinical subgroups of patients; however,
currently its full clinical presence and impact are not
adequately defined.
PMID: 2783527 [PubMed - indexed for MEDLINE]-
-
Medical and cellular implications of
stunning, hibernation, and preconditioning: an NHLBI workshop.
Kloner RA, Bolli R, Marban E, Reinlib L, Braunwald E.
Heart Institute, Good Samaritan Hospital, and University of
Southern California, Los Angeles 90017, USA.
Publication Types:
PMID: 9603540 [PubMed - indexed for MEDLINE]
15. Lopaschuk GD, Kozak R. Trimetazidine inhibits fatty acid oxidation
in rats. J Mol Cell Cardiol 1998; 30: abstr A124.
Therapeutic value of a cardioprotective
agent in patients with severe ischaemic cardiomyopathy.
Brottier L, Barat JL, Combe C, Boussens B, Bonnet J,
Bricaud H.
Hopital Cardiologique, Pessac, France.
Trimetazidine (TMZ) has been shown to have anti-ischaemic
properties improving exercise tolerance without haemodynamic
effects. A 6-month double-blind placebo-controlled study was
carried out in 20 patients, mean age 59 +/- 6 years, to
examine the benefit of adding 60 mg of TMZ vs placebo to the
classical therapy, excluding those previously treated with
calcium-antagonists, conversion enzyme inhibitors,
vasodilators and antiplatelet agents. All patients had severe
ischaemic cardiomyopathy, confirmed by coronary angiography;
six were in NYHA class IV; 14 in NYHA class III; four had mild
recurrent angina pectoris. assessment included clinical and
biological evaluation, electrocardiography (ECG), 24-h ECG
monitoring, cardiac volume evaluation with chest X-ray, left
ventricular fractional shortening by echocardiography, left
ventricular ejection fraction by radionuclide angiography.
Baseline characteristics were similar in placebo (11 patients)
and TMZ (nine patients) groups. Eighteen patients (nine in
each group) were followed up for 6 months. In eight patients
of the placebo group, treatment had to be modified (addition
of calcium antagonists: four patients, conversion enzyme
inhibitors: two patients; digitalics: one patient; diuretics:
one patient). In the TMZ group, digitalic therapy was
withdrawn in one patient and added in one patient (P less than
0.01). At 6 months, all TMZ group patients were free from
angina; dyspnoea was improved in all TMZ patients and in only
one placebo patient (P less than 0.001). Ejection fraction,
increased by 9.3% in the TMZ group and decreased by 15.6% in
the placebo group (P less than 0.018), CV decreased by 7% with
TMZ, increased by 4% with placebo. (P = 0.034).(ABSTRACT
TRUNCATED AT 250 WORDS)
Publication Types:
- Clinical Trial
- Controlled Clinical Trial
PMID: 2318223 [PubMed - indexed for MEDLINE]-
Effects of trimetazidine on heart rate
variability and left ventricular systolic performance in
patients with coronary artery disease after percutaneous
transluminal angioplasty.
Birand A, Kudaiberdieva GZ, Batyraliev TA, Akgul F, Usal A.
Cardiology Department, Cukurova University, Medical Faculty,
Balcali Hospital, Adana, Turkey.
Fifty-one patients (mean age 51.6 +/- 7.1 years) with
angiographically proven coronary artery disease (CAD) entered
the study. In 26 patients (Group I), trimetazidine treatment
started twenty-four hours after percutaneous transluminal
coronary angioplasty (PTCA). Another 25 patients (Group II)
without trimetazidine treatment were kept as controls. The
groups were comparable by age, gender, risk factors of CAD,
coronary anatomy, left ventricular performance, and heart rate
variability indices at baseline state. Power spectral analysis
of heart rate variability and two-dimensional and Doppler
echocardiographic examinations were performed before PTCA, and
twenty-four hours, ten days, thirty days, and three months
after PTCA. A statistically significant improvement of left
ventricular systolic performance (P < 0.001), augmentation
of the parasympathetic band of heart rate variability (P <
0.001), and decline of P1/P2 ratio (P < 0.01) were evident
in patients treated with trimetazidine, while no apparent
changes were observed in controls. The intergroup analysis
also showed marked difference between groups as recorded on
the day 30 and month 3 of observation (P < 0.001). During
follow-up period recurrences of angina pectoris and ischemia
were registered in Group II, while no evidence of ischemia was
discerned in Group I patients. In conclusion, trimetazidine
modulates the autonomic control of heart rate, ie, reduces
sympathetic overactivity and augments vagal influences,
improves left ventricular contractility, and diminishes the
clinical manifestations of ischemia in patients with CAD after
PTCA.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 9158385 [PubMed - indexed for MEDLINE]-
-
Effects of trimetazidine on ischemic left
ventricular dysfunction in patients with coronary artery
disease.
Lu C, Dabrowski P, Fragasso G, Chierchia SL.
Istituto Scientifico H. San Raffaele, Milan, Italy.
We studied 15 patients with chronic coronary artery disease
(13 men aged 62 +/- 8 years) undergoing dobutamine (5 to 40
microg/kg/min) echocardiography at the end of two 15-day
treatment periods with placebo and trimetazidine (20 mg 3
times daily) given in random order, according to a
double-blind, crossover design. Results show that
trimetazidine improves resting left ventricular function and
reduces the severity of dobutamine-induced ischemic myocardial
dysfunction.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 9781975 [PubMed - indexed for MEDLINE]
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