Optimal Heart Failure Therapy Research Articles

Clinical Characteristics and Outcomes of Patients with Amphetamine-Associated Cardiomyopathy in South Auckland, New Zealand

Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood. Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified. Mean age at presentation was 40±10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end-diastolic dimension 6.8±1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22±8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure. Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high.

Inzidenz der Herzinsuffizienz rückläufig?

Evaluation of the heart failure (HF) incidence in Olmsted County (Minnesota/USA) revealed a decline from 316 per 100,000 in 2000 to 219 per 100,000 in 2010 equating to a relative reduction of 37.5 %. The decline in HF incidence was greater for HFrEF than for HFpEF (– 45 % vs. – 28 %) und smaller in men than in women (-29 % vs. – 43 %). Notebly, it was independent from age. The 1-year mortality rate was 20.2 %. Noncardiovascular causes were the predominent reasons for both mortality and hospitalizations. Neither mortality nor hospitalization rate declined over time. Sound data on the HF incidence are currently not available for Germany. However, the total number of HF-related hospitalizations increased during the period from 2000 to 2014. This phenomenon is most likely due to an increased prevalence secondary to optimized HF therapy and changes in demography with a higher HF hospitalization rate in elderly patients.

Rationale and Design of the Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy Study (LAPTOP-HF)

BackgroundDaily measurements of left atrial pressure (LAP) may be useful for guiding adjustments in medical therapy that prevent clinical decompensation in patients with severe heart failure (HF). Study DesignLAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced heart failure in which the safety and clinical effectiveness of a physician-directed patient self-management therapeutic strategy based on LAP measured twice daily by means of an implantable sensor will be compared with a control group receiving optimal medical therapy. The trial will enroll up to 730 patients with New York Heart Association functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide level, regardless of ejection fraction, at up to 75 investigational centers. Randomization to the treatment group or control group will be at a 1:1 ratio in 3 strata based on the ejection fraction (EF > or ≤35%) and the presence of a de novo CRT device indication. SummaryLAPTOP-HF will provide essential information about the role of implantable LAP monitoring in conjunction with a new HF treatment paradigm across the spectrum of HF patients.

Twenty-four-hour heart rate lowering with ivabradine in chronic heart failure: insights from the SHIFT Holter substudy.

Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of ivabradine and to determine effects of ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR. The 24-h Holter monitoring was performed at baseline and 8 months after randomization to ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR ≥70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 ± 10.0 b.p.m. with ivabradine, from 75.4 ± 10.3 b.p.m. (P < 0.0001), and by 1.2 ± 8.9 b.p.m. with placebo, from 74.8 ± 9.7 b.p.m. (P < 0.0001 for difference vs. ivabradine). HR reduction with ivabradine was similar in resting office and in 24-h, awake, and asleep recordings, with beneficial effects on HR variability and no meaningful increases in supraventricular or ventricular arrhythmias. At 8 months, 21.3% on ivabradine vs. 8.5% on placebo had ≥1 episode of HR <40 b.p.m. (P < 0.0001). No episode of HR <30 b.p.m. was recorded; 3 (1.2%) patients had RR intervals >2.5 s on ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking ivabradine. Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.

Cardiovascular Magnetic Resonance GUIDEd management of mild-moderate left ventricular systolic Heart Failure (CMR GUIDE HF): study protocol for a randomised controlled trial

Background Current heart failure guidelines recommend insertion of implantable cardiac defibrillators (ICD) for primary prevention of sudden cardiac death (SCD) in patients whose left ventricular ejection fraction is (LVEF) ≤ 35% on maximally tolerated medical therapy. However, the majority of sudden cardiac death (SCD) in patients with heart failure occurs in those with mild-moderate systolic heart failure (LVEF 36%-50%) who currently do not qualify for an ICD. At present, our tools to reliably risk stratify patients with mild-moderate heart failure to predict the likelihood of SCD are limited. Recent data however suggest that ventricular scar and/or replacement fibrosis, reliably identified on Cardiac Magnetic Resonance Imaging (CMR), forms a substrate for malignant arrhythmia, thus potentially identifying a group at increased risk of SCD. The primary aim of the Cardiovascular Magnetic Resonance GUIDE dm anagement of mild-moderate left ventricular systolic Heart Failure (CMR GUIDE HF) trial is to test the hypothesis that among patients with mild-moderate heart failure, a routine CMR guided management strategy of implantable defibrillator (ICD) insertion is superior to a conservative strategy of standard care. Methods A multi-centre randomized control trial based in Australia and Europe, enrolling 428 patients with mild to moderate left ventricular systolic dysfunction, on optimal heart failure therapy. Participants will be recruited through heart failure clinics and echocardiography databases to undergo CMR assessment for myocardial scar and fibrosis. The study will have two arms: Firstly, those with myocardial scar/fibrosis will be enrolled into a prospective, blocked, randomized control trial to receive either primary prophylaxis ICD therapy or an implantable loop recorder (ILR). Secondly, a further 521 patients without scar/fibrosis will be enrolled into an observational registry. Follow-up with be at 3, 6, 12, 24 and 36 months for the implant groups (ICD and ILR) and at 12, 24 and 36 months for the registry group. Results

Statin withdrawal in stable heart failure patients results in no change in clinical status or quality of life

Background: The current role of statins in heart failure with reduced ejection fraction (HFREF) is unclear. We therefore sought to investigate the effect of statin withdrawal in such patients, while taking optimal doses of proven heart failure medications. Methods: This was a prospective, randomised, single-blind, placebo-controlled, two-arm cross-over trial. Participants were randomised to either statin continuation (“statin on”) or unmatched placebo (“statin off”) and crossed over at 3 months. Study statin was the participants’ regular statin at their usual dose. Standard HF clinical status and quality of life (QoL) endpoints were evaluated. Groups were compared using Student's paired t-test. Results: The 13 study participants had a mean age of 64±11 years, 62% male, duration of HF was 7.7±5.7 years, and mean ejection fraction was 38.1±10.4%. Aetiology of HF was idiopathic (12) and ischaemic (1). Compared with taking statin, withdrawal of statin resulted in no significant changes in plasma brain natriuretic peptide (BNP, statin on: 130±49 vs statin off: 129±50ng/L, p=0.92) and no change in 6 minute walk distance (statin on: 455±52 vs statin off: 450±55m, p =0.80). No changes in QoL measures were observed, including Minnesota Living with HF score (statin on: 32±7 vs statin off: 31±9, p=0.41), Cardiac Depression Score (statin on: 77±6 vs statin off: 81±6, p=0.44) and SF-36 (statin on: 93±5 vs statin off: 94±5, p=0.25). Conclusions: Withdrawal of statins in stable HFREF patients receiving optimal background heart failure therapy did not alter HF clinical status including plasma BNP levels, submaximal exercise capacity or quality of life measures.

Long-term effects of pentoxifylline in heart failure therapy

The aim of the present study is to investigate the effects of pentoxifylline on left ventricular ejection fractions (EF) and volumes, New York Heart Association (NYHA) functional class, left ventricular diastolic parameters and hospitalization for heart failure in patients with ischemic or non-ischemic cardiomyopathy. A total of 60 patients were randomised to either peroral 1200 mg/day pentoxifylline or control group. All patients were on optimal heart failure therapy and their EF was <40% by transthoracic echocardiography. The patients were followed up for 12 months. Twenty-one patients (70%) in pentoxifylline group and 20 (66.7%) in control group completed the study. Baseline and 12 months’ end-diastolic volume, end-systolic volume, EF and NYHA class were as follows in pentoxifylline group; 160.5±51.3 mL vs 156.6±43.1 mL, 109.1±40 mL vs 106.1±33.4 mL, 32.4±5.7% vs 33.2±5.2%, 2.4±0.5 vs 2.2±0.5, p=0.5411, 0.5257, 0.4099 and 0.1037; respectively. There were also no difference in baseline and follow-up diastolic parameters. Mean hospitalization numbers for heart failure were similar between groups (1.26±0.71 vs 1.60±1.04, p=0.1717). Contrary to previous reports, no beneficial effect of pentoxifylline was observed on clinical or echocardiographic parameters. J. Exp. Clin. Med., 2014; 31:19-23

Long-Term Effects of AAV1/SERCA2a Gene Transfer in Patients With Severe Heart Failure

Rationale: The Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease (CUPID 1) study was a phase 1/phase 2 first-in-human clinical gene therapy trial using an adeno-associated virus serotype 1 (AAV1) vector carrying the sarcoplasmic reticulum calcium ATPase gene (AAV1/SERCA2a) in patients with advanced heart failure. The study explored potential benefits of the therapy at 12 months, and results were previously reported. Objective: To report long-term (3-year) clinical effects and transgene expression in the patients in CUPID 1. Methods and Results: A total of 39 patients with advanced heart failure who were on stable, optimal heart failure therapy were randomized to receive intracoronary infusion of AAV1/SERCA2a in 1 of 3 doses (low-dose, 6×10 11 DNase-resistant particles; mid-dose, 3×10 12 DNase-resistant particles; and high-dose, 1×10 13 DNase-resistant particles) versus placebo. The following recurrent cardiovascular and terminal events were tracked for 3 years in all groups: myocardial infarction, worsening heart failure, heart failure–related hospitalization, ventricular assist device placement, cardiac transplantation, and death. The number of cardiovascular events, including death, was highest in the placebo group, high but delayed in the low- and mid-dose groups, and lowest in the high-dose group. Evidence of long-term transgene presence was also observed in high-dose patients. The risk of prespecified recurrent cardiovascular events was reduced by 82% in the high-dose versus placebo group ( P =0.048). No safety concerns were noted during the 3-year follow-up. Conclusions: After a single intracoronary infusion of AAV1/SERCA2a in patients with advanced heart failure, positive signals of cardiovascular events persist for years.

Multidrug and optimal heart failure therapy prescribing in older general practice populations: a clinical data linkage study

ObjectiveTo investigate multidrug therapy in the cardiovascular disease (CVD) population and whether it was associated with suboptimal drug prescribing in heart failure (HF).DesignA population-based cross-sectional clinical data linkage study.SettingThe clinical...

Optimal heart failure therapy and successful electrical cardioversion in heart failure patients with first detected atrial fibrillation: favorable effect on rehospitalization

Optimal heart failure therapy and successful electrical cardioversion in heart failure patients with first detected atrial fibrillation: favorable effect on rehospitalization

Intact skeletal muscle mitochondrial enzyme activity but diminished exercise capacity in advanced heart failure patients on optimal medical and device therapy

A skeletal myopathy, perhaps attributable to neuro-endocrine excitation or disuse, has been described in heart failure (HF) patients, and is thought to contribute to their exercise limitation. Our purpose was to assess biochemical and morphometric characteristics of skeletal muscles of HF patients on optimal HF therapy. A secondary purpose was to explore the effects of clonidine, which interrupts the neuro-endocrine excitation, on these same muscle characteristics. Eleven HF patients (50.8 ± 3.4 years, peak VO2 11.6 ± 2.5 ml/kg/min) underwent two vastus lateralis biopsies (pre/post clonidine). Baseline values were compared to biopsies in 11 age-matched, healthy controls. Scatter plots of individual values for each mitochondrial enzyme revealed almost complete overlap between HF and control groups; mean values, although tending to be greater in controls versus HF patients, were not significantly different. The proportion of type 1 fibers was diminished in 10 of 11 patients. There was no difference in any of the variables after 3 months clonidine versus placebo. In HF patients treated with optimal medical and device therapy, characteristic abnormalities of mitochondrial enzyme activity are not found, but muscle fiber type shifts are present. The remaining severe impairment in exercise capacity cannot be attributed to mitochondrial abnormalities.

Dual Renin–angiotensin System Blockade with Aliskiren in Patients with Heart Failure, with or without Diabetes Mellitus: Insights from ALOFT

Aims: Because of recent concerns about the safety of dual renin–angiotensin–aldosterone system (RAAS) blockade with a renin inhibitor in patients with hypertension and diabetes mellitus (DM), we have conducted a retrospective analysis of the effect of this treatment in patients with and without diabetes in the Aliskiren Observation of Heart Failure Treatment study (ALOFT). Methods and results: In ALOFT, patients with stable New York Heart Association class II–IV heart failure (HF) and plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL were randomised to Aliskiren 150 mg/d or placebo, added to optimal HF therapy, for 12 weeks. In addition to greater central adiposity and dysglycaemia, HF patients with DM had more oedema, elevated blood urea and urinary albumin/creatinine ratio, and increased plasma renin activity (PRA) and concentration. They also had evidence of greater left ventricular hypertrophy, increased collagen turnover, left atrial enlargement and mitral regurgitation. Aliskiren had similar effects in patients with and without DM, reducing BNP, NT proBNP and PRA equally in both groups. The incidence of adverse effects related to hypotension, hyperkalaemia and renal dysfunction was low in each patient group and was not increased, significantly, with Aliskiren. Conclusions: HF patients with DM have elevated PRA compared to those without DM. Aliskiren causes equivalent neurohumoral suppression in HF patients with and without DM.

Circulating Proangiogenic Progenitor Cells Independently Predict Functional Capacity in Heart Failure Patients

BackgroundEndothelial dysfunction is an important underlying mechanism in the pathophysiology of heart failure (HF). Circulating proangiogenic progenitor cells (CPCs) are endothelial and hematopoietic progenitor cells involved in the process of vasculogenesis repairing damaged and dysfunctional endothelium. Our aim was to evaluate whether an independent association exists between CPCs and functional capacity in HF patients. MethodsThis cross-sectional study included 121 ambulatory HF patients with reduced left ventricular ejection fraction seen at a single institution. We analyzed the association between CPCs, measured as circulating CD34+VEGFR2+ cells and early outgrowth colony forming units (EO-CFUs), and patients’ functional capacity measured as peak oxygen consumption (V˙o2). ResultsThe mean age was 55 ± 11 years; 96 patients (79%) were male. Forty-three patients (36%) had ischemic cardiomyopathy. Patients were taking optimal HF therapy (96% taking β-blockers, 91% taking renin-angiotensin inhibitors, and 60% had an implanted internal cardiac defibrillator). In univariate analyses, CD34+VEGFR2+ cells were inversely associated with peak V˙o2 (P = 0.02) while EO-CFUs showed a positive association with peak V˙o2 (P < 0.01). These associations persisted after adjusting for sex, New York Heart Association class, body mass index, diabetes, cardiac resynchronization therapy, ischemic cardiomyopathy and b-type natriuretic peptide levels. ConclusionsCultured EO-CFUs may represent a measure of functional capacity and vasculogenesis potential while CD34+VEGFR2+ cells represent the mobilized cells in response to endothelial damage. Our study suggests that lower EO-CFUs (worse cell function) and higher CD34+VEGFR2+ cells are associated with poorer functional capacity.

The predictive value of QRS duration in response to levosimendan therapy in patients with decompensated heart failure

Purpose We aimed to investigate the role of QRS duration on the surface electrocardiogram (ECG) in predicting response to levosimendan therapy in patients with acute systolic heart failure.Methods Patients with an ejection fraction (EF) lower than 35% who required intravenous inotropic support despite optimal heart failure therapy were included in this study. Patients were divided into two groups according to QRS durations on ECG. Group 1 (n = 16) included patients with a QRS duration equal to or shorter than 120 ms and group 2 (n = 14) included patients with a QRS duration longer than 120 ms. New York Heart Association (NYHA) functional class, plasma BNP levels and echocardiographic measurements were compared within and between groups before and after the infusion.Results In both groups statistically significant improvement was observed in NYHA class, plasma BNP levels and left ventricular end-systolic diameter after the levosimendan infusion compared to baseline (P < 0.025). In addition, in group 1 patients, left atrial diameter, left atrial volume, left ventricular end-diastolic diameter, left ventricular end-diastolic volume, left ventricular end-systolic volume (LVESV), left ventricular EF, mitral E velocity, mitral annular Aa and Sa parameters improved after the infusion compared to the baseline values (P < 0.025). Comparison of both groups revealed improvement of NYHA class, an increase of left ventricular EF and a signficant decrease of LVESV after levosimendan in group 1 (P < 0.05).Conclusion QRS duration on ECG may be used as a practical bedside indicator in estimating short-term response to levosimendan therapy.

Neurohumoral effects of aliskiren in patients with symptomatic heart failure receiving a mineralocorticoid receptor antagonist: the Aliskiren Observation of Heart Failure Treatment study

We evaluated the influence of concomitant mineralocorticoid receptor antagonists (MRAs) on the safety and neurohumoral effects of a direct renin inhibitor in the ALiskiren Observation of Heart Failure Treatment (ALOFT) study. Patients with stable New York Heart Association class II-IV heart failure (HF), plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL, and treated with an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker) and β-blocker were randomized to once-daily, double-blind treatment with aliskiren 150 mg or placebo, added to optimal HF therapy, for 12 weeks. Safety, tolerability, and effects of aliskiren on neurohumoral biomarkers were assessed in patients who received (MRA+) and did not receive (MRA-) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n = 52; placebo, n = 49). Mineralocorticoid receptor antagonist status did not affect the ability of aliskiren 150 mg, added to standard HF therapy, to lower BNP, N-terminal proBNP, plasma renin activity, and urinary aldosterone. For example, the end-of-study to baseline ratio of geometric mean for BNP was: MRA+ group: aliskiren 0.68 [95% confidence interval (CI) 0.47, 0.98], placebo 0.85 (0.58, 1.24); MRA- group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P= 0.720. The incidence of pre-specified adverse events (renal dysfunction, symptomatic hypotension, and hyperkalaemia) was low, and there were no significant differences between aliskiren and placebo in either MRA subgroup. Aliskiren 150 mg added to standard HF therapy was well tolerated over 12 weeks and provided beneficial changes in neurohumoral biomarkers regardless of concomitant MRA treatment.

Left Atrial Remodelling and Reverse Remodelling with Therapy in New-presentation Idiopathic Dilated Cardiomyopathy

Background: There is an established association betweenadverse left atrial (LA) remodellingandheart failure, however such evidence focuses on an advanced heart failure population. The aim of this study was to explore the relationship between LA structure, function and therapeutic response following optimal heart failure therapy in patients with newly diagnosed idiopathic dilated cardiomyopathy (DCM). Methods: Sixty-eight patients were studied a median of 13 days following a first presentation for DCM, and compared with 19 healthy controls. Participants underwent transthoracic echocardiography and cardiopulmonary exercise testing at baseline and amedian fivemonths later whilst receiving optimal heart failure therapy. LA strain was evaluated by speckle-tracking. Results: Median patient symptom duration prior to enrolment was nine weeks (interquartile range 2–26 weeks). Significant baseline adverse LA remodelling (LA v p 1 p h L 3 ( T f t a r

Heart failure and personalized medicine

Personalized medicine is a form of medicine that uses the patient's genomic information to improve diagnosis, prevention and therapy. In this review we discuss the personalized management of heart failure, from monogenic disorders, to modifier genes and pharmacogenomics. Monogenic disorders causing heart failure are cardiomyopathies. In this disease, recent guidelines assist the clinician in molecular diagnostics, genetic counseling and therapeutic choices. Several lines of evidence suggest the existence of common polymorphic variants of genes that modify the susceptibility to heart failure (modifier genes). A candidate gene approach has shown that common genetic variants of the renin-angiotensin-adrenergic pathway can also influence heart failure and may be associated with different outcomes. However, still little is known regarding this and it is expected that more advanced high throughput technologies will allow the discovery of a number of novel modifier genes that could be used for prognostic profiling and development of novel therapeutics. Finally, pharmacogenomics of heart failure appears very promising. Common genetic variants of beta-adrenergic receptors, alpha-adrenergic receptors and endothelin receptors, among others, significantly alter the response to heart failure therapy. This knowledge could be used to personalize and optimize heart failure therapy based on the patient's genetic profile. Whereas the advances in technologies will continue to transition personalized medicine from research to the clinical setting, physicians, and in particular cardiologists, need to reshape clinical diagnostics paradigms, learn how to use new genomic information to change management decisions, and provide the patients with appropriate education and management recommendations.

Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure

Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure

Effect of Medical Therapy on Left Ventricular Ejection Fraction in Patients With Systolic Heart Failure and Narrow QRS Duration With and Without Ischemic Heart Disease and Left Ventricular Mechanical Dyssynchrony

We studied 99 consecutive patients with class III-IV systolic heart failure with a left ventricular ejection fraction (LVEF) < or =35% and a QRS duration <120 milliseconds. Patients with cardiac resynchronization therapy were excluded. Echocardiography was performed in all patients before and after optimal standard heart failure therapy. The septal-to-posterior wall motion delay (SPWMD) > or =130 milliseconds on echocardiogram was defined as left ventricular mechanical dyssynchrony (LVMD). Sixty-nine of 99 patients (70%) had ischemic heart disease. During follow-up of 15.2 +/- 9.8 months, LVEF improvement > or =15% was greater patients in nonischemic group (50%, 15/30) than in ischemic group (9%, 6/69; P < 0.001). After adjustment for age, gender, and clinical and echocardiographic characteristics, ischemic heart disease and grade of coronary disease were persistently related to LVEF improvement > or =15% (P = 0.03 and 0.02, respectively). Twenty of 99 patients (20%) had SPWMD > or =130 milliseconds (LVMD group), and 79 of 99 patients (80%) had SPWMD <130 milliseconds (non-LVMD group). LVEF increased in both groups (P = 0.005) during follow-up, but the percentage of patients with LVEF improvement > or =15% in LVMD was greater compared with patients without LVMD (40% versus 16%, respectively, P = 0.03). In conclusion, the improvement of LVEF in patients with systolic heart failure and narrow QRS was greater in patients with nonischemic heart disease and LVMD compared with patients with ischemic heart disease and absence of LVMD during medical therapy without cardiac resynchronization therapy.

Improved left and right ventricular functions with trimetazidine in patients with heart failure: a tissue Doppler study

Downregulation of glucose and fatty acid oxidation occurs in heart failure (HF). Trimetazidine reduces fatty acid oxidation and increases glucose oxidation. In this single-blind study, trimetazidine, 20 mg three times per day (n = 51) or placebo (n = 36) was added to treatment of 87 HF patients receiving optimal HF therapy. Etiology of heart failure was coronary artery disease in 35 patients (68.6%) in the trimetazidine group and 22 (62.9%) in the placebo group. Fourteen (27.5%) patients in the trimetazidine group and 11 (31.4%) patients in the placebo group had diabetes. Peak systolic velocity (Vs), and the peak early diastolic (Vd) and late diastolic (Va) velocities of various segments left and right ventricles (RV) were obtained with tissue Doppler imaging (TDI) and averaged. Patients were re-evaluated three months later. Significant increases in mean left ventricular ejection fraction (LVEF) (33.3% +/- 5.6% to 42.4% +/- 6.3%, P < 0.001 and 30.6% +/- 8.2% to 33.2% +/- 6.6%, P = 0.021) and LV and RV myocardial velocities and mitral and tricuspid annular TDI velocities were observed in both groups. However, compared to placebo, increments in LVEF (9.1% +/- 4.2% vs. 2.5% +/- 1.4%, P < 0.001) and myocardial velocities were significantly higher with trimetazidine (P < 0.001 for LV Vs, Vd, Va; P = 0.035 for RV Vd; and P < 0.001 for RV Va and Vs). Increase in LVEF with trimetazidine was significantly correlated with presence of diabetes (r = 0.524, P < 0.001). With trimetazidine LVEF increased significantly more in diabetic patients compared to nondiabetics (P < 0.001). Also, patients having both diabetes and ischemic HF tended to have greater improvement in LVEF compared to ischemic HF patients without diabetes (P = 0.063). Addition of trimetazidine to current treatment of HF, especially for those who are diabetic, may improve LV and RV functions.