Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure

Fragasso, Gabriele; Perseghin, Gianluca; Cobelli, Francesco De; Esposito, Antonio; Palloshi, Altin; Lattuada, Guido; Scifo, Paola; Calori, Giliola; Maschio, Alessandro Del; Margonato, Alberto

doi:10.1093/eurheartj/ehi816

Cited by 211 publications

(159 citation statements)

References 39 publications

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“…In fact, artificial elevation of FFA in diabetic hearts reduces cardiac efficiency via an oxygen waste for noncontractile purposes (26). This scenario was supported by our finding in patients with heart failure in whom treatment with Trimetazidine, a partial fatty acids oxidation inhibitor, induced improvement of the LV function and PCr/ ATP ratio (27), likely switching the energy substrate preference (28). Hence, we may speculate that in patients with overt type 2 diabetes, the increased FFAs availability, pushing their own oxidative disposal, induces a detrimental and proportional effect on the PCr-to-ATP ratio (6).…”

Section: Effects Of Hemodynamic and Metabolic Variables On The Correlmentioning

confidence: 59%

Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance

Perseghin

Ntali²,

Cobelli

et al. 2007

Diabetes Care

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OBJECTIVE -Perturbations in cardiac energy metabolism might represent early alterations in diabetes preceding functional and pathological changes. We evaluated left ventricular (LV) structure/geometry and function in relation to energy metabolism and cardiovascular risk factors in overweight/obese men using magnetic resonance techniques. RESULTS -LV mass increased across quartiles of BMI; meanwhile, the volumes did not differ. Parameters of LV systolic and diastolic function were not different among quartiles. The phosphocreatine-to-ATP ratio was reduced across increasing quartiles of mean Ϯ SD BMI (2.25 Ϯ 0.52, 1.89 Ϯ 0.26, 1.99 Ϯ 0.38, and 1.79 Ϯ 0.29; P Ͻ 0.006) in association with insulin sensitivity (computer homeostasis model assessment 2 model); this relation was independent of age, BMI, blood pressure, wall mass, HDL cholesterol, triglycerides, smoking habits, and metabolic syndrome. RESEARCH DESIGN AND METHODSCONCLUSIONS -Abnormal LV energy metabolism was detectable in obese men in the presence of normal function, supporting the hypothesis that metabolic remodeling in insulin resistant states precedes functional and structural/geometrical remodeling of the heart regardless of the onset of overt hyperglycemia. Diabetes Care 30:1520-1526, 2007C ardiovascular disease is the leading cause of death in patients with type 2 diabetes (1,2). The existence of a diabetic cardiomyopathy distinct from ischemic injury was confirmed, but the challenge of recognizing its specific features remained unresolved because diabetes could also provoke cardiac damage via coronary macrovascular disease, autonomic dysfunction, and coronary microvascular disease (3). It was proposed that altered metabolism and impaired insulin action in the heart might be cause and consequence of altered cardiac function (4) and that metabolic remodeling in diabetes might precede, cause, and sustain the functional and structural/geometrical remodeling of the heart (5). In keeping with this hypothesis, cardiac energy metabolism was found to be abnormal in patients with type 2 diabetes despite the lack of major cardiac dysfunctions (6) or the presence of diastolic dysfunction (7). Those studies were performed in middleage individuals (52-57 years old) in whom diabetes was diagnosed 1 (7) to 3 (6) years earlier. Therefore, the question whether the alterations of cardiac energy metabolism were due to the hyperglycemic state itself or whether they were secondary to the metabolic features characterizing the prediabetic state remained unanswered.This study was undertaken to assess whether obesity was associated with impaired cardiac structure/geometry, function, and energy metabolism and to establish whether these potential alterations were associated with the cardiovascular and metabolic risk factors accompanying insulin resistance conditions. RESEARCH DESIGN AND METHODSWe selected 81 apparently healthy men with no previous history of diabetes, hypertension, dyslipidemias, coronary, cerebral, or peripheral vascular events, no history of dilated cardiomy...

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Section: Effects Of Hemodynamic and Metabolic Variables On The Correlmentioning

confidence: 59%

Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance

Perseghin

Ntali²,

Cobelli

et al. 2007

Diabetes Care

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“…Inhibition of this enzyme decreases fatty acid oxidation, which then stimulates glucose oxidation and inhibits glycolysis. These TMZ-induced chain effects increase the creatine phosphate/ATP ratio by a significant 33%, indicating preservation of myocardial high-energy phosphate levels and ion pump function, which translates into improved cardiac efficiency and reduced symptoms [38]. These effects no doubt account for the real-world benefits our study has shown with add-on TMZ …”

Section: Discussionmentioning

confidence: 58%

Real-world Evidence for the Antianginal Efficacy of Trimetazidine from the Russian Observational CHOICE-2 Study

Глезер

2017

Adv Ther

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Introduction: The guidelines recommend a beta-blocker or calcium channel blocker as the first-line medication for angina, supplemented by other agents for additional symptoms. One such agent is trimetazidine (TMZ), which has been shown to reduce the frequency of anginal episodes and improve exercise performance without affecting haemodynamic parameters. However, extensive real-world evidence for its efficacy in combination with first-line therapies has been lacking. Methods: The aim of this large-scale, Russian, multicentre, 6-month, open-label, prospective observational study was to assess the effect of adding TMZ modified release 35 mg bid to background antianginal therapy in the real--world clinical setting. Results: The study included 896 patients: 54% women, aged 29-90 years (42.6% [65 years), 63% with class II angina, and receiving beta-blockers alone or in combination (93%). Add-on TMZ reduced angina frequency and

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“…In patients with ischemic cardiomy opathy, a previous acute myocardial infarction, multivessel coronary artery disease and ventricular dysfunction (ejection fraction 33%), trimetazidine therapy (2 months) improved contractile response to lowdose dobutamine in chronically dysfunc tional myocardium. Fragasso et al demonstrated that trimetazidine restored the energetic status of myocardium in patients with heart failure [18]. In these patients, the phosphocreatine and adenosine triphosphate (PCr:ATP) ratio, an important index of energetic status, was similar to that in healthy individuals and significantly improved compared with that in a placebo group.…”

Section: Editorialmentioning

confidence: 97%

Trimetazidine: The Future of Cardiac Function?

Napoli

Taccardi

2009

Future Cardiol.

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Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure

Abstract: Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidine-induced increase in the PCr/ATP ratio, indicating preservation of the myocardial high-energy phosphate levels.

Cited by 211 publications

References 39 publications

Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance

Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance

Real-world Evidence for the Antianginal Efficacy of Trimetazidine from the Russian Observational CHOICE-2 Study

Trimetazidine: The Future of Cardiac Function?

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