Number 26, 2005
Cardiovascular effects of exercise

Sustained benefit of trimetazidine adjunct to standard treatment in severe heart failure

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Mario Marzilli
Department of Cardiology, University of Siena, Italy
Correspondence: Mario Marzilli, Department of Cardiology, University of Siena, Policlinico Le Scotte, V. Le Bracci, 53100 Siena, Italy. E-mail: marzilli@unisi.it

Case report
The patient was an 81-year-old gentleman, admitted to hospital on 2 January 2004 because of heart failure (New York Heart Association [NYHA] Class III).
He had been taking hypotensive drugs for more than 40 years. In the year 2000 he was first admitted to hospital for a syncope and discharged with a diagnosis of chronic obstructive lung disease and supraventricular tachycardia.
In January 2003, he began to complain of chest pain and dyspnea on effort. Since December 2003, chest pain had also occurred at rest. A myocardial perfusion scintigraphy obtained in December 2003 showed a marked reduction of tracer uptake in the anterolateral, apical, and inferoapical segments, with limited recovery at rest, consistent with a previous silent myocardial infarction.
On 2 January 2004, he was again admitted to hospital for worsening symptoms of heart failure and chest pain. At the time of admission, he was taking angiotensin-converting enzyme (ACE) inhibitors, nitrates, diuretics, digitalis, and antiplatelet agents.
The electrocardiogram (ECG) showed inverted T waves on the lateral leads (Figure 1).

Discussion
We report the case of a patient who had survived a silent myocardial infarction at the age of 81 years and had developed a severe ventricular dysfunction.
After acute myocardial infarctions, patients often experience a progressive deterioration of left ventricular function that eventually leads to overt heart failure. This phenomenon, known as left ventricular remodeling, is poorly understood and does not have a specific treatment. Myocardial revascularization may improve symptoms in a patient with postischemic dysfunction and viable myocardium.
In this particular patient, the severity and extension of the coronary lesions, together with associated illnesses and advanced age, made the risk of a revascularization procedure excessive.
Having excluded a myocardial revascularization, we decided to optimize the medical treatment by adding a metabolic agent, trimetazidine, to the standard combination of drugs. Trimetazidine is a cardioprotective agent that shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by selective inhibition of mitochondrial 3-ketoacyl coenzyme A thiolase [1]. Because of its purely metabolic mechanism of action, trimetazidine does not interfere with heart rate and arterial pressure, and has minimal, if any, side effects and optimal patients compliance [2,3].
Trimetazidine is commonly used as an antianginal agent and has been shown to reduce the number of ischemic attacks and to improve exercise tolerance in patients with chronic ischemic heart disease, including those with diabetes, patients who have undergone revascularization, and patients with angina resistant to ß-blockers and calcium channel blockers [4–7]. It has been shown to improve ejection fraction in patients with dilated cardiomyopathy and to improve the response to dobutamine stress in postischemic ventricular dysfunction [8–10].
The patient we report here appeared to be an ideal candidate for a metabolic approach to the presence of both angina and dyspnea on effort, both resistant to standard treatment. Given the severity of his condition, we decided to use a dose of trimetazidine double that recommended. After the addition of high-dose trimetazidine to his medication regimen, a progressive and significant improvement in symptoms was reported by the patient; furthermore, the amelioration in symptoms preceded objective evidence of improved ventricular function. Prolonged treatment with trimetazidine was associated with further improvement in exercise tolerance and quality of life, and with recovery of contractile function that was evident at echocardiography. ECG changes consistent with attenuation of myocardial ischemia were also observed after 10 months of treatment.

Conclusion
This case demonstrates the benefit of trimetazidine as adjunct to standard treatment in an elderly patient with severe ischemic left ventricular dysfunction, and confirms the good tolerability of this agent even at high dosage. ?

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REFERENCES

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