The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension

The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension Patients in National Cardiovascular Center Harapan Kita Hospital Indonesia

The study will evaluate the effect of trimetazidine versus placebo in addition to standard pulmonary arterial hypertension regime on right ventricular function in pulmonary arterial hypertension patients.

Right ventricular dysfunction is the worst mortality predictor in pulmonary arterial hypertension (PAH). Recent study has described that approximately 25% of PAH patients will developed into right ventricular failure despite therapeutic reduction of pulmonary vascular resistance. Subsequently, several studies have shown that fatty acid accumulation in right ventricle was inversely correlated with right ventricular function in PAH patients. Several PAH animal studies have revealed that metabolic glucose oxidation impairment through increased aerobic glycolysis, mitochondrial dysfunction, and lipotoxicity play significant role in right ventricular failure. Moreover, several pulmonary hypertension animal studies have demonstrated the benefit of partial fatty acid inhibitor such as trimetazidine on right ventricle function. It was hypothesize that trimetazidine improved right ventricular function through indirect effect of increased glucose oxidation by blocking the Randle cycle. Therefore, we hypothesize that trimetazidine can improve right ventricular function in pulmonary arterial hypertension patients.

Inclusion Criteria:

• Pre-capillary Pulmonary Hypertension patients assessed by right heart catheterization
• Signed informed consent

Exclusion Criteria:

• Patient belonging to post-capillary, Isolated post-capillary, or combined post -capillary and pre-capillary pulmonary hypertension according to 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.
• Moderate to severe chronic pulmonary obstructive disease
• Right Ventricular Ejection Fraction > 45% assessed by cardiac magnetic resonance.
• Documented left ventricular dysfunction with left ventricular ejection fraction < 50% assessed by cardiac magnetic resonance.
• Severe renal impairment (Serum creatinine > 2.5 mg/dL, eGFR < 30ml/min/1.73 m^2, or routine dialysis treatment).
• Malignant arrhythmia such as total atrioventricular block or ventricular fibrillation or unstable ventricular tachycardia.
• Patients who are receiving or have been receiving any investigational drugs within 1 month before the baseline visit
• Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements
• Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
• Females who are lactating or pregnant or those who plan to become pregnant during the study
• Known Parkinson disease
• Known hypersensitivity to any of the drug formulation