A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy (RAMP-DCM)

Recent data suggest that areas of fibrosis and hibernating myocardium develop in patients with non ischemic dilated cardiomyopathy. Ranolazine is a new drug, developed to releave symptoms of angina in patients with stable coronary disease that is not suitable for surgical or percutaneous revascularization. It has been shown that in patients with stable coronary disease Ranolazine improves myocardial perfusion as shown with myocardial nuclear imaging. The aim of this trial is to evaluate effects of ranolazine on myocardial perfusion in patients with dilated cardiomyopathy.

Recent data suggest that areas of fibrosis and hibernating myocardium develop in patients with non ischemic dilated cardiomyopathy. Ranolazine is a new drug, developed to releave symptoms of angina in patients with stable coronary disease that is not suitable for surgical or percutaneous revascularization. The main mechanism of action of Ranolazine is the inhibition of late I(Na) thus decreasing the Ca++ load in the cardiomyocites. Consequently oxygen consumption also decreases. It has also been shown that in patients with stable coronary disease Ranolazine improves myocardial perfusion as shown with myocardial nuclear imaging. The aim of this trial is to evaluate effects of ranolazine on myocardial perfusion in patients with dilated cardiomyopathy. Primary end-point: To determine wheather Ranolazine improves perfusion of the myocardium in patients with non-ischemic dilated cardiomyopathy. Secondary end-points: To determine wheather Ranolazine improves patients' NYHA functional class, excercise capacity, LV systolic and diastolic function and weather ranolazine affects supraventricular and ventricular arrhythmia occurance/frequency.

Initial dose is 375 mg bid. After 2 - 4 weeks the dose is increased to 500 mg bid and after another 2-4 weeks to 750 mg bid. In case of side effects the dose of the drug is to be decreased to the highest dose that the patient is still able to tolerate.

To determine wheather Ranolazine improves perfusion of the myocardium in patients with non-ischemic dilated cardiomyopathy assesed by myocardial nuclear imaging.

To determine wheather Ranolazine improves patients' LV systolic and diastolic function, assesed by LVEF, TDI, LV longitudinal strain and strain rate

To determine wheather Ranolazine affects the occurence of supraventricular and ventricular arrhythmia occurance/frequency using 24 holter monitor.

Inclusion Criteria: established diagnosis of non-ischemic dilated cardiomyopathy EF < 35% NYHA f.c. II - IV Optimal medical management > 6 months Age < 75 years and > 18 years Exclusion Criteria: known hypersensitivity to the medication age > 75 years or < 18 years EF > 35% renal insufficiency (GF < 30) liver dysfunction (liver tests > 3x the upper normal limit)) LQT syndrome drugs that affect CYP3A4 metabolism (azoles, macrolides, calcineurin inhibitors etc.) dementia active hemathological or malignant disease