Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross-over trial.

AIMS: Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. METHODS AND RESULTS: The DoPING-HFpEF trial was a phase II single-centre, double-blind, placebo-controlled, randomized cross-over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2-week wash-out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2 ); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI -2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6-min walking distance (mean change of -6 [95% CI -18, 7] m vs. -5 [95% CI -22, 22] m, respectively, P = 0.93), N-terminal pro-B-type natriuretic peptide (5 (-156, 166) ng/L vs. -13 (-172, 147) ng/L, P = 0.70), overall quality-of-life (KCCQ and EQ-5D-5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. CONCLUSIONS: Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.

The BRIGHT study: bifocal right ventricular resynchronization therapy: a randomized study.

AIMS: The BRIGHT study evaluated bifocal right ventricular (RV) (apex and outflow tract) pacing in a single, blind, randomized crossover study in patients eligible for cardiac resynchronization therapy (CRT). Forty-two patients were enrolled with the following characteristics: chronic drug refractory heart failure New York Heart Association (NYHA) class III-IV; ejection fraction (EF)<35%; QRS width >or= 120 ms; and a left bundle branch block. The aim of the study was to assess an improvement in left ventricular (LV) EF, 6 min walk test, Minnesota quality-of-life score, and NYHA classification. Methods and result Patients were randomized to receive either bifocal pacing or the control mode, each for a period of 3 months. Parameters were measured prior to randomization and after 3 months of control or bifocal pacing. Eight patients failed to make the 7 month follow-up, three patients died (one prior to randomization at the first month), five patients dropped out, and three patients refused further participation. One patient had a persistent lead problem, which was subsequently replaced with an LV lead, and one patient suffered with persistent atrial fibrillation. Compared with baseline, bifocal pacing improved EF from 26 +/- 12% to 36 +/- 11% (P < 0.0008), NYHA classification decreased from 2.8 +/- 0.4 to 2.3 +/- 0.7 (P < 0.007). Furthermore, the 6 min walk test improved from 372 +/- 129 m to 453 +/- 122 m (P < 0.05), and the Minnesota Living with Heart Failure scores decreased from 33 +/- 20 to 24 +/- 21 (P < 0.006). In the control group, no significant changes in any parameters were observed. Eight patients did not tolerate reprogramming from DDD BRIGHT to control pacing, with symptoms disappearing in all patients after reprogramming to bifocal pacing. CONCLUSION: Bifocal RV pacing in patients with a classic indication for CRT shows improvement in all parameters.