Pimobendan in Heart Failure With Preserved Ejection Fraction and Right Ventricular–Pulmonary Arterial Uncoupling　― A Randomized Clinical Trial ―

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV)-pulmonary arterial (PA) uncoupling, as assessed by a decrease ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP) on echocardiography, have poorer outcomes than patients without RV-PA uncoupling. METHODS AND RESULTS: The MONACO trial was an adaptive, randomized, double-blind, placebo-controlled study that enrolled hospitalized patients with HFpEF admitted to 12 centers in Japan. Patients who had left ventricular ejection fraction ≥50% and TAPSE/PASP <0.57 mm/mmHg at discharge were randomized 1 : 1 to receive pimobendan 1.25 mg b.i.d. or placebo. The primary objective was to evaluate changes from baseline (day 0) to day 30 in exercise capacity measured by the 6-minute walking test. Enrollment was terminated due to the invalid result of the planned interim analysis. The median age of participants was 82 years and 46% were women. Pimobendan (n=24) or placebo (n=26) was administrated orally. At day 30, mean changes in 6-minute walking distance in patients who received pimobendan (+26.9 m [95% confidence interval; -2.0, +55.8]) or placebo (+21.4 m [95% confidence interval; -14.3, +57.2]) were not significantly different (P=0.402). CONCLUSIONS: Among patients with HFpEF and RV-PA uncoupling, administration of pimobendan for 30 days did not result in significant improvement in exercise capacity compared with placebo.