Limitations
heart failure, HFpEF
REGRESSION, HEART FAILURE
There are a number of important limitations to the present study. PARABLE is a phase II, single-center randomized clinical trial in a selected population of predominantly European ancestry. The follow-up time was limited to 18 months and overlapped with the COVID-19 pandemic. Nine patients were lost to follow-up, 46 withdrew from the treatment phase, not all of whom were willing to return for the follow-up cardiac MRI, and a further 49 had delayed cardiac MRI examination. There were differences in the baseline characteristics of the population, including in the primary end point. While the primary analysis adjusted for these baseline differences and there were no baseline differences in left ventricular end diastolic volume index, we cannot exclude a contribution of regression to the mean in the imaging results. Confirmation of asymptomatic HFpEF at baseline was carried out by an experienced cardiology fellow and heart failure nurse specialist. However, 34 patients (13.6%) had high H2FpEF scores, and we did not carry out formal functional assessments, such as the Kansas City Cardiology Questionnaire or 6-minute walk test, nor did we carry out cardiac MRI assessments of patients at an interim 9-month period. Accordingly, we cannot comment on the time course of the observations reported. PARABLE is not designed or powered to provide definitive evidence on the cardiovascular outcomes over longer follow-up. Moreover, the generalizability of the PARABLE study maybe limited by the exclusion criteria adopted and the homogenous ancestry of the participating population.