Baseline characteristics of patients in the PARALLAX trial: insights into quality of life and exercise capacity in heart failure with preserved ejection fraction

Aims: We sought to describe the baseline characteristics of PARALLAX [a randomized controlled trial of sacubitril/valsartan vs. individualized medical therapy in heart failure (HF) with mildly reduced and preserved ejection fraction (HFpEF)]; compare PARALLAX to recent HFpEF trials; and examine the clinical characteristics associated with quality of life (QOL) and 6-min walk test distance (6MWD).

Methods and results: A total of 2566 patients with HF and left ventricular ejection fraction (LVEF) >40% were randomized, of whom 96% had an LVEF ≥45%. Multivariable linear regression was used to determine characteristics associated with Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and 6MWD. Mean age was 73 ± 8 years, 51% were female, and comorbidities were common. Of the QOL measures tested in PARALLAX, the Short Form Health Survey-36 physical functioning score was most closely correlated with 6MWD (R = 0.41, P < 0.001), and outperformed the KCCQ physical limitation score (R = 0.33) and KCCQ-CSS (R = 0.31) on multivariable analyses. Female sex, higher body mass index, history of coronary artery disease, lower LVEF, and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with worse (lower) KCCQ-CSS; older age, female sex, higher body mass index, diabetes, coronary artery disease, chronic obstructive pulmonary disease, prior HF hospitalization, lower LVEF, and higher NT-proBNP were associated with shorter 6MWD (P < 0.05 for all associations).

Conclusions: PARALLAX is the largest HFpEF study to date to examine 6MWD together with QOL. The KCCQ-CSS and 6MWD were modestly correlated, and several factors were associated with worse values of both. These results provide insight into the association between QOL and exercise capacity in HFpEF.