Abstract

Although atrial fibrillation/atrial flutter (AF/AFL) and heart failure with preserved ejection fraction (HFpEF) frequently coexist, the influence of AF/AFL on physical activity, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life in HFpEF is unclear and could have relevance to HFpEF trial design. We evaluated the association between AF/AFL and volitional physical activity, functional performance, NT-proBNP, and quality of life in patients with HFpEF in the Nitrate's Effect on Activity Tolerance (NEAT)-HFpEF trial. Of 99 patients with accelerometer data, 35 (35%) had AF/AFL. There were no differences between AF/AFL versus no AF/AFL in baseline average daily accelerometer units (ADAUs; 9.06 ± 0.54 vs 9.06 ± 0.48, p = 0.75), hours active per day (9.7 ± 2.3 vs 9.2 ± 2.2, p = 0.86), or 6-minute walk distance (6MWD; 307 ± 136m vs 321 ± 110m, p = 0.85). AF/AFL status was associated with higher baseline NT-proBNP (586 [25th to 75th percentile: 291 to 1254] pg/ml vs 154 [25th to 75th percentile: 92 to 288] pg/ml, p <0.001) and Kansas City Cardiomyopathy Questionnaire scores (69 [25th to 75th percentile: 46 to 88] vs 48 [25th to 75th percentile: 37 to 70], p = 0.01). Although treatment responses to isosorbide mononitrate measured by change in ADAUs, hours active per day, or 6MWD did not vary by AF/AFL status (interaction p >0.05 for all), AF/AFL patients had greater reductions in NT-proBNP after isosorbide mononitrate than patients without AF/AFL (interaction p <0.001), possibly due to regression to the mean. In conclusion, baseline measures and treatment-related changes in volitional physical activity (ADAUs) and functional performance (6MWD) did not differ by AF/AFL in NEAT-HFpEF, whereas NT-proBNP did. In HFpEF-where AF/AFL prevalence is high-functional measures may be superior to natriuretic peptides as trial endpoints.