Abstract 17050: Association of Kidney Dysfunction with Chronotropic Incompetence in Heart Failure with Preserved Ejection Fraction

Abstract

Introduction: Chronotropic incompetence (CI) is an important pathophysiologic factor underlying reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF), but clinical factors associated with CI in HFpEF are unknown. Based on anecdotal clinical experience, we hypothesized that coronary artery disease (CAD) and chronic kidney disease (CKD) are associated with CI in HFpEF. Methods: We studied 157 consecutive HFpEF patients undergoing cardiopulmonary exercise testing, and defined CI as maximal heart rate (HR) < 80% of estimated HR reserve (< 65% if using beta-blockers). Participants who achieved inadequate exercise effort (respiratory exchange ratio [RER] ≤ 1.05) were excluded. Unadjusted and multivariable-adjusted regression models were used to determine correlates of CI. Results were re-assessed using alternative formulations of chronotropic response. Results: Of 157 participants, 73% were women, 64% used beta-blockers, 32% had CKD, and 40% had CAD. RER > 1.05 was achieved by 108 (69%) participants, including 79/108 (76%) with CI. Lower estimated GFR, higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure (but not CAD) were each associated with CI. A 1-SD decrease in GFR was independently associated with CI (adjusted odds ratio = 2.4, 95% confidence interval = [1.3, 4.6]) after adjustment for smoking status, log BNP, and beta blocker usage. Linear regression models demonstrated that GFR was independently and linearly associated with %HR reserve (β=0.31, SE=0.10; P=0.002; Figure). Findings were unchanged after re-calculation of %HR reserve and CI based on alternative formulations used in the literature. Conclusions: CI is common and strongly associated with GFR in HFpEF. Our results indicate that kidney function may mark or contribute to the development of CI in HFpEF. HFpEF patients with CKD may need to be screened for CI prior to starting medications (e.g., beta blockers) that could exacerbate CI.