Association of Chronic Kidney Disease with Chronotropic Incompetence in Heart Failure with Preserved Ejection Fraction

Chronotropic incompetence (CI) is common in heart failure with preserved ejection fraction (HFpEF) and may be a key reason underlying exercise intolerance in these patients. However, the determinants of CI in HFpEF are unknown. We prospectively studied 157 patients with consecutive HFpEF who underwent cardiopulmonary exercise testing and defined CI according to specific thresholds of the percent heart rate reserve (%HRR). CI was diagnosed as present if %HRR <80 if not taking a β blocker and <62 if taking β blockers. Participants who achieved inadequate exercise effort (respiratory exchange ratio >1.05) on cardiopulmonary exercise testing were excluded. Multivariable-adjusted logistic regression was used to determine the factors associated with CI. Of the 157 participants, 108 (69%) achieved a respiratory exchange ratio >1.05 and were included in the final analysis. Of these 108 participants, 70% were women, 62% were taking β blockers, and 38% had chronic kidney disease. Most patients with HFpEF met criteria for CI (81 of 108; 75%). Lower estimated glomerular filtration rate (GFR), higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure were each associated with CI. A 1-SD decrease in GFR was independently associated with CI after multivariable adjustment (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4, p = 0.02). The association between reduced GFR and CI persisted when considering a variety of measures of chronotropic response. In conclusion, reduced GFR is the major clinical correlate of CI in patients with HFpEF, and further study of the relation between chronic kidney disease and CI may provide insight into the pathophysiology of CI in HFpEF.