Chronotropic Incompetence Is a Contributor to Cardiovascular Functional Impairment in Early-Stage CKD

Background: Chronotropic incompetence (CI) is a major complication in advanced chronic kidney disease (CKD). It is unclear if CI occurs in early-stage CKD and how it impacts cardiovascular functional capacity (CVC). Herein, we investigated the role of CI with mild-decrements in kidney function and its link with VO2Peak (gold-standard index of CVC). Methods: We analyzed 466 patients from the FIT-INDY cohort, an ambulatory referral cohort of patients who underwent cardiopulmonary exercise testing (CPET) and transthoracic echocardiography. Participants were stratified into tertiles per peak Heart Rate (HRPeak): >157 bpm (n=153), 124-156 bpm (n=159) and <123 bpm (n=154). Group differences were analyzed with ANOVA, Kruskal-Wallis, or chi-square tests. Inferential analysis utilized Pearson’s correlation analysis and multiple linear regression. Results: All groups were matched by gender (P=0.07). Patients with HRPeak <123 bpm were older, had higher BMI and comorbidity burden (hypertension, diabetes, heart failure), and greater beta-blocker use (77.8%; all P’s<0.001). Kidney function was incrementally worse in the lower HRPeak strata (HRPeak >15 7bpm: eGFR 99.5 (87.9, 115.0) vs 124-156 bpm: eGFR 89.3 (71.1, 105.0) vs <123bpm: eGFR 74.8 (54.7, 96.1) mL/min/1.73m2; P<0.001). The lower HR groups had reduced left ventricular (LV) ejection fraction and LV mass index (P’s<0.05). Significantly, a progressive decline in VO2Peak was observed with lower HRPeak (HRPeak >157bpm: VO2Peak 25.1 (20.2, 33.7) vs 124-156 bpm: VO2Peak 17.5 (13.5, 22.3) vs <123bpm: VO2Peak 12.7 (10.7, 17.0) mL/min/kg; P’s<0.001). VO2VT and VE/VCO2 slope were incrementally impaired in the lower HRPeak strata (P<0.001). HRPeak was positively correlated with both eGFR (r=0.40) and VO2Peak (r=0.64, all P’s <0.001). Moreover, HRPeak remained associated with VO2Peak on multiple regression after adjustment for age, gender, eGFR, beta-blocker use, diabetes, and ejection fraction. Conclusion: CI is a complication even with mild decrements in kidney function and is associated with impaired VO2Peak, ventilatory efficiency, and ventilation-perfusion mismatch. Funding: Private Foundation Support