Ventilatory and chronotropic incompetence during incremental and constant load exercise in end-stage renal disease: a comparative physiology study

Abstract

Background: Aerobic capacity is impaired in end-stage renal disease (ESRD), reducing quality of life and longevity. Whilst determinants of maximal exercise intolerance are well defined, little is known of limitation during submaximal exercise. By comparing ESRD and healthy controls, the aim of this study was to characterise mechanisms of exercise intolerance in ESRD by assessing cardiopulmonary physiology at rest and during exercise. Methods: Resting spirometry and echocardiography were performed in 20 ESRD participants and 20 healthy age and gender matched controls. Exercise tolerance was assessed with ventilatory gas exchange and central hemodynamics during a maximal cardiopulmonary exercise test (CPEX) and 30 minutes of submaximal constant load exercise (CLEX). Results: Left ventricular mass (292 ± 102 vs. 185 ± 83 g; p = 0.01) and filling pressure (E/e': 6.48 ± 3.57 vs. 12.09 ± 6.50 m/s; p = 0.02) were higher in ESRD; forced vital capacity (3.44 ± 1 vs. 4.29 ± 0.95 L/min; p = 0.03) and peak VO2 (13.3 ± 2.7 vs. 24.6 ± 7.3 ml.kg-1.min-1; p < 0.001) were lower. During CLEX, the relative increase in (a-v) O2 difference (13 ± 18 vs. 74 ± 18%) and heart rate (32 ± 18 vs. 75 ± 29%) were less in ESRD despite exercise being performed at a higher percentage of maximum VE (48 ± 3 vs 39 ± 3%) and HR (82 ± 2 vs. 64 ± 2%). Conclusion: Ventilatory and chronotropic incompetence contribute to exercise intolerance in ESRD. Both are potential targets for medical and lifestyle interventions.

The value of cardiopulmonary exercise testing and stress echocardiography in the prediction of all‐cause mortality in adults with end‐stage renal disease

“…Importantly, peak O 2 pulse and heart rate, which both centrally contribute to oxygen delivery and thus peak VO 2 , were also significantly lower in the all‐cause mortality group. These heart rate findings are indicative of a blunted chronotropic response as is common in more advanced disease states and is understood as a primary contributor to exercise intolerance in ESRD (McGuire et al, 2020), especially considering the prevalence of beta‐blockade in this population. Future work should consider the addition of other non‐invasive physiological methods, such as impedance cardiography, which may provide advanced mechanistic insight into the exercise intolerance in these individuals.…”

Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity

“…Chronotropic incompetence in patients with ESKD reflects autonomic dysfunction resulting from uremia, sympathetic overactivity, and vagal withdrawal. 21 Circulatory power is a surrogate of peak exercise cardiac power that incorporates heart rate, stroke volume, blood pressure, and arterial oxygen extraction responses to exercise. More important, circulatory power has been shown to be a robust predictor of poor outcome in patients with heart failure.…”

Rate-Responsive Cardiac Pacing: Technological Solutions and Their Applications

“…Undoubtedly, the use of beta-blockers, which are commonly used in patients with cardiac arrhythmias, has a strong influence on chronotropism [ 10 , 11 , 12 ]. CI is often observed in obese patients and in patients with type 2 diabetes, trisomy 21, rheumatoid arthritis, end-stage renal disease, kidney transplantation, or COVID-19 [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. In patients with hepatic failure, the altered chronotropic response correlates with the degree of organ failure, making it a valuable criterion in cardiovascular assessment when selecting candidates for liver transplantation [ 21 ].…”