Chronotropic Incompetence after Heart Transplantation Is Associated with Increased Mortality and Decreased Functional Capacity

Robert S Zhang; Thomas C Hanff; Yuhui Zhang; Michael V Genuardi; Carli J Peters; Allison Levin; Maria Molina; Rhondalyn C McLean; Jeremy A Mazurek; Payman Zamani; Monique S Tanna; Joyce Wald; Pasquale Santangeli; Pavan Atluri; Lee R Goldberg; Edo Y Birati

doi:10.3390/jcm12103487

Chronotropic Incompetence after Heart Transplantation Is Associated with Increased Mortality and Decreased Functional Capacity

J Clin Med. 2023 May 16;12(10):3487. doi: 10.3390/jcm12103487.

Authors

Robert S Zhang¹, Thomas C Hanff^{2

3}, Yuhui Zhang⁴, Michael V Genuardi^{2

3}, Carli J Peters^{1

2}, Allison Levin², Maria Molina³, Rhondalyn C McLean^{2

3}, Jeremy A Mazurek^{2

3}, Payman Zamani^{2

3}, Monique S Tanna^{2

3}, Joyce Wald^{2

3}, Pasquale Santangeli^{2

3}, Pavan Atluri⁵, Lee R Goldberg^{2

3}, Edo Y Birati^{2

3

6}

Affiliations

¹ Division of Cardiovascular Medicine, NYU Langone Health, New York, NY 10016, USA.
² Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19123, USA.
³ Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19123, USA.
⁴ Fuwai Hospital, Peking Union Medical College, Beijing 100005, China.
⁵ Department of Cardiothoracic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19123, USA.
⁶ The Lydia and Carol Kittner, Lea and Banjamin Davidai Division of Cardiovascular Medicine and Surgery, Padeh-Poriya Medical Center, Tiberias 1528001, Israel.

Abstract

Introduction: The contribution of chronotropic incompetence to reduced exercise tolerance after a heart transplant is well known, but its role as a prognostic marker of post-transplant mortality is unclear. The aim of this study is to examine the relationship between post-transplant heart rate response (HRR) and survival.

Methods: We performed a retrospective analysis of all adult heart transplant recipients at the University of Pennsylvania between the years 2000 and 2011 who underwent a cardiopulmonary exercise test (CPET) within a year of transplant. Follow-up time and survival status were observed through October 2019, using data merged from the Penn Transplant Institute. HRR was calculated by subtracting the resting HR from the peak exercise HR. The association between HRR and mortality was analyzed using Cox proportional hazard models and Kaplan-Meier analysis. The optimal cut-off point for HRR was generated by Harrell's C statistic. Patients with submaximal exercise tests were excluded, defined by a respiratory exchange ratio (RER) cut-off of 1.05.

Results: Of 277 patients with CPETs performed within a year post-transplant, 67 were excluded for submaximal exercise. In the 210 included patients, the mean follow-up time was 10.9 years (Interquartile range (IQR) 7.8-14). Resting HR and peak HR did not significantly impact mortality after adjusting for covariates. In a multivariable linear regression analysis, each 10-beat increase in heart rate response was associated with a 1.3 mL/kg/min increase in peak V_O₂ and a 48 s increase in the total exercise time. Each beat/min increase in HRR was associated with a 3% reduction in the hazard of mortality (HR 0.97; 95% CI 0.96-0.99, p = 0.002). Using the optimal cut-off point generated by Harrell's C statistic, survival was significantly higher in patients with an HRR > 35 beats/min compared to those with an HRR < 35 beats/min (log rank p = 0.0012).

Conclusion: In heart transplant patients, a low HRR is associated with increased all-cause mortality and decreased exercise capacity. Additional studies are needed to validate whether targeting HRR in cardiac rehabilitation may improve outcomes.

Keywords: exercise; heart rate; heart rate response; prognosis; survival; transplant.

Grants and funding

This research received no external funding.