Heart rate response and chronotropic incompetence during cardiopulmonary exercise testing in childhood acute lymphoblastic leukemia survivors

Abstract

Cardiopulmonary exercise tests (CPET) focusing on analyses of heart rate (HR) responses and chronotropic incompetence (CI) could provide early information about treatment’s negative cardiac effects. We examined childhood acute lymphoblastic leukemia (ALL) survivors’ HR response during maximal CPET and identified survivors with CI. A total of 250 childhood ALL survivors underwent a CPET on ergocycle to assess their HR response. We used a multiparametric structure of three methods to assess survivors’ CI, as follows: 1) age-predicted HR_max (APMHR): failure to achieve 85% of the APMHR at the peak of CPET; 2) HR reserve (HRR): failure to achieve 80% of the HRR at the peak of CPET; and 3) metabolic chronotropic relationship (MCR): failure to reach an MCR slope ratio >0.8 at each stage of the CPET. Among 250 childhood ALL survivors, 216 survivors performed a maximum CPET. We observed that 73 males and 74 females did not achieve their predicted HR_max. We found that 6 survivors did not achieve 85% of their APMHR (80.9 ± 3.9%) and had an MCR below 80% (53.9 ± 13.8%). In addition, 16 survivors did not achieve 80% of their HRR (71.0 ± 7.4%) and among them, 15 survivors had an MCR below 80% (61.0 ± 12.1%). Survivors with CI had a significantly lower cardiorespiratory fitness than those without CI. This study shows that survivors are at risk of developing altered HR responses and CI many years after the end of their cancer treatments. These findings highlight the importance of early detection of cardiac damage due to cancer treatments.

Keywords:

• Acute lymphoblastic leukemia
• cardiopulmonary exercise
• chronotropic incompetence
• heart rate
• pediatric cancer survivorship
• testing

Acknowledgements

We appreciate the assistance of Ariane Levesque (McGill University) and Audrey Harvey (Université de Montréal) for their review of the article in the English language.

Declaration of conflicting interests

The authors report no conflicts of interest.

Data availability statement

Our data are not deposited in publicly available repositories. However, the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Institute of Cancer Research (ICR) of the Canadian Institutes of Health Research (CIHR), in collaboration with C17 Council, Canadian Cancer Society (CCS), Cancer Research Society (CRS), Garron Family Cancer Centre at the Hospital for Sick Children, Ontario Institute for Cancer Research (OICR) and Pediatric Oncology Group of Ontario (POGO). This research was also supported in part by PhD study grants from Cole Foundation, Fonds de Recherche du Québec – Santé (FRQS), Sainte-Justine University Hospital Center Foundation and Foundation of Stars. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.