Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy

Hayley T Dillon; Stephen Foulkes; Yuki A Horne-Okano; David Kliman; David W Dunstan; Robin M Daly; Steve F Fraser; Sharon Avery; Bronwyn A Kingwell; Andre La Gerche; Erin J Howden

doi:10.3389/fcvm.2022.926064

Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy

Front Cardiovasc Med. 2022 Dec 15:9:926064. doi: 10.3389/fcvm.2022.926064. eCollection 2022.

Authors

Hayley T Dillon^{1

2}, Stephen Foulkes^{1

2}, Yuki A Horne-Okano¹, David Kliman³, David W Dunstan^{1

2}, Robin M Daly², Steve F Fraser², Sharon Avery³, Bronwyn A Kingwell^{1

4}, Andre La Gerche¹, Erin J Howden¹

Affiliations

¹ Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
² Institute of Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia.
³ Malignant Haematology and Stem Cell Transplantation Service, Alfred Hospital, Melbourne, VIC, Australia.
⁴ CSL Ltd, Melbourne, VIC, Australia.

Abstract

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure for high-risk hematological malignancy; however, long-term survivors experience increased cardiovascular morbidity and mortality. It is unclear how allo-HCT impacts cardiovascular function in the short-term. Thus, this 3-month prospective study sought to evaluate the short-term cardiovascular impact of allo-HCT in hematological cancer patients, compared to an age-matched non-cancer control group.

Methods: Before and ~3-months following allo-HCT, 17 hematological cancer patients (45 ± 18 years) underwent cardiopulmonary exercise testing to quantify peak oxygen uptake (VO₂peak)-a measure of integrative cardiovascular function. Then, to determine the degree to which changes in VO₂peak are mediated by cardiac vs. non-cardiac factors, participants underwent exercise cardiac MRI (cardiac reserve), resting echocardiography (left-ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), dual-energy x-ray absorptiometry (lean [LM] and fat mass [FM]), blood pressure (BP) assessment, hemoglobin sampling, and arteriovenous oxygen difference (a-vO₂diff) estimation via the Fick equation. Twelve controls (43 ± 13 years) underwent identical testing at equivalent baseline and 3-month time intervals.

Results: Significant group-by-time interactions were observed for absolute VO₂peak (p = 0.006), bodyweight-indexed VO₂peak (p = 0.015), LM (p = 0.001) and cardiac reserve (p = 0.019), which were driven by 26, 24, 6, and 26% reductions in the allo-HCT group (all p ≤ 0.001), respectively, as no significant changes were observed in the age-matched control group. No significant group-by-time interactions were observed for LVEF, GLS, FM, hemoglobin, BP or a-vO₂diff, though a-vO₂diff declined 12% in allo-HCT (p = 0.028).

Conclusion: In summary, allo-HCT severely impairs VO₂peak, reflecting central and peripheral dysfunction. These results indicate allo-HCT rapidly accelerates cardiovascular aging and reinforces the need for early preventive cardiovascular intervention in this high-risk group.

Keywords: cardiac function; cardiopulmonary fitness; cardiotoxicity; cardiovascular disease; exercise testing; hematological cancer.