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

TITLE=Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.926064

DOI=10.3389/fcvm.2022.926064

ISSN=2297-055X

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>Before and ~3-months following allo-HCT, 17 hematological cancer patients (45 ± 18 years) underwent cardiopulmonary exercise testing to quantify peak oxygen uptake (VO<sub>2</sub>peak)—a measure of integrative cardiovascular function. Then, to determine the degree to which changes in VO<sub>2</sub>peak 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-vO<sub>2</sub>diff) estimation <italic>via</italic> the Fick equation. Twelve controls (43 ± 13 years) underwent identical testing at equivalent baseline and 3-month time intervals.</p></sec><sec><title>Results</title><p><italic>S</italic>ignificant group-by-time interactions were observed for absolute VO<sub>2</sub>peak (<italic>p</italic> = 0.006), bodyweight-indexed VO<sub>2</sub>peak (<italic>p</italic> = 0.015), LM (<italic>p</italic> = 0.001) and cardiac reserve (<italic>p</italic> = 0.019), which were driven by 26, 24, 6, and 26% reductions in the allo-HCT group (all <italic>p</italic> ≤ 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-vO<sub>2</sub>diff, though a-vO<sub>2</sub>diff declined 12% in allo-HCT (<italic>p</italic> = 0.028).</p></sec><sec><title>Conclusion</title><p>In summary, allo-HCT severely impairs VO<sub>2</sub>peak, 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.</p></sec>