Reduced cardiovascular reserve capacity in long-term allogeneic stem cell transplant survivors

Abstract

Premature cardiovascular mortality is increased in long-term allogeneic stem cell transplant (allo-SCT) survivors, but little information exists regarding subclinical cardiovascular dysfunction in this population. We compared peak oxygen uptake ($\dot{\mathrm{V}}$O_2peak), a prognostic cardiovascular marker, and its determinants between long-term allo-SCT survivors and non-cancer controls. Fourteen allo-SCT survivors (mean ± SD, 44 ± 15 years, 50% male, median time since allo-SCT: 6.5 years [range 2–20]) and 14 age- and sex-matched controls (46 ± 13 years, 50% male) underwent cardiopulmonary exercise testing to quantify $\dot{\mathrm{V}}$O_2peak. Resting echocardiography (left-ventricular ejection fraction and strain), exercise cardiac MRI (peak cardiac and stroke volume index [CI_peak, SVI_peak]), biochemistry (hemoglobin, troponin-I, B-natriuretic peptide), dual-energy x-ray absorptiometry (lean [LM] and fat [FM] mass, percent body fat [%BF]) and Fick-principal calculation (arteriovenous oxygen difference) were also performed. Survivors exhibited impaired $\dot{\mathrm{V}}$O_2peak as compared with controls (25.9 ± 5.1 vs. 33.7 ± 6.5 ml kg⁻¹ min⁻¹, p = 0.002), which coincided with reduced CI_peak (6.6 ± 0.8 vs. 8.6 ± 1.9 L min⁻¹ m⁻²; p = 0.001) secondary to reduced SVI_peak (48 ± 4 vs. 61 ± 8 ml m⁻²; p < 0.001) rather than chronotropic impairment, and higher %BF (difference, 7.9%, p = 0.007) due to greater FM (5.8 kg; p = 0.069) and lower LM (4.3 kg, p = 0.25). All other measures were similar between groups. Despite comparable resting cardiac function and biomarker profiles, survivors exhibited reduced $\dot{\mathrm{V}}$O_2peak and exercise cardiac function and increased %BF relative to controls. These results highlight potential therapeutic avenues and the utility of exercise-based cardiovascular assessment in unmasking cardiovascular dysfunction in allo-SCT survivors.