Cardiovascular disease following hematopoietic stem cell transplantation: Pathogenesis, detection, and the cardioprotective role of aerobic training

Abstract

Advances in hematopoietic cell transplantation (HCT) techniques and supportive care strategies have led to dramatic improvements in relapse mortality in patients with high-risk hematological malignancies. These improvements, however, conversely increase the risk of late-occurring non-cancer competing causes, mostly cardiovascular disease (CVD). HCT recipients have a significantly increased risk of CVD-specific mortality, including elevated incidence of coronary artery disease (CAD), cerebrovascular disease, and heart failure (HF) compared to age-matched counterparts. Accordingly, there is an urgent need to identify techniques for the detection of early CVD in HCT patients to inform early prevention strategies. Aerobic training (AT) is established as the cornerstone of primary and secondary disease prevention in multiple clinical settings, and may confer similar benefits in HCT patients at high-risk of CVD. The potential benefits of AT either before, immediately after, or in the months / years following HCT have received limited attention. Here, we discuss the risk and extent of CVD in adult HCT patients, highlight novel tools for early detection of CVD, and review existing evidence in oncology and non-oncology populations supporting the efficacy of AT to attenuate HCT-induced CVD. This knowledge can be utilized to optimize treatment, while minimizing CVD risk in individuals with hematological malignancies undergoing HCT.

Cardiomyopathy in patients after posttransplant cyclophosphamide–based hematopoietic cell transplantation

“…A body of literature has established predictors of cardiovascular events after transplantation, including demographic factors (age and female sex), traditional cardiovascular risk factors (hypertension, diabetes, dyslipidemia, and obesity), and cancer-related factors (chemotherapy, anthracycline exposure, and radiation exposure). 23,25 Our multivariate analysis revealed that age and diabetes, but not other traditional cardiovascular risk factors, predict posttransplant cardiomyopathy. A history of diabetes may be supplanted by the HCT-CI score, which incorporates a history of diabetes.…”

Coronary artery involvement in chronic graft‐versus‐host disease presenting as sudden cardiac arrest

“…Coronary lesions in a chronically rejected transplanted heart are characterized by concentric fibrointimal hyperplasia that contains a variable number of lymphocytes and plasma cells, and it is unlikely in usual coronary lesions of adults with high-risk factors but similar to those seen in reported patients with GVHD. 6 Biological evidence of endothelial activation and injury has been observed in patients with GVHD, suggesting that the coronary endothelium is a potential target for the graft-versus-host immune response in chronic GVHD. 15 These endothelial activation and injury after HSCT by chronic GVHD may cause coronary artery damage as like as fibrointimal hyperplasia seen in transplanted heart.…”

“…GVHD is caused by a lymphocyte immune response to recipient organs, and these immune responses cause the secretion of pro‐inflammatory cytokines and chemokines, and damage mainly the liver, lung, skin, and gut . Although heart involvement by GVHD is less common, some cardiac symptoms related to GVHD have been identified, including pericardial effusion and arrhythmias such as complete atrioventricular block or sinus node dysfunction . However, coronary artery complication related to chronic GVHD after HSCT is rarely reported and not yet well defined .…”

“…1,2 Although heart involvement by GVHD is less common, some cardiac symptoms related to GVHD have been identified, including pericardial effusion and arrhythmias such as complete atrioventricular block or sinus node dysfunction. [3][4][5][6][7] However, coronary artery complication related to chronic GVHD after HSCT is rarely reported and not yet well defined. [8][9][10][11] We report on a pediatric patient with chronic GVHD after HSCT who collapsed suddenly because of myocardial ischemia caused by coronary obstruction.…”

Whole body vibration training during allogeneic hematopoietic cell transplantation—the effects on patients’ physical capacity

“…Allogeneic hematopoietic cell transplantation (alloHCT) is usually associated with hospitalization lasting at least 4 weeks. The treatment itself, therapy-related side effects, and bed rest and physical inactivity lead to a general decline in physical performance, maximum oxygen consumption, muscular performance in particular, and quality of life (QoL) as a consequence of all impairments [1][2][3][4][5]. Poor maximum oxygen consumption and peak exercise capacity are associated with a higher risk of cardiovascular diseases and all-cause mortality [6][7][8][9].…”