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Graft-Versus-Host Disease as a Risk Factor for Heart Failure After Allogeneic Hematopoietic Stem Cell
Tong Wang1, Qian Zhu2, Hongfei Zhao1
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Background:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical therapeutic option for hematologic malignancies. However, it is associated with severe complications, including graft-versus-host disease (GVHD). While GVHD is widely recognized for its impact on various organs, its role in the development of heart failure (HF) remains insufficiently understood. This study investigates the association between GVHD and HF following allo-HSCT, focusing on identifying key risk factors contributing to HF development.
Methods:
A retrospective cohort study was conducted on 220 patients who underwent allo-HSCT between 2005 and 2024. HF was defined by clinical criteria and left ventricular ejection fraction. The association of GVHD severity (acute and chronic), inflammatory markers (tumor necrosis factor-alpha, interleukin-6), and cardiac biomarkers (B-type natriuretic peptide) with HF was analyzed. Multivariate logistic regression was performed to identify independent predictors of HF.
Results:
Patients with HF demonstrated significantly lower left ventricular ejection fraction (33.92% ± 6.73% vs 61.51% ± 6.18%, P = .021) and higher levels of B-type natriuretic peptide (393.29 ± 71.29 ng/L vs 307.92 ± 76.28 ng/L, P = .042), tumor necrosis factor-alpha (80.3 ± 20.4 pg/mL vs 40.2 ± 10.1 pg/mL, P < .001), and interleukin-6 (65.1 ± 15.7 pg/mL vs 25.4 ± 8.6 pg/mL, P < .001) compared to controls. Severe acute GVHD (Grade ≥III) significantly increased the risk of HF (odds ratio = 3.5, P < .001). Patients with multiple GVHD-related complications had a 3.6-fold higher likelihood of HF development (P < .01). Echocardiographic findings revealed significant cardiac remodeling in HF patients, with increased left ventricular end-diastolic diameter (68.76 ± 7.23 mm vs 44.18 ± 7.16 mm, P = .004) and left ventricular posterior wall thickness (12.18 ± 4.32 mm vs 4.46 ± 2.19 mm, P = .002). Additionally, HF patients experienced more severe transplant-related complications, including infections (29.0% vs 10.6%, P = .041) and hemorrhagic cystitis (23.4% vs 7.1%, P = .027). Mortality was significantly higher in the HF group (86.0% vs 41.6%, P < .001), with infection (71.0%) and HF (21.5%) being the leading causes of death. GVHD significantly heightens the risk of HF after allo-HSCT.
Conclusions:
These findings underscore the necessity for proactive cardiovascular monitoring and targeted therapeutic interventions in GVHD patients to prevent the development of HF.
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