Risk Factors Affecting Cardiac Left Ventricular Systolic and Diastolic Function and Hypertrophy in the Chronic Phase Post-Allogeneic Hematopietic Cell Transplantation
Authors: Nishimoto Mitsutaka , Nakamae Hirohisa , Nakane Takahiko , Koh Hideo , Hayashi Yoshiki , Nakamae Mika , Yoshida Masahiro , Bingo Masato , Okamura Hiroshi , Aimoto Mizuki , Manabe Masahiro , Yoshimura Takuro , Inaba Akiko , Nanno Satoshi , Hirose Asao , Hagihara Kiyoyuki , Nakao Yoshitaka , Terada Yoshiki , Hino Masayuki 
Published: October 2019

Abstract
Abstract 2000
The long-term survival rate after allogeneic hematopoietic cell transplantation (HCT) has been significantly improved over recent decades due to improvements in the HCT procedure. However, chronic complications such as cardiovascular disease have become increasingly evident and constitute a serious problem among long-term survivors after HCT.
It is well-known that high-dose cyclophosphamide (CY) used for conditioning is one of the major causes of acute cardiotoxicity after HCT; however, it is still unclear which factors contribute to chronic cardiotoxicity. Although there is a possibility that chronic GVHD (cGVHD) causes cardiac tissue damage via cytokines such as IL-2, or TNF-alpha, it is unclear whether or not cGVHD influences cardiac function.
In the present retrospective cohort study, we investigated which factors affected cardiac function and left ventricular hypertrophy (LVH) in the chronic phase after HCT. We examined left ventricular systolic and diastolic functions and LVH in patients who received HCT between April 2000 and March 2011 and survived for more than one year post-HCT. Only the patients who had undergone an echocardiographic examination before HCT were eligible for the study. We assessed left ventricular ejection fraction (LVEF) as a surrogate marker of LV systolic function and the early peak flow velocity/atrial peak flow velocity (E/A) as a surrogate marker of LV diastolic function using echocardiography. LVH after HCT was identified when the interventricular septal wall (IVS) and/or the posterior wall (PW) became more than 12 mm thick after HCT. We examined the factors that could have had some influence on cardiac function after HCT including age, sex, cumulative dose of anthracycline, use of high-dose CY in the conditioning, total body irradiation (TBI), intensity of conditioning regimen (myeloablative vs. reduced intensity conditioning), a history of hypertension, hemoglobin and serum ferritin levels.
A total of 58 patients (25 males and 33 females) were eligible for participation in the study. The median age of enrolled patients was 46 years (range: 21–73). The median cumulative dose of anthracycline was 90 mg/m2 (0–431mg/m2). Forty-nine patients received myeloablative conditioning and 20 of these patients received myeloabative conditioning with TBI 12 Gy. Twenty-four patients were treated for cGVHD and 7 had a history of hypertension and 2 had an LVEF of less than 55% before HCT. Six had an LVEF of less than 55% at more than 1 year after HCT. In the multiple regression analysis that assessed the relationship between LVEF or E/A and the factors, myeloablative conditioning with TBI 12Gy was significantly associated with a decrease in LVEF after HCT (coefficient= −7.57, P=.001). However, in a comparison of Ara-C/CY/TBI and CY/TBI conditioning, the degree of change in the LVEF before and after HCT was similar between the two groups (repeated measures of ANOVA analysis. P=.0972). Patients who had received myeloablative conditioning had a significant decrease in E/A after HCT(coefficient= -.31, P=.02). Furthermore, a history of hypertension was also slightly associated with a decrease in E/A after HCT(coefficient= -.30, P=.05). In addition, only age was identified as a significant risk factor of left ventricular hypertrophy after HCT in the multivariate logistic analysis. However, in the present study, we could not identify a significant impact of cGVHD on cardiac function and LVH post HCT.
We concluded, based on our results, that the presence of cGVHD did not significantly contribute to a decrease in cardiac function in the chronic phase after HCT. Our results also suggest that the intensity of conditioning for HCT had a significant effect on chronic cardiac function after HCT.

Disclosures:
No relevant conflicts of interest to declare.