Division of Cardiovascular Disease, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Division of Hematology and Oncology Disease, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Am J Cardiol. 2024 Sep 1;226:9-17. doi: 10.1016/j.amjcard.2024.06.033. Epub 2024 Jul 6.
Clonal hematopoiesis of indeterminate potential (CHIP) is a common risk factor for hematologic malignancies and cardiovascular diseases. This study aimed to investigate the association between CHIP-related mutations and symptomatic heart failure (HF) in patients diagnosed with acute myeloid leukemia (AML). A total of 563 patients with newly diagnosed AML who underwent DNA sequencing of bone marrow before treatment were retrospectively investigated. Cox proportional hazard regression models and Fine and Gray's subdistribution hazard regression models were used to assess the association between CHIP-related mutations and symptomatic HF. A total of 79.0% patients had at least 1 CHIP-related mutation; the most frequent mutations were DNMT3A, ASXL1, and TET2. A total of 51 patients (9.1%) developed symptomatic HF. The incidence of symptomatic HF was more frequent in patients with DNMT3A mutations (p <0.01), with a 1-year cumulative incidence of symptomatic HF in patients with DNMT3A mutations of 11.4%, compared with 3.9% in patients with wild-type DNMT3A (p <0.01). After adjustment for age and anthracyclines dose, DNMT3A mutations remained independently correlated with HF (hazard ratio 2.32, 95% confidence interval 1.26 to 4.29, p = 0.01). In conclusion, in patients with AML, the presence of DNMT3A mutations was associated with a twofold increased risk for symptomatic HF, irrespective of age and anthracyclines use.
不确定潜能的克隆性造血 (CHIP) 是血液恶性肿瘤和心血管疾病的常见危险因素。本研究旨在探讨 CHIP 相关突变与诊断为急性髓系白血病 (AML) 的患者的症状性心力衰竭 (HF) 之间的关系。对 563 例在治疗前接受骨髓 DNA 测序的新诊断 AML 患者进行了回顾性研究。使用 Cox 比例风险回归模型和 Fine 和 Gray 的亚分布风险回归模型来评估 CHIP 相关突变与症状性 HF 之间的关联。79.0%的患者至少存在 1 种 CHIP 相关突变；最常见的突变是 DNMT3A、ASXL1 和 TET2。共有 51 例（9.1%）患者发生症状性 HF。DNMT3A 突变患者发生症状性 HF 的频率更高（p<0.01），DNMT3A 突变患者 1 年累积症状性 HF 发生率为 11.4%，而野生型 DNMT3A 患者为 3.9%（p<0.01）。在调整年龄和蒽环类药物剂量后，DNMT3A 突变与 HF 仍然独立相关（风险比 2.32，95%置信区间 1.26 至 4.29，p=0.01）。总之，在 AML 患者中，DNMT3A 突变与症状性 HF 的风险增加两倍相关，与年龄和蒽环类药物的使用无关。
