AimsProgressive heart failure with reduced ejection fraction (HFrEF) is adversely affected by alterations in the myocardial balance between bone marrow‐derived pro‐inflammatory cardiac macrophages and embryo‐derived reparative cardiac resident macrophages. Mesenchymal precursor cells (MPCs) may restore this balance and improve clinical outcomes when inflammation is present. The purpose was to (i) identify risk factors for cardiovascular death (CVD) in control patients with HFrEF in the DREAM‐HF trial, and (ii) determine if MPCs improve major clinical outcomes (CVD, myocardial infarction [MI], stroke) in high‐risk patients with ischaemic HFrEF and inflammation.Methods and resultsCause‐specific regression analyses were used to identify CVD risk factors in DREAM‐HF control patients. Aalen–Johansen cumulative incidence curves were used to examine CVD, 2‐point major adverse cardiovascular events (MACE) (MI or stroke), and 3‐point MACE (CVD or MI or stroke) by treatment group in ischaemic vs non‐ischaemic HFrEF and in patients with or without baseline inflammation. In control DREAM‐HF patients, factors portending the greatest risk for CVD were inflammation (baseline plasma high‐sensitivity C‐reactive protein ≥2 mg/L; p = 0.003) and ischaemic HFrEF aetiology (p = 0.097), with increased CVD risk of 61% and 38%, respectively. Over 30‐month mean follow‐up, MPCs reduced 2‐point and 3‐point MACE by 88% (p = 0.005) and 52% (p = 0.018), respectively, in patients with ischaemic HFrEF and inflammation compared to controls.ConclusionIschaemic aetiology and inflammation were identified as major risk factors for MACE in control DREAM‐HF patients. A single intramyocardial MPC administration produced the most significant, sustained reduction in 2‐point and 3‐point MACE in patients with ischaemic HFrEF and inflammation.

中文翻译：

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间充质前体细胞可降低伴有炎症的缺血性心力衰竭的死亡率和主要发病率：DREAM-HF


目的射血分数降低的进行性心力衰竭 （HFrEF） 受到骨髓来源的促炎性心脏巨噬细胞和胚胎来源的修复性心脏常驻巨噬细胞之间心肌平衡改变的不利影响。间充质前体细胞 （MPC） 可以在存在炎症时恢复这种平衡并改善临床结果。目的是 （i） 在 DREAM-HF 试验中确定 HFrEF 对照患者心血管死亡 （CVD） 的危险因素，以及 （ii） 确定 MPC 是否改善缺血性 HFrEF 和炎症高危患者的主要临床结局 （CVD、心肌梗死 [MI]、中风）。方法和结果采用病因特异性回归分析确定 DREAM-HF 对照患者的 CVD 危险因素。Aalen-Johansen 累积发生率曲线用于检查缺血性与非缺血性 HFrEF 治疗组的 CVD、2 点主要不良心血管事件 （MACE） （MI 或中风） 和 3 点 MACE （CVD 或 MI 或中风） 以及有或没有基线炎症的患者。在对照 DREAM-HF 患者中，预示 CVD 风险最大的因素是炎症 （基线血浆高敏 C 反应蛋白 ≥2 mg/L;p = 0.003） 和缺血性 HFrEF 病因 （p = 0.097），CVD 风险分别增加 61% 和 38%。在 30 个月的平均随访中，与对照组相比，MPC 将缺血性 HFrEF 和炎症患者的 2 点和 3 点 MACE 分别降低了 88% （p = 0.005） 和 52% （p = 0.018）。结论缺血病因和炎症是对照 DREAM-HF 患者发生 MACE 的主要危险因素。 在缺血性 HFrEF 和炎症患者中，单次心肌内 MPC 给药对 2 点和 3 点 MACE 产生了最显着、最持续的降低。