Saltzman Russell G, Sundin Andrew, Caceres Lina V, Tovar Jairo A, Garzon Ana Maria, Cabreja Maria A, Shayestehyekta Hossein, Soto Jeanette, Jayaweera Dushyantha, Khan Aisha, Schulman Ivonne H, Mitrani Raul D, Hare Joshua M
Leonard M. Miller School of Medicine, Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL 33136, United States.
Loma Linda University Medical Center, Loma Linda, CA 92354, United States.
Stem Cells Transl Med. 2025 May 19;14(5). doi: 10.1093/stcltm/szaf010.
There is limited long-term clinical outcome data supporting the use of cell-based therapy to treat heart failure. The HYPERION study (NCT03071835) followed long-term outcomes of patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NIDCM) who received mesenchymal stromal cells (MSC). We hypothesized that improved cardiac parameters predict longer event-free survival.
We performed a Kaplan-Meier analysis to examine event-free survival as the primary outcome. Time-to-event information was captured from all eligible participants. Endpoint events were defined as death (all-cause), Left Ventricular Assist Device (LVAD) placement, or Heart Transplant. Subjects were categorized based on increase in Left Ventricular Ejection Fraction (LVEF) or decrease in Left Ventricular End Diastolic Volume (LVEDV) for comparisons within disease etiologies.
There were 134 men and 21 women, with mean age 60.0 ± 11.0 years. There were 121 (78%) with ICM and 34 (22%) with NIDCM. By the end of long-term follow-up (~13 years), 38 (24.5%) subjects had deceased, 5 (3.2%) received LVAD, and 8 (5.2%) underwent heart transplantation. Post-therapy increase of ≥5% LVEF was associated with longer event-free survival in NIDCM (HR:0.31; 95%CI, 0.11,0.86; P = .025), but not ICM (HR:1.14; 95%CI, 0.47,2.72; P = .776). Conversely, reduction in left ventricular end-diastolic volume (LVEDV) was associated with longer event-free survival in ICM (HR:0.16; 95%CI, 0.05, 0.55; P = .008) but not NIDCM (HR:0.35; 95%CI, 0.1,1.2; P = .098). ICM improvers had LVEDV of 225.7 ± 95.9 mL at baseline and 209.0 ± 100.6 mL by year 5 (P = .046). NIDCM improvers had LVEF of 27.2 ± 8.9% at baseline and 36.1 ± 11.6% by year 5 (P = .018).
In this long-term observational cohort analysis, improvement of LVEF and/or reduction in LVEDV was associated with survival benefits among subjects with NIDCM and ICM, respectively. In both etiologies the respective improvements are sustained for up to 5 years, providing evidence that cell-based therapy may be a promising and durable treatment option for patients with heart failure.
支持使用细胞疗法治疗心力衰竭的长期临床结局数据有限。HYPERION研究（NCT03071835）追踪了接受间充质基质细胞（MSC）治疗的缺血性心肌病（ICM）和非缺血性心肌病（NIDCM）患者的长期结局。我们假设心脏参数的改善可预测更长的无事件生存期。
我们进行了Kaplan-Meier分析，以检查无事件生存期作为主要结局。从所有符合条件的参与者中获取事件发生时间信息。终点事件定义为死亡（全因）、植入左心室辅助装置（LVAD）或心脏移植。根据左心室射血分数（LVEF）增加或左心室舒张末期容积（LVEDV）减少对受试者进行分类，以便在疾病病因内进行比较。
共有134名男性和21名女性，平均年龄60.0±11.0岁。其中121名（78%）为ICM患者，34名（22%）为NIDCM患者。到长期随访结束时（约13年），38名（24.5%）受试者死亡，5名（3.2%）接受了LVAD植入，8名（5.2%）接受了心脏移植。治疗后LVEF增加≥5%与NIDCM患者更长的无事件生存期相关（HR：0.31；95%CI，0.11，0.86；P = 0.025），但与ICM患者无关（HR：1.14；95%CI，0.47，2.72；P = 0.776）。相反，左心室舒张末期容积（LVEDV）减少与ICM患者更长的无事件生存期相关（HR：0.16；95%CI，0.05，0.55；P = 0.008），但与NIDCM患者无关（HR：0.35；95%CI，0.1，1.2；P = 0.098）。ICM改善者基线时LVEDV为225.7±95.9 mL，到第5年时为209.0±100.6 mL（P = 0.046）。NIDCM改善者基线时LVEF为27.2±8.9%，到第5年时为36.1±11.6%（P = 0.018）。
在这项长期观察性队列分析中，LVEF改善和/或LVEDV减少分别与NIDCM和ICM受试者的生存获益相关。在这两种病因中，各自的改善可持续长达五年，这为基于细胞的疗法可能是心力衰竭患者一种有前景且持久的治疗选择提供了证据。
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