Tsai Katy K, Chang Andrew Y, Abouzeid Christiane M, Aras Mandar A, Fang Qizhi, Bibby Dwight, Haghighat Leila, Hilton Joan F, Daud Adil I, Schiller Nelson B
Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California, USA.
Department of Medicine, Section of Cardiovascular Medicine, Yale University, New Haven, Connecticut, USA.
Echocardiography. 2025 Apr;42(4):e70158. doi: 10.1111/echo.70158.
Immune checkpoint inhibitor (ICI) anti-tumor therapy is commonly associated with reports of significant fatigue. Whether ICI-induced fatigue is linked to subclinical cardiac toxicity is not well understood.
We performed a prospective observational study to monitor cardiac function following initiation of ICI in cancer patients. Rest and staged exercise stress transthoracic echocardiograms (TTE) were captured at baseline, 3 and 6 months after ICI initiation.
Thirteen patients completed baseline testing, of whom 10 completed 3 month testing and 8 completed 6 month testing. Patients had elevated fatigue as per Common Terminology Criteria for Adverse Events (CTCAE) criteria and FACIT-Fatigue subscale scores (47.5 [42.5-52] vs. 47 [38-48], p = 0.001). Among resting echocardiographic parameters, left ventricular (LV) outflow tract velocity time integral (VTI) was reduced at 6 months (22.6 cm [21.2-24.5] vs. 19.8 cm [17.2-21.2], p = 0.001), albeit still within normal range. Measures of biventricular size and systolic function, along with LV global longitudinal strain (GLS) and LA global strain, were not significantly changed. Among exercise parameters, peak heart rate was reduced at 6 months (143.4 bpm [128.5-153.5] vs. 123.5 [110.2-130.8], p = 0.048); of those who completed 6 month testing, two (29%) were unable to achieve the previous peak stage of exercise.
In patients starting ICI, statistically-significant reductions in cardiac systolic function (LVOT VTI) and peak HR were observed, with nearly one-third unable to achieve peak exercise at 6 months. This finding, combined with reported fatigue and lack of changes to biventricular systolic functional measures, suggests induced functional cardiac limitations are due to deconditioning, rather than cardiotoxicity.
免疫检查点抑制剂（ICI）抗肿瘤治疗通常伴随着明显疲劳的报告。ICI诱导的疲劳是否与亚临床心脏毒性有关尚不清楚。
我们进行了一项前瞻性观察性研究，以监测癌症患者开始使用ICI后的心脏功能。在基线、ICI开始后3个月和6个月时进行静息和分级运动负荷经胸超声心动图（TTE）检查。
13例患者完成了基线检查，其中10例完成了3个月检查，8例完成了6个月检查。根据不良事件通用术语标准（CTCAE）标准和功能性评估癌症治疗-疲劳分量表评分，患者的疲劳程度有所升高（47.5 [42.5 - 52] 对 47 [38 - 48]，p = 0.001）。在静息超声心动图参数中，左心室（LV）流出道速度时间积分（VTI）在6个月时降低（22.6 cm [21.2 - 24.5] 对 19.8 cm [17.2 - 21.2]，p = 0.001），尽管仍在正常范围内。双心室大小和收缩功能的测量值，以及左心室整体纵向应变（GLS）和左心房整体应变，均无显著变化。在运动参数中，6个月时峰值心率降低（143.4次/分钟 [128.5 - 153.5] 对 123.5 [110.2 - 130.8]，p = 0.048）；在完成6个月检查的患者中，有2例（29%）无法达到之前的运动峰值阶段。
在开始使用ICI的患者中，观察到心脏收缩功能（LVOT VTI）和峰值心率有统计学意义的降低，近三分之一的患者在6个月时无法达到运动峰值。这一发现，结合报告的疲劳以及双心室收缩功能测量值无变化，表明诱导的功能性心脏限制是由于身体失健，而非心脏毒性。
