Egberts Briella K, Ananthakrishna Rajiv, Perry Rebecca, Woodman Richard J, Sutton Alison, Pasupathy Sivabaskari, Hecker Teresa, Bromley Tonia A, Yang Woo Sze, Karapetis Christos, Selvanayagam Joseph B
College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; Department of Cardiovascular Medicine, Flinders Medical Centre, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; Department of Cardiovascular Medicine, Flinders Medical Centre, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia; Ballarat Base Hospital, Grampians Health, Ballarat, Vic, Australia; Wimmera Base Hospital, Grampians Health, Horsham, Vic, Australia.
Heart Lung Circ. 2025 Jun;34(6):596-605. doi: 10.1016/j.hlc.2024.11.018. Epub 2025 Apr 8.
Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment, becoming a cornerstone therapy for various malignancies. Despite their efficacy, there are concerns about their potential cardiotoxicity, particularly, subclinical myocardial injury. However, there remains a scarcity of local data on the precise incidence of such cardiac complications. This prospective pilot study aims to assess myocardial injury in patients undergoing ICI therapy without known cardiovascular disease, using biochemical and cardiac imaging markers of myocardial injury.
A total of 41 patients (median age 68 years, 63% male) receiving ICI therapy without previous cardiac disease were prospectively enrolled. Serial assessments were conducted at baseline and 6 weeks, including measurement of cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and two-dimensional transthoracic echocardiography with speckle tracking strain. Cardiac magnetic resonance imaging (CMR) was performed at 6 weeks. A control group (n=10, median age 66 years, 50% male) with no ICI treatment with matched oncological profile was established. The primary outcome was the incidence of cTnI increase at 6 weeks, with secondary outcomes including changes in NT-proBNP, left ventricular (LV) ejection fraction, LV global longitudinal strain (LV-GLS), right ventricular free wall systolic strain, myocardial injury on CMR, and major adverse cardiac events.
Median baseline cTnI levels measured 4.0 (interquartile range 3.0-7.0) ng/L, with only one patient (2.7%) demonstrating significant cTnI increase after ICI therapy. Follow-up assessments revealed no significant mean differences in cTnI, NT-proBNP, LV ejection fraction, or right ventricular free wall systolic strain. However, a significant change in LV-GLS was noted in the ICI group (-1.2%, p=0.004) compared with controls (-0.7%, p=0.50, p=0.02). A total of 20 patients (54%) underwent CMR, with 11 (55%) exhibiting abnormalities (T1/T2 mapping and late gadolinium enhancement). Of the nine patients (45%) with increased T1 mapping on CMR, all demonstrated a reduction in LV-GLS between baseline and 6 weeks, with a mean reduction of 5% (3%-12%). Within 1 year, major adverse cardiac events occurred in 17 (45.9%) patients.
Although the occurrence of significant cTnI increase was low, subclinical myocardial injury can be detected through advanced cardiac imaging after ICI initiation. This underscores the importance of conducting larger studies to further elucidate the prevalence, mechanisms, and clinical implications of myocardial injury in patients receiving ICI treatment.
免疫检查点抑制剂（ICIs）彻底改变了癌症治疗方式，成为各种恶性肿瘤的基石疗法。尽管其疗效显著，但人们担心其潜在的心脏毒性，尤其是亚临床心肌损伤。然而，关于此类心脏并发症的确切发生率，当地数据仍然匮乏。这项前瞻性试点研究旨在使用心肌损伤的生化和心脏成像标志物，评估接受ICI治疗且无已知心血管疾病患者的心肌损伤情况。
前瞻性纳入了41例接受ICI治疗且既往无心脏病的患者（中位年龄68岁，63%为男性）。在基线和6周时进行了系列评估，包括测定心肌肌钙蛋白I（cTnI）、N末端脑钠肽前体（NT-proBNP）以及二维经胸超声心动图斑点追踪应变分析。在6周时进行了心脏磁共振成像（CMR）检查。设立了一个未接受ICI治疗且肿瘤学特征匹配的对照组（n = 10，中位年龄66岁，50%为男性）。主要结局是6周时cTnI升高的发生率，次要结局包括NT-proBNP的变化、左心室（LV）射血分数、左心室整体纵向应变（LV-GLS）、右心室游离壁收缩期应变、CMR上的心肌损伤以及主要不良心脏事件。
基线时cTnI水平中位数为4.0（四分位间距3.0 - 7.0）ng/L，ICI治疗后只有1例患者（2.7%）出现cTnI显著升高。随访评估显示，cTnI、NT-proBNP、LV射血分数或右心室游离壁收缩期应变的平均差异无统计学意义。然而，与对照组相比，ICI组的LV-GLS有显著变化（-1.2%，p = 0.004），而对照组为（-0.7%，p = 0.50，p = 0.02）。共有20例患者（54%）接受了CMR检查，其中11例（55%）表现出异常（T1/T2映射和延迟钆增强）。在CMR上T1映射增加的9例患者（45%）中，所有患者在基线和6周之间LV-GLS均降低，平均降低5%（3% - 12%）。1年内，17例（45.9%）患者发生了主要不良心脏事件。
尽管cTnI显著升高的发生率较低，但在ICI治疗开始后，通过先进的心脏成像可检测到亚临床心肌损伤。这突出了开展更大规模研究以进一步阐明接受ICI治疗患者心肌损伤的患病率、机制及临床意义的重要性。
