Supplementary Material for: Diagnostic yield of updated indications for endomyocardial biopsy and its clinical predictors in a Chinese cohort

Introduction: The challenging and restrictive settings have been proposed in the updated indications for endomyocardial biopsy (EMB), but no data shows its performance. This study aimed to evaluate the diagnostic yield and find its clinical predictors.
Methods: All EMB performed between 2018 and 2022 were reviewed. Their clinical scenario and diagnostic yield were categorized retrospectively. Repeated and inadequate biopsies were excluded. Multivariate analysis was used to find the predictors.
Results: A total of 681 cases were collected (median age 44.0 years, 65.5% male) and 230 cases (33.8%) yielded specific diagnosis. The higher yield (52.8%) was found in clinically suspected myocarditis while no significant difference between cases with and without acute unstable hemodynamics (66.7% vs 47.1%; P=0.130). There was a much higher yield in unexplained restrictive or hypertrophic cardiomyopathy (RCM/HCM) with suspected infiltrative or storage disorder compared to those without (86.2% vs 10.3%; P<0.001). Dilated cardiomyopathy showed a lower yield, with or without recent-onset moderate-to-severe cardiac dysfunction (13.6% vs 16.3%; P=1.000). The same was true for unexplained atrioventricular block and ventricular arrhythmias (AVB/VA), with or without obvious structural abnormalities (8.2% vs 10.3%; P=0.675). On multivariate analysis, diffuse late gadolinium enhancement (odds ratio [OR] 4.14, 95% confidence interval [CI] 1.86-9.25; P=0.001), time course of disease ≤12 months (OR 3.31, 95% CI 1.75-5.57; P<0.001), elevated（≥1250 pg/ml）NT-proBNP (OR 2.91, 95% CI 1.67-5.06; P<0.001), and elevated (>0.068 ng/ml) hs-cTnI (OR 2.37, 95% CI 1.33-4.22; P=0.004) were independently associated with diagnostic yield.
Conclusion: Our results partially support the restrictive settings. EMB can achieve higher yield for unexplained RCM/HCM with suspected infiltrative or storage disorder, as well as strictly defined clinically suspected myocarditis, even in hemodynamically stable patients. However, the restrictive settings of unexplained AVB/VA and dilated cardiomyopathy did not show a clear advantage in diagnostic yield. The predictors this study found may help clinicians in selecting adequate candidates.

引言：更新版心肌内膜活检（endomyocardial biopsy, EMB）适应证提出了兼具挑战性与限制性的临床应用场景，但目前尚无数据证实该场景下EMB的临床表现。本研究旨在评估EMB的诊断检出率，并明确其临床预测因素。
方法：回顾性分析2018至2022年间完成的所有EMB操作病例，对其临床特征与诊断检出率进行回顾性分类。排除重复活检及取材不合格的病例，采用多变量分析筛选独立预测因素。
结果：本研究共纳入681例病例（中位年龄44.0岁，男性占比65.5%），其中230例（33.8%）获得明确特异性诊断。临床疑似心肌炎患者的诊断检出率更高（52.8%），但合并与未合并急性不稳定血流动力学状态的患者间检出率无显著差异（66.7% vs 47.1%；P=0.130）。在疑似浸润性或蓄积性疾病的不明原因限制性心肌病/肥厚型心肌病（restrictive cardiomyopathy/hypertrophic cardiomyopathy, RCM/HCM）患者中，诊断检出率显著高于无此类疑似情况者（86.2% vs 10.3%；P<0.001）。扩张型心肌病患者无论是否合并新发中重度心功能不全，其诊断检出率均较低（13.6% vs 16.3%；P=1.000）。不明原因房室传导阻滞/室性心律失常（atrioventricular block/ventricular arrhythmias, AVB/VA）患者无论是否存在明确结构性心脏异常，检出率同样无显著差异（8.2% vs 10.3%；P=0.675）。多变量分析结果显示，弥漫性延迟钆强化（比值比（odds ratio, OR）4.14，95%置信区间（confidence interval, CI）1.86~9.25；P=0.001）、病程≤12个月（OR 3.31，95%CI 1.75~5.57；P<0.001）、N末端B型利钠肽原（NT-proBNP）升高（≥1250 pg/ml，OR 2.91，95%CI 1.67~5.06；P<0.001）以及高敏心肌肌钙蛋白I（hs-cTnI）升高（>0.068 ng/ml，OR 2.37，95%CI 1.33~4.22；P=0.004）均为诊断检出率的独立相关因素。
结论：本研究结果部分支持现行的限制性EMB适应证场景。对于疑似浸润性或蓄积性疾病的不明原因RCM/HCM患者，以及严格定义的临床疑似心肌炎患者，即使血流动力学稳定，EMB仍可获得较高的诊断检出率。但针对不明原因AVB/VA及扩张型心肌病的限制性适应证场景，并未体现出显著的诊断检出率优势。本研究筛选出的预测因素可辅助临床医师筛选合适的EMB适应证人群。