Endomyocardial Biopsy: Evaluating the Impact of Updated Indications on Diagnostic Yield

Endomyocardial biopsy (EMB) remains the definitive method for establishing tissue-level cardiac diagnoses, yet its role in clinical practice has narrowed over time due to procedural risks, improved noninvasive imaging, and variability in diagnostic yield. In response to this evolving landscape, the 2021 Seferović et al. [1] joint position statement by the Heart Failure Association of the ESC, the Heart Failure Society of America, and the Japanese Heart Failure Society provided updated, more narrowly defined clinical scenarios intended to guide EMB use in selected patients with heart failure, cardiomyopathies, arrhythmias, and suspected myocarditis. However, empirical validation of these scenarios in large patient cohorts has been limited.In this context, Duan et al. [2] presented a retrospective cohort study of 681 patients undergoing EMB at a high-volume tertiary care center in China, categorizing cases according to the 2021 updated indications and assessing diagnostic yield and its clinical predictors. Their findings contribute important real-world data on the performance of guideline-endorsed EMB strategies and raise critical questions about their diagnostic efficiency in specific patient populations.Duan et al. [2] reported an overall diagnostic yield of 33.8%, higher than prior large studies reporting yields between 12.5% and 25.5% [3‒5]. This elevated yield is partly attributable to a high proportion of cases with suspected cardiac amyloidosis and myocarditis, both conditions with known higher histopathologic detectability and a central role in contemporary EMB indications.In line with the 2021 position statement [1], EMB yields a high diagnostic return in patients with suspected infiltrative or storage disorders presenting as restrictive or hypertrophic cardiomyopathy (RCM/HCM). Among these, patients with a clinical suspicion of infiltrative disease had a diagnostic yield of 86.2%, compared to only 10.3% when no specific etiology was suspected. This result underscores the value of pre-biopsy clinical suspicion and supports the continued role of EMB when noninvasive testing is inconclusive or suggestive of infiltrative cardiomyopathy, particularly in the context of amyloidosis. Both the 2021 Seferović et al. [1] position statement and the 2021 ESC heart failure guidelines by McDonagh et al. [6] emphasize the importance of a clearly suspected clinical etiology (based on imaging, laboratory findings, or systemic features) when considering EMB. This marks a departure from earlier guidance, such as the 2007 AHA scientific statement by Cooper et al. [7], which offered broader recommendations around unexplained RCM/HCM, without the same emphasis on pretest probability or diagnostic specificity.Similarly, the study supports EMB in clinically suspected myocarditis, reporting a yield of 52.8%. Remarkably, no statistically significant difference in diagnostic yield was observed between hemodynamically stable and unstable patients, suggesting that clinical severity alone may not be a sufficient discriminator of biopsy benefit. This finding challenges the more selective approach of the 2021 Seferović et al. [1] position statement and the 2021 ESC heart failure guidelines [6], which emphasize EMB primarily in rapidly progressive or fulminant presentations. In contrast, the earlier 2013 ESC position statement by Caforio et al. [8] provides a broader recommendation, stating that all patients with clinically suspected myocarditis should be considered for EMB. The current findings align more closely with this earlier view and support the use of refined clinical phenotyping (including multimodal imaging and biomarker profiles) to guide biopsy decisions beyond hemodynamic status alone.In contrast, Duan et al. [2] found low diagnostic yields in two 2021 Seferović et al. [1] guideline-specified subgroups: dilated cardiomyopathy (DCM) and unexplained atrioventricular block or ventricular arrhythmias (AVB/VA). In the DCM subgroup, the authors applied the 2021 guideline-recommended stratification (recent onset and moderate-to-severe LV dysfunction), in accordance with previous guidelines [7], but observed no yield advantage over patients who did not meet these criteria (13.6% vs. 16.3%; p = 1.000). Similarly, in the AVB/VA group, no significant difference in yield was found between patients with minimal structural abnormalities (the group prioritized in the guidelines) and those with more advanced disease (10.3% vs. 8.2%; p = 0.675).These findings suggest that the restrictive definitions proposed in the 2021 statement may not, on their own, enhance diagnostic efficiency. The authors hypothesize that yield in these populations may depend more on the presence of specific imaging or biochemical abnormalities than on structural or hemodynamic parameters alone. This interpretation aligns with the 2021 Seferović et al. [1] statement’s broader recommendation for multimodal evaluation but suggests the need for more granular stratification criteria in these lower yield clinical scenarios.One of the central contributions by Duan et al. [2] is its identification of clinical and imaging predictors of diagnostic success. In multivariate analysis, four factors were independently associated with diagnostic yield: diffuse late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (odds ratio [OR] 4.14), disease duration ≤12 months (OR 3.31), elevated NT-proBNP (≥1,250 pg/mL, OR 2.91), and elevated high-sensitivity troponin I (>0.068 ng/mL, OR 2.37). These predictors remained significant even when amyloidosis cases were randomly excluded in sensitivity analyses, suggesting broader applicability across multiple pathologies.The prominence of diffuse LGE as a yield predictor is particularly worth highlighting. While the 2021 position paper [1] references the use of cardiac MRI in guiding EMB, the Duan et al. [2] findings empirically reinforce its value as a selection tool. Taken together, these predictors offer an actionable framework for clinicians seeking to identify patients most likely to benefit from biopsy and may help operationalize guideline recommendations in daily practice.The strengths of study by Duan et al. [2] include its large sample size, systematic application of guideline-defined clinical scenarios, and rigorous pathological classification supported by immunohistochemistry and mass spectrometry. These methods enhance the internal validity of yield assessments and ensure that diagnoses were based on reproducible, tissue-level criteria.However, the study has limitations that merit consideration. Its single-center, retrospective design limits generalizability, and the high proportion of amyloidosis cases may not reflect referral patterns in other settings. Genetic testing was underreported, especially in patients with HCM/RCM without suspected infiltrative disease, which may have reduced diagnostic yield in that subgroup. Additionally, electroanatomic mapping (i.e., a potentially yield-enhancing technique in patients with arrhythmias) was not used, which may have impacted findings in the AVB/VA group.Lastly, the study’s definition of “diagnostic yield,” limited to biopsies that resulted in a specific diagnosis with therapeutic implications, may underestimate the broader clinical use of EMB. As demonstrated by Bennett et al. [3] in a cohort of 851 patients undergoing EMB at a tertiary care center from 2000 to 2009, it is useful to distinguish between “diagnostic yield” (i.e., the proportion of biopsies that provided a definitive histological diagnosis) and “clinical yield,” defined as those that led to a change in patient management. This distinction highlights that even biopsies without a specific pathologic label may still have clinical value, such as by excluding alternative diagnoses or supporting suspected conditions with nonspecific histological findings.Duan et al. [2] provided an empirically grounded assessment of the diagnostic yield of EMB under the framework of the 2021 international position statement [1]. Their findings largely validate the use of EMB in scenarios involving suspected infiltrative disease and myocarditis when supported by imaging and biochemical evidence. However, they also highlight limitations in the current guideline stratification of DCM and arrhythmia-related indications and suggest that clinical predictors such as LGE, NT-proBNP, and hs-cTnI may better inform case selection.Taken together, this study supports a more nuanced, data-driven application of the 2021 guidelines [1]. As EMB continues to evolve alongside noninvasive diagnostics, the integration of risk prediction models into guideline frameworks may improve the precision and cost-effectiveness of myocardial tissue evaluation in contemporary practice.The author has no conflicts of interest to declare.This study was not supported by any sponsor or funder.María Teresa Politi drafted, critically revised, and reviewed the manuscript.