Incremental diagnostic value of left endomyocardial biopsy for non-ischemic left ventricular scar beyond imaging modalities

Background

A clear need exists for accurate etiological diagnosis in patients with non-ischemic left ventricular (LV) late gadolinium enhancement (LGE).

This spectrum includes myocarditis, left-dominant arrhythmogenic cardiomyopathy (ALVC), and isolated LV fibrosis. The incremental diagnostic value of left endomyocardial biopsy (EMB) in this setting remains incompletely defined. This study sought to characterize patients with non-ischemic LV scar and to evaluate the diagnostic contribution of EMB when integrated with multimodality assessment.

Methods

This single-center retrospective cohort study included 77 consecutive patients referred to a tertiary center between 2019 and 2024 for suspected non-ischemic LV disease. All patients underwent electroanatomical mapping (EAM)-guided left EMB. Clinical data, arrhythmic history, family history, and sports activity were systematically collected. Histological findings were integrated with cardiac magnetic resonance (CMR), EAM, and genetic testing to establish the final diagnosis. Concordance between LGE distribution and EAM abnormalities, as well as the diagnostic accuracy of clinical evaluation relative to genetic findings, was evaluated.

Results

The cohort was predominantly male (78.6%), with a median age of 42 years. Symptomatically, palpitations were most frequently reported (36.4%), followed by dyspnea (26.0%), chest pain (19.5%), and syncope (18.2%). Nearly three-quarters of patients experienced ventricular ectopy (72.7%), and more than half had ventricular arrhythmias (52%), while a history of prior cardiac arrest was seen in 11.7%. Mean left ventricular ejection fraction was moderately reduced (51.7±10.2%). Cardiac magnetic resonance (CMR), performed in 93.3% of patients, demonstrated LGE in 84% of patients, predominantly involving the basal and mid-inferolateral segments. Electroanatomical mapping identified unipolar and bipolar abnormalities and detected late potentials. Histological analysis via endomyocardial biopsy (EMB) revealed fibrotic replacement in 70%, inflammatory infiltrates in 27%, and fibrofatty infiltration in 4%. Ultimately, these findings translated to final diagnoses of scar substrate (54.5%), myocarditis (18.2%), arrhythmogenic cardiomyopathy (12.3%), dilated cardiomyopathy (9.1%), and amyloidosis (1.3%). Genetic testing in 50 patients identified pathogenic or likely pathogenic variants in 26%. EMB reclassified patients in 45% of cases, directly impacting clinical management.

Conclusions

Non-ischemic LV scar is associated with a heterogeneous patient population and a substantial arrhythmic burden. In cases of overlapping imaging features, left EMB can provide etiological clarification, complementing both imaging and genetic testing. By enabling more precise identification of underlying disease processes, this multimodality approach facilitates targeted therapies for patients.EMB diagnosis reclassification