Electroanatomic voltage mapping-guided endomyocardial biopsy and cardiac sarcoidosis: insights into disease activity and diagnostic reclassification

Background Endomyocardial biopsy (EMB) remains the histological gold standard for the diagnosis of cardiac sarcoidosis (CS), yet its sensitivity is limited by the patchy and phase-dependent nature of myocardial involvement. The 2025 ESC guidelines introduced electroanatomic mapping (EAM)–guided EMB as a Class IIa recommendation in suspected CS; however, real-world data regarding optimal patient selection and diagnostic impact remain limited. We hypothesized that EAM-guided EMB provides the greatest diagnostic value in patients with imaging evidence of active myocardial inflammation and enables clinically meaningful diagnostic reclassification. Methods We retrospectively analyzed consecutive patients with suspected CS who underwent EAM-guided EMB at a tertiary referral center between January 2023 and December 2025. All patients underwent comprehensive pre-procedural evaluation including cardiac magnetic resonance imaging (CMR) and FDG-PET. High-density bipolar voltage mapping was performed using the EnSite NavX™ system, with direct visualization of the bioptome tip within the three-dimensional map to enable targeted sampling of low-voltage and border-zone myocardium guided by electroanatomic and imaging abnormalities. Genetic testing was performed when clinically indicated. Final diagnosis (definite, probable, possible, or unlikely CS) was adjudicated according to Heart Rhythm Society (HRS) criteria, with sensitivity analyses using ESC and JMHW criteria. Associations between low-voltage areas and a final diagnosis of definite/probable CS were assessed using Fisher’s exact test. Results Twenty-six patients were included (mean age 58 years [range 24–84], 24% male). Low-voltage areas were identified in 9 patients (34%). Histological confirmation of CS was achieved in 3 patients (one unguided biopsy), all demonstrating active myocardial inflammation on FDG-PET. Six additional patients with extracardiac sarcoidosis and characteristic CMR and FDG-PET findings fulfilled HRS criteria for probable CS despite negative myocardial histology. In 4 patients, EAM-guided EMB in combination with genetic testing led to a revised diagnosis of arrhythmogenic cardiomyopathy. Two procedural complications occurred. The presence of low-voltage areas was strongly associated with a final diagnosis of definite/probable CS (8/9 vs. 4/17; Fisher’s exact p = 0.003). Conclusion In this exploratory cohort, EAM-guided EMB demonstrated meaningful diagnostic yield within a contemporary imaging-guided work-up of suspected cardiac sarcoidosis. No cases of histology-positive CS with negative FDG-PET were observed, underscoring the role of nuclear imaging in identifying active disease stages. Voltage-guided EMB appears to function best as a selective, imaging-enriched strategy and may additionally facilitate diagnostic clarification of relevant differential diagnoses.