Immunomodulation to target biopsy-proven myocardial inflammation in genetic cardiomyopathies: a pilot report

Abstract

Abstract Background Preclinical data support the rationale for targeting myocardial inflammation (M-Infl) in genetic nonischemic cardiomyopathies. However, no consistent clinical reports have been provided so far. Purpose To provide a pilot report on multimodal detection and targeting of biopsy-proven M-Infl in genetic cardiomyopathies. Methods We describe a series of patients (n=25) with genetic cardiomyopathy and M-Infl proven by endomyocardial biopsy (EMB). Multimodal diagnostic workup was extensively applied. Patient-tailored immunomodulatory therapy (IMT) was empirically started to target M-Infl whenever feasible. Multiple outcomes were retrospectively assessed by a dedicated multidisciplinary disease unit. Results Patients carrying desmosomal (DGV), cytoskeletal (CGV) and other gene variants, were 12 (48%), 10 (40%), and 3 (12%), respectively. DGV carriers uniformly presented with myocarditis-like chest pain and ventricular arrhythmias, whereas heart failure symptoms were found only in CGV carriers. Dilated cardiomyopathy phenotype and ring-like pattern on cardiac magnetic resonance allowed the best discrimination among genotypes. Noninvasive imaging was concordant with EMB in detecting M-Infl in 21 patients (83%). IMT was started in 17 patients (71%) with no safety issues. By the end of follow-up (median 69 months, range 21-182), signs of M-Infl were documented in 6/18 IMT receivers (33%) and 4/7 untreated cases (57%). For most genotypes, paucity of adverse events was noted while on IMT as compared to the off-treatment period. Conclusion Our preliminary data provide a clinical rationale for the research and targeting of M-Infl in a spectrum of genetic nonischemic cardiomyopathies.