Female gender is associated with DCM-like presentation and worse outcomes in inflammatory cardiomyopathy: long-term data from a large monocentric prospective cohort

Abstract Background Myocarditis with infarct-like presentation is associated with male sex and good prognosis, but the role of gender in myocarditis with dilated cardiomyopathy (DCM) phenotype has not been studied yet. Purpose To analyse diagnostic and prognostic implications of gender in a large prospective cohort of biopsy-proven (BP) or clinically-suspected (CS) myocarditis patients. Methods We retrospectively included myocarditis patients followed up at the Cardio-immunology outpatient clinics of our University Hospital. Diagnostic and prognostic data were compared between female and male patients. Deaths, heart transplantation (HTx) and myocarditis relapse were recorded. In addition, a composite outcome was identified considering symptoms persistence and/or reduced LVEF at last follow-up. Results A total of 1194 patients were included, of whom 370 were female and 824 male. Endomyocardial biopsy was available for 481 patients. Compared to males, female patients were older at diagnosis (43 vs 33 years old, p 0.001), less frequently had acute viral symptoms before diagnosis (28% vs 46%, p 0.001) and more frequently had associated immune mediated conditions (23% vs 10%, in particular autoimmune thyroiditis, systemic sclerosis, peripheral myopathies). Female patients were indeed more frequently ANA positive (17% vs 7%, p=0.005). Females had longer duration of symptoms before myocarditis diagnosis (2 vs 1 month, p= 0.019) and were in a worse functional class compared to males (35% in NYHA functional class 1 vs 22%, p 0.001); less frequently had angina at presentation (36% vs 46%, p= 0.022) and more frequently had normal troponin at diagnosis (28% vs 16%, p= 0.006). Moreover, when troponin was abnormal, it was lower in female than male patients (1286 vs 3480 ng/L, p 0.001). Similarly, in female patients, C-reactive protein (CRP) was more frequently normal (47% vs 3%, p = 0.003) and, when it was abnormal, it was lower (7 vs 17 mg/dl, p 0.001). On baseline echocardiography, the left ventricule (LV) was more often dilated in women than men (51% vs 33%, p0.001). When cardiac magnetic resonance was available, late gadolinium enhancement (LGE) mass was inferior in female than male patients (LGE/LV mass 1.7% vs 3.5%, p 0.001). After a median follow-up of 49 months (IQR 17-96), female patients more frequently presented low voltages on ECG (12% vs 4.7%, p= 0.014) and, although no absolute difference in deaths, HTx or relapse rates was observed, females more frequently presented the composite outcome (21% vs 14%, p= 0.02). Conclusions In BP or CS myocarditis, female patients more frequently have a dilated cardiomyopathy phenotype, normal troponin and CRP, subacute presentation and worse outcome than males. They also show more frequently autoimmune features. These findings are relevant to define a different clinical approach for female patients and to guide clinicians in investigating differences between idiopathic and inflammatory DCM in women.