Arrhythmogenic right ventricular cardiomyopathy as cause of severe heart failure leading to heart transplantation

Abstract

Purpose: Arrythmogenic right ventricular cardiomyopathy (ARVC) is predominantly known as a cause of sudden death and ventricular arrhythmias in the young, whereas the relationship between ARVC and heart failure (HF) has been scarcely investigated. We aimed this study to evaluate prevalence, incidence, pathophysiology and morphologic basis of ARVC leading to severe HF. Methods: We retrospectively analyzed 60 patients with ARVC evaluated at a single referral centre. We compared the clinical, electrocardiographic, hemodynamic and echocardiographic findings of ARVC patients with/without severe HF (NYHA III-IV) at first evaluation or during follow up. We also analyzed the histopathological findings of the explanted hearts of patients who underwent heart transplantation. Results: Severe HF was present in 10 patients at presentation (prevalence=16%) and occurred in other 9 during a median follow up of 68 months (IQR 24-127; incidence=2.3% person-years). Fourteen patients (23%) required heart transplantation and 40 patients (66%) underwent ICD implantation. Patients with advanced HF were younger at symptom onset (47±16 versus 37±12 years, p=0.01) and more often had epsilon waves in the right precordial leads (53% versus 8%, p=0.001) and low voltages in the peripheral leads (46% versus 16%, p=0.05); right ventricle (RV) was larger and more hypokinetic at echocardiography (RVOT 41±6 versus 37±6 mm, p=0.02; RV end diastolic internal diameter 35±12 versus 28±8 mm, p=0.01; fractional shortening area 24%±8 versus 31%±11, p= 0.016). Interestingly, left ventricle (LV) was slightly more dilated (75±30 ml/m2 versus 60±20, p= 0.02) and globally hypokinetic (LV Ejection Fraction =41%±16 versus 57%±12, p= 0.001). The hemodynamic profile of patients who underwent cardiac transplantation was characterized by low cardiac index (1.8±0.2 l//min/m2) with normal or nearly normal capillary wedge and pulmonary pressure (12±8 mmHg and 26±10 mmHg). A detailed histological analysis of the explanted hearts showed extensive (>60% of the surface) fibro-fatty infiltration of the right ventricle and isolated or confluent areas of LV fibrosis. In 4 patients (28%) flogistic infiltrations were also evident. Conclusions: In ARVC, HF can be the only symptom at presentation and leads to heart transplantation in a relevant subset of patients. Patients who develop advanced HF are younger, have more severe right ventricular involvement associated with slight dilation and global hypokinesia of the LV, due to fibrotic infiltration.