142 ADVANCED HEART FAILURE IN PATIENTS WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract

Abstract Background Arrhythmogenic Cardiomyopathy (ACM) is a primary disease of the heart muscle, characterized by fibro-fatty myocardial replacement. Improvements in the clinical diagnosis and antiarrhythmic therapy, including the use of the defibrillator (ICD) and endo-epicardial catheter ablation, have increased the survival of these patients, who experience late complications such as advanced heart failure, which sometimes requires cardiac transplantation. Aim of the study To evaluate clinical, instrumental and genetic features of patients affected with ACM who developed heart failure (HF) and to sought for possible predictive factors of HF. Methods From the entire cohort of probands and family members followed at the Cardiomyopathy unit of our University (555 patients), 34 patients (29%), both probands (n= 26, 77%) and family members who experienced HF (6%) were selected (24 males, 71%). Their anamnestic, clinical, and instrumental data were compared with those without episodes of HF (n-HF). Results The mean age at diagnosis in HF cohort was 45.2 (±18) years. In 14 patients (41%) HF was the first symptom that led to diagnosis. According to 2010 TFC 30 patients (88%) had a definite diagnosis of ACM. The most frequently observed phenotype was the biventricular ACM (n=27, 79%). A disease-related genetic variant was found in 18 (53%) and DSP was the more common disease-gene, accounting for 24% of cases. The mean duration of follow-up was 12.6 (±11.0) years (min-max, 1-20 years). During this period a total of 14 subjects (41.2%) experienced life-threatening arrhythmias (LTA), while 13 patients (38.2%) died, of whom 11 (84.6%) because of refractory HF. Eighteen patients (53%) underwent cardiac transplantation (mean age 43±17 years), approximately 4 (±3.5) years after the onset of symptoms. Comparison with the n-HF cohort of ACM patients showed a significant difference on presence of T-wave inversion (TWI) in V1-V3 (p=0.001), TWI in V4-V6 (p=0.010), low QRS voltages both in precordial and limb leads (both p<0.001) and presence of left bundle-branch block and right bundle-branch block (both p<0.001). Regarding CMR, HF cohort was characterized by a significantly more dilated right and left ventricle EDV (both p<0.001), EF reduction (both p<0.001), presence of wall motion alterations (respectively, p=0.007 and p<0.001) and LGE (respectively, p=0.002 and p=0.005) compared to n-HF group. Regarding outcomes evaluation, the HF group showed more frequently LTA (HF=41.2% vs n-HF 21.5%, p=0.008). Finally, the presence of right bundle-branch block at ECG (OR=20.562, CI 1.884-224.413, p=0.013) and of impaired RV ejection fraction (OR=0.821, CI 0.719-0.937, p=0.004) were found to be independent predictors of HF. Conclusions Heart failure is a rare complication in patients affected with ACM, with a prevalence of 6% in our study. The mean age of onset of HF was 45.2 (±18) years. Furthermore, 18 patients (53%) had an unfavorable progression to heart transplantation. The presence of right bundle branch block at ECG and an impaired CMR RV-EF were found to be predictors of HF. Our results suggest the importance of scheduling a close follow-up in ACM patients who show initial signs and/or symptoms of HF, taking into consideration the fast rate of progression to refractory HF, once established.