Left-Dominant Arrhythmogenic Cardiomyopathy

A 50-year-old recreational futsal player was referred to our sports cardiology outpatient clinic for palpitations and detection of frequent ( 5000) ventricular premature beats with bigeminy and runs of nonsustained ventricular tachycardia at 24-hour Holter monitoring. Rest ECG showed normal QRS morphology with negative T waves in precordial lateral (V4 to V6) and inferior leads (Figure 1A). Lessprominent negative T waves in lateral but not inferior leads also were present in previous ECGs obtained during routine sports preparticipation evaluation at age 26 years (Figure 1B) but in the absence of symptoms and arrhythmias at Holter monitoring; no other diagnostic test was performed at that time. A stress ECG failed to reveal ST-segment changes diagnostic for myocardial ischemia, whereas frequent polymorphic ventricular premature beats with right bundle branch block morphology and a short run of nonsustained ventricular tachycardia were observed during the recovery phase. Twodimensional echocardiography showed a mild reduction of ejection fraction with a diffuse apical a-dyskinesia of the left ventricle (LV), whereas the right ventricle (RV) presented normal dimensions and global function but hypokinesia of the apex and the basal portion of the free wall. Cardiac MRI showed the presence of an extensive akinetic area at the apex of the LV characterized by wall thinning and associated with midwall and subepicardial delayed enhancement of lateral and apical walls (Figure 2A through 2C). Apical and posterobasal segments of the RV also were characterized by wall thinning associated with wall motion abnormalities. In addition, areas of fatty replacement were observed in the epicardial portion of LV lateral and inferior walls (Figure 2D). The patient was then submitted to an invasive study, including cardiac catheterization with coronary angiography, electroanatomic mapping-guided endomyocardial biopsy, and programmed electric stimulation, to identify the substrate of the structural and functional cardiac abnormalities observed. Coronary angiography showed normal coronary arteries, whereas LV angiography confirmed the presence of an apical dyskinesia with a mildly reduced global systolic function. RV angiography showed a mild enlargement of the ventricle with moderate ectasia of the free wall (online-only Data Supplement Movies 1 and 2). Biventricular electroanatomic mapping revealed the presence of low-voltage areas at the apex of the LV and the basal portion of the RV free wall (Figure 3A and 3B). Multiple endomyocardial biopsies were drawn from low-voltage areas of both the LV and the RV as previously described,1 and programmed electric stimulation failed to induce sustained ventricular arrhythmias. Histological analysis of LV specimens showed extensive areas of replacement fibrosis with multiple areas of fatty replacement, whereas the RV specimens were characterized by areas of fibrofatty replacement with residual myocardial tissue inferior to 60% of the total area (Figure 4A and 4B). Mutation screening of 5 desmosomal genes (plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2) by direct sequencing failed to detect any gene mutation associated with arrhythmogenic cardiomyopathy. On the basis of clinical, ECG, and histological features, left-dominant arrhythmogenic cardiomyopathy (LDAC)2 was diagnosed. The patient was adequately informed about the risk of life-threatening ventricular arrhythmias and about the efficacy on preventing sudden death and the possible complications of both implantable cardioverter-defibrillator and radiofrequency catheter ablation, but he refused any invasive therapeutic intervention and was discharged to treatment with amiodarone. LDAC is a rare form of arrhythmogenic RV cardiomyopathy frequently associated with PKP2 gene mutations3 and characterized by fibrous or fibrofatty replacement of the LV, with possible less