Phospholamban cardiomyopathy: aCanadian perspective on aunique population

IntroductionPhospholamban cardiomyopathy is an inherited cardiomyopathy, characterised by adefect in regulation of the sarcoplasmic reticulum Ca2+ pump, often presenting with malignant arrhythmias and progressive cardiac dysfunction occurring at ayoung age.MethodsPhospholamban R14del mutation carriers and family members were identified from inherited arrhythmia clinics at 13sites across Canada. Cardiac investigations, including electrocardiograms, Holter monitoring (premature ventricular complexes, PVCs), and imaging results were summarised.ResultsFifty patients (10families) were identified (median age 30years, range 3-71, 46% female). Mutation carriers were more likely to be older, have low-voltage QRS, T-wave inversion, frequent PVCs, and cardiac dysfunction, compared to unaffected relatives. Increasing age, low-voltage QRS, T-wave inversion, late potentials, and frequent PVCs were predictors of cardiac dysfunction (p<0.05 for all). Older carriers (age 45years) were more likely to have disease manifestations than were their younger counterparts, with disease onset occurring at an older age in Canadian patients and their Dutch counterparts.DiscussionAmong Canadian patients with phospholamban cardiomyopathy, clinical manifestations resembled those of their Dutch counterparts, with increasing age amajor predictor of disease manifestation. Older mutation carriers were more likely to have electrical and structural abnormalities, and may represent variable expressivity, age-dependent penetrance, or genetic heterogeneity among Canadian patients.