Phospholamban cardiomyopathy: a Canadian perspective on a unique population
Cheung, C.C.; Healey, J.S.; Hamilton, R.; Spears, D.; Gollob, M.H.; Mellor, G.; Steinberg, C.; Sanatani, S.; Laksman, Z.W.; Krahn, A.D.
Netherlands Heart Journal Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 27(4): 208-213
2019
ISSN/ISBN: 1568-5888 PMID: 30806910 DOI: 10.1007/s12471-019-1247-0Document Number: 285953
Phospholamban cardiomyopathy is an inherited cardiomyopathy, characterised by a defect in regulation of the sarcoplasmic reticulum Ca2+ pump, often presenting with malignant arrhythmias and progressive cardiac dysfunction occurring at a young age. Phospholamban R14del mutation carriers and family members were identified from inherited arrhythmia clinics at 13 sites across Canada. Cardiac investigations, including electrocardiograms, Holter monitoring (premature ventricular complexes, PVCs), and imaging results were summarised. Fifty patients (10 families) were identified (median age 30 years, 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 ≥45 years) 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. Among Canadian patients with phospholamban cardiomyopathy, clinical manifestations resembled those of their Dutch counterparts, with increasing age a major 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.