Phospholamban cardiomyopathy: a Canadian perspective on a unique population

Area of Science:

• Cardiology
• Genetics
• Molecular Biology

Background:

• Phospholamban cardiomyopathy is an inherited condition affecting the heart's calcium regulation.
• It often leads to arrhythmias and heart dysfunction at a young age.

Purpose of the Study:

• To investigate the clinical characteristics and predictors of disease manifestation in Canadian phospholamban cardiomyopathy patients.
• To compare Canadian findings with those in Dutch counterparts.

Main Methods:

• Identified phospholamban R14del mutation carriers and family members across 13 Canadian sites.
• Collected and summarized cardiac investigation data, including ECGs, Holter monitoring for premature ventricular complexes (PVCs), and imaging.

Main Results:

• Fifty patients from 10 families were studied; carriers were more likely to be older and exhibit cardiac dysfunction, low-voltage QRS, T-wave inversion, and frequent PVCs.
• Increasing age, specific ECG findings, and frequent PVCs predicted cardiac dysfunction.
• Older carriers (≥45 years) showed higher disease manifestation rates, with disease onset occurring later in Canadian and Dutch patients.

Conclusions:

• Clinical manifestations in Canadian phospholamban cardiomyopathy patients align with Dutch counterparts.
• Increasing age is a significant predictor of disease manifestation.
• Older carriers exhibit more electrical and structural abnormalities, suggesting variable expressivity, age-dependent penetrance, or genetic heterogeneity.