Significance of the Carriage of Sarcomeric Mutations in Hypertrophic Cardiomyopathy in New Zealand

We compare the characteristics of genotype positive vs genotype negative hypertrophic cardiomyopathy (HCM) probands within the Cardiac Inherited Diseases Registry New Zealand (CIDRNZ). Data on HCM probands who have undergone genetic testing were extracted from CIDRNZ. Patients with class 4/5 variants were defined as gene-positive. 332 HCM probands were included, 64% male, mean age at diagnosis 45 yrs, 66% European, 11% Māori, 8% Pacific, 15% Other ethnicity. Thirteen probands (4%) were referred following sudden cardiac death (SCD). 131 (39%) were gene-positive. The commonest genes were MYBPC3 (58%), MYH7 (25%) and TNNT2 (5%), with 63% missense mutations, and 15% of mutations unique to New Zealand (NZ). Gene-positive patients were diagnosed younger (39 yrs vs 50 yrs, p<0.001), were more likely to have a family history of SCD (20% vs 12%, p=0.050), and to have experienced a cardiac arrest, appropriate implantable cardioverter defibrillator (ICD) discharge, or SCD event (22% vs 12%, p=0.021). Mutations were identified in 64% of the probands presenting with HCM as children/youths (<24yrs, n=55), compared to 30% of those presenting aged≥40yrs (n=221), p<0.001. A class 4/5 variant was identified in 27% of Polynesian (Māori or Pacific) probands compared with 43% European or 39% Other (p<0.030). Cascade genetic screening was achieved in 56% of gene-positive families with a mean of 3.9 family members tested and 2.1 gene-positive family members per gene-positive proband. Carriage of a sarcomeric gene mutation in HCM is associated with presentation at younger age, positive family history and cardiac arrest or sudden death events. Mutations were less commonly identified in Polynesian probands.