Premature Mortality in Familial Cardiomyopathy

Study Questions:

What is the risk of premature death (age <60 years) from cardiomyopathy in familial cardiomyopathy?


The study cohort was comprised of 3,890 cardiomyopathies with 89 million years of follow-up, which was constructed from 3.9 million persons of the Danish National Register database. The investigators estimated the incidence of rate ratios for cardiomyopathy by family history of premature death utilizing Poisson regression.


The median age was 38 years. The incident rate ratios for cardiomyopathy before age 50 years by history of premature death from cardiomyopathy in first- and second-degree relatives were 25.0 (95% confidence interval [CI], 17.6-35.4) and 7.23 (95% CI, 3.00-17.4), respectively. Among women, the incident rate ratio for cardiomyopathy by history of premature death from cardiomyopathy in first-degree relatives was 43.4 (95% CI, 28.7-65.6; p-value for homogeneity of estimates for males and females, 0.05). Incident rate ratios for premature death from cardiomyopathy in parents and siblings were 26.7 (95% CI, 19.7-36.0) and 29.7 (17.4-50.6), respectively. Persons with a family history of premature death from cardiomyopathy in a first-degree relative had a 7-fold increase in the rate of ventricular arrhythmia (incident rate ratio, 7.21; 95% CI, 4.60-11.3) compared with persons without such a family history. The corresponding estimate for those with premature death in a second-degree relative was 3.82 (95% CI, 1.43-10.2). They found 29- and 6-fold increases in the rate of cardiomyopathy when there were premature cardiomyopathy deaths in first- and second-degree relatives, respectively. The rate of cardiomyopathy increased 100-fold when the first-degree relative died aged <35 years, and by 400-fold when >2 premature deaths occurred in first-degree relatives. However, there was only a 3-fold increase in mortality when the family history of premature death was due to other cardiac or noncardiac conditions. Premature noncardiac death in first-degree relatives was associated with only a 24% increase in the rate of cardiomyopathy. There was 3- to 7-fold increase in risk of ventricular arrhythmia in relatives.


The authors concluded that family history of premature cardiomyopathy death was associated with an increase in risk of cardiomyopathy ranging from 6- to 400-fold, depending on age, kinship, gender, and number of affected family members.


Genotyping is limited by the fact that disease-causing mutations have not yet been identified in the proband in nearly 50% of the families screened. This is an important study because it suggests that key facts in the family history will help identify patients at risk for cardiomyopathy. We now need similar studies in other analogous cohorts to determine whether elements in the history identified by these investigators are generally applicable.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Quality Improvement, Acute Heart Failure

Keywords: Arrhythmias, Cardiac, Cardiomyopathies, Cardiomyopathy, Hypertrophic, Familial, Family, Genotype, Heart Conduction System, Heart Defects, Congenital, Heart Failure, Mortality, Premature, Risk Factors

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