Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM). Although the annual rate of SCD in the general HCM population is <1% per year according to contemporary series, there is still a small subset of patients who are at increased risk of SCD. The greatest challenge in the management of HCM is identifying those at increased risk as an implantable cardioverter defibrillator is a potentially life-saving therapy. In this review, we sought to summarize the available data on SCD in HCM and provide a clinical perspective on the current differing and somewhat conflicting European and American recommendations on risk stratification, with balanced guidance with regards to rational clinical decision making. Additionally, we sought to learn more on the actual implementation of the guidelines by HCM experts worldwide.
Background: Hypertrophic cardiomyopathy (HCM) is considered a leading cause of sudden cardiac death (SCD) in younger people. The incidence of HCM-related SCD and its relationship to exercise have not been well studied in large comprehensive studies outside of tertiary care settings. This study sought to estimate the incidence of HCM-related SCD and its association with exercise in a large unselected population. Methods: Using the Office of the Chief Coroner of Ontario database encompassing all deaths attended by the coroner, we identified all HCM-related SCDs in individuals 10 to 45 years of age between 2005 and 2016 (70 million person-years). Confirmation of HCM was based on typical macroscopic and microscopic features (definite HCM-related SCD). Sudden deaths with a prior clinical diagnosis of HCM but no autopsy were considered probable HCM-related SCDs. Cases with typical features but no myofiber disarray were considered possible HCM. The completeness of data was verified in a subset of patients in the Toronto area with the use of a registry of all emergency medical services–attended cardiac arrests, with an autopsy rate of 94%. To estimate the number of HCM-related aborted cardiac arrests and lives potentially saved by implantable cardioverter-defibrillators, all de novo implantations for secondary prevention and all implantations and appropriate shocks for primary prevention in patients with HCM 10 to 45 years of age, respectively, were identified with the use of a registry containing data on implantable cardioverter-defibrillator implantations from all implanting sites throughout Ontario. Results: Forty-four, 3, and 6 cases of definite, probable, and possible HCM-related SCDs, respectively, were identified, corresponding to estimated annual incidence rates of 0.31 per 1000 HCM person-years (95% CI, 0.24–0.44) for definite HCM-related SCD, 0.33 per 1000 HCM person-years (95% CI, 0.34–0.62) for definite or probable HCM-related SCD, and 0.39 per 1000 HCM person-years (95% CI, 0.28–0.49) for definite, probable, or possible HCM-related SCD (estimated 140 740 HCM person-years of observation). The estimated annual incidence rate for HCM-related SCD plus aborted cardiac arrest and HCM-related life-threatening arrhythmia (SCD, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks) was 0.84 per 1000 HCM person-years (95% CI, 0.70–1.0). The majority (70%) of SCDs occurred in previously undiagnosed individuals. Most SCDs occurred during rest (64.8%) or light activity (18.5%). Conclusions: The incidence of HCM-related SCD in the general population 10 to 45 years of age is substantially lower than previously reported, with most cases occurring in previously undiagnosed individuals. SCDs are infrequently related to exercise.
Background-Available data suggests that double mutations in patients with hypertrophic cardiomyopathy are not rare and are associated with a more severe phenotype. Most of this data, however, is based on noncontemporary variant classification. Methods and Results-Clinical data of all hypertrophic cardiomyopathy patients with 2 rare genetic variants were retrospectively reviewed and compared with a group of patients with a single disease-causing variant. Furthermore, a literature search was performed for all studies with information on prevalence and outcome of patients with double mutations. Classification of genetic variants was reanalyzed according to current guidelines. In our cohort (n=1411), 9% of gene-positive patients had 2 rare variants in sarcomeric genes but only in 1 case (0.4%) were both variants classified as pathogenic. Patients with 2 rare variants had a trend toward younger age at presentation when compared with patients with a single mutation. All other clinical variables were similar. In data pooled from cohort studies in the literature, 8% of gene-positive patients were published to have double mutations. However, after reanalysis of reported variants, this prevalence diminished to 0.4%. All patients with 2 radical mutations in MYBPC3 in the literature had severe disease with death or heart transplant during the first year of life. Data on other specific genotype-phenotype correlations were scarce. Conclusions-Double mutations in patients with hypertrophic cardiomyopathy are much less common than previously estimated. With the exception of double radical MYBPC3 mutations, there is little data to guide clinical decision making in cases with double mutations. (Circ Cardiovasc
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