October 1, 2018Circulation860 citationsOpen Access
Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy
Key Points
- To assess how genetic profile and age at diagnosis influence long-term clinical outcomes and cumulative lifetime disease burden in hypertrophic cardiomyopathy.
- Multicenter longitudinal cohort analysis of 4,591 HCM patients (2,763 genotyped) followed across 8 international centers for a mean of 5.4 ± 6.9 years (24,791 patient-years).
Structured PICO
Do sarcomere mutations and young age at diagnosis predict adverse outcomes and lifetime disease burden in patients with hypertrophic cardiomyopathy?
P
Population
4,591 patients with hypertrophic cardiomyopathy (2,763 genotyped), median age of diagnosis 45.8 years, 37% female, from eight international HCM specialty centers (SHaRe registry).
I
Intervention
Presence of pathogenic/likely pathogenic sarcomere mutations and young age at diagnosis
C
Comparator
Absence of sarcomere mutations and older age at diagnosis
O
Outcome
Overall composite endpoint of cardiac arrest, cardiac transplantation, appropriate implantable cardioverter-defibrillator (ICD) therapy, all-cause death, atrial fibrillation, stroke, New York Heart Association Functional Class III/IV symptoms, and left ventricular ejection fraction (LVEF)<35%composite
In patients with hypertrophic cardiomyopathy, young age at diagnosis and the presence of a sarcomere mutation are powerful predictors of a substantial lifetime burden of adverse outcomes, particularly heart failure and atrial fibrillation.
Abstract
Background: A better understanding of the factors that contribute to heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy (HCM) is critically needed to improve patient management and outcomes. The Sarcomeric Human Cardiomyopathy Registry (SHaRe) was established to provide the scale of data required to address these issues, aggregating longitudinal datasets curated by eight international HCM specialty centers. Methods: Data on 4591 HCM patients (2763 genotyped), followed for a mean of 5.4±6.9 years (24,791 patient-years; median interquartile range 2.9 0.3-7.9 years) were analyzed regarding cardiac arrest, cardiac transplantation, appropriate implantable cardioverter-defibrillator (ICD) therapy, all-cause death, atrial fibrillation, stroke, New York Heart Association Functional Class III/IV symptoms (all comprising the overall composite endpoint), and left ventricular ejection fraction (LVEF)60 years. Young HCM patients (20-29 years) had 4-fold higher mortality than the general United States population at a similar age. Patients with pathogenic/likely pathogenic sarcomere mutations had two-fold greater risk for adverse outcomes compared to patients without mutations; sarcomere variants of uncertain significance were associated with intermediate risk. Heart failure and atrial fibrillation were the most prevalent adverse events, although typically not emerging for several years after diagnosis. Ventricular arrhythmias occurred in 32% 23%, 40% of patients 60 years. Conclusions: The cumulative burden of HCM is substantial and dominated by heart failure and atrial fibrillation occurring many years following diagnosis. Young age of diagnosis and the presence of a sarcomere mutation are powerful predictors of adverse outcomes. These findings highlight the need for close surveillance throughout life, and the need to develop disease-modifying therapies.