Distinct Subgroups in Hypertrophic Cardiomyopathy in the NHLBI HCM Registry
Stefan Neubauer1, Paul Kolm2, Carolyn Y Ho3
1Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
Insights
The Hypertrophic Cardiomyopathy Registry (HCMR) study reveals distinct patient subgroups based on genetic and imaging markers. Incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data can improve risk prediction in hypertrophic cardiomyopathy (HCM).
Area of Science:
- Cardiology
- Genetics
- Medical Imaging
Background:
- The Hypertrophic Cardiomyopathy Registry (HCMR) is a prospective study funded by the National Heart, Lung, and Blood Institute.
- It includes 2,755 patients with hypertrophic cardiomyopathy (HCM) from 44 sites across 6 countries.
Purpose of the Study:
- To enhance risk prediction models for HCM by integrating cardiac magnetic resonance (CMR) imaging, genetic data, and specific biomarkers.
- To identify distinct patient subgroups within the HCMR cohort.
Main Methods:
- Collected demographic and echocardiographic data.
- Performed CMR including cine imaging, late gadolinium enhancement (LGE) for fibrosis, and T1 mapping for interstitial fibrosis.
- Assessed biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), alongside genetic analysis.
Main Results:
- The HCMR cohort (n=2,755) showed characteristics of low-risk HCM, with 93% having mild functional limitation.
- Sarcomere mutation-positive patients often had reverse septal curvature, more fibrosis (LGE, extracellular volume), and less outflow tract obstruction.
- Sarcomere mutation-negative patients tended to have isolated basal septal hypertrophy, less fibrosis, and more outflow tract obstruction. Biomarker levels correlated with fibrosis extent.
Conclusions:
- The HCMR population can be broadly categorized into two groups based on genetic and imaging findings.
- These subgroups exhibit different morphological and obstructive patterns, suggesting potential differences in disease progression.
- Further analysis of this cohort will refine risk prediction models for HCM by incorporating comprehensive data.
Background:
The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries.
Objectives:
The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data.
Methods:
Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis.
Results:
A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion.
Conclusions:
The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers.
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