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3D Strain Analysis of Hypertrophic Cardiomyopathy Registry
Quick Takes
- This study aimed to define associations between baseline demographic, clinical, imaging, and biomarker variables and abnormal global longitudinal strain (GLS) derived from cardiac MRI in hypertrophic cardiomyopathy patients in the NHLBI Hypertrophic Cardiomyopathy Registry (HCMR).
- Abnormal GLS on intake CMR was found to be associated with certain HCM morphologies (e.g., apical aneurysm, apical curvature, reverse curvature) and other imaging findings (e.g., LV mass index, presence of systolic anterior motion) and serum biomarkers (e.g., NT-proBNP, troponin) of increased risk.
- Female sex had a strong inverse association with abnormal GLS.
- Abnormal GLS was significantly associated with abnormal Holter testing.
Study Questions:
What baseline demographic, clinical, imaging, and biomarker variables are associated with abnormal global longitudinal strain (GLS) in hypertrophic cardiomyopathy (HCM) patients in the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR)?
Methods:
The HCMR is a prospective, international registry study of 2,755 HCM patients with extensive clinical, imaging (echocardiography and contrast-enhanced CMR cardiac magnetic resonance [CMR]), electrocardiographic (Holter and exercise treadmill testing [ETT]), genetic, and biomarker analyses. All testing occurred at the time of informed consent and enrollment. Comprehensive three-dimensional (3D) left ventricular (LV) myocardial strain was obtained from cine CMR using in-house validated feature-tracking software and analyzed by two blinded core laboratories. Associations between strain parameters and other variables (demographics, genetics, serum biomarkers, echo and CMR findings, and electrocardiographic testing) were evaluated using multivariable linear regression, linear mixed-effects modeling, and elastic net regression to evaluate the effect size of independent predictors.
Results:
Of 2,755 participants in the HCMR, 84% had CMR image quality sufficient for strain analysis. Patients were stratified according to median GLS (-11.0%) with normal GLS being < -11.0% and abnormal GLS > -11.0%. Some demographic variables (e.g., female sex) were associated with normal GLS, while others (e.g., body mass index, Black race) were correlated with abnormal GLS. Patients with abnormal GLS had higher N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin T levels, higher LV mass index and maximal wall thickness, lower LV ejection fraction (LVEF) and right ventricular (RV) ejection fractions, and higher presence and extent of late gadolinium enhancement (LGE) on CMR. The proportion of patients with abnormal GLS varied significantly based on HCM morphology, with GLS most preserved in patients with isolated basal septal hypertrophy and most often abnormal in those with apical aneurysm. After adjustment, some covariates remained significantly associated with abnormal GLS—either positively (e.g., apical or other morphology, LV mass index, Black or Pacific Islander race, history of syncope, NT-proBNP, and troponin) or inversely (e.g., female sex, LVEF, RV end-diastolic volume, presence of systolic anterior motion [SAM]). Other variables, including sarcomere mutation status, were not found to be independently associated with GLS. Abnormal GLS was significantly associated with abnormal Holter testing (odds ratio, 1.25; 95% confidence interval, 1.09-1.43) but not ETT.
Conclusions:
- In the NHLBI HCMR, abnormal GLS on intake CMR was found to be associated with certain HCM morphologies (e.g., apical aneurysm, apical morphologies, reverse curvature) and other imaging findings (e.g., LV mass index, presence of SAM) and serum biomarkers (e.g., NT-proBNP, troponin) of increased risk.
- Female sex had a strong inverse association with abnormal GLS, suggesting sex-related differences in phenotype and/or progression of disease.
- Abnormal GLS was significantly associated with abnormal Holter testing, suggesting a potential role in prognostic evaluation of HCM patients.
Perspective:
The association between abnormal strain derived from echocardiography and adverse prognosis in HCM has been previously described, but validation using large-scale, prospective datasets has been lacking. The current study confirms this association using the HCMR, the first registry to include CMR, genetic testing, and prospective collection biomarker analysis in a large number of HCM patients. This study has a number of limitations. First and foremost, its cross-sectional design (all datapoints were measured at the time of enrollment) prevents determination at this time of causal relationships between variables, meaning that they should not be referred to as “predictors” of GLS or vice versa. Moreover, the association of GLS with abnormal Holter testing is fairly weak and its clinical significance in the HCMR remains unclear, pending follow-up of clinical events. Long-term follow-up will be needed to determine the prognostic utility of strain in HCM for the development of adverse clinical events. In addition, it will be interesting to see how these CMR-derived strain parameters will help differentiate HCM from other cardiomyopathies (such as hypertensive heart disease, amyloid Fabry cardiomyopathy, or athlete’s heart).
Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Magnetic Resonance Imaging
Keywords: Biomarkers, Cardiomyopathy, Hypertrophic, Diagnostic Imaging, Echocardiography, Exercise Test, Gadolinium, Heart Failure, Hypertrophy, Magnetic Resonance Imaging, Natriuretic Peptide, Brain, Phenotype, Sarcomeres, Stroke Volume, Syncope, Troponin T
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