Modeling the Relationship Between Diastolic Phenotype and Outcomes in Pediatric Hypertrophic Cardiomyopathy

Minh B Nguyen; Maelys Venet; Chun-Po Steve Fan; Andreea Dragulescu; Craig G Rusin; Luc L Mertens; Seema Mital; Olivier Villemain

doi:10.1016/j.echo.2023.11.025

Modeling the Relationship Between Diastolic Phenotype and Outcomes in Pediatric Hypertrophic Cardiomyopathy

J Am Soc Echocardiogr. 2024 May;37(5):508-517.e3. doi: 10.1016/j.echo.2023.11.025. Epub 2023 Dec 12.

Authors

Minh B Nguyen¹, Maelys Venet², Chun-Po Steve Fan³, Andreea Dragulescu², Craig G Rusin⁴, Luc L Mertens², Seema Mital⁵, Olivier Villemain²

Affiliations

¹ Department of Pediatric Cardiology, Baylor College of Medicine, Houston, Texas; Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address: minh.nguyen@bcm.edu.
² Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
³ Ted Rogers Computational Program, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
⁴ Department of Pediatric Cardiology, Baylor College of Medicine, Houston, Texas.
⁵ Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada.

PMID: 38097053
DOI: 10.1016/j.echo.2023.11.025

Abstract

Background: Pediatric hypertrophic cardiomyopathy (HCM) is associated with adverse events. The contribution of diastolic dysfunction to adverse events is poorly understood. The aim of this study was to explore the association between diastolic phenotype and outcomes in pediatric patients with HCM.

Methods: Children <18 years of age with diagnosed with HCM were included. Diastolic function parameters were measured from the first echocardiogram at the time of diagnosis, including Doppler flow velocities, tissue Doppler velocities, and left atrial volume and function. Using principal-component analysis, key features in echocardiographic parameters were identified. The principal components were regressed to freedom from major adverse cardiac events (MACE), defined as implantable cardioverter-defibrillator insertion, myectomy, aborted sudden cardiac death, transplantation, need for mechanical circulatory support, and death.

Results: Variables that estimate left ventricular filling pressures were highly collinear and associated with MACE (hazard ratio, 0.86; 95% CI, 0.75-1.00), though this was no longer significant after controlling for left ventricular thickness and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with outcomes in the covariate-adjusted model (hazard ratio, 0.69; 95% CI, 0.5-0.94). The covariate-adjusted model had an Akaike information criterion of 213, an adjusted R² value of 0.78, and a concordance index of 0.82 for association with MACE.

Conclusion: Echocardiographic parameters of diastolic dysfunction were associated with MACE in this population study, in combination with the severity of left ventricular hypertrophy and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with adverse events. Additional study of diastolic function parameters adjusted for patient size could facilitate the prediction of adverse events in pediatric patients with HCM.

Keywords: Diastolic function; Echocardiography; Hypertrophic cardiomyopathy; Pediatric cardiology; Sudden cardiac death.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Cardiomyopathy, Hypertrophic* / complications
Cardiomyopathy, Hypertrophic* / diagnosis
Cardiomyopathy, Hypertrophic* / physiopathology
Child
Child, Preschool
Diastole*
Echocardiography, Doppler / methods
Female
Humans
Male
Phenotype*
Prognosis
Ventricular Dysfunction, Left / etiology
Ventricular Dysfunction, Left / physiopathology