Pediatric Hypertrophic Cardiomyopathy: Exploring the Genotype-Phenotype Association

Overview

Journal J Am Heart Assoc

Specialty Cardiology & Vascular Diseases

Date 2022 Feb 18

PMID 35179047

Authors

Minh B Nguyen

Seema Mital

Luc Mertens

Aamir Jeewa

Mark K Friedberg

Julien Aguet

Arnon Adler

Christopher Z Lam

Andreea Dragulescu

Harry Rakowski

Olivier Villemain

Affiliations

Soon will be listed here.

Abstract

Pediatric hypertrophic cardiomyopathy (HCM) is the most common form of cardiomyopathy in children and a leading cause of sudden cardiac death. Yet, the association between genotype variation, phenotype expression, and adverse events in pediatric HCM has not been fully elucidated. Although the literature on this topic is evolving in adult HCM, the evidence in children is lacking. Solidifying our understanding of this relationship could improve risk stratification as well as improve our comprehension of the underlying pathophysiological characteristics of pediatric HCM. In this state-of-the-art review, we examine the current literature on genetic variations in HCM and their association with outcomes in children, discuss the current approaches to identifying cardiovascular phenotypes in pediatric HCM, and explore possible avenues that could improve sudden cardiac death risk assessment.

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References

Karamitsos T, Dass S, Suttie J, Sever E, Birks J, Holloway C . Blunted myocardial oxygenation response during vasodilator stress in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2013; 61(11):1169-76. PMC: 3595528. DOI: 10.1016/j.jacc.2012.12.024. View

Lorenzini M, Norrish G, Field E, Ochoa J, Cicerchia M, Akhtar M . Penetrance of Hypertrophic Cardiomyopathy in Sarcomere Protein Mutation Carriers. J Am Coll Cardiol. 2020; 76(5):550-559. PMC: 7397507. DOI: 10.1016/j.jacc.2020.06.011. View

Burkhoff D, Mirsky I, Suga H . Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers. Am J Physiol Heart Circ Physiol. 2005; 289(2):H501-12. DOI: 10.1152/ajpheart.00138.2005. View

Ostman-Smith I, Sjoberg G, Alenius Dahlqvist J, Larsson P, Fernlund E . Sudden cardiac death in childhood hypertrophic cardiomyopathy is best predicted by a combination of electrocardiogram risk-score and HCMRisk-Kids score. Acta Paediatr. 2021; 110(11):3105-3115. DOI: 10.1111/apa.16045. View

Villemain O, Baranger J, Friedberg M, Papadacci C, Dizeux A, Messas E . Ultrafast Ultrasound Imaging in Pediatric and Adult Cardiology: Techniques, Applications, and Perspectives. JACC Cardiovasc Imaging. 2019; 13(8):1771-1791. DOI: 10.1016/j.jcmg.2019.09.019. View

Hoss S, Habib M, Silver J, Care M, Chan R, Hanneman K . Genetic Testing for Diagnosis of Hypertrophic Cardiomyopathy Mimics: Yield and Clinical Significance. Circ Genom Precis Med. 2020; 13(2):e002748. DOI: 10.1161/CIRCGEN.119.002748. View

Pagiatakis C, Di Mauro V . The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies. Int J Mol Sci. 2021; 22(16). PMC: 8395924. DOI: 10.3390/ijms22168721. View

Linglart L, Gelb B . Congenital heart defects in Noonan syndrome: Diagnosis, management, and treatment. Am J Med Genet C Semin Med Genet. 2020; 184(1):73-80. PMC: 7682536. DOI: 10.1002/ajmg.c.31765. View

Mathew J, Zahavich L, Lafreniere-Roula M, Wilson J, George K, Benson L . Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy. Clin Genet. 2017; 93(2):310-319. DOI: 10.1111/cge.13157. View

10.

Dallaire F, Slorach C, Hui W, Sarkola T, Friedberg M, Bradley T . Reference values for pulse wave Doppler and tissue Doppler imaging in pediatric echocardiography. Circ Cardiovasc Imaging. 2015; 8(2):e002167. DOI: 10.1161/CIRCIMAGING.114.002167. View

11.

Raja A, Farhad H, Valente A, Couce J, Jefferies J, Bundgaard H . Prevalence and Progression of Late Gadolinium Enhancement in Children and Adolescents With Hypertrophic Cardiomyopathy. Circulation. 2018; 138(8):782-792. PMC: 6173664. DOI: 10.1161/CIRCULATIONAHA.117.032966. View

12.

Ho C, Sweitzer N, McDonough B, Maron B, Casey S, Seidman J . Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation. 2002; 105(25):2992-7. DOI: 10.1161/01.cir.0000019070.70491.6d. View

13.

Almomani R, Verhagen J, Herkert J, Brosens E, Spaendonck-Zwarts K, Asimaki A . Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy. J Am Coll Cardiol. 2016; 67(5):515-25. DOI: 10.1016/j.jacc.2015.10.093. View

14.

Cecchi F, Olivotto I, Gistri R, Lorenzoni R, Chiriatti G, Camici P . Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. N Engl J Med. 2003; 349(11):1027-35. DOI: 10.1056/NEJMoa025050. View

15.

Nagueh S, Smiseth O, Appleton C, Byrd 3rd B, Dokainish H, Edvardsen T . Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016; 29(4):277-314. DOI: 10.1016/j.echo.2016.01.011. View

16.

Dragulescu A, Mertens L, Friedberg M . Interpretation of left ventricular diastolic dysfunction in children with cardiomyopathy by echocardiography: problems and limitations. Circ Cardiovasc Imaging. 2013; 6(2):254-61. DOI: 10.1161/CIRCIMAGING.112.000175. View

17.

Kehl D, Buttan A, Siegel R, Rader F . Clinical utility of natriuretic peptides and troponins in hypertrophic cardiomyopathy. Int J Cardiol. 2016; 218:252-258. DOI: 10.1016/j.ijcard.2016.05.031. View

18.

Jhaveri S, Komarlu R, Worley S, Shahbah D, Gurumoorthi M, Zahka K . Left Atrial Strain and Function in Pediatric Hypertrophic Cardiomyopathy. J Am Soc Echocardiogr. 2021; 34(9):996-1006. DOI: 10.1016/j.echo.2021.04.014. View

19.

Norrish G, Kolt G, Cervi E, Field E, Dady K, Ziolkowska L . Clinical presentation and long-term outcomes of infantile hypertrophic cardiomyopathy: a European multicentre study. ESC Heart Fail. 2021; 8(6):5057-5067. PMC: 8712843. DOI: 10.1002/ehf2.13573. View

20.

Pieles G, Alkon J, Manlhiot C, Steve Fan C, Kinnear C, Benson L . Association between genetic variants in the HIF1A-VEGF pathway and left ventricular regional myocardial deformation in patients with hypertrophic cardiomyopathy. Pediatr Res. 2020; 89(3):628-635. DOI: 10.1038/s41390-020-0929-z. View