Institute for Clinical and Experimental Medicine
Published January 1, 2024 | Version v1
Journal article Open

Clinical features and outcomes of pediatric MYH7-Related Dilated Cardiomyopathy

Creators

  • 1. Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro IDIPHISA Madrid Spain
  • 2. Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Cardiology Northwestern University Feinberg School of Medicine Chicago IL USA
  • 3. European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD‐Heart Amsterdam the Netherlands
  • 4. Department of Cardiology Aarhus University Hospital Aarhus Denmark
  • 5. CIBER Cardiovascular Instituto de Salud Carlos III Madrid Spain
  • 6. Cardiology Unit Meyer Children's Hospital IRCCS Florence Italy
  • 7. Complejo Hospitalario Universitario de Badajoz Spain
  • 8. Inheritance Cardiovascular Disease Unit, Pediatric Cardiology Hospital Materno Infantil Gregorio Marañón Madrid Spain
  • 9. Cardiology Department AP‐HP, Cochin Hospital Paris Cedex 14 France
  • 10. Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic
  • 11. Department of Cardiology, Boston Children's Hospital Harvard Medical School Boston MA USA

Description

Background: Although genetic variants in MYH7 are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric MYH7-related DCM. Methods and Results: We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.54 [interquartile range, 0.01-10.8] years) with pathogenic/likely pathogenic variants in MYH7 diagnosed with DCM at pediatric age (<18 years) followed at 13 international centers. We also explored risk factors associated with a composite end point of end-stage heart failure defined as heart transplantation or heart failure-related death. Twenty-two patients (50%) were diagnosed at age <6 months, including 7 (16%) at birth. Left ventricular (LV) hypertrabeculation features were present in 15 (38%), particularly among patients with genetic variants in the head domain. After a median follow-up of 6.1 years (interquartile range, 1.9-13.4), 15 patients (36%) required a heart transplant (n=14) or died due to end-stage heart failure (n=1), 15 patients (36%) persisted with systolic dysfunction despite treatment, 12 (29%) had a significant increase in LV ejection fraction, and 2 were lost to follow-up. Overall, end-stage heart failure event rate was 25% at 5 years. New York Heart Association class III to IV (hazard ratio [HR], 7.67 [95% CI, 2.16-27.2]; P=0.002) and LV ejection fraction <= 35% (HR, 4.00 [95% CI, 1.11-14.4]; P=0.03) were the best predictors of bad prognosis. Conclusions: Pediatric MYH7-related DCM is characterized by early onset, frequent LV hypertrabeculation, and poor prognosis. Advanced New York Heart Association class and low LV ejection fraction emerged as predictors of end-stage heart failure.

Notes

This study was funded by Instituto de Salud Carlos III through the projects PI18/0004, PI20/0320, and PT17/0015/0043 (cofunded by the European Regional Development Fund/European Social Fund [“A way to make Europe”/“Investing in your future”]). The Centro Nacional de Investigaciones Cardiovasculares is supported by the Instituto de Salud Carlos III, Ministry of Science and Innovation (MCIN), the Pro‐CNIC Foundation, and the Severo Ochoa Centers of Excellence program (CEX2020‐001041‐S). The Hospital Universitario Puerta de Hierro, the Hospital Sant Joan de Déu, Institute for Clinical and Experimental Medicine, the University Medical Centre Utrecht, the Hospital General Universitario Gregorio Marañón, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD–Heart (http://guardheart.ern‐net.eu). Dr de Frutos receives grant support from Instituto de Salud Carlos III (CM20/00101). Dr Kubanek received grant support from the Ministry of Health of the Czech Republic (NV19‐08‐00122), MH CZ—DRO (Institute for Clinical and Experimental Medicine—IKEM, IN 00023001), and by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU. This work was supported by the Netherlands Cardiovascular Research Initiative with the support of the Dutch Heart Foundation (CVON2014‐40 DOSIS, DCVA [Dutch Cardiovascular Alliance] 2020B005 DoubleDose to Drs Jansen and Annette F Baas) and the Dutch Heart Foundation (Dekker 2015T041 to Drs Annette F Baas and Jansen).

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Has metadata
39494569 (PMID)
Is part of
2047-9980 (ISSN)
2047-9980 (ISSN)
References
10.1161/JAHA.124.036208 (DOI)