Emanuel Kaltenecker1, Julia Schleihauf1, Christian Meierhofer1, Nerejda Shehu1, Naira Mkrtchyan1, Alfred Hager1, Andreas Kühn1, Julie Cleuziou2,3, Karin Klingel4, Heide Seidel5, Martin Zenker6, Peter Ewert1, Gabriele Hessling1, Cordula M Wolf1. 1. Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. 2. Department of Cardiovascular Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany. 3. (INSURE) Institute for Translational Cardiac Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany. 4. Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany. 5. Institute of Human Genetics, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. 6. Institute of Human Genetics, University Hospital, Otto-von-Guericke-University, Magdeburg, Germany.
Abstract
BACKGROUND: To compare outcome and cardiac pathology between patients with Noonan syndrome (N-HCM) and sarcomere protein-associated (S-HCM) childhood onset hypertrophic cardiomyopathy (HCM). METHODS: Clinical data were recorded from medical charts. Primary endpoint was survival. Secondary endpoints were survival without hospitalization, without intervention or without arrhythmic events. Functional clinical status and results from genetic testing, imaging, electrocardiographic (ECG) studies, cardiopulmonary exercise testing (CPET) and histopathology were compared between groups. RESULTS: Childhood HCM was diagnosed in 29 N-HCM and 34 S-HCM patients. Follow-up time was greater than 10 years in more than half of all patients. Mortality was below 7% and not different between groups. Children with N-HCM presented at a younger age and there was less time of survival without hospitalization for heart failure or intervention in N-HCM compared to S-HCM patients. Clinical functional status improved over time in N-HCM patients. On long-term follow-up, left ventricular posterior wall thickness indexed to body surface area decreased in N-HCM and increased in S-HCM patients. There was a trend to lower risk for severe arrhythmic events in N-HCM patients and only S-HCM individuals received an implantable cardioverter-defibrillator. There were no differences between groups in ventricular function, ECG and CPET parameters. Myocardial fibrosis as assessed by histopathology of myocardial specimens and cardiovascular magnetic resonance with late gadolinium enhancement or T1 mapping was present in both groups. CONCLUSIONS: When compared to S-HCM patients, children with N-HCM have increased morbidity during early disease course, but favorable long-term outcome with low mortality, stagnation of myocardial hypertrophy, and low risk for malignant arrhythmias. 2019 Cardiovascular Diagnosis and Therapy. All rights reserved.
BACKGROUND: To compare outcome and cardiac pathology between patients with Noonan syndrome (N-HCM) and sarcomere protein-associated (S-HCM) childhood onset hypertrophic cardiomyopathy (HCM). METHODS: Clinical data were recorded from medical charts. Primary endpoint was survival. Secondary endpoints were survival without hospitalization, without intervention or without arrhythmic events. Functional clinical status and results from genetic testing, imaging, electrocardiographic (ECG) studies, cardiopulmonary exercise testing (CPET) and histopathology were compared between groups. RESULTS: Childhood HCM was diagnosed in 29 N-HCM and 34 S-HCM patients. Follow-up time was greater than 10 years in more than half of all patients. Mortality was below 7% and not different between groups. Children with N-HCM presented at a younger age and there was less time of survival without hospitalization for heart failure or intervention in N-HCM compared to S-HCM patients. Clinical functional status improved over time in N-HCM patients. On long-term follow-up, left ventricular posterior wall thickness indexed to body surface area decreased in N-HCM and increased in S-HCM patients. There was a trend to lower risk for severe arrhythmic events in N-HCM patients and only S-HCM individuals received an implantable cardioverter-defibrillator. There were no differences between groups in ventricular function, ECG and CPET parameters. Myocardial fibrosis as assessed by histopathology of myocardial specimens and cardiovascular magnetic resonance with late gadolinium enhancement or T1 mapping was present in both groups. CONCLUSIONS: When compared to S-HCM patients, children with N-HCM have increased morbidity during early disease course, but favorable long-term outcome with low mortality, stagnation of myocardial hypertrophy, and low risk for malignant arrhythmias. 2019 Cardiovascular Diagnosis and Therapy. All rights reserved.
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Authors: Anna B Meier; Sarala Raj Murthi; Hilansi Rawat; Christopher N Toepfer; Gianluca Santamaria; Manuel Schmid; Elisa Mastantuono; Thomas Schwarzmayr; Riccardo Berutti; Julie Cleuziou; Peter Ewert; Agnes Görlach; Karin Klingel; Karl-Ludwig Laugwitz; Christine E Seidman; Jonathan G Seidman; Alessandra Moretti; Cordula M Wolf Journal: iScience Date: 2021-12-09