Heart rate reduction as a marker to optimize carvedilol treatment and enhance myocardial recovery in pediatric dilated cardiomyopathy

Rachele Adorisio; Giuseppe Pontrelli; Nicoletta Cantarutti; Elisa Bellettini; Martina Caiazza; Erica Mencarelli; Giuseppe Limongelli; Daniela Poli; Fabrizio Drago; Richard Kirk; Antonio Amodeo

doi:10.3389/fphys.2022.1001752

Heart rate reduction as a marker to optimize carvedilol treatment and enhance myocardial recovery in pediatric dilated cardiomyopathy

Front Physiol. 2022 Dec 2:13:1001752. doi: 10.3389/fphys.2022.1001752. eCollection 2022.

Authors

Affiliations

¹ Advanced Cardiovascular Therapies Unit- Heart Failure, Transplant and Mechanical Assist Device, Department of Cardiology, Cardiac Surgery and Heart Lung Transplant, Bambino Gesù Pediatric Hospital and Research Institute, Rome, Italy.
² Quality Team of Clinical Study- Director, Department of Pediatrics, Bambino Gesù Pediatric Hospital and Research Institute, Rome, Italy.
³ Cardiology and Cardiac Arrhythmias Unit, Department of Cardiology, Cardiac Surgery and Heart Lung Transplant, Bambino Gesù Pediatric Hospital and Research Institute Bambino Gesù Pediatric Hospital and Research Institute, Rome, Italy.
⁴ Genetic Disease and Rare Cardiovascular Disorder, Luigi Vanvitelli University, AORN Colli, Monaldi Hospital, Naples, Italy.
⁵ Heart Failure, Transplant and Mechanical Assist Device, Department of Cardiology, Cardiac Surgery and Heart Lung Transplant, Bambino Gesù Pediatric Hospital and Research Institute Bambino Gesù Pediatric Hospital and Research Institute, Rome, Italy.
⁶ Centro Cardiologico Pediatrico del Mediterraneo-Bambino Gesù Hospital-Taormina-Italia, Villagonia, Italy.

Abstract

Introduction: An elevated heart rate is associated with an increased risk of death or cardiac transplant in children with dilated cardiomyopathy (DCM). Whether heart rate is a clinical marker to address therapy, is poorly investigated in children. Aim: To investigate the relationship between heart rate reduction (HRR) and left ventricular ejection fraction (LVEF) in DCM, treated with carvedilol. Methods: This is a multi center retrospective analysis conducted on all children with DCM (aged <18 years) between 2013 and 2020, with LVEF <40% and treated with carvedilol. Carvedilol was up titrated to the maximal tolerated dose or to 1 mg/kg/day. Echocardiographic data on left ventricular function and dimension were collected. The relationship between HRR and LVEF, left ventricular end-diastolic (LVEDd) and end-systolic diameter (LVESd) was assessed before and after HRR with carvedilol, using regression analysis. Results: 100 patients were enrolled (M: 51%; age 7 ± 8 years). The mean LVEF was 30.2 ± 10% before treatment and 43.7 ± 9.6% after treatment, at the maximum therapeutic dose (p < 0.0001). There was a positive relationship between HRR and increase in LVEF (R ² = 0.06, p = 0.014). A HRR of >20% correlated with an improvement in LVEF >13%. At 3 years follow up, HRR demonstrated a significant reduction of LVESd (R2 = 0.1, p = 0.003) LVEDd (R2 = 0.07, p = 0.008) and LVEF recovery up to 15% (p < 0.0001). No deaths or heart transplant occurred during follow-up. Conclusion: This study demonstrates that HRR is safe and improvement in LVEF is related to the degree of HRR. The magnitude of LVEF improvement was enhanced by a major reduction in HR. It provides evidence that HRR could be used as a clinical marker to treat HF in children.

Keywords: carvedilol; children; dilated cardiomyopathy; heart failure; heart rate.