Cardiomyopathy in Duchenne Muscular Distrophy: Clinical Insights and Therapeutic Implications

Duchenne muscular dystrophy cardiomyopathy (DMD-DCM) is characterized by progressive ventricular dilation and dysfunction that can begin at any age and worsens over time. Thanks to the lengthening of life expectancy due to better management of respiratory involvement, end-stage heart failure (HF) is becoming the main cause of death for DMD patients. Therefore, from the time of DMD diagnosis, every effort should be focused to early detect the onset and the worsening of the DMD-DCM, with the aim of starting and modulating the therapy to slow the progression of cardiac dysfunction. In cardiac evaluation, biomarkers, electrocardiograms, and echocardiograms must be considered, but cardiac magnetic resonance (CMR) is now acquiring a leading role due to its sensitivity in the earlier identification of cardiac involvement. The management of DMD-DCM at end stage is a difficult challenge that requires a multidisciplinary team composed of clinical cardiologists, electrophysiologists, cardiac surgeons, neuromuscular specialists, and psychologists. Because of the lack of specific drugs for DMD, we will review the actual cardiovascular armamentarium including drugs used for HF

Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: A systematic review and meta-analysis

Aims: To perform a systematic literature review and meta-analysis of clinical risk factors for sudden cardiac death (SCD) in childhood hypertrophic cardiomyopathy.Methods: Medline and PubMed databases were searched for original articles published in English from 1963 through to December 2015 that included patients under 18 years of age with a primary or secondary end-point of either SCD or SCD-equivalent events (aborted cardiac arrest or appropriate implantable cardioverter-defibrillator discharge) or cardiovascular death (CVD).Results: Twenty-five studies (3394 patients) met the inclusion criteria. We identified four conventional major risk factors that were evaluated in at least four studies and that we found to be statistically associated with an increased risk of death in at least two studies: previous adverse cardiac event (pooled hazard ratio [HR] 5.4, 95% confidence interval [CI] 3.67-7.95, p < 0.001); non-sustained ventricular tachycardia (pooled HR 2.13, 95% CI 1.21-3.74, p = 0.009); unexplained syncope (pooled HR 1.89, 95% CI 0.69-5.16, p = 0.22); and extreme left ventricular hypertrophy (pooled HR 1.80, 95% CI 0.75-4.32, p = 0.19). Left atrial diameter did not meet the major risk factor criteria; however, this is likely to be an additional significant risk factor. Minor' risk factors included a family history of SCD, gender, age, symptoms, electrocardiogram changes, abnormal blood pressure response to exercise and left ventricular outflow tract obstruction.Conclusions: A lack of well-designed, large, population-based studies in childhood hypertrophic cardiomyopathy means that the evidence base for individual risk factors is not robust. We have identified four clinical parameters that are likely to be associated with increased risk of SCD, SCD-equivalent events or CVD. Multi-centre prospective studies are needed in order to further determine the relevance of these factors in predicting SCD in childhood hypertrophic cardiomyopathy and to identify novel risk markers.Condensed abstract: A systematic review and meta-analysis of clinical risk factors predicting sudden cardiac death in childhood hypertrophic cardiomyopathy was performed, identifying four major' factors: previous adverse cardiac event; non-sustained ventricular tachycardia; syncope; and extreme left ventricular hypertrophy. Well-designed multi-centre studies are required in the future in order to confirm these findings

Cardiac Manifestations in Children with SARS-COV-2 Infection: 1-Year Pediatric Multicenter Experience

Since the spread of COVID-19, pediatric patients were initially considered less affected by SARS-COV-2, but current literature reported subsets of children with multisystem inflammatory syndrome (MIS-C). This study aims to describe the cardiac manifestation of SARS-COV-2 infection in a large cohort of children admitted to two Italian pediatric referral centers. Between March 2020 and March 2021, we performed a cardiac evaluation in 294 children (mean age 9 ± 5.9 years, male 60%) with active or previous SARS-COV-2 infection. Twenty-six showed ECG abnormalities: 63 repolarization anomalies, 13 Long QTc, five premature ventricular beats, two non-sustained ventricular tachycardia, and one atrial fibrillation. In total, 146 patients underwent cardiac biomarkers: NT-proBNP was elevated in 57, troponin in 34. An echocardiogram was performed in 98, showing 54 cardiac anomalies: 27 left-ventricular dysfunction, 42 pericarditis, 16 coronaritis. MIS-C was documented in 46 patients (mean age 9 ± 4.8 years, male 61%) with cardiac manifestations in 97.8%: 27 ventricular dysfunctions, 32 pericarditis, 15 coronaritis, 3 arrhythmias. All patients recovered, and during follow-up, no cardiac anomalies were recorded. Our experience showed that cardiac involvement is not rare in children with SARS-COV-2, and occurred in almost all patients with MIS-C. However, patients’ recovery is satisfactory and no additional events were reported during FU

Heart rate reduction strategy using ivabradine in end-stage duchenne cardiomyopathy

Background: End-stage dilated cardiomyopathy (DCM) is the leading cause of morbidity and mortality in patients with Duchenne Muscular Dystrophy (DMD). No studies are available on the effect of ivabradine on long-term outcomes in end-stage DMD/DCM. Methods: We prospectively enrolled a cohort of end-stage DMD/DCM patients with LV ejection fraction <40%, on chronic HF treatment with an ACE inhibitor referred consecutively from 2012 to 2017 to Bambino Gesù Children's Hospital. In each patient, before starting HRR strategy and after 1 year, we collected medical records comprehensive of clinical, demographic and imaging parameters, BNP levels, neurological and respiratory assessment. Results: Twenty male patients with DMD/DCM with a mean age of 15.0 ± 3.5 (13–19 IQR) years were enrolled and divided into 2 groups according to ivabradine therapy. This group showed a higher incidence of MACEs compared to others in treatment with ivabradine (87.5% vs 12.5%, p = 0.025). At Kaplan Meier survival analysis curves, the rate free from MACEs was higher in patients treated with ivabradine (log rank p = 0.017). At multivariate Cox regression analysis, ivabradine therapy was an independent predictor of freedom from MACEs (H.R. 0.078, 95% CI 0.007–0.877, p = 0.039). Conclusion: HRR strategy, whether achieved by beta blockers alone or in combination with ivabradine, seemed to be effective in reducing the incidence of acute adverse events, reaching optimal target heart rate and improving left ventricular function in DMD/DCM patients

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

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 &lt; 18 years) between 2013 and 2020, with LVEF &lt; 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 &amp; PLUSMN; 8 years). The mean LVEF was 30.2 &amp; PLUSMN; 10% before treatment and 43.7 &amp; PLUSMN; 9.6% after treatment, at the maximum therapeutic dose (p &lt; 0.0001). There was a positive relationship between HRR and increase in LVEF (R (2) = 0.06, p = 0.014). A HRR of &gt; 20% correlated with an improvement in LVEF &gt; 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 &lt; 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

Duchenne Dilated Cardiomyopathy: Cardiac Management from Prevention to Advanced Cardiovascular Therapies

Duchenne muscular dystrophy (DMD) cardiomyopathy (DCM) is characterized by a hypokinetic, dilated phenotype progressively increasing with age. Regular cardiac care is crucial in DMD care. Early recognition and prophylactic use of angiotensin converting enzyme inhibitors (ACEi) are the main stay therapeutic strategy to delay incidence of DMD-DCM. Pharmacological treatment to improve symptoms and left ventricle (LV) systolic function, have been widely implemented in the past years. Because of lack of DMD specific drugs, actual indications for established DCM include current treatment for heart failure (HF). This review focuses on current HF strategies to identify, characterize, and treat DMD-DCM

Long-Term Cardiovascular Outcome in Children with MIS-C Linked to SARS-CoV-2 Infection&mdash;An Italian Multicenter Experience

MIS-C is a multisystem inflammatory syndrome that is characterized by multi-organ failure and cardiac involvement. The aim of this study was to describe the long-term cardiovascular outcome in a cohort of MIS-C pediatric patients, who were admitted to two Italian Pediatric Referral Centers. Sixty-seven patients (mean age 8.7 &plusmn; 4.7 years, male 60%) were included; 65 (97%) of them showed cardiac involvement. All of the patients completed one month of the follow-up, and 47% completed 1 year of it. ECG abnormalities were present in 65% of them, arrhythmias were present in 9% of them during an acute phase and it disappeared at the point of discharge or later. Pericarditis were detected in 66% of them and disappeared after 6 months. Coronaritis was observed in 35% of the children during an acute phase, and there were no more instances at the 1-year point. An LV dysfunction was present in 65% of the patients at the beginning of the study, with them having a full recovery at the point of discharge and thereafter. Elevated values of the NTproBNP and hsTp were initially detected, which progressively decreased and normalized at the points of discharge and FU. The CMR at the point of FU, there was a presence of long-term myocardial scars in 50% of the patients that were tested. No deaths that were caused by MIS-C during the FU were recorded. Cardiac involvement in MIS-C patients is almost the rule, but the patients&rsquo; clinical course was satisfactory, and no additional events or sequelae were observed apart from there being long-term myocardial scars in 50% of the patients that underwent CMR