For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes. N euromuscular diseases (NMDs) encompass a broad spectrum of diagnoses with overlapping but distinct phenotypes. Common to many NMDs is cardiac involvement. Although the past 3 decades have seen marked advances in our understanding of many NMDs, significant gaps in knowledge remain on how best to approach cardiac care in these patients. For example, survival in Duchenne muscular dystrophy (DMD) has been extended through the use of glucocorticoid use and respiratory support, yet cardiac complications remain a significant cause of morbidity and mortality.1-3 To achieve further gains in care, we will need to improve our understanding of the pathophysiologies driving cardiac involvement in NMDs and advance treatments aimed at preventing the progression of heart failure (HF) and sudden death in NMDs. The recently published findings of an expert working group on cardiac involvement in DMD, which outlined key gaps in knowledge and made specific recommendations aimed at improving diagnosis and management, are a step toward this goal. 4 In this statement, we include a comprehensive overview of the major categories of NMDs with cardiac involvement. For each, a brief background of the gene defect(s), common clinical manifestations (particularly cardiac findings), and current therapies is summarized. Gaps in knowledge are highlighted, and where possible, clinical treatment suggestions are made by the expert writing group appointed by the American Heart Association to review the available literature. Selection of the writing group was performed in accordance with the American Heart Association's conflict-of-interest management policy. Participants volunteered to write sections relevant to their expertise and experience. CLINICAL STATEMENTS AND GUIDELINESconducted a general search of the literature, restricted to human subjects research published between 1980 and 2016. Drafts of each section were written and sent to the chair of the writing group for incorporation into a single document, which was then edited. The edited document was discussed electron...

Background Ventricular Assist Devices (VADs) have come into increasing use in recent years for children. One year survival rates are now above 80% in multiple reports. This report describes adverse events experienced by children with durable ventricular assist devices, using a national-level registry (Pedimacs, a component of Intermacs) Methods Pedimacs is a national registry that contains clinical data on patients who are less than 19 years of age at the time of implantation with a VAD. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. Pedimacs was launched on September 1, 2012 and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions. Results This report comprises data from 200 patients, with median age of 11 years (range 11 days-18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n=146, 73%), myocarditis (17, 9%), congenital heart disease (35, 18%), and other (2, 1%). Pulsatile flow devices were used in 91 patients (45%), and continuous flow devices in 109 (55%). Actuarial survival was 86% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n=79), infection (78), neurological dysfunction (52), and bleeding (68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event, 16% of patients had 5 or more adverse events. Adverse events occurred at all times following implantation but were most likely to occur in the first 30 days. For continuous flow devices, there were broad similarities in adverse event rates between this cohort, and historical rates from the Intermacs population. Conclusions In this cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient months, and of late adverse events, 20.4 events per 100 patient months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurological dysfunction, bleeding and infection. For continuous flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurological dysfunction and respiratory failure. Compared to an adult Intermacs cohort, the overall rate and distribution of adverse events appears similar.

For one-quarter of a century, major advances have occurred in mechanical support technology for children, thereby expanding the capability to bridge to HTx without compromising post-HTx outcomes. Significant challenges remain, especially for neonates and patients with CHD, but ongoing innovation portends improved methods of support during the next decade.

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BACKGROUND Dexmedetomidine, an α-2 receptor agonist, is widely used in children with cardiac disease. Significant hemodynamic responses, including systemic and pulmonary vasoconstriction, have been reported after dexmedetomidine administration. Our primary goal of this prospective, observational study was to quantify the effects of dexmedetomidine initial loading doses on mean pulmonary artery pressure (PAP) in children with and without pulmonary hypertension. METHODS Subjects were children undergoing cardiac catheterization for either routine surveillance after cardiac transplantation (n = 21) or pulmonary hypertension studies (n = 21). After anesthetic induction with sevoflurane and tracheal intubation, sevoflurane was discontinued and anesthesia was maintained with midazolam 0.1 mg/kg IV (or 0.5 mg/kg orally preoperatively) and remifentanil IV infusion 0.5 to 0.8 μg/kg/min. Ventilation was mechanically controlled to maintain Pco2 35 to 40 mm Hg. When end-tidal sevoflurane was 0% and fraction of inspired oxygen (Fio2) was 0.21, baseline heart rate, mean arterial blood pressure, PAP, right atrial pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic pressure, cardiac output, and arterial blood gases were measured, and indexed systemic vascular resistance, indexed pulmonary vascular resistance, and cardiac index were calculated. Each subject then received a 10-minute infusion of dexmedetomidine of 1 μg/kg, 0.75 μg/kg, or 0.5 μg/kg. Measurements and calculations were repeated at the conclusion of the infusion. RESULTS Most hemodynamic responses were similar in children with and without pulmonary hypertension. Heart rate decreased significantly, and mean arterial blood pressure and indexed systemic vascular resistance increased significantly. Cardiac index did not change. A small, statistically significant increase in PAP was observed in transplant patients but not in subjects with pulmonary hypertension. Changes in indexed pulmonary vascular resistance were not significant. CONCLUSION Dexmedetomidine initial loading doses were associated with significant systemic vasoconstriction and hypertension, but a similar response was not observed in the pulmonary vasculature, even in children with pulmonary hypertension. Dexmedetomidine does not appear to be contraindicated in children with pulmonary hypertension.

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BackgroundDuchenne muscular dystrophy incurs nearly universal dilated cardiomyopathy by the third decade of life, preceded by myocardial damage and impaired left ventricular strain by cardiac magnetic resonance. It has been shown that (1) mineralocorticoid receptor antagonist therapy with spironolactone attenuated damage while maintaining function when given early in a mouse model and (2) low‐dose eplerenone stabilized left ventricular strain in boys with Duchenne muscular dystrophy and evident myocardial damage but preserved ejection fraction. We hypothesized that moderate‐dose spironolactone versus eplerenone would provide similar cardioprotection in this first head‐to‐head randomized trial of available mineralocorticoid receptor antagonists, the AIDMD (Aldosterone Inhibition in Duchenne Muscular Dystrophy) trial.Methods and ResultsThis was a multicenter, double‐blind, randomized, noninferiority trial. Subjects were randomized to eplerenone, 50 mg, or spironolactone, 50 mg, orally once daily for 12 months. The primary outcome was change in left ventricular systolic strain at 12 months. Among 52 enrolled male subjects, aged 14 (interquartile range, 12–18) years, spironolactone was noninferior to eplerenone (∆strain, 0.4 [interquartile range, −0.4 to 0.6] versus 0.2 [interquartile range, −0.2 to 0.7]; P=0.542). Renal and pulmonary function remained stable in both groups, and no subjects experienced serious hyperkalemia. Infrequent adverse events included gynecomastia in one subject in the spironolactone arm and facial rash in one subject in the eplerenone arm.ConclusionsIn boys with Duchenne muscular dystrophy and preserved left ventricular ejection fraction, spironolactone added to background therapy is noninferior to eplerenone in preserving contractile function. These findings support early mineralocorticoid receptor antagonist therapy as effective and safe in a genetic disease with high cardiomyopathy risk.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354352.