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Danon disease is a rare X-linked autophagic vacuolar cardioskeletal myopathy associated with severe heart failure that can be accompanied with extracardiac neurologic, skeletal, and ophthalmologic manifestations. It is caused by loss of function variants in the LAMP2 gene and is among the most severe and penetrant of the genetic cardiomyopathies. Most patients with Danon disease will experience symptomatic heart failure. Male individuals generally present earlier than women and die of either heart failure or arrhythmia or receive a heart transplant by the third decade of life. Herein, the authors review the differential diagnosis of Danon disease, diagnostic criteria, natural history, management recommendations, and recent advances in treatment of this increasingly recognized and extremely morbid cardiomyopathy., Competing Interests: Funding Support and Author Disclosures This paper represents the consensus opinions of the authors, borne from an International Advisory Board meeting funded by Rocket Pharmaceuticals, who also provided support for development of the Central Illustration. Dr Garcia-Pavia has received consulting fees from Lexeo Therapeutics and Rocket Pharmaceuticals. Dr Adler has served as Chief Science Officer for Lexeo Therapeutics; and has served as an advisor for Rocket Pharmaceuticals., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Danon disease (DD) is a rare X-linked autophagic vacuolar myopathy, characterized by high penetrance and severe cardiomyopathy. Because of its rarity, the natural history (NH) is uncertain., Objectives: We aimed to describe disease variability and outcomes through a systematic review of all published DD cases., Methods: Among 83 manuscripts in MEDLINE and EMBASE on DD cases published until October 2017, we identified 146 patients with positive genetic testing for DD or positive muscle biopsy in a relative of a genetically diagnosed proband., Results: 56 females and 90 males were identified. 92.5% of patients had cardiac abnormalities. Females presented with either hypertrophic cardiomyopathy (HCM, 70.3%) or dilated cardiomyopathy (DCM, 29.3%) whereas males presented with HCM 96.2% of the time. The composite outcome of death, heart transplant or ventricular assist devices occurred equally in both sexes (32% of females and 37% of males, p = 0.60) but later in females (median age 38 years) than in males (median age 21 years, p < 0.001). Whereas women present with isolated cardiac disease 73% of the time, in males DD was frequently multisystemic and presented as a triad of cognitive impairment, skeletal myopathy, and HCM in 42% of patients., Conclusions: In this first systematic review of DD, we confirmed the severe morbidity and mortality associated with disease in both sexes. Women presented with both HCM and DCM and generally with isolated cardiac disease, whereas in men DD usually presented as HCM and was frequently multi-systemic. Further prospective NH studies will be required to confirm these findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported.Objectives: Based on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM.Methods: The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.Results: Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026).Conclusions: EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome. [ABSTRACT FROM AUTHOR]

Background: Danon Disease (DD) is a rare X-linked disorder with high morbidity and mortality. Clinical features include skeletal myopathy, hypertrophic cardiomyopathy (HCM), and neurologic symptoms. The first cases were described in 1981; however, gender differences are still poorly understood. Methods: From 773 manuscripts published from 2000-2017 in MEDLINE and EMBASE, we identified 180 cases. We included in the principal analysis 146 patients diagnosed with a genetic test (if index case) or muscle biopsy (if a relative of the index case). Results: Symptoms first occurred in males significantly earlier than females (median age 9 years vs. 23 p<0.001). Cardiomyopathy occurred in 91% of patients, the majority of whom had HCM. Thirty-seven (25.3%) patients received automated cardiac defibrillators, as primary prevention in 64.9% of cases. Males with hypertrophy were twice as likely to develop advanced heart failure at a median age of 21 years. Conversely, dilated cardiomyopathy (DCM) was 4 times more prevalent in females (n=12, 75%) compared to males (n=3, 19%). Intellectual disability was significantly more frequent in males (53.9% males vs. 9% females with a median age of onset of 6 and 19, respectively, p=0.829). Abnormalities in the laboratory tests, such as AST, ALT or CK were described in 62.5 % of the population (83.3% of males and 15.6% female). Muscle myopathy was described in 64 (49%) cases - 57 (63.3%) males and 7 (12.7%) females- at a median age of 13 years and 19, respectively (p=0.826). Overall, 51 patients (34.9 %) died or required a left ventricular assist device (LVAD) or heart transplant (HTx). Median age at the time of death/HTx/LVAD was 26 years and 52 years in males and females, respectively (p <0.001 by the log-rank test) (fig 1). Although not statistically significant, males were more likely to experience temporary complications after HTx compared to females (25% vs. 0%, p=0.136). Conclusions: Despite being an X linked disease, females with Danon have significant morbidity and a shortened lifespan. DCM is more prevalent in females, while HCM and post-Htx complications were more prevalent in males. Both genders had a prolonged survival as compared to prior studies, possibly reflecting increased awareness and earlier diagnosis. [ABSTRACT FROM AUTHOR]

BACKGROUND Severe right ventricular failure necessitating a right ventricular assist device (RVAD) complicates 6% to 11% of left ventricular assist device (LVAD) implants. Patient outcomes for those receiving durable continuous-flow VADs in a biventricular configuration (i.e., BiVAD) have been reported in limited case series. METHODS Data from United States centers with ≥ 6 BiVAD implants were collected. Characteristics and outcomes of patients receiving contemporaneous (i.e., same surgery) vs staged implantation of the HVAD as a BiVAD were compared. RESULTS From 2011 to 2017, 46 patients received durable BiVADs and had the following characteristics: median age, 46 years (interquartile range [IQR], 19–67 years), non-ischemic cardiomyopathy (80%), bridge to transplant (83%), Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 or 2 (92%), use of temporary circulatory support (37%), right atrial pressure 19 mm Hg (IQR, 14–23 mm Hg), and cardiac index of 1.6 liters/min/m2 (IQR, 1.2–2.1 liters/min/m2). Operative mortality was 33%. Equal numbers of patients received a right atrial or right ventricular implant. Contemporaneous BiVAD implantation occurred in 31 patients (67%), and compared with 15 patients (33%) with staged implants, these patients had a shorter intensive care unit length of stay of 12 days (IQR, 7–23 days) vs 42 days (IQR, 28–48 days, p = 0.035) and were more likely to be discharged from the hospital on BiVAD support (61% vs 27%, p = 0.04). RVAD thrombosis developed in 17 patients (37%). Patients with contemporaneous BiVAD implants had a 1-year survival of 74% compared with 40% in staged BiVAD patients ( p = 0.11). CONCLUSIONS Patients receiving durable BiVADs represent a critically ill patient population with severe biventricular failure who have high operative mortality and RVAD thrombosis rates. The 1-year survival for patients receiving contemporaneous BiVADs in experienced centers mirrors other contemporary durable biventricular support strategies. [ABSTRACT FROM AUTHOR]