Passive Transfer of Hepatitis B Antibodies through Intravenous Immunoglobulin in a Neonate.

Passive transfer of antibodies secondary to intravenous immunoglobulin infusion is a rare but important side effect that can lead to the wrong diagnosis and therapeutic decisions. It has never been reported in a newborn. A male newborn, vaccinated against hepatitis B and diagnosed with dilated cardiomyopathy, presented positive hepatitis B core antibodies at 12 days of life. Exclusion of hepatitis B infection was mandatory as it would be a contraindication to heart transplant. Passive transfer of antibodies was confirmed at 44 days of age, after seroreversion of hepatitis B core antibodies. Passive transfer of antibodies after intravenous immunoglobulin infusion can lead to a misleading diagnosis if not recognized. In our patient it could have been especially harmful had it prevented heart transplant. Screening for hepatitis B should be performed at least 1 month after intravenous immunoglobulin infusion.

A transferência passiva de anticorpos secundária à infusão de imunoglobulina endovenosa é um efeito secundário raro, mas importante, que pode levar a um diagnóstico e decisões terapêuticas erradas. Nunca foi descrito num recém-nascido. Um recém-nascido do sexo masculino, vacinado contra a hepatite B e diagnosticado com miocardiopatia dilatada, apresentou anticorpos anti-core do vírus da hepatite B aos 12 dias de vida. A exclusão da infecção por hepatite B foi obrigatória, pois seria uma contra-indicação ao transplante cardíaco. A transferência de anticorpos através de imunoglobulina endovenosa foi confirmada aos 44 dias de idade, após sero-reversão dos níveis de anticorpos anti-core do vírus da hepatite B. A transferência passiva de anticorpos após a infusão de imunoglobulina endovenosa pode levar a um diagnóstico errado se não for reconhecida. Neste doente poderia ter sido especialmente prejudicial caso tivesse impedido o transplante de coração. O rastreio para hepatite B deve ser realizado pelo menos um mês após a infusão.

Prediction of postnatal clinical course in primary congenital dilated cardiomyopathy.

BACKGROUND: The aim of this study was to investigate the prediction of postnatal prognosis using fetal and perinatal data in patients with primary congenital dilated cardiomyopathy (PCDCM), and to estimate the incidence of this disease. METHODS: We examined correlations between fetal or perinatal data and postnatal clinical course in a multicenter retrospective study of eight patients with PCDCM. Incidence was calculated in a population-based study. RESULTS: All patients developed heart failure at a median of 8 days (range, 0-43 days), and six patients died or required extracorporeal artificial heart therapy at a median of 67 days (range, 0-92 days). The cardiothoracic area ratio from fetal echocardiography, the Apgar score, and the standard deviation of birth weight correlated significantly with the date at onset of heart failure. However, no data correlated with survival. Cumulative incidence of PCDCM was calculated as 1.21 per 100 000 total births (95% confidence interval, 0.37 to 2.06). CONCLUSIONS: Primary congenital dilated cardiomyopathy has a poor prognosis, but cardiothoracic area ratio from fetal echocardiography, body weight at birth, and Apgar score correlate with the timing of the onset of heart failure, and these indicators might therefore be useful for peri- and postnatal management.

Miocardiopatía dilatada: presentación de un caso, 2018 / Dilatedcardiomyopathy. Presentation of a case. 2018

Introducción: miocardiopatía significa enfermedad del músculo cardíaco. Es una enfermedad crónica y algunas veces progresiva en la cual el músculo cardíaco (miocardio) se agranda, se engrosa y/o se pone rígido de manera anormal, y el corazón ya no puede contraerse ni relajarse normalmente. Presentación de caso: lactante masculino de 5 meses de nacido, ingresado en el servicio de Terapia Intensiva del Hospital Pediátrico Docente General Luis A. Milanés Tamayo, con antecedentes de salud, que es atendido en nuestro centro por bronquiolitis moderada, aparece aumento del área cardiaca por rayos X de tórax , EKG que muestra una taquicardia sinusal y ECG evidenciándose severa dilatación de VI de forma ovoide, válvula mitral con signos de bajo gasto cardiaco, con limitación en su apertura con contractilidad cardiaca global disminuida, diagnosticándose una miocardiopatía dilatada. Discusión:la miocardiopatía dilatada (MD), también llamada congestiva, se caracteriza por agrandamiento del ventrículo izquierdo y/o ventrículo derecho con hipocontractilidad de sus paredes, traduciéndose en signos y síntomas de insuficiencia cardíaca congestiva. Conclusiones: es importante resaltar la necesidad de conocer las formas de presentación de las miocardiopatíaspara poder hacer un correcto y oportuno diagnóstico(AU)

Introduction: cardiomyopathy means heart muscle disease. It is a chronic and sometimes progressive disease in which the heart muscle (myocardium) enlarges, thickens and / or stiffens abnormally, and the heart can no longer contract or relax normally. Case presentation: a 5-month-old male infant admitted to the Intensive Care Unit of the Teaching Pediatric Hospital General Luis A. Milanés Tamayo, with a health history, which is treated in our center for moderate bronchiolitis. cardiac area by chest X-rays, EKG showing a sinus tachycardia and ECG evidencing severe ovoid LV dilatation, mitral valve with signs of low cardiac output, with limited opening with decreased global cardiac contractility, diagnosing a dilated cardiomyopathy. Discussion:dilated cardiomyopathy (MD), also called congestive, is characterized by enlarged left ventricle and / or right ventricle with hypocontractility of its walls, resulting in signs and symptoms of congestive heart failure. Conclusions: it is important to highlight the need to know the forms of presentation of cardiomyopathies in order to make a correct and timely diagnosis(EU)

Heart Transplantation from Biventricular Support in Infant with Novel SMYD1 Mutation.

SET and MYND domain-containing protein 1 (SMYD1) has been shown to be responsible for the development of fast twitch and cardiac muscle. Mutations in SMYD1 have been shown to be uniformly fatal in laboratory studies, and not previously described in living humans. We describe here the care of an infant suffering from cardiac failure due to an SMYD1 mutation requiring biventricular assist devices as a bridge to successful heart transplantation. The patient is now doing well 2 years post-transplant and represents a known survivor of a suspected uniformly fatal genetic mutation.

Improvement of the outcome in patients with infantile dilated cardiomyopathy over three decades - The usefulness of long-term gradually medical supportive care.

BACKGROUND: The treatment of heart failure has changed with the use of angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers since the middle of the 1990s. However, the outcome in infantile dilated cardiomyopathy (DCM) when treated with them remains poorly understood. METHODS: We reviewed the medical records of infants with DCM within 24 months old in our hospital between 1979 and 2012, and compared the outcome in the later group (1997-2012) with that in the early group (1979-1996). The survival and cardiac event (CE)-free survival rates were calculated by the Kaplan-Meier method. RESULTS: There were 20 patients in the early group and 24 patients in the later group. The median left ventricular fractional shortening at the onset of disease in the early and later groups were 11% (range 4-17%) and 12% (range 4-25%), respectively. In the later group, ACEIs and beta-blockers were administered in 22 and 21 patients, respectively. An usual low-dose induction of carvedilol therapy (0.01-0.02mg/kg/day) sometimes worsened the heart failure in 9 patients (43%) after the successful initial conventional treatment for acute heart failure. Nineteen patients died and 25 survived. The CEs were as follows: heart transplantation 4, mitral valvuloplasty 1, Batista operation with mitral valve replacement 1, and cardiac resynchronization therapy in the late period 1. The 20-year survival rate in the early and later groups were 5% (95% CI 0.7-28) and 100%, respectively (p<0.001). The 2-year CE-free survival rate in the early and later groups were 5% (95% CI 0.7-28) and 83% (95% CI 59-91), respectively (p<0.001). CONCLUSIONS: The outcome in patients with infantile DCM has significantly improved with careful acute and chronic treatments using ACEIs and beta-blockers since the 2000s. Adopting a long-term supportive treatment during a period of low ventricular function and the use of beta-blockers corresponding to each patient's condition were key to survival.

Congenital Titinopathy: Comprehensive characterization and pathogenic insights.

OBJECTIVE: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder. METHODS: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients. RESULTS: All patients had prenatal or early onset hypotonia and/or congenital contractures. None had ophthalmoplegia. Scoliosis and respiratory insufficiency typically developed early and progressed rapidly, whereas limb weakness was often slowly progressive, and usually did not prevent independent walking. Cardiac involvement was present in 46% of patients. Relatives of 2 patients had dilated cardiomyopathy. Creatine kinase levels were normal to moderately elevated. Increased fiber size variation, internalized nuclei and cores were common histopathological abnormalities. Cap-like regions, whorled or ring fibers, and mitochondrial accumulations were also observed. Muscle magnetic resonance imaging showed gluteal, hamstring and calf muscle involvement. Western blot analysis showed a near-normal sized titin protein in all samples. The presence of 2 mutations predicted to impact both N2BA and N2B cardiac isoforms appeared to be associated with greatest risk of cardiac involvement. One-third of patients had 1 mutation predicted to impact exons present in fetal skeletal muscle, but not included within the mature skeletal muscle isoform transcript. This strongly suggests developmental isoforms are involved in the pathogenesis of this congenital/early onset disorder. INTERPRETATION: This detailed clinical reference dataset will greatly facilitate diagnostic confirmation and management of patients, and has provided important insights into disease pathogenesis. Ann Neurol 2018;83:1105-1124.

Giant right atrium: an extreme case of idiopathic dilation of the right atrium.

An adult with a grossly dilated right atrium of unknown etiology is presented. The right atrial volume was estimated at more than 1,900 mL, with normal sized left atrium and ventricles. She presented in atrial fibrillation and right ventricular failure. She underwent subsequent reduction atrioplasty of the right atrium and tricuspid valve ring annuloplasty. Atrioplasty alone was unsuccessful in controlling the atrial fibrillation. Postoperatively, her course was complicated by pericardial space problems, eventually requiring a partial pericardiectomy. At her 2-year follow-up she was asymptomatic, although still in atrial fibrillation.

Human-induced pluripotent stem cell models of inherited cardiomyopathies.

PURPOSE OF REVIEW: This article provides an overview of the latest advances in in-vitro modeling of inherited cardiomyopathies using human-induced pluripotent stem cells (iPSCs). RECENT FINDINGS: Inherited cardiomyopathies have been recently modeled by generating iPSCs from patients harboring mutations in genes associated with the pathogenesis of hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy/dysplasia. SUMMARY: Patient-specific iPSCs and their differentiated cardiomyocytes (induced pluripotent stem cell-derived cardiomyocytes) now provide a novel model to study the underlying molecular mechanism of the pathogenesis of familial cardiomyopathies as well as for in-vitro drug screening and drug discovery.

Recovery of echocardiographic function in children with idiopathic dilated cardiomyopathy: results from the pediatric cardiomyopathy registry.

OBJECTIVES: This study sought to determine the incidence and predictors of recovery of normal echocardiographic function among children with idiopathic dilated cardiomyopathy (DCM). BACKGROUND: Most children with idiopathic DCM have poor outcomes; however, some improve. METHODS: We studied children <18 years of age from the Pediatric Cardiomyopathy Registry who had both depressed left ventricular (LV) function (fractional shortening or ejection fraction z-score <-2) and LV dilation (end-diastolic dimension [LVEDD] z-score >2) at diagnosis and who had at least 1 follow-up echocardiogram 30 days to 2 years from the initial echocardiogram. We estimated the cumulative incidence and predictors of normalization. RESULTS: Among 868 children who met the inclusion criteria, 741 (85%) had both echocardiograms. At 2 years, 22% had recovered normal LV function and size; 51% had died or undergone heart transplantation (median, 3.2 months), and 27% had persistently abnormal echocardiograms. Younger age (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.88 to 0.97) and lower LVEDD z-score (HR: 0.78; 95% CI: 0.70 to 0.87) independently predicted normalization. Nine children (9%) with normal LV function and size within 2 years of diagnosis later underwent heart transplantation or died. CONCLUSIONS: Despite marked LV dilation and depressed function initially, children with idiopathic DCM can recover normal LV size and function, particularly those younger and with less LV dilation at diagnosis. Investigations related to predictors of recovery, such as genetic associations, serum markers, and the impact of medical therapy or ventricular unloading with assist devices are important next steps. Longer follow-up after normalization is warranted as cardiac failure can recur. (Pediatric Cardiomyopathy Registry; NCT00005391).

Cardiomyocyte Ogt is essential for postnatal viability.

The singly coded gene O-linked-ß-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. In mature cells, this enzyme catalyzes the posttranslational modification known as O-GlcNAc to various cellular proteins. Several groups, including our own, have shown that acute increases in protein O-GlcNAcylation are cardioprotective both in vitro and in vivo. Yet, little is known about how OGT affects cardiac function because total body knockout (KO) animals are not viable. Presently, we sought to establish the potential involvement of cardiomyocyte Ogt in cardiac maturation. Initially, we characterized a constitutive cardiomyocyte-specific (cm)OGT KO (c-cmOGT KO) mouse and found that only 12% of the c-cmOGT KO mice survived to weaning age (4 wk old); the surviving animals were smaller than their wild-type littermates, had dilated hearts, and showed overt signs of heart failure. Dysfunctional c-cmOGT KO hearts were more fibrotic, apoptotic, and hypertrophic. Several glycolytic genes were also upregulated; however, there were no gross changes in mitochondrial O2 consumption. Histopathology of the KO hearts indicated the potential involvement of endoplasmic reticulum stress, directing us to evaluate expression of 78-kDa glucose-regulated protein and protein disulfide isomerase, which were elevated. Additional groups of mice were subjected to inducible deletion of cmOGT, which did not produce overt dysfunction within the first couple of weeks of deletion. Yet, long-term loss (via inducible deletion) of cmOGT produced gradual and progressive cardiomyopathy. Thus, cardiomyocyte Ogt is necessary for maturation of the mammalian heart, and inducible deletion of cmOGT in the adult mouse produces progressive ventricular dysfunction.

Triphasic mitral and tricuspid flows: a sign of diastolic dysfunction in a young patient with severely dilated atria and giant pulmonary veins.

This report presents a case with severe dilation of both atria and giant pulmonary veins manifested with atrial fibrillation. The following cardiac magnetic resonance findings are highly suggestive of restrictive physiology: E/A ratio greater than two, prominent A wave across the pulmonary veins and inferior vena cava, and more interestingly, a triphasic flow across the mitral and tricuspid valves.

Congenital atresia of the left main coronary artery with noncompaction of the ventricular myocardium in an asymptomatic young child.

Congenital atresia of the left main coronary artery (LMCA) is an extremely rare cardiac anomaly, and no cases have been reported from the mainland of China. The diagnosis for the 20-month-old boy in the reported case highlights the essentiality of comprehensive diagnostic measures. To avoid a misdiagnosis, electrocardiographic and echocardiographic evidence should be vigilantly explored in young children suspected of having dilated cardiomyopathy. This is the first case report of LMCA atresia associated with noncompaction of the left ventricular myocardium.

An infant case of dilated cardiomyopathy associated with congenital cytomegalovirus infection.

A 2-month-old infant with congestive heart failure was referred to the authors' hospital. Echocardiography exhibited a dilated left ventricle (LV), poor LV systolic function, and intraventricular thrombus. Laboratory data showed a normal creatinine phosphokinase level and negative troponin T test results. The congestive heart failure was managed using a beta-blocker, an angiotensin receptor blocker, and diuretics. Head computed tomography performed during the treatment course showed periventricular calcifications. Congenital cytomegalovirus infection was subsequently diagnosed. Fetal echocardiography performed during pregnancy showed impaired LV function, suggesting that the cardiomyopathy was associated with cytomegalovirus infection in utero.

A fetal dilated and hypertrophic cardiomyopathy associated with maternal gestational diabetes--a case report.

There is an increased risk of a hypertrophic cardiomyopathy and congenital heart defects among newborns of diabetic mothers. We report a case of hypertrophic cardiomyopathy preceded with dilated cardiomyopathy in a fetus of a diabetic mother. The fetal echocardiography at the 23rd week of gestation revealed signs of dilated cardiomyopathy with signs of cardiac failure. Under the echocardiographic monitoring the successful treatment was performed. In spite of poor prognosis, the child was born at the 39th gestation week in a good condition.

A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.

Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease.