Search

Myocarditis most often affects otherwise healthy athletes and is one of the leading causes of sudden death in children and young adults. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder with increased risk for paroxysmal ventricular arrhythmias and sudden cardiac death. The clinical picture of myocarditis and ARVC may overlap during the early stages of cardiomyopathy, which may lead to misdiagnosis. In the literature, we found several cases that presented with episodes of myocarditis and ended up with a diagnosis of arrhythmogenic cardiomyopathy, mostly of the left predominant type. The aim of this case presentation is to shed light upon a possible link between myocarditis, a desmoplakin (DSP) gene variant, and ARVC by describing a case of male monozygotic twins who presented with symptoms and signs of myocarditis at 17 and 18 years of age, respectively. One of them also had a recurrent episode of myocarditis. The twins and their family were extensively examined including electrocardiograms (ECG), biochemistry, multimodal cardiac imaging, myocardial biopsy, genetic analysis, repeated cardiac magnetic resonance (CMR) and echocardiography over time. Both twins presented with chest pain, ECG with slight ST‐T elevation, and increased troponin T levels. CMR demonstrated an affected left ventricle with comprehensive inflammatory, subepicardial changes consistent with myocarditis. The right ventricle did not appear to have any abnormalities. Genotype analysis revealed a nonsense heterozygous variant in the desmoplakin (DSP) gene [NM_004415.2:c.2521_2522del (p.Gln841Aspfs*9)] that is considered likely pathogenic and presumably ARVC related. There was no previous family history of heart disease. There might be a common pathophysiology of ARVC, associated with desmosomal dysfunction, and myocarditis. In our case, both twins have an affected left ventricle without any right ventricular involvement, and they are carriers of a novel DSP variant that is likely associated with ARVC. The extensive inflammation of the LV that was apparent in the CMR may or may not be the primary event of ARVC. Nevertheless, our data suggest that irrespective of a possible link here to ARVC, genetic testing for arrhythmogenic cardiomyopathy might be advisable for patients with recurrent myocarditis associated with a family history of myocarditis.

Background Theoretical literature and cross-sectional studies suggest empowerment is associated with other patient-reported outcomes (PROs). However, it is not known if patient empowerment is leading to improvements in other PROs or vice versa. Aims The present study aimed to examine the direction of effects between patient empowerment and PROs in young persons with congenital heart disease (CHD). Methods As part of the STEPSTONES-CHD trial, adolescents with CHD from seven pediatric cardiology centers in Sweden were included in a longitudinal observational study (n = 132). Data were collected when patients were 16 (T0), 17 (T1) and 18 ½ years old (T2). The Gothenburg Young Persons Empowerment Scale (GYPES) was used to measure patient empowerment. Random intercepts cross-lagged panel models between patient empowerment and PROs (communication skills; patient-reported health; quality of life; and transition readiness) were undertaken. Results We found a significant cross-lagged effect of transition readiness over patient empowerment between T1 and T2, signifying that a higher level of transition readiness predicted a higher level of patient empowerment. No other significant cross-lagged relationships were found. Conclusion Feeling confident before the transition to adult care is necessary before young persons with CHD can feel in control to manage their health and their lives. Clinicians interested in improving patient empowerment during the transitional period should consider targeting transition readiness.

Introduction: Sudden cardiac death (SCD) and early onset cardiomyopathy (CM) in the young will always lead to suspicion of an underlying genetic disorder. Incited by the rapid advances in genetic testing for disease we have revisited families, which previously tested &ldquo, gene-negative&rdquo, for familial predominantly pediatric CM, in hopes of finding a causative gene variant. Methods: 10 different families with non-syndromic pediatric CM or hypertrophic cardiomyopathy (HCM) with severe disease progression and/or heredity for HCM/CM related SCD with &ldquo, results were included. The index patient underwent genetic testing with a recently updated gene panel for CM and SCD. In case of failure to detect a pathogenic variant in a relevant gene, the index patient and both parents underwent clinical (i.e., partial) exome sequencing (trio-exome) in order to catch pathogenic variants linked to the disease in genes that were not included in the CM panel. Results: The mean age at clinical presentation of the 10 index cases was 12.5 years (boys 13.4 years, n = 8, girls 9 years, n = 2) and the family history burden was 33 HCM/CM cases including 9 HCM-related SCD and one heart transplantation. In 5 (50%) families we identified a genetic variant classified as pathogenic or likely pathogenic, in accordance with the American College of Medical Genetics and Genomics (ACMG) criteria, in MYH7 (n = 2), RBM20, ALPK3, and PGM1, respectively, and genetic variants of unknown significance (VUS) segregating with the disease in an additional 3 (30%) families, in MYBPC3, ABCC9, and FLNC, respectively. Conclusion: Our results show the importance of renewed thorough clinical assessment and the necessity to challenge previous genetic test results with more comprehensive updated gene panels or exome sequencing if the initial test failed to identify a causative gene for early onset CM or SCD in children. In pediatric cardiomyopathy cases when the gene panel still fails to detect a causative variant, a trio exome sequencing strategy might resolve some unexplained cases, especially if a multisystemic condition is clinically missed.

An ECG risk-score has been described that predicts high risk of subsequent cardiac arrest in young patients with hypertrophic cardiomyopathy (HCM). Myocardial fibrosis measured by cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) also affects prognosis. We assessed whether an ECG risk-score could be used as an indicator of myocardial fibrosis or perfusion deficit on CMR in HCM. In total 42 individuals (7-31 years); 26 HCM patients, seven genotype-positive, phenotype-negative individuals at risk of HCM (first-degree relatives) and nine healthy volunteers, underwent CMR to identify, and grade extent of, myocardial fibrosis and perfusion defect. 12-lead ECG was used for calculating the ECG risk-score (grading 0-14p). High-risk ECG (risk-score 5p) occurred only in the HCM group (9/26), and the proportion was significantly higher vs mutation carriers combined with healthy volunteers (0/16, p = 0.008). Extent of LGE correlated to the ECG-score (R

Providing continuous follow-up care to patients with congenital heart disease (CHD) remains a challenge in many settings. Previous studies highlight that patients with CHD experience discontinuation of follow-up care, but mainly describe a single-centre perspective, neglecting inter-institutional variations. Hospital-related factors above and beyond patient-related factors are believed to affect continuity of care. The present multicentre study therefore investigated (i) proportion of "no follow-up care"; (ii) transfer destinations after leaving paediatric cardiology; (iii) variation in proportions of no follow-up between centres; (iv) the association between no follow-up and outpatient volumes, and (v) its relationship with staffing resources at outpatient clinics.An observational, multicentre study was conducted in seven university hospitals. In total, 654 adolescents with CHD, born between 1991 and 1993, with paediatric outpatient visit at age 14-18 years were included. Transfer status was determined 5 years after the intended transfer to adult care (23y), based on medical files, self-reports and registries.Overall, 89.7% of patients were receiving adult follow-up care after transfer; 6.6% had no follow-up; and 3.7% were untraceable. Among patients in follow-up care, only one remained in paediatric care and the majority received specialist adult CHD care. Significant variability in proportions of no follow-up were identified across centres. Higher outpatient volumes at paediatric outpatient clinics were associated with better continued follow-up care after transfer (OR = 1.061; 95% CI = 1.001 - 1.124). Medical staffing resources were not found predictive.Our findings support the theory of hospital-related factors influencing continuity of care, above and beyond patient-related characteristics.

Aims To determine if myocardial perfusion (MP) during hyperaemia is decreased in young patients with hypertrophic cardiomyopathy (HCM). Also, to determine if an MP decrease is associated with diastolic dysfunction, and to investigate if young subjects at risk of HCM show differences in MP compared with controls. Methods and results This study included 10 HCM patients (age 22.3 ± 6.4 years), 14 subjects at risk for HCM ‘HCM risk’ (age 18.9 ± 3.8 years), and 12 controls (age 22.8 ± 4.5 years). HCM patients were examined at rest and during hyperaemia (adenosine 140 µg/kg/min) with cardiovascular magnetic resonance (CMR) and echocardiography. MP was calculated as the ratio of coronary sinus flow and left ventricular mass (LVM) from CMR. Myocardial fibrosis was assessed using late gadolinium enhancement. Diastolic function was quantified with both echocardiography and CMR. At rest, MP (mL/min/g) was similar in the control, HCM risk, and HCM patients (0.8 ± 0.1, 1.0 ± 0.1, and 0.9 ± 0.1, respectively, P = ns). During adenosine, MP was lower in HCM patients (2.5 ± 0.4, P < 0.05) compared with both HCM risk (5.0 ± 0.5) and controls (3.9 ± 0.3). Subjects at HCM risk showed no significant difference in MP during adenosine compared with controls. One HCM patient showed mild diastolic dysfunction. Neither controls nor HCM risk individuals showed any sign of myocardial fibrosis, whereas 7/10 HCM patients had fibrosis (5 ± 1% of the total LVM). Conclusion Young individuals with HCM, but not those at risk, show decreased MP during hyperaemia compared with controls even in the absence of diastolic dysfunction or LV outflow obstruction. These results may suggest that microvascular disease contributes to the decreased MP in the investigated population.

Introduction Sudden cardiac death (SCD) in the young is rare and should always lead to suspicion of a genetic cardiac disorder. We describe a family, in which the proband was a girl deceased by sudden cardiac death in the playground at thirteen years of age. The index-patient had short stature, cleft palate but no previous cardiac symptoms. We found an uncommon cause of cardiomyopathy, due to a congenital disorder of glycosylation (CDG), previously described to cause a variable range of usually mild symptoms, and not previously found to cause SCD as the first symptom of the condition. Methods The index patient underwent postmortem genetic testing/molecular autopsy for genes known to cause SCD, without a detection of causative agent, why two siblings of similar phenotype as the deceased sister underwent clinical-exome genetic sequencing (next generation sequencing). All first-degree relatives underwent clinical examination including cardiac ultrasound, Holter-ECG, exercise stress test and biochemistry panel. Results A genetic variant in the gene for phosphoglucomutase 1 (PGM1) was identified in the index patient and her two brothers, all were found to be homozygous for the genetic variant (G230E) NM_002633.2:c.689 G > A in PGM1. This variant has been linked to a congenital disorder of glycosylation (PGM1-CDG), explaining the clinical picture of short stature, cleft palate, liver engagement and cardiomyopathy. During follow-up one of the brothers died unexpectedly after physical exertion during daily life at the age of twelve years. The other brother fainted during similar circumstances at the age of thirteen years. Both parents and three other siblings were found to be heterozygous gene carriers without risk for the disease. Conclusion Our findings suggest that there is a need of multidisciplinary discussion and genetic testing after unexpected cardiac death in the young. We have to be more flexible in our evaluation of diseases and to consider even uncommon diseases including rare recessive inherited disorders. Our findings also suggest that the autosomal recessive PGM1-CDG might be highly associated with life-threatening cardiomyopathy with arrhythmia or sudden cardiac death as the first symptom presenting from childhood and adolescence.

Introduction The conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on the conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG scoring could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3 HCM with greater specificity. Methods Five-minute 12-lead ECGs were obtained from 15 young patients (mean age 13.2 years, range 0-30 years) with MYBPC3 mutation and phenotypic HCM. The conventional and A-ECG results of these patients were compared to those of 198 healthy children and young adults (mean age 13.2, range 1 month-30 years) with unremarkable echocardiograms, and to those of 36 young endurance-trained athletes, 20 of whom had athletic (physiologic) left ventricular hypertrophy. Results Compared with commonly used, age-specific pooled criteria from the conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 derived vectorcardiographic parameters (spatial QRS-T angle and the change in the vectorcardiographic QRS azimuth angle from the second to the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 46% to 87% (p

Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered. Funding Agencies|KIRCNET (Karolinska Institutet Circulation and Respiratory Research Network)||Magn. Bergvalls Foundation||Jerring Foundation||Stiftelsen Samariten||Karolinska Institute||Royal Swedish Academy of Sciences||Swedish Research Council||Goran Gustafsson Foundation||Torsten and Ragnar Soderberg Foundation||King Gustaf Vth 80-Year Foundation||Swedish Foundation for Strategic Research||Heart-Lung Foundation||Swedish Rheumatism Association

Recurrent copy number variants (CNVs) are found in a significant proportion of patients with congenital heart disease (CHD) and some of these CNVs are associated with other developmental defects. In some syndromic patients, CHD may be the first presenting symptom, thus screening of patients with CHD for CNVs in specific genomic regions may lead to early diagnosis and awareness of extracardiac symptoms. We designed a multiplex ligation-dependent probe amplification (MLPA) assay specifically for screening of CHD patients. The MLPA assay allows for simultaneous analysis of CNVs in 25 genomic regions previously associated with CHD. We screened blood samples from 402 CHD patients and identified 14 rare CNVs in 13 (3.2%) patients. Five CNVs were de novo and six where inherited from a healthy parent. The MLPA screen led to early syndrome diagnosis in two of these patients. We conclude that the MLPA assay detects clinically relevant CNVs and suggest that it could be used within pediatric cardiology as a first tier screen to detect clinically relevant CNVs and identify syndromic patients at an early stage. (C) 2012 Wiley Periodicals, Inc. (Less)

The relationship between hypertrophy, perfusion abnormalities and fibrosis is unknown in young patients with hypertrophic cardiomyopathy (HCM). Since mounting evidence suggests causal relationship between myocardial ischemia and major adverse cardiac events, we sought to investigate whether (1) regional myocardial perfusion is decreased in young HCM patients and in individuals at risk of HCM, and (2) hypoperfused areas are larger than areas with fibrosis. HCM patients (n = 12), HCM-risk subjects (n = 15) and controls (n = 9) were imaged on a 1.5 T MRI scanner. Myocardial hypertrophy was assessed on cine images. Perfusion images were acquired during adenosine hyperemia and at rest. Maximum upslope ratios of perfusion (stress/rest) were used for semiquantitative analysis. Fibrosis was assessed by late gadolinium enhancement (LGE). Results are presented as median and range. Perfusion in HCM-risk subjects and in non-hypertrophied segments in HCM patients showed no difference compared to controls (P = ns). Hypertrophic segments in HCM patients without LGE showed decreased perfusion compared to segments without hypertrophy [1.5 (1.1-2.3) vs. 2.0 (1.8-2.6), P < 0.001], and hypertrophic segments with LGE showed even lower perfusion using a segmental analysis [0.9 (0.6-1.8), P < 0.05]. The extent of hypoperfused myocardium in HCM patients during adenosine exceeded the extent of fibrosis on LGE [20 (0-48) vs. 4 (0-7) % slice area, P < 0.05] and hypoperfused areas at rest (P < 0.001). Regional perfusion is decreased in hypertrophied compared to non-hypertrophied myocardium and is lowest in fibrotic myocardium in young HCM patients but does not discriminate HCM-risk subjects from controls. The stress-induced hypoperfused regions exceed regions with LGE, indicating that hypoperfusion precedes fibrosis and may be a more sensitive marker of diseased myocardium in HCM.