Association of HLA class II DRB1, DPA1 and DPB1 polymorphism with genetic susceptibility to idiopathic dilated cardiomyopathy in Chinese Han nationality

Although the aetiology of idiopathic dilated cardiomyopathy (IDC) remains unclear, many immunological abnormalities involving changes in cell-mediated and humoral immunity may be associated with cardiac impairment in IDC. Autoimmune mechanisms are likely to participate in the pathogenesis of at least a subgroup of IDC and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, which are highly polymorphic, play an important role in the activating of immune responses and thus control the predisposition for or protection from IDC. This study explores the possible contribution of HLA-DRB and DP polymorphisms to IDC susceptibility. DNA genotyping for HLA-DRB1, DPA1 and DPB1 was performed using polymerase chain reaction-sequencing based typing (PCR-SBT) method in 198 IDC patients and 136 random selected healthy Han ethnic individuals living in Northern China. IDC patients were, sub-grouped into asymptomatics (subgroup A), with arrhythmia (subgroup B) and with overt congestive heart failure (subgroup C) according to the clinical manifestations and electrocardiogram or echocardiographic characteristics. ADP/ATP autoantibody was detected in IDC group by immunoblot analysis. The results revealed that HLA-DR15, -DPB*0601 frequencies were significantly elevated in IDC group compared with normal control. The DPB1*0601 allele in homozygous form or in combination with allele DPB1*2301 or *3901, was found present more often in IDC patients. The predominance of HLA-DR4 allele was observed in subgroup B after stratification. However, the frequency of DPB1*0101 allele increased in the control than in the IDC group. The frequency of HLA-DPB1*0601 allele was significantly higher in IDC patients with positive autoantibody against ADP/ATP carrier of myocardial mitochondria in contrast to those with negative autoantibody. We conclude that HLA-DR4, -DR15, -DPB1*0601 alleles confers susceptibility to, while DPB1*0101 allele confers protection from IDC among individuals of northern Chinese Han nationality. The glutamate at position 69 in the second exon of DPB1*0601, as a key residue for special conformation of HLA-DP, may confer predisposition to IDC. HLA-DR and -DP alleles polymorphisms may serve as genetic markers for IDC and be involved in the regulation of the immune specific response to auto or exterior anti-myocardium antibodies.     

Cardiac myosin binding protein-C restricts intrafilament torsional dynamics of actin in a phosphorylation-dependent manner

We have determined the effects of myosin binding protein-C (MyBP-C) and its domains on the microsecond rotational dynamics of actin, detected by time-resolved phosphorescence anisotropy (TPA). MyBP-C is a multidomain modulator of striated muscle contraction, interacting with myosin, titin, and possibly actin. Cardiac and slow skeletal MyBP-C are known substrates for protein kinase-A (PKA), and phosphorylation of the cardiac isoform alters contractile properties and myofilament structure. To determine the effects of MyBP-C on actin structural dynamics, we labeled actin at C374 with a phosphorescent dye and performed TPA experiments. The interaction of all three MyBP-C isoforms with actin increased the final anisotropy of the TPA decay, indicating restriction of the amplitude of actin torsional flexibility by 15–20° at saturation of the TPA effect. PKA phosphorylation of slow skeletal and cardiac MyBP-C relieved the restriction of torsional amplitude but also decreased the rate of torsional motion. In the case of fast skeletal MyBP-C, its effect on actin dynamics was unchanged by phosphorylation. The isolated C-terminal half of cardiac MyBP-C (C5–C10) had effects similar to those of the full-length protein, and it bound actin more tightly than the N-terminal half (C0–C4), which had smaller effects on actin dynamics that were independent of PKA phosphorylation. We propose that these MyBP-C-induced changes in actin dynamics play a role in the functional effects of MyBP-C on the actin–myosin interaction.     

Could the unfortunate outcome of pediatric acute myocarditis be predicted? Factors contributing to a poor outcome in myocarditis

ObjectiveMyocarditis has spontaneous resolution in 50% of patients. Our study aimed to define risk factors for developing dilated cardiomyopathy (DCM) and death in pediatric patients with acute myocarditis (AM).MethodsThe retrospective cohort study included all patients with treated AM. The Mother and Child Health Institute from January 2011 to March 2019.ResultsIn the study, 62 patients were included, 40 boys and 22 girls (11.15±5.86 years) with AM. Twelve out of sixty-two children had acute fulminant myocarditis. Four patients died in the acute phase of AM, and 11 developed DCM. Follow up was 27.14±36.52 months. Patients with poor outcome (DCM development) were under the age of seven (odds ratio [OR] 10.1; p=0.003), more likely to be girls (OR 4.6; p=0.03), and had fulminant myocarditis (OR 27.0; <0.001). An ejection fraction (EF) <55% and fractional shortening (FS) <30% increased risk of DCM 13- and 5-fold, respectively, but patients with EF between 40 and 55% remain at highest risk of developing DCM. There was a 12-fold increased risk for DCM in patients with left ventricular end-diastolic diameter Z score >2+. The receiver operator curve showed that the lactate dehydrogenase (LDH) cut-off value for developing DCM was 1780 mmol/l (sensitivity 80%, specificity 100%).ConclusionAcute fulminant myocarditis was an independent risk factor for DCM. Children with EF between 40 and 50% at admission were at highest risk of developing DCM. Lactate dehydrogenase value could be a significant prognostic value for the outcome of pediatric myocarditis.     

Clinical outcomes of catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy: Insights from the Johns Hopkins ARVC Program

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Infarction of the septomarginal band and tricuspid papillary muscle rupture related to alcohol septal ablation for hypertrophic cardiomyopathy

We presented a 77‐year‐old man with hypertrophic obstructive cardiomyopathy applied with flail tricuspid leaflet and severe tricuspid regurgitation leading to right heart failure 2 months after the failed septal ablation. The ruptured anterior tricuspid papillary muscle resulted from infarction of the base of anterior papillary muscle of the right ventricle (RV) confirmed by magnetic resonance imaging. As the septomarginal band is frequently lit up by intracoronary contrast that particular attention should be paid to the RV papillary muscles. And, if the papillary muscles or the RV free wall is brightened, then the use of that septal artery should be avoided.