Heart failure in patients with arrhythmogenic right ventricular cardiomyopathy: What are the risk factors?

BACKGROUND: We previously demonstrated that heart failure (HF) was one of the major causes of death in arrhythmogenic right ventricular cardiomyopathy (ARVC). The purpose of this study was to elucidate the clinical impact and risk factors of HF in patients with ARVC. METHODS AND RESULTS: We evaluated cardiac adverse outcomes including HF in 113 consecutive patients with ARVC (85 men, mean age: 44±15years). During a median follow-up of 10.0years (interquartile range: 5.2 to 15.7years), 29 patients (26%) were hospitalized for progressive HF. The patients with one or more episodes of HF hospitalization had about a 10-fold increased incidence of cardiac death (14/29 [48%] vs. 4/84 [4.7%], p<0.0001). Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) were significantly lower in the patients with HF hospitalization compared to the patients without HF hospitalization (LVEF, 45±15 vs. 54±13%, p=0.001; RVEF, 26±10 vs. 33±11%, p=0.003, respectively). Regarding the ECG findings, the prevalence of first-degree atrioventricular block (AVB, PR interval >200ms) and epsilon waves were significantly higher in patients with HF hospitalization than those without HF hospitalization (first-degree AVB, 14/29 [48%] vs. 11/84 [13%], p<0.0001; epsilon waves, 10/29 [34%] vs. 12/84 [14%], p=0.02). In multivariate analysis, first-degree AVB at baseline was the strongest independent risk factor for HF hospitalization in patients with ARVC (hazard ratio 4.24, 95% confidence interval 1.79-10.47, p=0.0011). CONCLUSION: HF hospitalization has a significant relation with malignant clinical course in ARVC patients. First-degree AVB was an independent determinant for increased risk of HF hospitalization.

Potentially Lethal Ventricular Arrhythmias and Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy: What Are the Differences Between Men and Women?

OBJECTIVES: The aim of this study was to assess sex-related differences in sporadic cases of arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: Previous studies have suggested male predominance in ARVC. However, the impact of sex on the heterogeneous clinical profile and prognosis of ARVC were not fully recognized. METHODS: The study population included 110 patients with ARVC who fulfilled the revised Task Force criteria (median age 48 years [interquartile range (IQR): 36 to 57 years]). All patients were sporadic cases without family history of ARVC. Male patients had a 3:1 predominance (75%). Ninety-seven patients (88%) were considered to have "definite" ARVC based on revised Task Force criteria. RESULTS: At the initial evaluation, there were no significant sex-related differences in age, 12-lead electrocardiogram findings, late potentials by signal-averaged electrocardiogram, left ventricular ejection fraction, or right ventricular ejection fraction. During a median follow-up of 10.0 years (IQR: 5.2 to 15.6 years), 18 patients died from cardiac causes. Kaplan-Meier analysis, considering patients' lives since birth, revealed that male patients had a significantly higher risk of ventricular tachycardia/ventricular fibrillation than did female patients (56% vs. 90%, p = 0.02), whereas female patients had a significantly higher risk of heart failure (HF) death or heart transplantation (22% vs. 5%, p = 0.002). On multivariate Cox regression analysis, female sex was an independent risk factor for HF death or heart transplantation due to HF (hazard ratio: 6.29, 95% confidence interval: 1.29 to 40.2; p = 0.02). CONCLUSIONS: Among patients with sporadic ARVC, men had a significantly higher risk of ventricular tachycardia/ventricular fibrillation, whereas women had a significantly higher risk of HF death or heart transplantation due to HF.

Defibrillation lead placement using a transthoracic transatrial approach in a case without transvenous access due to lack of the right superior vena cava.

A 65-year-old woman with a history of syncope was diagnosed with hypertrophic cardiomyopathy. She had previously undergone mastectomy of the left breast owing to breast cancer. Holter electrocardiogram (ECG) and monitor ECG revealed sick sinus syndrome (Type II) and non-sustained ventricular tachycardia. Sustained ventricular tachycardia and ventricular fibrillation were induced in an electrophysiological study. Although the patient was eligible for treatment with a dual chamber implantable cardioverter defibrillator (ICD), venography revealed lack of the right superior vena cava (R-SVC). Lead placement from the left subclavian vein would have increased the risk of lymphedema owing to the patient׳s mastectomy history. Consequently, the defibrillation lead was placed in the right ventricle by direct puncture of the right auricle through the tricuspid valve. The atrial lead was sutured to the atrial wall, and the postoperative course was unremarkable. Defibrillation lead placement using a transthoracic transatrial approach can be an alternative method in cases where a transvenous approach for lead placement is not feasible.

Distribution and haplotype analysis of all the non-synonymous and autoimmunity-related single nucleotide polymorphisms in the human deoxyribonuclease II gene using worldwide populations.

We have focused on the 14 SNPs including all the non-synonymous and autoimmunity-related ones in the DNase II gene (DNASE2). The distribution of each allele and haplotype in these SNPs was examined in eight Asian, three African, three Mexican and two Caucasian populations using the newly developed PCR-RFLP methods. Eight SNPs among nine non-synonymous ones were monomorphic, indicating that a specific allele generating the intact activity-harboring DNase II in these SNPs is well conserved in worldwide populations. On the other hand, five other SNPs (-1951G>A, -1066G>C, -390A>C, +2630T>C, and +6235G>C) related to autoimmunity exhibited polymorphism common in worldwide populations, and especially their distributions were ethnic-dependent in the same manner as those of haplotypes. Furthermore, a strong linkage between SNPs -1951G>A and -1066G>C was confirmed in most populations. This study was the first to report any worldwide population analysis regarding all the non-synonymous and autoimmunity-related SNPs in the DNASE2, providing genetic information on the DNASE2 as a genetic marker for personal identification and/or genetic factor for susceptibility to autoimmunity.

Genetic and expression analysis of SNPs in the human deoxyribonuclease II: SNPs in the promoter region reduce its in vivo activity through decreased promoter activity.

Five SNPs in the human DNase II gene have been reported to be associated with rheumatoid arthritis (RA). Genotype and haplotype analysis of 14 SNPs, nine SNPs of which reported in the NCBI dbSNP database in addition to these five SNPs, was performed in healthy subjects. The enzymatic activities of the amino acid substituted DNase II corresponding to each SNP and serum DNase II in healthy Japanese, and promoter activities derived from each haplotype of the RA-related SNPs were measured. Significant correlations between genotype in each RA-related SNP and enzymatic activity levels were found; alleles associated with RA exhibited a reduction in serum DNase II activity. Furthermore, the promoter activities of each reporter construct corresponding to predominant haplotypes in three SNPs in the promoter region of the gene exhibited significant correlation with levels of serum DNase II activity. These findings indicate these three SNPs could alter the promoter activity of DNASE2, leading to a decline in DNase II activity in the serum through gene expression. Since the three SNPs in the promoter region of the DNase II gene could affect in vivo DNase II activity through reduction of the promoter activity, it is feasible to identify these SNPs susceptible to RA.