Circulation Journal最新文献

Background: The impact of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) on long-term clinical outcomes remains controversial.

Methods and results: Of 14,927 consecutive patients with their first coronary revascularization in the CREDO-Kyoto Registry Cohort-3, we extracted data for 1,483 undergoing CABG without prior atrial fibrillation (AF). POAF was defined as newly documented AF during hospitalization for CABG and was diagnosed in 337 (23%) patients during the index hospitalization. The remaining 1,146 patients were categorized as the non-POAF group. The median follow-up after discharge was 5.7 years. The cumulative 5-year incidence of all-cause death did not differ significantly between the POAF and non-POAF groups (15.9% vs. 13.0%, respectively; P=0.38), whereas the cumulative 5-year incidence of stroke, heart failure, and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the POAF group. There was no excess adjusted risk of the POAF group relative to the non-POAF group for all-cause death (hazard ratio 0.96; 95% confidence interval 0.70-1.31; P=0.81). The risk of the POAF group relative to the non-POAF group was numerically higher for stroke and heart failure, and significantly higher for BARC type 3 or 5 bleeding.

Conclusions: The long-term risk of patients with POAF relative to those without was significantly higher for major bleeding and numerically higher for stroke and heart failure, with no difference for mortality.

Background: Despite active research into the pathophysiology of Brugada syndrome (BrS), the mechanisms of the genesis of changes in the characteristic electrocardiogram (ECG) are still controversial.

Methods and results: Using multiscale computer simulation of ECGs, we compared 3 hypotheses to identify the mechanisms of the BrS-type ECG caused by a mutation in cardiac sodium channels. In addition to the dominant repolarization disorder and depolarization disorder hypotheses, we tested a new hypothesis assuming the combination of a slow conduction property, upregulation of transient outward potassium current channels, and reduced expression levels of sodium channels in the right ventricular outflow tract (embryonic phenotype model). We found that only the embryonic phenotype model reproduced the clinically observed BrS-type ECG by strongly inhibiting sodium current selectively in the right ventricular outflow tract. We also simulated a ventricular wedge experiment and confirmed that strong inhibition of the sodium current was the prerequisite for a change in the ECG.

Conclusions: Strong selective inhibition of the sodium current in the right ventricular outflow tract generates the characteristic BrS-type ECG in the precordial leads without affecting the waveforms in other lead positions. This change can only be achieved using the embryonic phenotype model in which reduced expression levels of sodium channels play an essential role.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease with a poor prognosis and no curative therapy. It may present as arrhythmogenic sudden cardiac death and inevitably progress to terminal heart failure due to the loss of contractile tissue. This study aimed to generate knock-in (KI) mice carrying the 2 genetic variants (DSG2 p.R292C and p.D494A) most frequently found in Japanese ARVC patients, characterize their cardiac phenotype, and compare the results with those of human ARVC.

Methods and results: Variants were introduced using CRISPR/Cas9 genome editing at the corresponding mouse locations: Dsg2 p.R297C (RC) and p.D499A (DA). Cardiac function, morphology, and electrophysiology were evaluated using echography, magnetic resonance imaging, and telemetry. Tissue and cardiomyocytes were examined histologically. All mice with the variants developed biventricular cardiac dysfunction after 8 weeks of age, and it progressed with age. There was a significant variability in phenotype expression. Mice with RC died suddenly at 9 weeks of age. Some homozygous RC mice showed arrhythmia and conduction abnormalities on telemetry. In both variants, staining of cardiac sections revealed significant fibrosis, and apoptosis was detected using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay.

Conclusions: We generated a KI ARVC mouse model with significant similarities to human disease. This model could be used for the elucidation of pathogenesis and the development of optimal therapy for ARVC.

Background: Hospitalization for heart failure (HF) is associated with poor outcomes, yet the temporal patterns of laboratory biomarkers surrounding such events remain inadequately described. This study aimed to characterize trajectories of routinely measured biomarkers before and after HF hospitalization.

Methods and results: We retrospectively analyzed patients hospitalized for acute HF at Nagoya University Hospital between January 2018 and December 2023. In the main cohort, outpatient levels of B-type natriuretic peptide (BNP), creatinine, hemoglobin, hematocrit, uric acid, sodium, and potassium were evaluated for 1 year following discharge. A second cohort included patients with ≥2 hospitalizations, assessing biomarker trends 1 year before and after the second admission. The main cohort included 709 patients (7,299 laboratory visits). Of them, 191 patients with rehospitalization comprised the second cohort (3,318 visits). In the main cohort, BNP, creatinine, uric acid, hemoglobin, and hematocrit declined for 60 days post-discharge, followed by increases. In the second cohort, BNP, creatinine, and uric acid levels began to rise 60 days before rehospitalization (e.g., BNP increased by 185.2 pg/mL per 30 days, 95% confidence interval: 138.1 to 232.3, P<0.001), while hemoglobin, hematocrit, and sodium declined.

Conclusions: Biomarkers exhibited distinct patterns before and after HF hospitalization. A BNP increase of approximately 200 pg/mL per 30 days within 60 days prior to admission may represent a practical, non-invasive marker to guide early intervention.

Background: In Japan, the implantation of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) is not covered by insurance reimbursement, and the underuse of ICDs has been noted. Therefore, this study analyzed the medical costs incurred due to a lack of primary prevention ICD therapy for SCD.

Methods and results: This retrospective cohort study analyzed data from 4 advanced critical care centers between January 2020 and December 2024. From a database of 3,606 cases of cardiac arrest, there were 348 patients with a documented rhythm at the time of arrest that could have been treated with an ICD. Of these patients, 43 (12.4%) had documented evidence of heart failure treatment and were eligible for ICD implantation before experiencing a cardiac arrest. The total mean (±SD) medical cost for these patients was US $11,679±14,666 (¥1,775,150±2,229,272).

Conclusions: In this multicenter retrospective analysis, we identified a subset of patients who were eligible for primary prevention ICD therapy but did not receive it prior to experiencing sudden cardiac arrest. These cases were associated with substantial post-arrest medical costs. Our findings highlight the potential clinical and economic impact of the underutilization of ICDs in Japan and suggest that broader implementation of guideline-directed ICD therapy for primary prevention may reduce both mortality and healthcare expenditure.