Circulation Journal最新文献

Background: In patients with atrial fibrillation-related ischemic stroke despite oral anticoagulation (AFIDA), left atrial appendage closure (LAAC) may be an additional strategy to prevent further stroke events.

Methods and results: AFIDA was defined as ischemic stroke occurring despite ≥3 weeks of oral anticoagulation (OAC). We evaluated patients with AFIDA treated either with OAC alone (n=141; further divided into aggressive OAC [n=73] and conventional OAC [n=68] subgroups) or with additional LAAC (+LAAC; n=95; further divided into continued OAC [n=44] and discontinued OAC within 1 year after LAAC [n=51] subgroups). Patients in the +LAAC group were younger, had higher HAS-BLED scores, and lower HELT-E₂S₂scores. Three-year cumulative incidence rates of ischemic stroke and major bleeding were comparable between the OAC alone and +LAAC groups (15.2% vs. 14.5% [log-rank P=0.75] and 23.4% vs. 5.3% [log-rank P=0.38], respectively), whereas those of fatal or disabling stroke and fatal bleeding were lower in the +LAAC than OAC alone group (3.4% vs. 14.7% [log-rank P=0.06] and 0% vs. 6.0% [log-rank P=0.03], respectively). Results of propensity score-matched and subgroup analyses were largely consistent with those of the main analysis. Notably, fatal bleeding occurred only in patients switched to aggressive OAC.

Conclusions: LAAC may potentially prevent fatal or disabling stroke and fatal bleeding in patients with AFIDA. These hypothesis-generating findings support the need for randomized controlled trials.

Background: The Amplatzer^TMPFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-Marketing Surveillance (PFO Japan PMS) study started in December 2019. This analysis presents clinical outcomes of study patients through 1 year of follow-up.

Methods and results: PFO Japan PMS is a prospective single-arm multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the Amplatzer^TMPFO Occluder, with no age restrictions. PFO closure was evaluated at 1 year via a bubble study, and patients will be followed for 3 years. From December 2019 to July 2021, 500 patients were enrolled across 53 sites. The mean (±SD) patient age was 52.7±15.4 years, with 29.8% of patients aged >60 years. Low adverse event rates were observed through 1 year of follow-up, including atrial fibrillation (2.4%; predominantly transient and within the first 30 days) and ischemic stroke (0.6%). Among patients in whom a 1-year bubble study was performed, a high rate (91.5%) of clinically relevant PFO closure (<20 bubbles) was achieved.

Conclusions: Through 1 year of follow-up in this real-world Japanese study with 30% of patients aged >60 years, a high degree of closure was achieved with the Amplatzer^TMPFO Occluder, along with low rates of atrial fibrillation, ischemic stroke, and overall adverse events.

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.