BACKGROUND: Atrial fibrillation (AF) recurrence after ablation requires predictors for better management. This study evaluated early post-ablation changes in echocardiographic parameters, clarifying the relative importan...BACKGROUND: Atrial fibrillation (AF) recurrence after ablation requires predictors for better management. This study evaluated early post-ablation changes in echocardiographic parameters, clarifying the relative importance of left ventricle (LV) diastolic function and left atrium (LA) strain for recurrence prediction. METHODS AND RESULTS: The study prospectively enrolled 165 consecutive patients undergoing de novo AF ablation between 2019 and 2021. Echocardiography was performed before and 3 months after ablation. Three months after ablation, LA volume and LA strain (reservoir and contraction phases) decreased significantly and the LV ejection fraction improved. Extrapulmonary vein LA ablation was associated with significantly lower LA strain at 3 months. Over a median follow-up of 359 days, atrial tachyarrhythmia recurred in 45 (27.3%) patients. Three months after ablation, there was no significant difference in LA strain between groups with and without recurrence, but mitral E/e' and right ventricular systolic pressure (RVSP) were significantly higher in the group with recurrence (mitral E/e' 7.4±2.2 vs. 10.4±4.1; RVSP 23.1±3.5 vs. 28.4±4.8 mmHg; P<0.001 for both). Multivariable analysis identified E/e' and RVSP at 3 months as independent predictors of recurrence (hazard ratios 1.246 and 1.111, respectively), but not LA strain. CONCLUSIONS: Following AF ablation, hemodynamic factors appear to be more significant predictors of recurrence than LA strain. Assessment of LV diastolic function during the early post-ablation period may help identify patients at high risk of recurrence.
BACKGROUND: Brugada syndrome (BrS) is an arrhythmic disease associated with SCN5A loss-of-function variants. We identified a novel single nucleotide substitution, SCN5A c.1338G>A, in the last codon of exon10 in a patient...BACKGROUND: Brugada syndrome (BrS) is an arrhythmic disease associated with SCN5A loss-of-function variants. We identified a novel single nucleotide substitution, SCN5A c.1338G>A, in the last codon of exon10 in a patient with drug-induced BrS. The aim of this study was to investigate the impact of this splice-altering variant and examine whether antisense oligonucleotides (ASOs) could correct the splice alteration. METHODS AND RESULTS: Genomic DNA was extracted from the patient's blood lymphocytes. Coding exons of inherited arrhythmia genes were screened and SCN5A c.1338G>A was identified. SpliceAI predicted its prominent potential to alter splicing among 168 single nucleotide variants in the SCN5A region including 10 variants with allele frequency (AF) <0.01, and the usage of a cryptic splice donor site 4 bp downstream from the authentic splice donor site. Minigene splicing reporter assays were performed using HEK-293 cells and induced pluripotent stem cells-cardiomyocytes, and successfully demonstrated a dominant selection of the predicted splice site. Three different ASOs were tested in the same platform. Although the ASOs reduced the production of splice error products, they did not succeed in increasing authentically spliced products. CONCLUSIONS: We confirmed a splice site alteration by SCN5A c.1338G>A and propose extended use of SpliceAI for screening a target genomic region. The attempts to correct mis-splicing near the canonical splice site were not entirely successful, so further development of technology is awaited.
BACKGROUND: Changes in mitral valve (MV) morphology during MV transcatheter edge-to-edge repair (MV-TEER) are associated with short-term reduction of mitral regurgitation (MR). However, whether these changes are associat...BACKGROUND: Changes in mitral valve (MV) morphology during MV transcatheter edge-to-edge repair (MV-TEER) are associated with short-term reduction of mitral regurgitation (MR). However, whether these changes are associated with prognosis remains unclear. Using 3-dimensional transesophageal echocardiography, this study evaluated the impact of MV morphological parameters on the mid-term prognosis of patients with functional MR (FMR). METHODS AND RESULTS: We analyzed 99 patients with FMR who were treated with MV-TEER. The primary endpoint was a composite of all-cause mortality and hospitalization due to heart failure. Patients were divided into 2 groups based on the post-procedural sphericity index of the mitral valve (SI-MV), which is the ratio of the vertical to horizontal MV diameter. Using receiver operating characteristic curve (ROC) analysis for the primary endpoint, the SI-MV cut-off value was determined to be 0.86. The incidence of the primary endpoint was significantly (log-rank P=0.013) higher among patients with a post-procedural SI-MV >0.86 (circular MV morphology) than among those with post-procedural SI-MV ≤0.86 (elliptical MV morphology). Post-procedural SI-MV >0.86 was an independent determinant of the primary endpoint in multivariate analysis (hazard ratio 2.35; 95% confidence interval 1.25-4.42; P=0.0077). CONCLUSIONS: A larger post-procedural SI-MV is associated with increased mid-term adverse clinical events after MV-TEER in patients with FMR.
BACKGROUND: Heart failure with mildly reduced ejection fraction (HFmrEF) is a distinct but relatively understudied phenotype of heart failure. Traditional measures, such as ejection fraction and global longitudinal strai...BACKGROUND: Heart failure with mildly reduced ejection fraction (HFmrEF) is a distinct but relatively understudied phenotype of heart failure. Traditional measures, such as ejection fraction and global longitudinal strain (GLS), have limited prognostic value in HFmrEF, prompting interest in global myocardial work (GMW) as a more comprehensive marker. This study investigated the prognostic utility of GMW in HFmrEF. METHODS AND RESULTS: In this retrospective study, 273 patients with HFmrEF diagnosed between 2014 and 2018 were followed for a median of 31 months. Forty-eight patients experienced hospitalization for heart failure (HHF). The global work index (GWI), GLS, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) use were significantly associated with HHF risk. Univariate Cox regression showed that GWI (hazard ratio [HR] 0.998; 95% confidence interval [CI] 0.997-0.999; P=0.003), global constructive work (HR 0.999; 95% CI 0.998-1.000; P=0.010), ACEi/ARB use (HR 0.464; 95% CI 0.239-0.902; P=0.024), and GLS (HR 1.058; 95% CI 1.004-1.116; P=0.035) were significant predictors of HHF. In multivariable analysis, higher GWI was independently associated with a lower risk of HHF (HR 0.997; 95% CI 0.996-0.998; P=0.001). Notably, GWI ≥850 mmHg% was associated with a significantly lower HHF risk (HR 0.075; 95% CI 0.0288-0.196; P=0.001). CONCLUSIONS: GWI is an independent prognostic marker for HHF in HFmrEF, offering incremental value beyond conventional echocardiographic parameters. However, validation in prospective and multicenter studies is warranted.
BACKGROUND: Outdoor air pollutants are known to have adverse health impacts, but knowledge of the relationship between exposure to air pollutant mixtures and cardiovascular health (CVH) remains limited. METHODS AND RESUL...BACKGROUND: Outdoor air pollutants are known to have adverse health impacts, but knowledge of the relationship between exposure to air pollutant mixtures and cardiovascular health (CVH) remains limited. METHODS AND RESULTS: We examined the association of air pollutant mixtures with CVH using the American Heart Association's Life's Essential 8 (LE8), which is based on 4 health behaviors and 4 biometric health factors. Data from a nationally representative sample of 27,763 adults were analyzed. One-year moving average concentrations of PM, PM, SO, NO, CO, and Owere estimated through air pollution modeling. CVH was evaluated using LE8 scores (range 0-100), with higher scores indicating superior CVH. The association of a 1-quantile increment in air pollutant mixture with the expected change in LE8 score was evaluated using Quantile g-computation. The mean LE8 score in study participants was 63.7. In the adjusted model, a 1-quantile increment in air pollutant mixture was linked to a 1.67-point (95% confidence interval -2.18, -1.16) decrease in LE8 score. CO, O, PM, and NOaccounted for 43.7%, 28.7%, 23.9%, and 3.7%, respectively, of the inverse association of the air pollutant mixture with the overall LE8 score. CONCLUSIONS: Our study revealed that long-term exposure to outdoor air pollutants is associated with poor CVH, suggesting the need for supporting policy interventions to reduce air pollutant levels and mitigate their health impacts.
BACKGROUND: Loss-of-function SCN5A variants are primarily associated with Brugada syndrome (BrS), but can also present with overlapping phenotypes. We investigated Cys1384Phe of SCN5A, a novel missense variant associated...BACKGROUND: Loss-of-function SCN5A variants are primarily associated with Brugada syndrome (BrS), but can also present with overlapping phenotypes. We investigated Cys1384Phe of SCN5A, a novel missense variant associated with BrS, sick sinus syndrome (SSS), and dilated cardiomyopathy (DCM). METHODS AND RESULTS: This study included a large 4-generation Japanese family consisting of 15 individuals (1 proband and 14 family members). Among them, the proband, a cousin, a second cousin and the second cousin's father were diagnosed with BrS. Two of these 4 BrS patients experienced VF events, while the other 2 remained asymptomatic. Another cousin was diagnosed with DCM, and 3 additional family members exhibited complete right bundle branch block and/or SSS. Comprehensive genetic analysis using a target panel sequencing identified a novel missense variant, Cys1384Phe in SCN5A, in the proband and affected family members; however, the phenotypes were different. Whole-cell patch-clamp experiments using HEK293 cells transfected wild-type or Cys1384Phe plasmid demonstrated a complete loss-of-function in the sodium current of the Cys1384Phe cells. Furthermore, the heterozygous expression of Cys1384Phe and wild-type (WT) channels showed a significant reduction of peak sodium current compared with the WT, suggesting a dominant-negative suppression, but no trafficking defect was observed. CONCLUSIONS: The novel Cys1384Phe variant in SCN5A is a complete loss-of-function mutation with dominant-negative suppression, and associated with overlapping phenotypes of BrS, SSS, and DCM.
BACKGROUND: Early risk stratification for acute myocardial infarction (AMI) using prehospital vital signs, including percutaneous oxygen before oxygen supply (pre-SpO), remains underexplored. METHODS AND RESULTS: We anal...BACKGROUND: Early risk stratification for acute myocardial infarction (AMI) using prehospital vital signs, including percutaneous oxygen before oxygen supply (pre-SpO), remains underexplored. METHODS AND RESULTS: We analyzed 3,006 AMI patients from the Mie ACS Registry. Patients were stratified by the prehospital Simple Risk Index (pre-SRI = [heart rate × (age / 10)] / systolic blood pressure) and pre-SpOlevels. The primary outcome was 30-day death. Combined assessment of pre-SRI and pre-SpOwas superior to individual parameters for predicting 30-day death. In the multivariate analysis, combined assessment (SRI ≥34 and SpO≤94%) was the strongest independent predictors of 30-day death (hazard ratio 3.98, P<0.001). CONCLUSIONS: Prehospital vital signs including pre-SpOenable early high-risk identification, improving clinical decision-making for hospital selection.
BACKGROUND: In Japan, intravascular lithotripsy (IVL) is indicated during percutaneous coronary intervention (PCI) for calcified lesions when the calcium score assessed by intravascular ultrasound (IVUS) or optical coher...BACKGROUND: In Japan, intravascular lithotripsy (IVL) is indicated during percutaneous coronary intervention (PCI) for calcified lesions when the calcium score assessed by intravascular ultrasound (IVUS) or optical coherence tomography (OCT) is ≥3. This study evaluated the effectiveness of IVL in achieving optimal stent expansion in lesions with an OCT calcium score ≥3, regardless of the IVUS calcium score. METHODS AND RESULTS: We retrospectively compared 26 consecutive PCIs in 23 patients who underwent IVL with pre-PCI OCT or optical frequency domain imaging and simultaneous pre- and post-PCI IVUS with 102 patients who underwent PCI without atherectomy but similar imaging protocols. Of all 128 PCIs, 84 with an OCT calcium score ≥3 and a simultaneous IVUS calcium score ≤2 were analyzed. Stent expansion was measured by IVUS. Among the 84 PCIs included in the analysis, 17 were performed using IVL and 67 were performed without atherectomy or IVL (non-IVL group). Stent expansion at the site of maximum superficial calcium was greater in the IVL than non-IVL group (90.9% vs. 84.6%, respectively; P=0.028). The non-IVL group was independently associated with reduced stent expansion at the site of maximum superficial calcium, even after adjusting for IVUS calcium score components (B=-0.817; P<0.001). CONCLUSIONS: Even in calcified lesions with an IVUS calcium score ≤2, IVL was independently associated with favorable stent expansion when the OCT calcium score was ≥3.
BACKGROUND: Direct oral anticoagulants (DOACs) are commonly used oral anticoagulants for patients with venous thromboembolism (VTE). Sometimes these patients receive concomitant antiplatelet therapy, with limited data su...BACKGROUND: Direct oral anticoagulants (DOACs) are commonly used oral anticoagulants for patients with venous thromboembolism (VTE). Sometimes these patients receive concomitant antiplatelet therapy, with limited data supporting the practice. This study investigated the effect of concomitant antiplatelet therapy (CAT) on clinical outcomes in VTE patients treated with anticoagulants. METHODS AND RESULTS: The COMMAND VTE Registry-2 is a multicenter registry that enrolled 5,197 consecutive patients with acute symptomatic VTE across 31 centers in Japan between January 2015 and August 2020. After excluding 407 patients without oral anticoagulants, there were 4,790 VTE patients treated with oral anticoagulants. After propensity score matching, 676 patients (338 matched pairs in the CAT and anticoagulant only [AC] groups) were included for analysis. There were no significant differences between the CAT and AC groups in the cumulative 3-year incidence of recurrent VTE (4.9% vs. 7.3%, respectively; P=0.50), major bleeding (9.4% vs. 12.4%, respectively; P=0.36), or stroke (6.7% vs. 4.1%, respectively; P=0.24). However, the cumulative 3-year incidence of clinically relevant non-major bleeding (CRNMB) was significantly higher in the CAT group than in the AC group (17.7% vs. 10.0%; P=0.047). CONCLUSIONS: In a large VTE registry in the DOAC era, concomitant antiplatelet and anticoagulant therapy, compared with anticoagulant alone, was not significantly associated with risks of recurrent VTE, major bleeding, or stroke, but did increase the risk of CRNMB.
BACKGROUND: Patients with infective endocarditis (IE) on maintenance hemodialysis (HD) have poor outcomes, but contemporary data remain limited. METHODS AND RESULTS: We conducted a retrospective analysis using a nationwi...BACKGROUND: Patients with infective endocarditis (IE) on maintenance hemodialysis (HD) have poor outcomes, but contemporary data remain limited. METHODS AND RESULTS: We conducted a retrospective analysis using a nationwide Japanese administrative database and identified 12,158 patients hospitalized with IE between 2018 and 2021, including 806 (6.6%) on maintenance HD. The inhospital mortality rate was significantly higher in HD patients (30.0% vs. 13.5%, P<0.05). CONCLUSIONS: Maintenance HD patients with IE had worse outcomes, underscoring the need for early recognition and tailored management in this highrisk group.
BACKGROUND: Current guidelines recommend early revascularization in patients with cardiogenic shock (CS) following acute myocardial infarction (AMI). However, guideline-recommended first medical contact-to-device times i...BACKGROUND: Current guidelines recommend early revascularization in patients with cardiogenic shock (CS) following acute myocardial infarction (AMI). However, guideline-recommended first medical contact-to-device times is reportedly achieved in only 40% of patients. METHODS AND RESULTS: We retrospectively analyzed 369 patients with AMI complicated by CS from the Kanagawa-Acute Cardiovascular Registry to evaluate factors influencing delays in treatment and their effect on in-hospital mortality. Patients were stratified into 2 groups based on the median door-to-cardiac catheterization laboratory (D2C) time (≤39 or >39 min). In the group with D2C time ≤39 min, the first-contact physician was more frequently a cardiologist (71.9% vs. 47.0%; P<0.001) and significantly more patients had chest pain as the chief complaint (70.3% vs. 47.4%; P<0.001). Although pre- and post-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow was similar between the 2 groups, in-hospital mortality was significantly lower in the D2C time ≤39 min group (18.8% vs. 37.6%; P<0.001). Multivariate logistic regression analysis revealed that D2C time >39 min was independently associated with a non-cardiologist being the first-contact physician, the absence of chest pain, a higher heart rate, and elevated creatinine levels. CONCLUSIONS: D2C time ≤39 min is correlated with reduced mortality in AMI patients with CS. Implementing systems to ensure cardiologists are the initial responders and optimizing in-hospital workflows could reduce the D2C time and improve outcomes.