Background: Left ventricular (LV) dyssynchrony worsens with heart failure (HF) progression. However, the early identification of LV dyssynchrony is challenging, and its prognostic value remains unclear. We aimed to evaluate the prognostic value of LV dyssynchrony based on bandwidth (time width within which 95% of the LV myocardium begins to contract), assessed using Heart Risk View (HRV) analysis of myocardial perfusion scintigraphy data.

Methods and Results: This was a post hoc analysis of a prospective, non-randomized, single-center cohort study conducted between January 2019 and December 2023. This study included 584 patients (mean age 72.2±13.0 years; 425 [72.8%] males; non-ischemic 29.8%; LV ejection fraction [LVEF] 46.4±15.0%) who were admitted for HF and had LV dyssynchrony evaluated using HRV-based analysis. The composite endpoint was all-cause mortality and HF rehospitalization. Univariate and multivariate logistic regression showed LV dyssynchrony as a significant predictor of HF prognosis (bandwidth threshold 28.0°). Multiple regression analysis identified QRS width, LVEF, and ischemic cardiomyopathy as significant determinants of bandwidth. Prognosis was poorer in high-bandwidth groups defined by the median (21.0°) or threshold bandwidth (28.0°). Combined with B-type natriuretic peptide, bandwidth improved prognostic utility. Bandwidth showed a moderate correlation with QRS width and strong correlations with end-systolic volume and LVEF.

Conclusions: HRV-derived bandwidth is a non-invasive and safe method providing automatic, objective, and reproducible measurements. It is useful for predicting HF prognosis.

Background: This study prospectively collected and analyzed real-world clinical outcomes of cancer patients with venous thromboembolism (VTE) receiving rivaroxaban in Japan.

Methods and Results: From August 2018 to December 2021, cancer patients with VTE treated with rivaroxaban or warfarin were enrolled at 27 Japanese institutions. A total of 322 patients treated with rivaroxaban were analyzed. The VTE recurrence/worsening-free survival rate by Kaplan-Meier estimate was 98.0% and neither VTE-related nor cardiovascular deaths occurred during 24-week rivaroxaban treatment.

Conclusions: VTE recurrence/worsening occurred in only a small percentage of Japanese cancer-VTE patients treated with rivaroxaban.

Background: Although percutaneous coronary intervention (PCI) has become safer due to advances in devices and procedural standardization, in-hospital outcomes may still vary depending on the involvement of certified interventional cardiologists (ICs). This study evaluated the association between board-certified IC involvement and in-hospital outcomes following PCI using a nationwide Japanese registry.

Methods and Results: We analyzed PCI cases between 2020 and 2023, classifying them according to the involvement (defined as acting as a primary operator or supervising assistant) of board-certified members of the Japanese Association of Cardiovascular Intervention and Therapeutics (BMCVIT). Among 842,335 PCI cases analyzed, 579,459 (68.8%) were performed with BMCVIT involvement. The frequency of BMCVIT involvement was higher for the treatment of patients with prior revascularization and complex lesions, but lower for patients admitted with acute coronary syndrome (ACS) or hemodynamic instability. After adjusting for baseline characteristics, BMCVIT involvement remained independently associated with lower in-hospital mortality (odds ratio [OR] 0.89; 95% confidence interval [CI] 0.86–0.92; P<0.001), composite in-hospital complications (OR 0.94; 95% CI 0.91–0.97, P<0.001), and access site bleeding (OR 0.88; 95% CI 0.80–0.97, P=0.012). Subgroup analyses revealed consistent mortality benefits across age, sex, dialysis status, lesion complexity, and institutional PCI volume, with stronger protection in patients without ACS or cardiogenic shock.

Conclusions: BMCVIT involvement in PCI was independently associated with lower in-hospital mortality and complications, underscoring the quality gains of IC participation.

Background: Little is known about the recently emerging entity, heart failure with supranormal ejection fraction (HFsnEF).

Methods and Results: Subanalysis of a nationwide, prospective, observational registry that included compensated ambulatory patients with chronic HF and left ventricular ejection fraction (LVEF) >40%. Among the 4,387 patients (mean age 77 years, 43% female), 1,423 had HFsnEF. They were older, more often female, had lower natriuretic peptide levels, and exhibited smaller LV. The prescription rate of guideline-directed medical therapy was lower.

Conclusions: HFsnEF is a common and distinct phenotype characterized by a unique profile and treatment.

Background: Predicting the origin of premature ventricular contractions (PVCs) is challenging when a transition zone (TZ) appears in leads V3 and V4. The aim of this study was to develop a deep-learning model to predict PVC origins and identify electrocardiographic (ECG) features that contribute to the model’s decisions.

Methods and Results: ECG data from 314 patients with PVCs showing an inferior axis and TZ in leads V3 or V4 who underwent catheter ablation were analyzed. A convolutional neural network (CNN) was trained to predict an origin in the right or left ventricular outflow tract. Patients were divided into 3 cohorts for training, validation, and holdout (3 : 1 : 1 ratio). The CNN model was trained using paired data consisting of PVC and intrinsic QRS (iQRS). Five datasets per patient were used for training and validation; performance was evaluated using a single holdout dataset per patient. The CNN model achieved 92.1% accuracy, an F1 score of 0.91, and an area under the receiver operating characteristic curve of 0.96 on the holdout. Our model demonstrated superior diagnostic performance compared with conventional ECG indices. Gradient-weighted class activation mapping revealed that model attention was primarily focused on leads V3–V4 in iQRS, but was more diffusely distributed in PVC, notably the inferior limb leads and leads V2–V3.

Conclusions: The CNN-based prediction of PVC origin demonstrated clinical utility.

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: Non-home discharge (NHD) after endovascular therapy (EVT) for chronic limb-threatening ischemia (CLTI) signals frailty and higher healthcare costs.

Methods and Results: The nationwide J-EVT Registry (2021–2023) captured data for 31,025 patients with CLTI who underwent EVT. NHD, defined as transfer to chronic-care hospitals, occurred in 12.9%. Independent predictors of NHD were age ≥70 years, non-ambulatory status, and perioperative complications.

Conclusions: Because 1 in 8 Japanese CLTI patients required NHD after EVT, risk stratification and minimizing procedural invasiveness are essential to improve home-discharge rates.

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: Emerging evidence highlights the clinical significance of lipid variability in cardiovascular disease and adverse outcomes. This study investigated the relationship between lipid variability and incident peripheral artery disease (PAD) risk.

Methods and Results: We identified 93,948 patients in the Chang Gung Research Database in Taiwan who had been diagnosed with hyperlipidemia between 2007 and 2013 and had annual lipid measurements over 4 consecutive years. Lipid levels, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides, as well as their visit-to-visit variability, were assessed over the 4-year period. Patients were followed until December 31, 2019 for incident PAD development. Over a mean 5.9-year follow-up, 2,735 patients (2.5%) developed PAD. Mean lipid levels were significantly associated with incident PAD. Of note, the average real variability (ARV) in HDL-C was independently associated with increased PAD risk (adjusted hazard ratio 1.13; 95% confidence interval 1.004–1.27 for highest vs. lowest quartile of HDL-C ARV; P for trend=0.002). Sensitivity analysis using variability independent of the mean as the HDL-C variability index confirmed this finding. Consistency was observed across all subgroup analyses.

Conclusions: In this multi-institutional database analysis, visit-to-visit variability in HDL-C was significantly associated with the risk of incident PAD, independent of traditional risk factors for atherosclerosis, mean lipid levels, and the use of lipid-lowering therapy.

Background: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement in hemodialysis patients; however, contemporary outcomes and risk stratifications remain unreported.

Methods and Results: Using data from a multicenter database, this study included 2,888 patients who underwent TAVI between 2021 and 2024: 336 (11.6%) on hemodialysis and 2,552 (88.4%) not. The primary outcome was all-cause death after TAVI; the median follow-up was 527 days. Hemodialysis patients were younger, predominantly male, and had more comorbidities with higher surgical risk. Hemodialysis and non-hemodialysis patients had similar 30-day mortality (2.9% vs. 1.5%, respectively) and major procedural complications. Hemodialysis patients had 2- to 3-fold higher rates of all-cause death (14.4% vs. 6.5% at 1-year; 21.5% vs. 11.0% at 2 years), cardiovascular death, and the composite of all-cause death and heart failure hospitalization. After adjusting for confounders, hemodialysis had no significant effect on all-cause death and the composite endpoint. Body mass index, Clinical Frailty Scale, and albumin levels were associated with all-cause death in hemodialysis patients, allowing risk stratification into low-, intermediate-, and high-risk groups.

Conclusions: In this study, hemodialysis patients were younger and had more comorbidities, but 30-day mortality and complications were similar to the non-hemodialysis group. Although hemodialysis patients had higher all-cause mortality, the worse outcomes in this group were attributed to comorbidities rather than the hemodialysis itself.

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: 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: 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: 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 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 PM₁₀, PM_2.5, SO₂, NO₂, CO, and O₃were 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, O₃, PM_2.5, and NO₂accounted 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 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: 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: 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: The usefulness of non-sustained ventricular tachycardia (NSVT) in predicting sudden cardiac death is not clear. The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan (HINODE) investigated the effectiveness of implantable cardioverter defibrillator (ICD) treatment for primary prevention in Japanese patients. This subanalysis examined associations between NSVT and clinical outcomes.

Methods and Results: Patients with ICD/cardiac resynchronization therapy defibrillator (CRT-D) for primary prevention (n=164) were divided into NSVT (n=25) and no NSVT (n=139) groups. NSVT was defined as ventricular tachycardia of <30 s duration regardless of pulse rate. The median follow-up period was 19 months, mean patient age was 67 years, and 21% of patients were female. There were no significant differences between the 2 groups in the frequency ischemic cardiomyopathy, mean left ventricular ejection fraction, or (in Kaplan-Meier analysis) in all-cause mortality (log-rank P=0.613), ventricular arrhythmia (VA; log-rank P=0.282), or the composite endpoint of all-cause death and VA events (log-rank P=0.352). Cox proportional hazards analysis indicated that NSVT was not a prognostic factor.

Conclusions: Prognosis was similar between the NSVT and no NSVT groups. NSVT, although recommended in guidelines for risk stratification, was not associated with appropriate ICD therapy in patients with ICD/CRT-D for primary prevention. The utility of NSVT in guiding ICD indication may depend on its definition and the characteristics of the studied population, and requires further investigation.

Background: Atriogenic tethering (AT) is a characteristic feature of the mitral valve in atrial functional mitral regurgitation (AFMR). However, the factors associated with AT are not well known.

Methods and Results: This was a post hoc analysis of REVEAL-AFMR, a retrospective observational study involving patients with moderate or greater AFMR. A stepwise binary logistic regression model was used to identify factors associated with AT. The primary endpoint was a composite of cardiovascular death, heart failure hospitalization, and mitral valve intervention. Of 1,007 patients, 245 (24%) had AT and 762 (76%) did not. Of 15 clinical variables related to AT in AFMR, greater left ventricular end-systolic dimension and left atrial diameter were independently associated with AT. The 3-year rate of freedom from the primary outcome was significantly lower in the group with than without AT (63.2% vs. 71.2%; P=0.002). The risk of the primary outcome was significantly higher in the group with than without AT (adjusted hazard ratio 1.34; 95% confidence interval 1.04–1.74; P=0.026), although the results were inconsistent in the sensitivity analysis using propensity score overlap weighting.

Conclusions: AT was identified in 24% of patients with moderate or greater AFMR. Greater left ventricular end-systolic and left atrial anteroposterior dimensions were factors associated with AT. Among patients with AFMR, those with AT showed a poor prognosis.

Background: Coronary microvascular dysfunction (CMD) is characterized by impaired myocardial flow reserve (MFR) in patients with non-obstructive coronary artery disease (CAD). The real-world incidence of CMD, risk factors for decreased MFR, and characteristics of the two CMD endotypes (classical and endogenous) in this population remain unclear.

Methods and Results: After screening 1,313 patients with suspected or known CAD who underwent ¹³N-ammonia positron emission tomography (PET), 345 with non-obstructive CAD were retrospectively enrolled in the study. Stress/resting myocardial blood flow (MBF) was quantified using ¹³N-ammonia PET. PET-assessed CMD (impaired MFR <2.0) was diagnosed in 60 (17%) patients. Independent predictors of decreased MFR included older age, female sex, anemia, and hypertension; however, these factors accounted for only 32% of the observed variability in MFR. Symptomatic status was not an independent predictor of decreased MFR. Patients with classical CMD (resting MBF <1.3 mL/min/g) had higher summed stress scores and stress/resting coronary vascular resistance, whereas patients with endogenous CMD (resting MBF ≥1.3 mL/min/g) showed female dominance, higher stress MBF, and a higher resting rate-pressure product.

Conclusions: Among patients with non-obstructive CAD, approximately 1 in 5 had PET-assessed CMD. Age, female sex, anemia, and hypertension were independent clinical factors associated with impaired MFR, which explained a limited portion of its variability. Further examination of unidentified or unmeasured factors is warranted.

Background: The diagnostic utility of the exercise electrocardiogram (ECG) in detecting coronary microvascular dysfunction (CMD) remains unclear.

Methods and Results: We analyzed 101 patients without obstructive coronary artery disease (CAD) who underwent the Master double 2-step exercise ECG and invasive coronary physiological assessment. The sensitivity, specificity, positive predictive value, and negative predictive value of ischemic ECG changes for detecting CMD were 0.44, 0.97, 0.85, and 0.84, respectively. The post-test probability of CMD increased from 24.8% to 82.8% with a positive ECG finding.

Conclusions: The Master double 2-step exercise ECG demonstrated high specificity for detecting CMD in patients without obstructive CAD.

Background: Passive leg lifting (PLL) may serve as a simple alternative to simulate exercise stress.

Methods and Results: We evaluated 33 patients with PH who underwent PLL-RHC and exercise right heart catheterization (RHC); 25 patients were classified as having PLL-induced PH (LIPH), demonstrating significant increases in mean pulmonary arterial pressure (mPAP) and mPAP–cardiac output slopes. Strong correlations were observed between PLL-RHC and exercise RHC measurements.

Conclusions: PLL-RHC may represent a simple method for detecting EIPH.

Background: This study evaluated early and mid-term clinical outcomes of surgical correction for anomalous aortic origin of a coronary artery (AAOCA) and expansion of surgical indications beyond current guidelines, particularly for asymptomatic patients with anomalous aortic origin of the right coronary artery (AAORCA).

Methods and Results: Between December 2004 and July 2023, 34 patients underwent surgery for AAOCA. Surgical indications included evidence of myocardial ischemia and high-risk anatomy. AAOCA was assessed pre- and postoperatively using imaging and functional studies. Early and mid-term outcomes were evaluated retrospectively. AAORCA was the predominant type (n=32; 94.1%), and 32 of 34 patients (94.1%) underwent unroofing. Five (14.7%) asymptomatic AAORCA patients had a history of Kawasaki disease. There were no surgical mortalities or coronary artery-related complications. Of 12 patients with symptoms or signs likely related to the coronary artery in the early postoperative period, 2 had persistent symptoms until the last follow-up. During follow-up, 2 patients had suspicious mild coronary stenosis on computed tomography, and 1 had decreased stress perfusion on a myocardial perfusion scan. Among patients with preoperative abnormalities, 92.3% exhibited postoperative functional improvement.

Conclusions: Surgical treatment of AAOCA, primarily through unroofing, is safe and effective, with favorable early and mid-term outcomes. Our findings support consideration of surgery for asymptomatic AAORCA patients with high-risk anatomy due to the potential risk of sudden cardiac events and the substantial benefits of the procedure.

The management of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease, particularly those with acute coronary syndrome (ACS), has evolved significantly. Recent evidence emphasizes the importance of early and intensive LDL-C lowering for reducing recurrent cardiovascular events by stabilizing vulnerable plaques. Global guidelines now advocate for more aggressive LDL-C targets, with a common recommendation of <55 mg/dL for high-risk ACS patients. However, regional variations persist in specific target levels, pharmacologic strategies, and follow-up schedules due to differences in healthcare infrastructure, epidemiology, and risk assessment frameworks. Despite guideline updates, achieving recommended LDL-C levels in real-world practice remains challenging, primarily due to issues like healthcare system limitations, patient adherence, and clinical inertia. Some regions in Japan have established local clinical pathways that demonstrate improvements in attainment of LDL-C targets and clinical outcomes. This article explores the current global LDL-C targets and treatment strategies for ACS patients, aiming to enhance the achievement of optimal LDL-C levels and reduce subsequent adverse events.

Background: Right ventricular endomyocardial biopsy may cause conduction disturbances, particularly complete right bundle branch block (CRBBB); however, the impact of using the venous access site remains unclear.

Methods and Results: In 274 patients, CRBBB occurred more frequently with the transfemoral than with the transjugular approach (29.2% vs. 6.7%, P<0.001). The transjugular approach independently reduced CRBBB risk (odds ratio 0.17, P<0.001). Sustained CRBBB was also less frequent (8.3% vs. 1.1%, P=0.007). Major complications, including stroke, pacemaker implantation, and death, were absent.

Conclusions: The transjugular approach reduces CRBBB risk and is a safer option for patients at risk of complete atrioventricular block.

Background: In the presence of a potent P2Y₁₂inhibitor such as prasugrel, the additional clinical antithrombotic benefit of aspirin is unclear. The feasibility of prasugrel monotherapy without aspirin after percutaneous coronary intervention (PCI) has been demonstrated in chronic coronary syndrome, but is yet to be assessed in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) and low anatomical complexity.

Methods and Results: ASET-Japan is a single-arm study investigating the safety of prasugrel 12-month monotherapy with a locally approved dose (loading 20 mg; maintenance 3.75 mg), started immediately after successful PCI using platinum-chromium everolimus-eluting SYNERGY stents. The primary ischemic endpoint is a composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis; the primary bleeding endpoint is Bleeding Academic Research Consortium (BARC) Type 3 and 5 bleeding. ASET-Japan recruited 101 NSTE-ACS patients from 11 Japanese sites. The mean (±SD) age was 69.1±12.3 years and 36.6% had a PRECISE-DAPT score >25. The mean anatomical SYNTAX score was 7.9±4.7. At 1 year, the primary ischemic endpoint occurred in 1 patient (1.0%; cardiac death). Two BARC Type 3a bleeding events occurred (2.0%): 1 due to a gastric ulcer and 1 to a descending colon malignancy.

Conclusions: Low-dose (3.75 mg/day) prasugrel monotherapy started immediately after SYNERGY stent deployment was feasible and safe in selected NSTE-ACS patients.

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.

Cancer is widely recognized as one of the major risk factors for thrombosis, and cancer-associated thrombosis (CAT) is a concept that also encompasses arterial and venous thromboembolism. The risk factors for CAT of clinical concern are assumed to be a complex combination of patient-related factors, the cancer itself, factors related to anticancer therapy, tissue factors expressed on cancer cell membranes, and cytokines released by cancer cells to increase inflammation and coagulation at remote sites. In addition, some anticancer agents are known to damage vascular endothelial cells and cause thrombus formation; early diagnosis and treatment of CAT is recommended because CAT is a significant risk factor for poor prognosis in cancer patients.

Background: Cardiac sarcoidosis (CS) is a rare, potentially life-threatening condition associated with ventricular tachycardia (VT). Outcomes of catheter ablation for VT in patients with histologically diagnosed sarcoidosis and those with suspected or clinically diagnosed sarcoidosis have not been well studied. This study addressed this knowledge gap.

Methods and Results: We conducted an observational retrospective chart review of patients with CS who underwent VT ablation between 2007 and 2024 at Mayo Clinic Hospital. The cohort was divided into 2 groups: those with histologically diagnosed sarcoidosis and those with clinical or suspected sarcoidosis diagnosed according to Japanese Circulation Society 2016 guidelines. The primary endpoints were VT recurrence, cardiovascular mortality, and heart transplantation. Eighty-eight patients were included in the study: 33 with histologically confirmed CS and 55 with clinical/suspected CS. Systemic sarcoidosis was more common in the group with histologically confirmed CS, whereas mid-myocardial non-ischemic late gadolinium enhancement was more prevalent in the group with clinical/suspected CS. The 1-year composite event-free survival rate was 56.1%. In multivariate analysis, systemic sarcoidosis was independently associated with lower event-free survival rates.

Conclusions: Patients with histologically confirmed CS had worse VT ablation outcomes than those with clinical/suspected CS. This difference may be driven by a higher prevalence of systemic sarcoidosis in the former group. These findings highlight the need for a comprehensive management approach in both groups.