Background: In repaired tetralogy of Fallot (TOF) and related diseases, reoperation for pulmonary regurgitation (PR) may be delayed unless marked right ventricular (RV) enlargement is present.

Methods and Results: 32 patients with significant PR post-repair underwent catheterization and 4D flow MRI for reoperation evaluation. The Non-severe RV Dilation group (n=20) did not meet the surgical volume criteria, whereas the Severe RV Dilation group (n=12) did. The Non-severe RV Dilation group had higher biventricular filling pressures. The RV-Energy loss index in both groups was high.

Conclusions: Diastolic dysfunction could serve as a therapeutic target in PR patients with heterogeneous etiologies.

Cardiac conduction is a central determinant of normal rhythm and arrhythmia susceptibility. Although arrhythmias have traditionally been attributed to abnormal automaticity, triggered activity, and re-entry, emerging evidence indicates that conduction abnormalities integrate structural, electrical, and immune-derived signals into a common arrhythmogenic substrate. This review summarizes multiscale mechanisms of impulse propagation, with an emphasis on gap junction-mediated coupling. Connexin 43 (Cx43), the principal ventricular connexin, maintains intercellular current flow through phosphorylation-dependent localization at intercalated discs; its remodeling leads to conduction slowing, heterogeneous propagation, and reentrant vulnerability. Recent studies have revealed that cardiac resident macrophages preserve ventricular conduction by promoting Cx43 phosphorylation via amphiregulin–epidermal growth factor receptor signaling. Loss of this macrophage-derived pathway causes Cx43 disorganization, atrioventricular block, ventricular fibrillation, and sudden death during cardiac stress, establishing an immune–electrical interface essential for conduction stability. This review further highlights conduction abnormalities in human disease, differences between mice and humans, and insights derived from electrocardiography and advanced computational modeling. Simulations linking molecular alterations to organ-level activation patterns provide a mechanistic bridge between cellular coupling, Purkinje network integrity, fibrosis distribution, and clinical electrophysiology. Together, these findings position conduction as a dynamic, regulated property of the ventricular myocardium and suggest that targeting gap junction and immune pathways may enable future conduction-based precision cardiology.

Background: Ischemic heart disease remains the leading cause of death worldwide, and although early coronary revascularization is essential, it can paradoxically induce additional myocardial damage known as ischemia–reperfusion (I/R) injury, driven in part by excessive generation of reactive oxygen species (ROS). This study evaluated the cardioprotective potential of resorcimoline (RML), a newly developed free radical scavenger, in mitigating ROS-mediated myocardial injury in a preclinical setting.

Methods and Results: ROS production was induced in primary cardiomyocytes through hypoxia, angiotensin II, or hydrogen peroxide treatment. The antioxidant effects of RML were assessed by cytosolic and mitochondrial ROS assays. Cell viability and cytotoxicity were evaluated by metabolic activity and lactate dehydrogenase release assays. In vivo, myocardial I/R injury was induced in rats by transient coronary artery ligation followed by reperfusion. RML significantly reduced intracellular and mitochondrial ROS levels and improved cardiomyocyte viability in vitro. Consistently, in vivo DHE staining demonstrated that RML suppressed myocardial ROS accumulation, decreased infarct size, lowered serum troponin I, reduced apoptosis, and preserved left ventricular function, whereas these protective effects were not observed without reperfusion.

Conclusions: RML exerts cardioprotective effects by scavenging ROS and mitigating downstream oxidative damage in both in vitro and in vivo models of myocardial I/R injury, suggesting promise as a therapeutic agent against reperfusion-induced myocardial injury.

Background: Congenital heart disease involving outflow tract (OFT) malformations remains a major clinical challenge, particularly in 22q11.2 deletion syndrome. Although folic acid (FA) reduces the incidence of neural tube defects, its mechanistic role in cardiac OFT development is not fully understood.

Methods and Results: Using Tbx1^neo/neo hypomorphic mice as a model of 22q11.2 deletion syndrome, we investigated the effects of maternal FA supplementation on cardiac development. Pregnant dams received FA through diet or intraperitoneal injection and embryonic cardiac morphology was assessed at E15.5 and E18.5. Maternal FA administration significantly improved the persistent truncus arteriosus (PTA) phenotype, with 60% of Tbx1^neo/neo embryos exhibiting a partially septated PTA (Van Praagh type A1) vs. complete PTA (type A2) in controls. Neural crest cell (NCC) migration from the neural tube into the OFT was enhanced. GFP lineage tracing confirmed the presence of increased NCCs in the OFT and reduced ectopic neuronal differentiation. Single-cell RNA-sequencing and immunohistochemistry revealed activation of the Notch and Midkine signaling pathways in NCCs following FA treatment.

Conclusions: Maternal FA supplementation improved cardiac OFT malformations in Tbx1^neo/neo embryos by enhancing NCC migration and fate specification, possibly mediated by Notch and Midkine signaling activation. Our findings provide mechanistic insights into the observed reduction in congenital heart defects with FA and suggest its potential as a minimally invasive prenatal intervention.

Renal denervation is a catheter-based therapy that interrupts renal sympathetic traffic and lowers blood pressure through durable neuromodulation. Contemporary catheter-based systems deliver energy to the periadventitial space with an acceptable safety profile. Across blinded placebo-controlled trials in off-medication and on-medication settings, renal denervation achieves greater reductions in ambulatory and office blood pressure than placebo, with a uniform 24-h effect that includes night-time and early-morning periods. Long-term follow-up data from randomized programs and large registries show sustained separation in blood pressure between renal denervation and control groups, preserved renal function, and low re-intervention rates over several years, with select cohorts approaching a decade. This review summarizes the mechanism and target anatomy of renal denervation, key features and results of placebo-controlled trials, and practical considerations for integrating the procedure with contemporary pharmacologic therapy in patients with uncontrolled hypertension.

Catheter ablation has become the cornerstone therapy for cardiac arrhythmias, supported by continuous technological innovation. Since the introduction of radiofrequency (RF) ablation in the 1980s, remarkable progress, such as open irrigation, contact force sensing, local impedance monitoring, and index-guided ablation, has significantly improved procedural safety, reproducibility, and efficacy. In atrial fibrillation ablation, pulmonary vein isolation remains the fundamental strategy, and advances in RF technology have contributed to durable lesion formation and reduced complications. Although new non-thermal energy sources such as pulsed-field ablation (PFA) have recently emerged, RF ablation continues to play a central role in clinical practice. Its ability to provide precise lesion control and adaptability across a wide range of arrhythmia substrates, including supraventricular and ventricular tachycardias, remains unmatched. Furthermore, recent developments such as dual-energy catheters capable of delivering both RFA and PFA suggest a complementary future for both modalities. RF ablation has evolved in pursuit of greater safety and efficiency through sustained technological advancement. These innovations have improved lesion predictability and procedural outcomes, and RF ablation will remain an indispensable component of arrhythmia management in the coming era of energy diversification.

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: Patients with bradyarrhythmia requiring pacemaker implantation often report disrupted sleep, which could be related to bradyarrhythmia, apprehension of having heart disease and undiagnosed sleep disorders, resulting in impaired quality of life (QOL). We aimed to assess the prevalence of poor subjective sleep quality in patients with bradyarrhythmia requiring pacemaker implantation and its effect on sleep quality.

Methods and Results: Patients undergoing permanent pacemaker implantation for bradyarrhythmia were evaluated for subjective sleep quality and health-related QOL using the Pittsburgh Sleep Quality Index (PSQI) and Short Form-8 (SF-8) before and after pacemaker implantation. Poor subjective sleep quality was defined as PSQI score ≥6. Of 89 enrolled patients, 54 (60.7%) reported poor subjective sleep quality. A greater PSQI score indicative of poor sleep quality was likely to be observed in patients who had greater left ventricular ejection fraction and were treated with calcium-channel blockers, as well as in patients with more frequent sleep disturbance-related complaints/symptoms. After pacemaker implantation, the PSQI score improved significantly (from a median score of 6.0 to 5.0; P=0.015) proportional to an improvement in the mental component summary score.

Conclusions: Poor subjective sleep quality is common among patients with bradyarrhythmia, contributing to impaired QOL. Pacemaker implantation may have a favorable effect on subjective sleep quality, and QOL for such patients.

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized, non-atherosclerotic cause of acute coronary syndrome (ACS), predominantly affecting younger women without traditional cardiovascular risk factors. SCAD results from an intramural hematoma or intimal tear that compresses the coronary lumen, leading to myocardial ischemia. Diagnosis is critical, as management differs fundamentally from atherosclerotic ACS. Conservative therapy is preferred for hemodynamically stable patients due to high rates of spontaneous vessel healing; revascularization is reserved for ongoing ischemia, hemodynamic instability or left main/multivessel involvement. Long-term management focuses on reducing recurrence risk through β-blocker therapy, strict blood pressure control, and individualized cardiac rehabilitation. Although outcomes are generally favorable, recurrence occurs in up to 20% of patients. Ongoing research is needed to refine antiplatelet strategies, identify genetic and vascular risk factors, and optimize preventive care.

Background: Cardiac computed tomography (CCT) not only evaluates coronary artery disease but also characterizes myocardial features through late iodine enhancement (LIE). This study evaluated the clinical characteristics and prognostic significance of incidentally detected non-ischemic LIE patterns in patients undergoing CCT for coronary artery evaluation.

Methods and Results: We retrospectively analyzed 465 patients who underwent CCT between January 2020 and December 2021. The primary outcome was all-cause death, and the secondary outcome was cardiovascular events, defined as cardiac death and unplanned cardiovascular hospitalization. Cox hazard analysis was performed to identify parameters significantly associated with the outcomes. After excluding patients with non-ischemic cardiomyopathy diagnosed before and after undergoing CCT, coronary stenosis and previous revascularization, 57 patients had non-ischemic LIE and 408 showed no LIE. Compared with patients without LIE, non-ischemic LIE was significantly associated with increased high-sensitivity cardiac troponin T and B-type natriuretic peptide levels, left ventricular (LV) diastolic diameter, LV thickness, and impaired LV ejection fraction. The cumulative incidence of cardiovascular events was significantly higher in patients with non-ischemic LIE than in those without LIE (log-rank P=0.024). In the Cox multivariable analysis, non-ischemic LIE was associated with cardiovascular events (hazard ratio 7.01; 95% confidence interval 1.09–42.2; P=0.041).

Conclusions: CCT may provide prognostic significance through the assessment of myocardial properties.

Background: The effect of residual pulmonary hypertension (PH) on clinical outcomes in patients with secondary mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER) remains unexplored.

Methods and Results: We analyzed 62 patients with secondary MR who underwent TEER. In 32 (51.6%) patients with residual PH after TEER, adverse clinical events were observed more frequently compared with those without residual PH. Multivariate analysis confirmed residual PH as an independent predictor of all-cause death or hospitalization for heart failure.

Conclusions: In patients with secondary MR, residual PH after TEER is an independent predictor of adverse clinical outcomes.

Background: HeartMate 3 (HM3), a magnetically levitated centrifugal-flow pump, has demonstrated superior hemocompatibility and reduced adverse events compared to HeartMate II (HMII), an axial-flow pump, in global studies. However, because long-term comparative data in Japanese patients remain scarce, in the present study we evaluated the 5-year outcomes of HM3 support by comparing them with those of HMII at 2 leading left ventricular assist device (LVAD) centers in Japan.

Methods and Results: We retrospectively analyzed 364 patients who underwent primary LVAD implantation (HM3: n=168; HMII: n=196) between 2010 and 2023. The primary endpoint included survival to transplant, recovery, or continued LVAD support free from stroke or pump replacement. At 5 years, freedom from the composite endpoint was higher in the HM3 group (75% vs. 52%; hazard ratio [HR] 0.52; P=0.001), although overall survival was comparable (90% vs. 85%; P=0.44). The HM3 group experienced significantly fewer strokes (HR 0.40; P=0.0008), bleeding events (HR 0.22; P<0.0001), and pump thrombosis (HR 0.09; P=0.003). Rates of rehospitalization, driveline infections, and late right heart failure did not differ between the groups.

Conclusions: HM3 support significantly improved long-term event-free outcomes compared to HMII, despite comparable overall survival, supporting the use of HM3 as durable mechanical circulatory support devices in Japan.

Background: Timely initiation of temporary mechanical circulatory support (tMCS), with appropriate escalation and de-escalation strategies, is critical in managing cardiogenic shock (CS). However, how tMCS utilization and outcomes differ by CS etiology remains unclear.

Methods and Results: Using data from the Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD), we evaluated the differences in tMCS use and outcomes among 3,678 Impella-supported patients with acute myocardial infarction-related CS (AMI-CS, n=2,418 (65.7%)), de novo heart failure-related CS (de novo HF-CS, n=758 (20.6%)), and acute-on-chronic HF-related CS (acute-on-chronic HF-CS, n=502 (13.7%)). The median shock-to-support time was significantly shorter in AMI-CS (123 min) than in de novo HF-CS (186 min) and acute-on-chronic HF-CS (205 min; P<0.001 for each). De novo HF-CS patients were more likely to receive multiple tMCS (64.2%) devices compared with AMI-CS (51.4%; P<0.001) and acute-on-chronic HF-CS (55.2%; P=0.001). Compared with de novo HF-CS, the adjusted odds ratio (OR) for in-hospital death was higher in AMI-CS (OR 1.34, 95% confidence interval (CI) 1.08–1.66; P=0.008) and acute-on-chronic HF-CS (OR 1.67, 95% CI 1.25–2.22; P<0.001).

Conclusions: tMCS timing and utilization differed by CS type. De novo HF-CS was associated with the lowest in-hospital mortality rate.

Background: Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM). Validation of the Japanese Circulation Society (JCS)/Japanese Heart Failure Society (JHFS) guidelines for SCD prevention needs to be undertaken in a large cohort of Japanese patients with HCM.

Methods and Results: In a subanalysis of the REVEAL-HCM registry comprising 3,611 patients, we enrolled 3,547 patients after excluding 64 patients with missing data required for calculating the HCM Risk-SCD score. The endpoint was a composite of SCD or an equivalent event. During a median 5.8-year follow-up period, SCD events occurred in 247 (7.0%) patients. The 5-year cumulative incidence of SCD events differed significantly between Class 2a and 2b recommendations (6.7% vs. 4.9%, respectively; P=0.006) and between Class 2b and 3 recommendations (4.9% vs. 1.7%, respectively; P<0.001). Excess risk of SCD was also significant for patients with Class 2a and 2b compared with Class 3 recommendations, with hazard ratios of 3.59 (95% confidence interval [CI] 2.40–5.37; P<0.001) and 2.09 (95% CI 1.47–2.97; P<0.001), respectively. The 2018 JCS/JHFS guidelines had an area under the curve of 0.75 (95% CI 0.71–0.80; P<0.001) for discriminating SCD events at 5 years.

Conclusions: The 2018 JCS/JHFS guidelines showed good discriminatory performance for SCD risk stratification, particularly among patients with Class 2a recommendations for an implantable cardioverter defibrillator.

Background: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death in patients with heart failure, but the value of ICD therapy after left ventricular ejection fraction (LVEF) recovery is uncertain.

Methods and Results: We retrospectively studied 118 patients undergoing primary prevention ICD therapy (2013–2022). Of them, 40 (34%) improved to LVEF >35% (impEF). Over 4.4 years, appropriate ICD therapy occurred significantly less in the impEF group vs. the persistently low LVEF group (P=0.008), but 4 impEF patients still required antitachycardia pacing therapy. No patient with LVEF ≥40% received such therapy.

Conclusions: LVEF recovery reduces but does not eliminate ventricular arrhythmia risk, supporting individualized ICD management.

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: 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: 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: 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 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: 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: 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.