Several errors appeared in the article titled "Difference in the Association between Growth Differentiation Factor 15 and Coronary Calcified Plaque According to Chronic Kidney Disease" by Hayato Shimizu, Satoshi Hoshide, Hiroshi Funayama, and Kazuomi Kario (Vol. 66 No.4, 540-6, 2025). In the "Results" on page 543, "the percentage of calcified plaque volume (r = 0.275, P < 0.001) " should be replaced by "the percentage of calcified plaque volume (r = 0.275, P = 0.012) ". In addition, Figure 2 on page 544 should be replaced by following.

To determine whether heart rate variability (HRV) indices derived from 24-hour ambulatory electrocardiography provide complementary prognostic information in machine-learning prognostic models using conventional clinical variables in patients with heart failure, particularly with regard to calibration and threshold-based performance.We analyzed 353 patients with heart failure. The primary endpoint was cardiovascular death or hospitalization for worsening heart failure. Patients were randomly divided into training and test cohorts in a 3:2 ratio. Two gradient boosting models were developed: one using clinical variables and HRV indices, and the other incorporating clinical variables only. To ensure a fair comparison and limit model complexity, the number of selected predictors was restricted to five in both models.The primary endpoint occurred in 49 patients (14%) during a median follow-up of 740 days (interquartile range 566-870 days). In the independent test cohort (n = 141), discrimination (AUC) was similar between the two models (0.77 versus 0.71; DeLong P = 0.263). However, the HRV model showed higher threshold-based classification performance (higher F1 score and accuracy) and a calibration slope closer to 1.0 (slope 1.01 versus 0.73).In machine-learning-based prognostic modeling for heart failure, Holter-derived HRV indices may be associated with clinically relevant classification performance and a calibration slope closer to 1.0, although the improvement in discrimination as assessed by AUC was not statistically significant. These findings suggest that heart rate variability may provide complementary prognostic information not fully captured by standard clinical variables alone.

Cardiogenic shock (CS) is a life-threatening syndrome characterized by severe pump failure and systemic hypoperfusion, with persistently high mortality. Red blood cell distribution width (RDW) has been associated with adverse outcomes in several cardiovascular conditions, but its prognostic role in CS, particularly for long-term mortality and machine learning-based risk stratification, remains incompletely defined. We aimed to investigate the association between RDW and mortality in patients with CS and to evaluate its value in interpretable machine learning models for 1-year mortality prediction.We identified 2,014 patients with CS from the MIMIC-IV database (2008-2019). Associations between RDW and in-hospital mortality were assessed using logistic regression, and associations with 1-year mortality were evaluated using Cox regression. RDW was analyzed both as a continuous variable and by tertiles (T1 ≤ 14.40%, T2 14.40-16.27%, T3 > 16.27%). Kaplan-Meier curves and restricted cubic splines (RCS) were used to examine survival patterns and dose-response relationships. Patients were randomly divided into training and test cohorts (8:2). Feature selection was performed using Boruta and random forest-derived importance metrics. Six machine learning models (LR, DT, RF, SVM, XGBoost, and TabPFN) were developed for 1-year mortality prediction and evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, F1 score, and decision curve analysis (DCA). Model interpretability was assessed using SHapley Additive exPlanations (SHAP).Among 2,014 patients with CS, 1-year mortality was 53.2%. Higher RDW was independently associated with increased 1-year mortality after multivariable adjustment (HR = 1.043, 95% CI: 1.015-1.071). For in-hospital mortality, the association remained significant in fully adjusted analysis but was attenuated (OR = 1.055, 95% CI: 1.001-1.112). Compared with T1, patients in T3 had a significantly higher risk of 1-year mortality (HR = 1.626, 95% CI: 1.376-1.921; P for trend = 0.004). RCS analysis showed a significant overall association between RDW and 1-year mortality, with risk increasing above approximately 14.4%, although the test for nonlinearity was not statistically significant. Among the evaluated models, TabPFN achieved the highest observed AUC for 1-year mortality prediction (AUC = 0.861), with sensitivity of 0.80 and specificity of 0.72, and showed the most favorable net benefit on DCA. SHAP analysis indicated that model predictions were driven by multiple clinically meaningful domains, including treatment-related variables, shock severity, metabolic disturbance, cardiovascular substrate, and RDW.Elevated RDW is an independent predictor of 1-year mortality in patients with CS. An RDW level above approximately 14.4% may serve as a practical marker of increased risk. Integrating RDW into interpretable machine learning-based risk assessment, particularly with TabPFN, may improve early prognostic stratification in CS. Prospective external validation is warranted.

Despite remarkable advances in guideline-directed medical therapy, congestion remains a major determinant of hospitalization and mortality in patients with heart failure. Loop diuretics are indispensable for symptom relief; however, prolonged or high-dose use may induce neurohormonal activation, renal dysfunction, electrolyte imbalance, and diuretic resistance, highlighting the need for alternative decongestive strategies. Goreisan, a traditional Japanese Kampo medicine, has recently attracted attention as an adjunctive approach for heart failure because of its unique ability to regulate body water homeostasis. Unlike conventional diuretics that promote forced diuresis, Goreisan appears to "modulate" aquaporin-mediated water transport, facilitating physiological water balance while minimizing excessive intravascular volume depletion. Emerging experimental studies also suggest anti-inflammatory and cardio-protective effects. Clinical evidence has generated increasing interest in its potential role for managing refractory congestion. This review summarizes the pathophysiological basis of congestion in heart failure, the limitations of current diuretic therapy, the pharmacological mechanisms of Goreisan, and the available clinical evidence supporting its use. Although current evidence remains limited, Goreisan may represent a promising adjunctive strategy for optimizing congestion management alongside contemporary guideline-directed medical therapy.

Iodinated contrast media (ICM), commonly used in radiological tests such as coronary angiography, can cause hypersensitivity reactions (HSRs). The mechanism of ICM HSRs is thought to be complex; while IgE-mediated allergic reactions appear to be involved, the details remain unclear. This study aims to elucidate the pathogenesis of ICM HSRs through genetic analysis. To date, a few case-control studies have been conducted exclusively on East Asians, but the results have been inconclusive and have not been replicated.We conducted a multistage GWAS for ICM HSRs in Japanese individuals. The study population comprised 153 cases with ICM HSRs (ranging from mild to severe form), 632 controls with no history of ICM-induced allergies, and < 38,721 individuals from the general population. We identified genome-wide significant association signals in the HLA region and also found that these signals originated from the three HLA alleles-B*52:01, C*12:02, DRB1*15:02-previously reported in a Korean candidate gene study. Using instrumental variable analysis with a polygenic score for pediatric asthma (PGSasthma) as a proxy, we demonstrated that ICM HSRs are associated with the allergic predisposition thought to be shared by asthma and ICM HSRs. There was a significant difference in the distribution of PGSasthma between ICM HSR patients and non-disease controls (per-SD odds ratio: 1.26, P = 0.021).Our genome-wide approach shows that HLA alleles are among the genetic factors underlying ICM HSRs. Furthermore, it provides evidence for the potential usefulness of predicting the risk of developing ICM HSRs based on allergic predisposition.

Implantable cardioverter-defibrillator (ICD) therapy is essential for preventing sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, real-world data regarding transvenous ICD (TV-ICD) and subcutaneous ICD (S-ICD) systems in patients with HCM remain limited.We retrospectively analyzed 279 patients diagnosed with HCM at Nippon Medical School Hospital between 2003 and 2025. Among them, 75 patients who underwent ICD implantation were included. Baseline characteristics, ICD therapies, and device-related complications were compared between TV-ICD and S-ICD groups.Of the 75 patients, 63 received TV-ICDs and 12 received S-ICDs. Patients in the S-ICD group were younger and taller, with shorter follow-up duration. Established risk factors for sudden cardiac death were generally more frequent in the TV-ICD group, with significant differences in syncope and inducible ventricular fibrillation. During follow-up, there were no significant differences between groups in total ICD therapies, appropriate shocks, inappropriate shocks, or mortality. Anti-tachycardia pacing (ATP) was observed exclusively in the TV-ICD group. Device infections requiring system removal occurred only in the TV-ICD group.In this single-center observational cohort, no statistically significant differences in major clinical outcomes were observed between S-ICD and TV-ICD groups during follow-up. Given its favorable complication profile, S-ICD may represent a feasible alternative in selected younger patients with HCM.

An increased incidence of ventricular fibrillation (VF) has been reported in patients with Marfan syndrome (MFS) compared with the general population. Although reduced left ventricular systolic function and severe valvular disease are recognized as major risk factors for ventricular arrhythmias (VAs) in MFS, we report a case of VF that developed despite the absence of these risk factors.A 22-year-old man with MFS who had previously undergone a valve-sparing aortic root replacement with the David procedure, lost consciousness and was diagnosed with VF. After resuscitation, no new abnormal findings were observed except for mild QT prolongation (QTc 471 msec) and a slightly elevated B-type natriuretic peptide level (89.0 pg/mL). An echocardiogram revealed no significant changes compared with the previous examination. It showed that the ejection fraction was preserved and that there was mild aortic valve regurgitation and mild-to-moderate mitral valve regurgitation. Whole-exome sequencing analysis revealed no pathogenic variants, except for an FBN1 variant that was already known to be present. He was diagnosed with idiopathic VF and was implanted a subcutaneous implantable cardioverter-defibrillator.This case underscores the risk of VAs in MFS even in the absence of ventricular dysfunction or severe valvular diseases. A combination of various factors, such as subtle depolarization abnormalities, moderate valvular abnormalities, and underlying myocardial damage, may contribute to the development of VF. More careful surveillance and precise identification of risk factors for arrhythmias are warranted.

Atrial fibrillation (AF) is common, and recurrence after catheter ablation remains clinically important. We retrospectively explored factors associated with late recurrence after first-time AF ablation in the overall cohort and in paroxysmal AF and persistent/long-standing persistent AF subgroups. Consecutive patients undergoing first-time AF ablation at a single center between January 2017 and March 2022 were included. After excluding patients with documented early recurrence within 90-day blanking period who did not undergo repeat ablation, 304 of 368 eligible patients comprised the primary analytic cohort. Late recurrence was defined as AF, atrial tachycardia, or atrial flutter lasting > 30 seconds between days 91 and 365. Overall, late recurrence occurred in 53 patients (17.4%) and was more frequent in persistent/long-standing persistent AF than in paroxysmal AF (40/135 [29.6%] versus 13/169 [7.7%]). In exploratory paroxysmal AF subgroup analyses, patients with late recurrence were older, shorter, and had higher brain natriuretic peptide levels. In a parsimonious multivariable model adjusted for height, brain natriuretic peptide, and cavotricuspid isthmus ablation, but not fully adjusted for age and sex because of the small event number, greater height was inversely associated with late recurrence (odds ratio per 10-cm increase, 0.54; 95% confidence interval, 0.41-0.90; P = 0.038). No significant associations were found in persistent/long-standing persistent AF. Given the older age of patients with recurrent paroxysmal AF, the small number of events, and possible residual confounding by age, sex, frailty, nutritional status, or unmeasured atrial substrate, this inverse association should be interpreted cautiously as hypothesis-generating rather than confirmatory or causal.

Lipid-rich plaque detected by near-infrared spectroscopy combined with intravascular ultrasound (NIRS-IVUS) may be related to adverse outcomes after percutaneous coronary intervention (PCI). The relationship between NIRS-derived lipid burden and target vessel failure (TVF)-particularly non-target lesion failure (TLF) TVF-remains unclear.We retrospectively analyzed 151 consecutive patients (163 lesions) who underwent NIRS-IVUS-guided drug-eluting stent implantation at a single center. The maximum 4-mm lipid core burden index (MaxLCBI4mm) was measured before and after stent implantation. Primary outcomes were TLF, TVF, and non-TLF TVF. During a median 3.1-year follow-up, TLF, TVF and non-TLF TVF occurred in 9 (5.5%), 15 (9.2%) and 6 (3.7%) lesions, respectively. Lesions with TVF demonstrated significantly greater frequency of post MaxLCBI4mm > 400. Receiver-operating characteristic analysis identified optimal post MaxLCBI4mm cutoff values of 289 for TVF (area under the curve [AUC] 0.65) and 408 for non-TLF TVF (AUC 0.85). Kaplan-Meier analysis showed significantly higher cumulative TVF and non-TLF TVF in lesions with post MaxLCBI4mm > 400 (log-rank P = 0.0272 and P < 0.0001, respectively).No significant association was found between MaxLCBI4mm and TLF.In a real-world PCI cohort, post MaxLCBI4mm > 400 was related to TVF, especially non-TLF TVF. NIRS-IVUS may help identify patients at risk of vessel-level events despite contemporary DES implantation.

Atypical atrial flutter (AFL) is a macro-reentrant atrial tachycardia that most frequently develops after atrial fibrillation ablation or cardiac surgery. Although ablation-related circuit modification is recognized, the occurrence of multiple sequential AFL transformations within a single procedure, particularly in a previously untreated atrium, is exceedingly rare.A 76-year-old woman with hypertension and paroxysmal atrial fibrillation, without prior cardiac surgery or catheter ablation, presented with drug-refractory AFL. Electrophysiological study initially demonstrated an activation characteristic suggestive of CTI-related AFL. Following stepwise ablation, the arrhythmia sequential left atrial activation pattern changes involved posterior wall-related activation pattern AFL, peri-right superior pulmonary vein AFL, and mitral isthmus-related AFL. Despite apparent endocardial conduction block, the tachycardia persisted with dynamic coronary sinus (CS) activation reversal. The distal CS musculature appeared to participate in the remaining tachycardia conduction pathway. Epicardial ablation within the CS resulted in immediate termination, and no atrial tachyarrhythmias were inducible thereafter.This case illustrates a rare example of sequential transformation among dynamic atypical AFL activation changes in a previously untreated atrium, ultimately suggesting likely participation of the CS musculature in the remaining tachycardia conduction pathway. Multiple LA macro-reentry mechanisms, dynamic CS activation reversals, and eventual reliance on a CS epicardial pathway created a diagnostic and therapeutic challenge. Recognizing the possibility of epicardial CS involvement is crucial when typical ablation strategies fail to terminate atypical AFL.

Macrophages are vital for heart repair after myocardial infarction (MI), a process that requires their transition from M1 to M2 type. However, the underlying mechanisms are unclear. This study aimed to explore the role of TNFAIP3 in regulating macrophage polarization post-MI.mRNA and protein levels of target genes were measured via qPCR and ELISA. Western blot and immunofluorescence were used to analyze protein expression and cell proportions. Primary human CD14+ monocytes were polarized into M1 (with LPS/IFNγ) or M2 (with IL-4) macrophages. TNFAIP3 was knocked down or overexpressed in vitro using shRNA or adenovirus. For in vivo studies, TNFAIP3 was overexpressed in mice via AAV, and myocardial infarction was induced by permanent left anterior descending coronary artery ligation.TNFAIP3 mRNA was elevated in PBMCs from AMI patients versus controls. Although both M1 (TNF-α, IL-6) and M2 (IL-10, TGF-β) serum cytokines increased in patients, TNFAIP3 was negatively correlated with M1 markers. Functionally, TNFAIP3 knockdown exacerbated LPS/IFNγ-induced M1 polarization, increasing TNF-α/IL-6 mRNA expression and NOS2-positive cells, while its overexpression suppressed these effects. In contrast, neither intervention altered IL-4-induced M2 polarization. Mechanistically, TNFAIP3 deficiency enhanced JAK2/STAT1 phosphorylation to promote M1 polarization, which was reversed by pharmacological inhibition and genetic knockdown of JAK2/STAT1. In vivo, systemic TNFAIP3 overexpression attenuated MI-induced JAK2/STAT1 activation, TNF-α/IL-6 mRNA upregulation, and NOS2-positive macrophage infiltration, without affecting IL-10/TGF-β mRNA and ARG1-positive cells.TNFAIP3 functions as an important modulator of post-MI inflammation by limiting M1 macrophage polarization through JAK2/STAT1 suppression.

Oxidative stress-induced cardiomyocyte injury constitutes a pivotal pathogenic mechanism driving heart failure progression. Emerging evidence implicates lncRNA NEAT1 in cardiovascular pathophysiology. This study delineates the mechanistic cascade through which NEAT1 orchestrates redox adaptation via glutamine metabolic reprogramming. Using H2O2-treated H9c2 rat cardiomyocytes as an oxidative stress model, we identified dose-dependent NEAT1 upregulation concomitant with miR-23b-3p suppression. NEAT1 silencing or miR-23b-3p overexpression exacerbated oxidative vulnerability, manifested by elevated viability loss and apoptosis rate. Bioinformatic prediction coupled with RNA pulldown and dual-luciferase assays established NEAT1/miR-23b-3p ceRNA interaction. Sublethal oxidative stress triggered adaptive glutaminolysis activation characterized by elevated glutamine uptake and GLS activity. Luciferase assay validated miR-23b-3p directly targeted GLS 3'UTR, while metabolic rescue assays demonstrated GLS reconstitution reversed miR-23b-3p-mediated metabolic suppression and restored oxidative tolerance. Epistatic analysis confirmed NEAT1's cardioprotection requires miR-23b-3p/GLS axis modulation, with miR-23b-3p restoration abrogating NEAT1-overexpression benefits. These findings were further corroborated in an in vivo rat model of myocardial ischemia-reperfusion injury, which recapitulated the upregulation of NEAT1 and GLS, downregulation of miR-23b-3p, and enhanced glutaminase activity in the infarct risk zone. Collectively, these results suggest the existence of a novel NEAT1/miR-23b-3p/GLS regulatory axis governing redox-stress adaptation in both cellular and animal models.

We report a case of a 90-year-old woman with prior transcatheter aortic valve replacement (TAVR) who presented with symptomatic structural valve deterioration. Imaging revealed a critically short valve-to-coronary distance (< 4 mm), suggesting a high risk for coronary obstruction during valve-in-valve (TAV-in-TAV) procedure. Although preventive techniques such as BASILICA and chimney stenting have been considered, these approaches require advanced technical expertise and are associated with procedural risks. Given the patient's advanced age and high surgical risk, we therefore opted for a hybrid strategy combining TAV-in-TAV with concomitant off-pump coronary artery bypass grafting to the left anterior descending artery for coronary protection. The procedure was successfully completed without complications. Postoperative imaging confirmed good prosthetic valve function, graft patency, and preserved coronary flow. To our knowledge, few reports have described TAV-in-TAV with simultaneous surgical coronary revascularization as a preventive approach for coronary obstruction. This case highlights the potential utility of surgical-transcatheter hybrid strategy in anatomically high-risk patients unsuitable for conventional transcatheter preventive techniques.