BACKGROUND: Acute coronary syndrome (ACS) patients remain at risk from non-culprit lesions. This study used serial optical coherence tomography (OCT) to explore metabolic profiles and morphological evolution (vulnerabili...BACKGROUND: Acute coronary syndrome (ACS) patients remain at risk from non-culprit lesions. This study used serial optical coherence tomography (OCT) to explore metabolic profiles and morphological evolution (vulnerability progression or regression) of non-culprit lesions in ACS patients. METHODS AND RESULTS: This study included 406 ACS patients with 1,054 non-culprit lesions who underwent OCT at baseline and at the 1-year follow-up (median 368 days). Non-culprit plaques were classified as lipid rich (thin- [TCFA] or thick [ThCFA]-cap fibroatheroma [fibrous cap thickness <65 and ≥65 μm, respectively]), fibrous, or calcified. Patients were stratified into vulnerability progression (≥1 plaque progressing from non-TCFA to TCFA), regression (≥1 plaque regressing from TCFA to non-TCFA), or no-change groups. Vulnerability progression occurred in 10 patients (11 lesions), all from ThCFA to TCFA. Vulnerability regression occurred in 96 patients (118 lesions), mainly from TCFA to ThCFA (109 lesions). Patients with progression were older (mean age 64.4 vs. 53.1 years; P=0.005) and had higher rates of diabetes (80.0% vs. 34.4%; P<0.001) and hypertension (70.0% vs. 56.3%; P=0.046). Regression was accompanied by an increase in layered plaques (+17%) and calcium deposition (+9%), associated with greater reductions in low-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B. Changes in lipid arc and fibrous cap thickness were positively correlated with on-treatment low-density lipoprotein cholesterol levels. CONCLUSIONS: Serial OCT identified divergent non-culprit lesion trajectories closely associated with lipid lowering. Intensive lipid-lowering therapy is critical for high-risk patients, and OCT enables objective evaluation of plaque stabilization.
Oka T, Takahara M, Kataoka S
… +14 more, Nagashima M, Onuki K, Yagishita D, Ikeda Y, Kanai R, Terazaki Y, Yoshiga Y, Fukuda M, Tsurugi T, Fujiu K, Hasumi E, Nishii N, Iguchi H, Sakata Y
BACKGROUND: Heart failure (HF) is a progressive disease characterized by an increasing incidence of hospitalization over time. HeartLogic(HL) is a multiparametric remote monitoring system designed to detect early signs o...BACKGROUND: Heart failure (HF) is a progressive disease characterized by an increasing incidence of hospitalization over time. HeartLogic(HL) is a multiparametric remote monitoring system designed to detect early signs of HF decompensation. Using a multicenter database, this real-world study evaluated whether responses to HL alerts could reduce HF-related hospitalization. METHODS AND RESULTS: We retrospectively analyzed 246 patients implanted with an HL-enabled implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator across 8 Japanese centers. Patients were categorized as alert-responsive (AR; n=167) or non-responsive (NR; n=79). Alert responses included multidisciplinary review and telephone triage to determine the need for clinical visits. HF hospitalization rates during the alert-off (before activation) and the alert-on (after alert activation) periods were compared. During the alert-off period, 50 hospitalizations occurred over 648 person-years (77.1 per 1,000 person-years); during the alert-on, 91 hospitalizations occurred over 498 person-years (182.6 per 1,000 person-years). From the alert-off to the alert-on period, HF hospitalization increased 3.24-fold (95% confidence interval [CI] 1.63-6.41) in the NR group, but only 1.28-fold (95% CI 0.81-2.03) in the AR group. The relative increase in HF hospitalization was significantly attenuated in the AR group (adjusted relative ratio 0.40; 95% CI 0.18-0.89; P=0.025). CONCLUSIONS: Although HF-related hospitalizations progressively increase as the disease advances, real-world alert responses may reduce hospitalizations and healthcare costs in clinical practice.
Tamura Y, Kusunose K, Yamashita Y
… +52 more, Akagi T, Atsukawa M, Fukumoto Y, Goda A, Goto S, Hatano M, Ikeda M, Ishida K, Kataoka M, Kuwana M, Matsubara H, Mo M, Nagaoka T, Ogo T, Okada Y, Sakao S, Sawada H, Shinke T, Tanabe N, Yamada N, Yamagishi H, Yano S, Abe K, Adachi S, Hosokawa K, Ikeda N, Inami T, Jinzaki M, Kato M, Kitai T, Kogaki S, Koizumi J, Morio Y, Nishizaki M, Ogihara Y, Ohta-Ogo K, Shigematsu K, Sugimura K, Tamura Y, Taniguchi Y, Tsujino I, Uchida K, Yamamoto T, Yao A, Yaoita N, Emoto N, Kitaoka H, Nakamura M, Ogino H, Satoh T, Watanabe H, Japanese Circulation Society and Japanese Pulmonary Circulation and Pulmonary Hypertension Society Joint Working Group
BACKGROUND: F-FDG PET/CT patterns in cardiac sarcoidosis (CS) across diagnostic subgroups are incompletely characterized. METHODS AND RESULTS: We analyzed 221 patients with definite CS (DCS), probable CS with active extr...BACKGROUND: F-FDG PET/CT patterns in cardiac sarcoidosis (CS) across diagnostic subgroups are incompletely characterized. METHODS AND RESULTS: We analyzed 221 patients with definite CS (DCS), probable CS with active extracardiac sarcoidosis (PCS-A), or probable CS without extracardiac involvement (PCS-N). DCS exhibited more severe perfusion defects than PCS-A and PCS-N. FDG uptake was similar in DCS and PCS-A, but lower in PCS-N. Abnormalities predominated in the basal/mid-septum and apical cap. CONCLUSIONS: Distinct PET patterns characterize CS diagnostic categories and support current diagnostic criteria.
Aida H, Tanaka M, Sato T
… +11 more, Abe K, Nishizawa K, Kawaharata W, Matsumori R, Hosaka I, Akiyama Y, Nakata K, Kouzu H, Yama N, Hanawa N, Furuhashi M
BACKGROUND: Beyond low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C) is a residual risk factor for atherosclerotic cardiovascular disease. However, whether sdLDL-C levels can predict the developmen...BACKGROUND: Beyond low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C) is a residual risk factor for atherosclerotic cardiovascular disease. However, whether sdLDL-C levels can predict the development of chronic kidney disease remains unclear. METHODS AND RESULTS: We investigated the association between the sdLDL-C level calculated using Sampson's equation and the progression of renal impairment in 16,814 Japanese individuals (10,806 men, 6,008 women; mean age: 47 years) who underwent annual health checkups. Participants were divided into 4 groups according to high (H) or low (L) sdLDL-C and LDL-C levels. Over a 10-year follow-up period, 2,533 participants progressed renal impairment, defined as an estimated glomerular filtration rate <60 mL/min/1.73 mor positive for urine protein. Cox proportional hazards model with a restricted cubic spline after adjustment for confounders showed a gradual increase in the hazard ratio (HR) for renal impairment with high levels of sdLDL-C. Compared with the L-sdLDL-C/L-LDL-C group (reference) the adjusted HRs for renal impairment were significantly higher in the H-sdLDL-C/H-LDL-C and H-sdLDL-C/L-LDL-C groups (1.13 [95% confidence interval 1.03-1.25] and 1.15 [95% confidence interval 1.03-1.29], respectively). The addition of a high sdLDL-C level (≥35.7 mg/dL) to traditional risk factors significantly improved the discriminatory capacity for renal impairment. CONCLUSIONS: A high calculated sdLDL-C level was an independent predictor for the progression of renal impairment regardless of LDL-C level in a general Japanese population.
BACKGROUND: The aim of this study was to investigate changes in cortical thickness in patients with cardiac allograft vasculopathy (CAV) using magnetic resonance imaging (MRI), and links to myocardial fibrosis and cognit...BACKGROUND: The aim of this study was to investigate changes in cortical thickness in patients with cardiac allograft vasculopathy (CAV) using magnetic resonance imaging (MRI), and links to myocardial fibrosis and cognitive function. METHODS AND RESULTS: In all, 77 patients after heart transplantation (35 with CAV, 42 without CAV), as well as 45 healthy controls (HC), underwent brain MRI and cardiac MRI (CMR). Analysis of covariance (ANCOVA), partial correlation and mediation analyses were performed. The CAV group exhibited significant cortical thinning in several brain regions, including the bilateral superior frontal gyrus, left angular gyrus, and left supramarginal gyrus (false discovery rate [FDR] P<0.05). Cortical thickness in the left cingulate gyrus (r=-0.377, P=0.015) and right cuneus (r=-0.297, P=0.009) was negatively correlated with extracellular volume (FDR P<0.05). Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination scores were lower in the CAV than non-CAV and HC groups. Cortical thickness in the bilateral inferior frontal gyrus, left cingulate gyrus, right angular gyrus, and right postcentral sulcus was positively correlated with MoCA scores (FDR P<0.05). The cortical thickness of the left cingulate gyrus partially mediated the association between extracellular volume and MoCA scores (β=-0.135; 95% confidence interval -0.323, -0.025). CONCLUSIONS: Our findings reveal a cardiocerebral interaction, highlighting cortical thinning as a neuroimaging marker for CAV-related myocardial fibrosis and cognitive decline.
BACKGROUND: The retrograde approach improves the procedural success rate of chronic total occlusion percutaneous coronary interventions (CTO-PCIs). However, it remains unclear whether the primary retrograde approach (PRA...BACKGROUND: The retrograde approach improves the procedural success rate of chronic total occlusion percutaneous coronary interventions (CTO-PCIs). However, it remains unclear whether the primary retrograde approach (PRA) offers benefits in terms of procedural success and burden/resource use in challenging cases. Therefore, we compared efficacy between the primary antegrade approach (PAA) and PRA in complex CTO-PCIs. METHODS AND RESULTS: This single-center retrospective cohort study included all patients undergoing coronary CTO-PCI attempted by experienced high-volume operators between January 2016 and July 2023. The difficulty of the antegrade approach was determined using the Japanese CTO score, and the feasibility of interventional collaterals was determined using the collateral channel score. In 698 patients undergoing CTO-PCI, the overall technical and initial guidewire success rates were 91.4% and 83.8%, respectively. Of 380 patients with a Japanese CTO score ≥3 and a collateral channel score ≥2, PAA and PRA were performed in 161 (42.4%) and 219 (57.6%) patients, respectively. Initial guidewire success was higher with PRA than PAA (88.1% vs. 78.9%; P=0.01), and bail-out success was higher for a retrograde than antegrade approach (91.2% vs. 56%; P=0.0019). PRA was associated with longer guidewire crossing time, longer fluoroscopy time, and greater contrast use. CONCLUSIONS: In patients with challenging CTO, poor antegrade conditions, and feasible interventional collaterals, PRA achieved higher initial guidewire success at the expense of higher procedural burden/resource use.
BACKGROUND: Chronic kidney disease is associated with an increased incidence of stent thrombosis (ST) following drug-eluting stent (DES) implantation, but the clinical outcomes after DES-ST in hemodialysis (HD) patients...BACKGROUND: Chronic kidney disease is associated with an increased incidence of stent thrombosis (ST) following drug-eluting stent (DES) implantation, but the clinical outcomes after DES-ST in hemodialysis (HD) patients compared with non-HD patients have not been fully elucidated. METHODS AND RESULTS: From the REAL-ST registry, we evaluated 655 patients with DES-ST, divided into 2 groups: HD group (n=59) and non-HD group (n=596). The primary endpoint was the cumulative 3-year incidence of all-cause death after the index ST event. Late ST was more prevalent in the HD group, whereas early and very late ST were common in the non-HD group. Following the index ST event, the HD group showed significantly higher 3-year incidences of all-cause death (48.2% vs. 22.9%, P=0.0005), cardiac death (33.4% vs.15.8%, P=0.003) and target lesion revascularization (TLR: 36.2% vs. 17.5%, P=0.0002) compared with the non-HD group. The cumulative 3-year incidence of recurrent ST did not differ significantly between groups (7.3% vs. 5.9%, P=0.88). After multivariable adjustment, HD remained significantly associated with an increased risk of all-cause death (adjusted hazard ratio [aHR], 1.95; 95% confidence interval [CI], 1.25-3.04; P=0.003), cardiac death (aHR, 1.75; 95% CI, 1.02-2.99; P=0.04) and TLR (aHR, 2.63; 95% CI, 1.52-4.57; P<0.001). CONCLUSIONS: Compared with non-HD patients, HD patients experienced worse clinical outcomes following their index DES-ST event.
Nakagawa A, Matsuoka Y, Seo M
… +21 more, Abe H, Nakagawa Y, Masaki T, Suna S, Akazawa Y, Nakamoto K, Mano T, Yano M, Hirai M, Iwakura K, Yokoi T, Yamada T, Okamura S, Yamada T, Yasumura Y, Sunaga A, Okada K, Nakatani D, Sotomi Y, Hikoso S, Sakata Y
BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV)-pulmonary arterial (PA) uncoupling, as assessed by a decrease ratio of tricuspid annular plane systolic excursio...BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV)-pulmonary arterial (PA) uncoupling, as assessed by a decrease ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP) on echocardiography, have poorer outcomes than patients without RV-PA uncoupling. METHODS AND RESULTS: The MONACO trial was an adaptive, randomized, double-blind, placebo-controlled study that enrolled hospitalized patients with HFpEF admitted to 12 centers in Japan. Patients who had left ventricular ejection fraction ≥50% and TAPSE/PASP <0.57 mm/mmHg at discharge were randomized 1 : 1 to receive pimobendan 1.25 mg b.i.d. or placebo. The primary objective was to evaluate changes from baseline (day 0) to day 30 in exercise capacity measured by the 6-minute walking test. Enrollment was terminated due to the invalid result of the planned interim analysis. The median age of participants was 82 years and 46% were women. Pimobendan (n=24) or placebo (n=26) was administrated orally. At day 30, mean changes in 6-minute walking distance in patients who received pimobendan (+26.9 m [95% confidence interval; -2.0, +55.8]) or placebo (+21.4 m [95% confidence interval; -14.3, +57.2]) were not significantly different (P=0.402). CONCLUSIONS: Among patients with HFpEF and RV-PA uncoupling, administration of pimobendan for 30 days did not result in significant improvement in exercise capacity compared with placebo.
BACKGROUND: Nationwide data on in-hospital deaths and complications between leadless pacemakers (LPMs) and transvenous pacemakers (TVPMs) in Japan remain limited. METHODS AND RESULTS: Using a nationwide database, we iden...BACKGROUND: Nationwide data on in-hospital deaths and complications between leadless pacemakers (LPMs) and transvenous pacemakers (TVPMs) in Japan remain limited. METHODS AND RESULTS: Using a nationwide database, we identified adults who underwent TVPM or LPM implantation between 2017 and 2023. LPM implantation increased from 0.5% to 25% (P for trend <0.001). LPMs were selected more often as patient age increased and those undergoing dialysis or with dementia and atrial fibrillation (P<0.001). After propensity score matching (12,599 per group), composite outcomes (in-hospital deaths and all complications) were comparable between the LPM and TVPM groups (5.41% vs. 5.59%, respectively; P=0.44; odds ratio [OR] 0.95; 95% confidence interval [CI] 0.84-1.07). All-cause in-hospital death did not differ between groups (LPM, 1.09%; TVPM, 1.05%; P=0.55; OR 1.07; 95% CI 0.83-1.38), whereas all-cause death within 7 days after implantation was higher in the LPM group (0.58% vs. 0.33%; P=0.003; OR 1.80; 95% CI 1.21-2.67). All complications was comparable between the LPM and TVPM groups (LPM, 4.78%; TVPM, 4.82%; P=0.59; OR 0.96; 95% CI 0.85-1.09), but cardiac tamponade was more frequent in the LPM group (0.29% vs. 0.06%; P<0.001; OR 5.42; 95% CI 2.38-12.32). CONCLUSIONS: Composite outcomes were comparable between the LPM and TVPM groups, but the rates of cardiac tamponade and all-cause death within 7 days after implantation were higher in the LPM group.
Kabuki S, Amino M, Kunieda E
… +14 more, Kuroki T, Fukuzawa T, Sugawara A, Hashimoto J, Ueda A, Kato R, Shimokawa T, Mori S, Wakatsuki M, Iimura K, Iijima A, Yagishita A, Ikari Y, Yoshioka K
BACKGROUND: Clinical outcome determinants in cardiac stereotactic body radiotherapy (cardiac-SBRT)/stereotactic arrhythmia radioablation (STAR), a minimally invasive therapy for refractory ventricular tachycardia (VT), r...BACKGROUND: Clinical outcome determinants in cardiac stereotactic body radiotherapy (cardiac-SBRT)/stereotactic arrhythmia radioablation (STAR), a minimally invasive therapy for refractory ventricular tachycardia (VT), remain unclear. We report the final analysis of Japan's first prospective study following a previously published interim report. METHODS AND RESULTS: Between 2019 and 2024, 8 patients with recurrent VT refractory to medical therapy and unsuitable for or refractory to catheter ablation were enrolled. Primary endpoints were safety and VT suppression. Exploratory analyses examined irradiation distribution and autonomic function. Median age was 69 years (75% male), ejection fraction 25%, and median follow-up 2.2 years. Targets were defined using multimodal assessment, with a median planning target volume of 88.9 cc. Treatment-related adverse events included only grade 1 nausea (n=1). Implantable cardioverter-defibrillator shock suppression was 73.6% at 6 months and 76.8% at 1 year. Antitachycardia pacing suppression reached 97.9%, with near-complete suppression in 5 survivors. Analyses remained descriptive and hypothesis-generating. Heart rate variability suggested increased parasympathetic activity, and I-metaiodobenzylguanidine imaging indicated reduced washout rate. Three patients died within 2 years but had advanced preexisting heart failure; irradiation more often involved inferior segments. Survival differences were not explained by cohort-level B-type natriuretic peptide levels or systolic function changes. CONCLUSIONS: Cardiac-SBRT/STAR achieved sustained arrhythmia suppression. Heart failure severity, irradiation location, and autonomic function, with their interaction, may be associated with clinical outcomes.
Shiraishi Y, Nakamaru R, Kohsaka S
… +11 more, Sandhu AT, Heidenreich PA, Ikemura N, Sawano M, Niimi N, Kimura T, Katsumata Y, Nishiyama T, Ueda I, Takatsuki S, Ieda M
BACKGROUND: The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire is endorsed for symptom and quality-of-life assessment in atrial fibrillation (AF) but is typically measured once. Because patient-repor...BACKGROUND: The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire is endorsed for symptom and quality-of-life assessment in atrial fibrillation (AF) but is typically measured once. Because patient-reported health status changes with treatment, serial AFEQT assessments may better reflect disease burden over time. We evaluated whether repeated AFEQT measurements are associated with subsequent outcomes and whether the most recent score is informative. METHODS AND RESULTS: We analyzed a multicenter, prospective registry of stable outpatients with AF referred to 11 hospitals in Japan (2012-2018). Associations of baseline ("prior"), 12-month ("current"), and change in AFEQT overall summary (os) scores with all-cause death and heart failure (HF) hospitalization were examined using multivariable Cox models. Among 2,743 patients (mean [±SD] age 67.8±11.1 years; 31.9% women), 146 (5.3%) experienced HF hospitalization and 134 (4.9%) died over a median follow-up of 4.0 years. Higher current AFEQT-os and change scores, but not prior AFEQT-os, were associated with a lower risk of death/HF hospitalization, with adjusted hazard ratios (95% confidence intervals) per 5-point increase of 0.94 (0.91-0.97) and 0.96 (0.92-0.99), respectively. When modeled together, only current AFEQT-os remained independently associated with outcomes. In time-varying analyses, time-updated AFEQT-os predicted both death/HF hospitalization and all-cause death. CONCLUSIONS: The most recent AFEQT-os is associated with mortality and HF hospitalization, whereas baseline scores provide limited prognostic value. Updating patient-reported health status may help with risk assessment in AF.
Yanagisawa S, Kato H, Kanzaki Y
… +15 more, Murase Y, Fujita M, Nakagomi T, Ishikawa S, Kamikubo Y, Suzuki H, Murakami H, Morishima I, Imai H, Kaneko S, Yoshida Y, Okumura T, Shibata R, Inden Y, Murohara T
BACKGROUND: His bundle (HB) pacing (HBP) can achieve an ideal pattern of ventricular activation. The long-term efficacy and clinical outcomes of HBP in Japan remain unclear. METHODS AND RESULTS: This multicenter prospect...BACKGROUND: His bundle (HB) pacing (HBP) can achieve an ideal pattern of ventricular activation. The long-term efficacy and clinical outcomes of HBP in Japan remain unclear. METHODS AND RESULTS: This multicenter prospective observational study enrolled 115 patients undergoing HBP implantation at 8 experienced centers in Japan. Inclusion criteria comprised atrioventricular block or conduction disturbance and an anticipated ventricular pacing of ≥40% in patients scheduled for HBP implantation. All patients were followed for 3 years after implantation. The primary endpoints were all-cause mortality, hospitalization for heart failure, and upgrade to cardiac resynchronization therapy. Secondary endpoints were changes in echocardiographic parameters and laboratory biomarkers after implantation. Seventy-eight (68%) patients continued HBP after the procedure (procedural success), whereas 68 (59%) patients exhibited clinical success (HB capture threshold ≤2.5 V at 1.0 ms). Six months after implantation, echocardiographic parameters improved, and brain B-type natriuretic peptide (BNP) levels decreased substantially. Major adverse clinical events (MACE), defined as the composite of the primary endpoints, occurred in 16 (21%) patients; 18 (23%) patients discontinued HBP during the follow-up period. Multivariable analysis identified elevated BNP levels at baseline as an independent predictor of MACE. CONCLUSIONS: HBP implantation presents technical challenges and exhibits a moderate success rate in real-world clinical practice. The high incidence of elevated HB capture thresholds and HBP abandonment mean that careful patient selection and rigorous long-term surveillance are required.
BACKGROUND: Cardiovascular disease (CVD) is an increasingly important contributor to maternal morbidity and mortality worldwide, but contemporary nationwide data in Japan remain limited. METHODS AND RESULTS: We conducted...BACKGROUND: Cardiovascular disease (CVD) is an increasingly important contributor to maternal morbidity and mortality worldwide, but contemporary nationwide data in Japan remain limited. METHODS AND RESULTS: We conducted a retrospective cohort study using the Japan Society of Obstetrics and Gynecology Perinatal Database from 2014 to 2023. Among 2,189,852 registered pregnancies, 26,894 (1.23%) were complicated by maternal CVD. Pregnancies with CVD were compared with the low-risk population (pregnancies without any medical comorbidities; n=1,882,896). Pregnancies with CVD had lower parity and more frequently required cesarean delivery, general anesthesia, and labor analgesia than the low-risk population. Maternal cardiovascular complications, including hypertensive disorders of pregnancy, pulmonary embolism and pulmonary edema, occurred at higher rates among pregnancies with CVD. Maternal death was rare in both groups, but was more frequent in pregnancies with CVD than in the low-risk population (0.03% vs 0.01%, P<0.001). Neonatal outcomes were generally similar between groups. CONCLUSIONS: In this nationwide registry analysis, approximately 1% of pregnancies in Japan were complicated by maternal CVD. Women with CVD underwent more obstetric and anesthetic interventions and had a modestly higher risk of maternal morbidity and mortality. These findings underscore the importance of continued registry surveillance and may help inform risk-stratified perinatal management.
BACKGROUND: Increasing use of mitral valve repair has shifted operations to older patients, potentially increasing the post-repair thromboembolic risk. However, the incidence, timing, and determinants of ischemic stroke/...BACKGROUND: Increasing use of mitral valve repair has shifted operations to older patients, potentially increasing the post-repair thromboembolic risk. However, the incidence, timing, and determinants of ischemic stroke/transient ischemic attack (TIA) after mitral repair in patients without preoperative atrial fibrillation (AF) remain undetermined. METHODS AND RESULTS: We retrospectively analyzed 636 patients (mean age, 58±13 years) with degenerative mitral regurgitation and sinus rhythm who underwent mitral valve repair. The primary endpoint was stroke/TIA. Over a mean follow-up of 7.4±5.5 years (4,681 patient-years), 28 (4.4%) developed stroke/TIA. Incidence peaked in the first postoperative year (1.4%/year), declined thereafter, and rose again at 10-15 years (0.67%/year). New-onset AF occurred in 54 patients (8.4%), based on 3,119 ECGs (mean, 4.9±5.8 per patient). Early events (≤1 year) rather than late events (>1 year) occurred in older patients (early vs. late events: 72±8.8 vs. 62±13 years, P=0.052). Later events were associated with larger left atrial size (48±6.7 vs. 41±7.6 mm, P=0.016) and a higher prevalence of new-onset AF (58% vs. 11%, P=0.039). Age ≥70 years (adjusted hazard ratio (HR), 4.4; P<0.001), new-onset AF (adjusted HR, 4.0; P<0.001) and NYHA class (adjusted HR: 2.0, P=0.02) were identified by Fine-Gray regression as independent determinants of stroke/TIA. CONCLUSIONS: After mitral repair, ischemic stroke/TIA occurred in 4.4% of patients without preoperative AF, associated with advanced age, new-onset AF, and higher NYHA functional class. This supports close rhythm surveillance and heart failure management.
BACKGROUND: Cardiac allografts show poorer long-term survival and decreased tolerance compared to renal allografts, but the underlying mechanisms remain unclear. METHODS AND RESULTS: We established heterotopic heart and...BACKGROUND: Cardiac allografts show poorer long-term survival and decreased tolerance compared to renal allografts, but the underlying mechanisms remain unclear. METHODS AND RESULTS: We established heterotopic heart and kidney allotransplantation models in Bama miniature pigs. Single-cell RNA sequencing (scRNA-seq) was performed to analyze normal heart/kidney tissues and allografts. Transcription factor analysis focused on T-cell subsets, with key findings validated using clinical human heart tissues (normal vs. acute rejection) and a mouse heart transplantation model (to test MYC inhibition). T/NK (TNK) subsets in cardiac allografts exhibited higher expression of genes linked to immune system activation, mature B-cell differentiation, and immune memory. The TNFRSF4+ CD4+ T-cell subset was selectively expanded in cardiac allografts (but reduced in renal allografts) during acute rejection, with transcriptional analysis identifying MYC as a master regulator of glycolysis-related genes in this subset. In the mouse heart transplant model, inhibition of MYC (via 10058-F4) reduced the proportion of TNFRSF4+ CD4+ T cells and significantly prolonged cardiac allograft survival. CONCLUSIONS: Our study identified a MYC-driven, glycolysis-dependent expansion of TNFRSF4+ CD4+ T cells as a key mechanism contributing to the heightened rejection susceptibility of cardiac allografts (vs. renal allografts). These findings provide a rationale for developing cardiac-targeted immunosuppressive strategies.
BACKGROUND: Heart failure (HF) is characterized by recurrent clinical deterioration, and multidimensional frailty (i.e., functional status, nutritional status, sarcopenia-related phenotypes, and cognitive impairment) is...BACKGROUND: Heart failure (HF) is characterized by recurrent clinical deterioration, and multidimensional frailty (i.e., functional status, nutritional status, sarcopenia-related phenotypes, and cognitive impairment) is a key determinant of prognosis. We explored longitudinal changes in these multidimensional domains across recurrent hospitalizations for HF. METHODS AND RESULTS: This single-center retrospective cohort study analyzed 337 patients initially hospitalized for HF between 2016 and 2024 who subsequently experienced ≥1 rehospitalization (total 780 admissions). Longitudinal changes across repeated hospitalizations were evaluated using age- and sex-adjusted linear mixed-effects models. The median age was 83 years, and 47.2% were women. Across repeated hospitalizations, frailty and functional status worsened (Clinical Frailty Scale, β=0.40, P<0.001; Barthel Index, β=-4.21, P<0.001; Short Physical Performance Battery score, β=-0.56, P=0.043). Gait speed also declined, although this trend did not reach statistical significance (β=-0.03, P=0.089). Nutritional status deteriorated (Controlling Nutritional Status score, β=0.56, P<0.001; Geriatric Nutritional Risk Index, β=-2.37, P<0.001). Sarcopenia-related indices deteriorated (appendicular skeletal muscle index, β=-2.79, P=0.006; grip strength, β=-4.64%, P<0.001). Cognitive function assessed by the Mini-Mental State Examination showed no significant longitudinal change (β=0.11, P=0.501). CONCLUSIONS: Many domains of frailty deteriorated across recurrent hospitalizations for HF, suggesting cumulative frailty progression.
BACKGROUND: Intracoronary imaging-derived physiologic indices enable vessel-level assessment of coronary flow impairment by integrating obstructive plaque burden. However, accurately evaluating hyperemic flow remains cha...BACKGROUND: Intracoronary imaging-derived physiologic indices enable vessel-level assessment of coronary flow impairment by integrating obstructive plaque burden. However, accurately evaluating hyperemic flow remains challenging due to the difficulty of simultaneously incorporating both vascular geometry and plaque composition. METHODS AND RESULTS: We aimed to develop and validate a deep learning algorithm using optical coherence tomography (OCT) to predict continuous, lesion-specific changes in fractional flow reserve (∆FFR) along coronary segments. Model performance was evaluated using Pearson's correlation, a confusion matrix, and a receiver operating characteristic (ROC) curve, with invasive wire-based FFR as the reference. The model was trained and tested on 157 OCT pullbacks from 86 patients, demonstrating enhanced predictive performance by incorporating anatomical and compositional OCT features compared to conventional feature-based machine learning approaches. Predicted ∆FFRvalues correlated strongly with wire-based ∆FFR (R=0.932, P<0.001), achieving an accuracy of 0.952 for detecting physiologically significant lesions and an area under the curve of 0.953 in the ROC analysis. The model accurately localized segmental pressure gradients, effectively distinguishing focal from diffuse disease patterns. CONCLUSIONS: This novel deep learning-based algorithm enabled lesion-specific, pressure wire-free physiologic assessment from a single OCT pullback. By integrating anatomical and compositional data, it supported improved diagnostic accuracy and personalized treatment for coronary artery disease.