BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), but the shape and potential nonlinearity of its association remain uncertain. We assessed the linear and...BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), but the shape and potential nonlinearity of its association remain uncertain. We assessed the linear and nonlinear associations between Lp(a) levels and ASCVD risk using observational and Mendelian randomization (MR) approaches. METHODS AND RESULTS: We analyzed 351,858 UK Biobank participants (2006-2023), stratified into Lp(a) percentiles: <70th, 70th-<80th, 80th-<90th, and ≥90th. Outcomes included ASCVD events from hospital, primary care, self-report, and death registry data. Cox models estimated the hazard ratios (HRs). MR analyses used a polygenic risk score from 10 Lp(a)-associated single-nucleotide polymorphisms, with nonlinearity tested by doubly ranked MR. Higher Lp(a) levels were associated with increased ASCVD risk. Compared with the <70th percentile, adjusted HRs (95% confidence interval) were 1.11 (1.07-1.16), 1.18 (1.14-1.22), and 1.25 (1.21-1.30) for the 70th-<80th, 80th-<90th, and ≥90th groups. Kaplan-Meier curves diverged early by group. Spline models suggested nonlinearity with an inflection near 130 nmol/L (P=0.007). MR showed a 2% higher ASCVD risk per 10 nmol/L genetically predicted Lp(a) (P<2×10). Nonlinear MR suggested steeper gradients at higher levels, though not statistically significant (P=0.087). CONCLUSIONS: Elevated Lp(a) concentrations were causally associated with ASCVD risk, showing a predominantly graded relationship with possible nonlinearity at very high levels, supporting routine Lp(a) measurement and the development of Lp(a)-lowering therapies.
BACKGROUND: The efficacy and safety of early direct oral anticoagulant (DOAC) (re)initiation in patients with non-valvular atrial fibrillation (NVAF) after acute onset of intracranial hemorrhage (ICH) are unknown. This s...BACKGROUND: The efficacy and safety of early direct oral anticoagulant (DOAC) (re)initiation in patients with non-valvular atrial fibrillation (NVAF) after acute onset of intracranial hemorrhage (ICH) are unknown. This study evaluated ischemic and hemorrhagic risks following early DOAC (re)initiation after ICH in patients with NVAF. METHODS AND RESULTS: SAFE-ICH is a multicenter prospective observational single-arm registry study at 32 Japanese hospitals. Eligible patients had NVAF, were aged ≥20 years, and (re)initiated DOAC ≤14 days following symptomatic ICH. Among 240 patients who (re)initiated DOAC (61.3% male; mean [±SD] age 79.4±9.3 years), intraparenchymal hemorrhage predominated (84.6%), followed by subdural (12.9%), intraventricular (1.7%), and epidural (0.8%) hemorrhage. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (3-16) and time to DOAC (re)initiation was 7 days (5-10 days). Edoxaban, apixaban, and rivaroxaban were used in 55.0%, 35.8%, and 9.2% of patients, respectively. The primary endpoint (composite of symptomatic ICH, any stroke, or death ≤30 days following DOAC [re]initiation) occurred in 12 (5.0%) patients. There were 4 recurrent ICH events (1.7%; all recurrent subdural hemorrhages). Five (2.1%) patients died of non-vascular causes. CONCLUSIONS: In Japanese patients with NVAF, early DOAC (re)initiation ≤14 days after ICH appears to have an acceptable risk for ischemic and hemorrhagic events, particularly in patients with intraparenchymal hemorrhage. In patients with subdural hematoma, early DOAC (re)initiation requires vigilant monitoring.
BACKGROUND: Decreased exercise tolerance after pulmonary resection for lung cancer is strongly associated with a poor prognosis, but its determinants remain underexplored. We investigated the mechanisms of postoperative...BACKGROUND: Decreased exercise tolerance after pulmonary resection for lung cancer is strongly associated with a poor prognosis, but its determinants remain underexplored. We investigated the mechanisms of postoperative effort intolerance in lung cancer using combined exercise-stress echocardiography and cardiopulmonary exercise testing (ESE-CPET). METHODS AND RESULTS: We prospectively analyzed 38 patients with suspected non-small cell lung cancer who underwent pulmonary resection. Preoperative and 6-month postoperative evaluations included resting echocardiography, ESE-CPET, and pulmonary function tests. Pulmonary vascular function was assessed using the mean pulmonary artery pressure/cardiac output (MPAP/CO) slope (n=38). Postoperative peak oxygen consumption (V̇O) significantly decreased (19.4 vs. 17.3 mL/min/kg, P<0.001). Multiple regression analysis identified left atrial reservoir strain (B 0.797 [95% confidence interval: 0.138-1.456], P=0.019) and number of resected segments (-5.448 [-10.99 to -0.047], P=0.048) as independent predictors of postoperative change in peak V̇O. Subgroup analysis showed greater changes in systolic pulmonary artery pressure during exercise (∆SPAP) and steeper postoperative MPAP/CO slopes in patients with ≥3 resected segments vs. <3 (P<0.001 and P=0.052 for time-group interaction). A preoperative MPAP/CO slope >2.0 predicted larger increases in peak SPAP following ≥3-segment resection (P=0.006), signifying increased pulmonary vascular stress. CONCLUSIONS: ESE-CPET demonstrated that extensive pulmonary resection adversely affects postoperative exercise tolerance and pulmonary vascular function, leading to greater ∆SPAP and steeper MPAP/CO slopes.
BACKGROUND: Whether the components of sarcopenia provide sex-specific prognostic information in heart failure (HF) remains uncertain. METHODS AND RESULTS: We enrolled 604 patients with HF (259 women; median age, 73 years...BACKGROUND: Whether the components of sarcopenia provide sex-specific prognostic information in heart failure (HF) remains uncertain. METHODS AND RESULTS: We enrolled 604 patients with HF (259 women; median age, 73 years) undergoing dual-energy X-ray absorptiometry. During 2.18-year follow-up, 124 deaths occurred. All sarcopenia components as continuous variables were associated with death in the overall cohort. Asian Working Group for Sarcopenia (AWGS2019) cutoffs for weak handgrip strength, prolonged fivetimes sittostand time (FTSS), or low Short Physical Performance Battery (SPPB) score showed the strongest association, whereas low appendicular skeletal muscle mass index (ASMI) did not predict death. No significant sex interactions were observed for ASMI, gait speed, FTSS, or SPPB, and only handgrip strength showed a borderline interaction trend (P=0.058), with a stronger association for death in women. Despite a nonsignificant interaction (P=0.284), the AWGS2019 criteria predicted death in men (adjusted HR, 2.23; 95% confidence interval (CI), 1.21-4.09, P=0.013) but not in women (aHR, 1.28; 95% CI, 0.70-2.34, P=0.423). Exploratory analyses showed that optimized, HF-specific ASMI thresholds improved prognostic performance. CONCLUSIONS: Performancebased sarcopenia components can provide valuable mortality risk stratification in HF irrespective of sex. Although sex interactions were limited, population-derived muscle mass thresholds showed reduced prognostic performance in women, indicating that refining disease-specific or sex-adapted thresholds may enhance risk stratification in HF.
BACKGROUND: Because monocyte chemoattractant protein-1 (MCP-1) and high-sensitivity C-reactive protein (hs-CRP) are crucial biomarkers in the early stages of atherosclerosis, we examined the association of their serum le...BACKGROUND: Because monocyte chemoattractant protein-1 (MCP-1) and high-sensitivity C-reactive protein (hs-CRP) are crucial biomarkers in the early stages of atherosclerosis, we examined the association of their serum levels with all-cause and cause-specific deaths in a healthy population. METHODS AND RESULTS: Between 2004 and 2007, 568 participants (64% women, mean age 64.4 years) underwent health check-ups from which their serum MCP-1 and hs-CRP levels were categorized as high or low based on the median values of each biomarker. We analyzed all-cause deaths using Kaplan-Meier curves and used a multivariable Cox regression model to calculate hazard ratios for all-cause, cardiovascular disease (CVD), and cancer deaths both individually and in combination. During a median follow-up of 17.9 years, 140 deaths occurred: 43 from CVD and stroke, and 33 from cancer. The cumulative all-cause mortality rate was higher in participants with both high serum MCP-1 and hs-CRP levels than in those with lower levels. The adjusted hazard ratios for combined high serum MCP-1 and hs-CRP levels vs. low levels were 1.86 (95% confidence interval (CI): 1.09-3.17) for all-cause, 3.24 (95% CI: 1.07-9.82) for CVD and stroke, and 3.28 (95% CI: 1.06-10.18) for cancer deaths. CONCLUSIONS: Combined serum MCP-1 and hs-CRP levels could predict all-cause and cause-specific mortality rates in the general population.
BACKGROUND: Although Achilles tendon thickening (ATT) is associated with poor prognosis after percutaneous coronary intervention (PCI), its impact may differ between acute coronary syndrome (ACS) and chronic coronary syn...BACKGROUND: Although Achilles tendon thickening (ATT) is associated with poor prognosis after percutaneous coronary intervention (PCI), its impact may differ between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). METHODS AND RESULTS: We retrospectively analyzed 1,362 patients after PCI. ATT was present in 228 patients (16.7%) and associated with more 3-year major adverse cardiovascular events (MACE) (P<0.001). The association was pronounced in ACS patients (P=0.001), whereas in CCS patients, ATT showed a non-significant trend toward a higher incidence of MACE (P=0.066). CONCLUSIONS: ATT may be a simple, non-invasive marker for risk stratification after PCI, particularly in ACS patients.
BACKGROUND: Chest symptoms, such as angina and palpitation, are common complaints in patients with cardiovascular diseases, but few studies have addressed how cardiac afferent information is processed through the brain....BACKGROUND: Chest symptoms, such as angina and palpitation, are common complaints in patients with cardiovascular diseases, but few studies have addressed how cardiac afferent information is processed through the brain. METHODS AND RESULTS: We recruited 10 patients (mean age 74.7±1.9 years; 9 men) with cardiac pacemaker implantation. The patients underwent brain HO positron emission tomography (PET) followed by blood sampling during right ventricular pacing of sham (1.5 V) and stimulation (7.5-8 V) conditions with a 10min interval. A voxel-wise analysis of the brain PET images identified the anterior cingulate cortex (ACC), posterior cingulate cortex, prefrontal cortex, thalamus, amygdala and midbrain as regions of increased regional cerebral blood flow (rCBF) under stimulation compared to sham conditions at a family-wise error-corrected cluster-extent threshold of P<0.05 with an underlying voxel level of P<0.001. The stimulation conditions increased rCBF in the ACC (59.8±4.4 vs. 49.2±3.5 mL/100 g/min, P<0.001) and plasma noradrenaline levels (332.3±139.0 vs. 312.0±139.8 pg/mL, P=0.004) compared to the sham stimulation. A linear mixed-effects model showed a significant positive correlation between the changes in rCBF in the ACC and those in plasma noradrenaline levels (P<0.001). CONCLUSIONS: Cardiac electrical stimulation increased both rCBF in the ACC and plasma noradrenaline levels, and the changes were correlated. The ACC may be the brain center that transfers cardiac afferent information into autonomic arousal during cardiac pacing.
BACKGROUND: Although early right ventricular failure (eRVF) following durable left ventricular assist device (dLVAD) implantation is associated with a poor prognosis, reliable predictive parameters have not yet been esta...BACKGROUND: Although early right ventricular failure (eRVF) following durable left ventricular assist device (dLVAD) implantation is associated with a poor prognosis, reliable predictive parameters have not yet been established. In this study we evaluated the predictive value of right ventricular (RV) to pulmonary artery (PA) uncoupling, measured by the ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP), in patients undergoing dLVAD implantation. METHODS AND RESULTS: We conducted a single-center retrospective study of adult patients who underwent dLVAD implantation between January 2008 and December 2024. eRVF was defined as receiving short- or long-term right-sided circulatory support, or continuous inotropic support for more than 14 days within 30 days after dLVAD implantation. Preoperative echocardiographic variables, including the TAPSE/PASP ratio and right-sided heart catheter parameters, were analyzed using univariate and multivariate logistic regression models to identify eRVF predictors. We analyzed data for 111 patients who underwent dLVAD implantation and 46.8% developed eRVF postoperatively. The TAPSE/PASP ratio was an independent predictor of eRVF, even after adjustments for other echocardiographic variables (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.67, P=0.024) and right-sided heart catheter variables (OR, 0.04; 95% CI, 0.002-0.69, P=0.027). CONCLUSIONS: Preoperative RV-PA uncoupling, assessed using the TAPSE/PASP ratio, may predict eRVF following dLVAD implantation. This parameter is clinically accessible and valuable for preoperative risk stratification and may facilitate improved perioperative management.
BACKGROUND: To provide evidence from randomized controlled trials (RCTs) for large-vessel vasculitis (LVV), including Takayasu arteritis (TAK) and giant cell arteritis (GCA), to inform the forthcoming 2026 Japanese Circu...BACKGROUND: To provide evidence from randomized controlled trials (RCTs) for large-vessel vasculitis (LVV), including Takayasu arteritis (TAK) and giant cell arteritis (GCA), to inform the forthcoming 2026 Japanese Circulation Society (JCS) clinical practice guideline. METHODS AND RESULTS: We drafted 4 and 7 clinical questions for TAK and GCA, respectively. A systematic review (SR) of RCTs was conducted using PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society through March 2024. Assessed with the GRADE approach, the certainty of evidence was very low for the most critical outcomes, low for some outcomes, and moderate for only 1 outcome. Evidence for TAK was limited. Tocilizumab (TCZ) resulted in a numerically lower relapse rate vs. placebo (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.39-1.37) and was similar to adalimumab. No clear difference between mycophenolate mofetil (MMF) and methotrexate (MTX), or between abatacept (ABA) and placebo was observed. In GCA, TCZ reduced relapse (RR 0.29, 95% CI 0.09-0.98) and increased remission (RR 3.56, 95% CI 2.29-5.54) over placebo at 52 weeks. Tumor necrosis factor inhibitor, ABA, and MTX showed no benefit in cranial GCA. Serious adverse events were comparable between treatment groups. Geographic variation and differences in entry criteria were noted. CONCLUSIONS: This SR was comprehensive synthesis of evidence from RCTs for LVV therapies to support the 2026 JCS guideline.
BACKGROUND: Because a disease-modifying therapy is now available, bone scintigraphy plays a crucial role in diagnosing transthyretin cardiac amyloidosis (ATTR-CM). METHODS AND RESULTS: We retrospectively analyzed 24 pati...BACKGROUND: Because a disease-modifying therapy is now available, bone scintigraphy plays a crucial role in diagnosing transthyretin cardiac amyloidosis (ATTR-CM). METHODS AND RESULTS: We retrospectively analyzed 24 patients with ATTR-CM to determine the amyloid accumulation volume (AAV: mean standardized uptake value×volume) of the left ventricular wall. AAV showed a significant decrease (591.1±426.0 vs. 213.8±201.9, P<0.0001) after tafamidis treatment, and correlated with troponin T (R=0.49, P=0.022). CONCLUSIONS: AAV provided a precise quantitative evaluation of the amyloid burden in ATTR-CM.
Matsuda Y, Masuda M, Tanaka N
… +28 more, Watanabe T, Minamiguchi H, Egami Y, Oka T, Miyoshi M, Okada M, Kawasaki M, Mano T, Tsujimura T, Uematsu H, Ooka H, Kudo S, Okamoto S, Ishihara T, Nanto K, Hata Y, Nakao S, Kusuda M, Ariyasu W, Inoue K, Hikoso S, Sunaga A, Dohi T, Okada K, Nakatani D, Sotomi Y, Sakata Y, Osaka Cardiovascular Conference (OCVC)-Arrhythmia Investigators
BACKGROUND: The EARNEST-PVI trial showed that left atrial ablation in addition to pulmonary vein isolation (PVI) reduced atrial fibrillation (AF) recurrence after catheter ablation for persistent AF; however, the efficac...BACKGROUND: The EARNEST-PVI trial showed that left atrial ablation in addition to pulmonary vein isolation (PVI) reduced atrial fibrillation (AF) recurrence after catheter ablation for persistent AF; however, the efficacy of left atrial additional ablation in patients with diabetes mellitus (DM) is not well known. The aim of this study was to evaluate the efficacy of left atrial additional ablation after PVI in patients with and without DM. METHODS AND RESULTS: This study, a subanalysis of the EARNEST-PVI trial, a multicenter, prospective, randomized, controlled trial, analyzed 493 consecutive patients undergoing initial radiofrequency catheter ablation for persistent AF. Patients were randomized to PVI alone (PVI-alone group) or PVI plus linear and/or complex fractionated atrial electrogram ablation (PVI-plus group). The primary outcome was defined as AF recurrence during the 12-month follow-up period after ablation. A total of 84 (17%) patients had DM. The primary outcome occurred in 120 (24%) patients. In patients without DM, freedom from AF recurrence was significantly higher in the PVI-plus group than in the PVI-alone group (80.0% vs. 71.1%, P=0.034). In contrast, in patients with DM, freedom from AF recurrence was similar between the PVI-plus and PVI-alone groups (75.4% vs. 72.9%, P=0.696). CONCLUSIONS: The efficacy of left atrial additional ablation after PVI in reducing AF recurrence following catheter ablation for persistent AF was diminished in patients with DM.
BACKGROUND: Harmonytranscatheter pulmonary valve implantation (TPVI) was developed to treat pulmonary regurgitation (PR) in patients with an enlarged native right ventricular outflow tract. Favorable outcomes have been r...BACKGROUND: Harmonytranscatheter pulmonary valve implantation (TPVI) was developed to treat pulmonary regurgitation (PR) in patients with an enlarged native right ventricular outflow tract. Favorable outcomes have been reported in cohorts from the USA, but data from other regions are limited. METHODS AND RESULTS: This prospective single-center study included 55 Japanese adults who underwent HarmonyTPVI between March 2023 and September 2024. Echocardiography and cardiac magnetic resonance imaging were performed at baseline and at 3 months. The median age was 45 years (interquartile range [IQR]: 29-54 years) and the median body mass index (BMI) was 20 kg/m(IQR: 18-24). Procedural success was achieved in all patients. The PR fraction improved from 46% to 2.3% (P<0.01). Right ventricular end-diastolic and end-systolic volume indices decreased from 156 to 108 mL/mand from 84 to 69 mL/m, respectively (P<0.01). Stroke volume increased from 59 to 64 mL, and cardiac index from 2.4 to 2.6 L/min/m(P<0.05). During a median follow-up of 17 months, all patients remained free from reintervention. CONCLUSIONS: In Japanese patients characterized by older age and lower BMI, HarmonyTPVI achieved high procedural success and rapid right ventricular reverse remodeling, indicating it is a safe and effective treatment option.