Background: Abdominal aortic aneurysm (AAA) is a vascular disease strongly associated with immune dysregulation and metabolic disturbances. Although lactate metabolism and its associated process, lactylation, have been implicated in various diseases, their specific role in AAA pathogenesis remains poorly understood.

Methods and Results: In this study, we used a multi-faceted approach, integrating single-cell and bulk RNA data analyses, with the objective of elucidating the interrelationship between lactylation and immune response in AAA patients. The result revealed significant heterogeneity in lactylation levels across different immune cell types. Cells with higher lactylation activity exhibited markedly elevated immune response scores. Differential expression and correlation analyses identified 65 lactylation-associated genes, which were further evaluated in the bulk RNA sequencing data to assess their relationship with the immune microenvironment in patients with AAA. Using 113 combinations of machine-learning algorithms, we identified 8 lactylation-related hub genes. The immune infiltration analysis demonstrated that these genes were linked to a multitude of immune cells. The animal experiments corroborated that Tnfsf8, Hist1 h2ag, Cd79b, Cd69, and Bank1 were upregulated in the AAA group, while Rpl36a and Rps29 were downregulated in the AAA group.

Conclusions: This study highlighted a potentially critical link between lactylation and immune dysregulation in AAA, thereby advancing our comprehension of the function of lactylation in AAA.

Background: Statins can effectively reduce low-density lipoprotein cholesterol (LDL-C), but additional options are needed for inadequate responses to statins or statin intolerance. Bempedoic acid is a small-molecule oral LDL-C-lowering drug that inhibits ATP citrate lyase, an enzyme 2 steps upstream of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the metabolic pathway for cholesterol synthesis.

Methods and Results: The CLEAR-J trial evaluated bempedoic acid 180 mg/day for 12 weeks in Japanese patients with inadequately controlled LDL-C. Percentage changes in LDL-C between baseline and Week 12 (primary endpoint) were −25.25% and −3.46% in the bempedoic acid and placebo groups, respectively, with a significant between-group difference (−21.78%; 95% confidence interval [CI] –26.71%, –16.85%; P<0.001). Changes in secondary endpoints in the bempedoic acid and placebo groups were as follows: non-high-density lipoprotein cholesterol, −20.33% and −2.76%, respectively (between-group difference −17.57%; 95% CI −22.03%, −13.12%); total cholesterol −16.36% and −2.23%, respectively (between-group difference –14.13%; 95% CI −17.79%, −10.47%); and apolipoprotein B −18.10% and −0.67%, respectively (between-group difference −17.43%; 95% CI –21.97%, −12.89%). At 12 weeks, 62.5% of the bempedoic acid group had achieved target LDL-C values. Treatment-emergent adverse events appeared in 3 patients taking bempedoic acid and 2 patients taking placebo.

Conclusions: This study confirmed the safety and efficacy of bempedoic acid after 12 weeks treatment in Japanese patients with high LDL-C who had inadequate response to statins or statin intolerance.

Background: The efficacy of exercise-based cardiac rehabilitation (CR) in patients with angina and non-obstructive coronary artery disease (ANOCA) remains unclear. This study investigated whether a multidisciplinary CR program improves myocardial flow reserve (MFR), symptom status, and exercise capacity in patients with ANOCA.

Methods and Results: Myocardial blood flow at rest and during ATP-induced hyperemia was quantified using ¹³N-ammonia positron emission tomography (PET) in 29 patients diagnosed with ANOCA and impaired MFR (<2.5). Overall, 16 patients completed the 5-month CR program (complete CR group) and 13 did not (non-complete CR group). At baseline and the 5-month follow-up PET, symptom status and exercise capacity were assessed using the Seattle Angina Questionnaire (SAQ)-7 and cardiopulmonary exercise testing, respectively. The MFR in the complete CR group increased significantly (P=0.001) from a median of 1.60 (interquartile range [IQR] 1.43–1.98) to 2.09 (IQR 1.83–2.48). Significant improvements were also seen in the median SAQ-7 total score (from 16 [IQR 11–20] to 11 [IQR 8–14]; P=0.008) and peak oxygen consumption (V̇O₂; from 14.2 [IQR 12.4–15.8] to 15.3 [13.0–17.9] mL/kg/min; P=0.02). In contrast, there were no improvements in MFR (P=0.83) or peak V̇O₂(P=0.27) in the non-complete CR group.

Conclusions: The 5-month exercise-based CR significantly improved MFR, symptom status, and exercise capacity in patients with ANOCA and impaired MFR.

Background: The effects of sacubitril/valsartan (angiotensin receptor–neprilysin inhibitor [ARNI]) on myocardial tissue in heart failure (HF) with left ventricular ejection fraction (LVEF) <50% remain unclear.

Methods and Results: Sixty-four HF outpatients with LVEF <50% were randomized to ARNI (switching from an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker [ACEi/ARB] to ARNI) or control (continuing with ACEi/ARB). Left ventricular (LV) structure and myocardial tissue, including changes in LV extracellular volume fraction (ECV), were evaluated before and after the 9-month program using cardiac magnetic resonance imaging. The primary endpoint was changes in ECV. Secondary endpoints were changes in LVEF, LV volume and mass, and extra- and intracellular mass. Fifty-nine patients completed the 9-month intervention. ARNI decreased systolic blood pressure from the first month. The ARNI group showed significant reductions in LV volume, LV mass, and extra- and intracellular mass from baseline to 9 months, but there was no change in LVEF, or in ECV (31.6±5.0% vs. 31.9±5.0%, respectively; P=0.795). In the control group, there was no change in systolic blood pressure, LV volume, LV mass, ECV, or extra- and intracellular mass. There was no significant difference in the change in ECV between the ARNI and control groups (0.3±5.1% vs. 1.2±4.1%, respectively; P=0.461), whereas the change in extracellular mass was greater in the ARNI group (P=0.025).

Conclusions: ARNI reduced LV volume and mass, resulting from decreases in both extra- and intracellular mass, without changing ECV. This suggests ARNI has potential to improve LV tissue characteristics in HF patients with LVEF <50%.

Background: Preoperative risk assessment is very important to ensure surgical safety and predict postoperative complications. However, no large-scale studies have evaluated the risk of perioperative cardiovascular events in Japan. This study evaluated perioperative cardiovascular events using real-world data. In addition, the applicability of machine learning to risk stratification was examined to develop a predictive model for perioperative cardiovascular events.

Methods and Results: This was an observational cohort study using the Japan Medical Data Center database, which includes claim and health examination data in Japan, between January 2005 and April 2021. In all, 133,634 gastrointestinal surgeries were included in the analysis. The primary outcome was 30-day risk of major adverse cardiovascular events (MACE). The 30-day MACE incidence rate following surgery was 3.8%. Machine learning was used to perform a binary classification task to predict MACE occurrence within 30 days after surgery. A clustering algorithm was developed based on the Shapley additive explanation values obtained from training data, and generalizability was evaluated using test data. Of the variables, age, history of ischemic heart disease or heart failure, history of stroke, diabetes, hypertension, atrial fibrillation, cases of malignancy, and pancreatic biliary surgery were identified as factors associated with MACE occurrence.

Conclusions: A machine learning model built from basic clinical information, comorbidities, and surgical information demonstrated the capacity to stratify MACE risk in patients undergoing gastrointestinal surgery.

Background: Few studies have examined the characteristics of heart failure (HF) patients with cachexia using the Asian Working Group for Cachexia (AWGC) 2023 criteria. This study assessed the characteristics and clinical impact of cachexia in older adults with HF.

Methods and Results: Results of laboratory measurements, echocardiography, physical function, depression, nutritional status, and the prevalence of cachexia, frailty, and sarcopenia were assessed in older adults (≥65 years) with HF in a stable condition just before discharge. After discharge, all participants were prospectively followed for adverse clinical events. Patients were classified based on the presence or absence of cachexia, and their frailty, sarcopenia, and clinical outcomes were compared. The prevalence of cachexia diagnosed by AWGC 2023 and Evans criteria was 24.7% and 12.9%, respectively. Among HF patients with cachexia, 71.6% had frailty and 86.7% had sarcopenia. Patients with cachexia had significantly poorer physical function and nutrition than those without. Cox proportional hazards analysis identified cachexia as an independent predictor of all-cause and cardiovascular death.

Conclusions: Cachexia in older adults with HF is strongly associated with poor physical function, malnutrition, and adverse clinical outcomes. Early identification and management of cachexia may help improve the prognosis in this population.

Background: Landiolol is a short-acting, intravenously administered β₁-adrenergic receptor blocker that can rapidly control heart rate in refractory and urgent fatal arrhythmias (ventricular fibrillation [VF] and hemodynamically unstable ventricular tachyarrhythmia [VT]). This indication was approved in Japan in 2019 based on results of the J-Land II clinical trial. We conducted post-marketing surveillance (PMS) to assess the safety and effectiveness of landiolol in real-world settings in Japan.

Methods and Results: This PMS examined the safety, focusing on adverse drug reactions (ADRs) related to the safety specifications (_SS), namely hypotension-decreased blood pressure_SS, bradycardia_SS, and heart failure_SS, and effectiveness (physician-rated) in patients treated with landiolol for the target indication. Among 253 registered patients, 13.0% experienced ADRs related to the safety specifications: bradycardia_SS(7.1%), hypotension-decreased blood pressure_SS(6.7%), and heart failure_SS(1.2%). Serious ADRs related to the safety specifications occurred in 6.7% of patients, including those related to bradycardia_SS(3.2%), hypotension-decreased blood pressure_SS(3.2%), and heart failure_SS(1.2%). The effectiveness of landiolol within 48 h after starting treatment was rated as effective (52.4%), slightly effective (27.0%), not effective (18.7%), and indeterminate (2.0%).

Conclusions: The safety profile of landiolol in this PMS was similar to that observed in a prior clinical trial, and no new safety signals were identified. Landiolol is an option for treating refractory and potentially fatal VF or hemodynamically unstable VT.

Background: This study compared postoperative outcomes in patients with a preoperative left ventricular ejection fraction (LVEF) of ≤35% who underwent multiple (MAG) or single (SAG) arterial grafting during off-pump isolated coronary artery bypass grafting.

Methods and Results: Of 1,627 patients who underwent isolated coronary artery bypass grafting at Shiga University of Medical Science between 2002 and 2023, 176 with a preoperative LVEF ≤35% underwent MAG (n=115) or SAG (n=61). Baseline patient characteristics were comparable in the MAG and SAG groups after adjustment using inverse probability of treatment weighting. The study’s mean (±SD) follow-up duration was 4.8±4.7 years. In the MAG and SAG groups, the adjusted estimated 5-year rates of freedom from all-cause death were 71.5% and 69.1%, respectively, while those of cardiac death were 94.1% and 89.5%, respectively. Kaplan-Meier curves showed significant differences in all-cause death (P=0.013) and cardiac death (P=0.001) favoring the MAG group. In a multivariable Cox hazards model, MAG was a predictor of all-cause death (hazard ratio 0.568; P=0.034) and cardiac death (hazard ratio 0.276; P=0.008).

Conclusions: Compared with SAG, MAG was associated with significantly lower rates of all-cause death and cardiac death.

Background: Hospital-associated disability (HAD), characterized by a worsening of activities of daily living and physical function following hospitalization, is a common complication in older adults during the course of acute care hospitalization. HAD is a significant concern affecting older adults undergoing transcatheter aortic valve implantation (TAVI).

Methods and Results: This retrospective study investigated 243 consecutive patients who underwent elective transfemoral TAVI between January 2016 and April 2022. HAD was defined as a decrease of at least 1 point in the Short Physical Performance Battery (SPPB) assessed before discharge compared with before TAVI. Logistic regression identified the first ambulation day after TAVI as an independent predictor of HAD incidence (odds ratio 1.500; 95% confidence interval [CI] 1.115–2.008; P=0.007). Patients with HAD had significantly lower body mass index, hemoglobin, and albumin, and higher serum creatinine. All-cause mortality was significantly higher in patients with than without HAD (log-rank P<0.001). Kaplan-Meier analysis confirmed poorer survival in patients with HAD, regardless of the degree of decline in SPPB. Multivariate Cox analysis regression identified HAD as a predictor of all-cause death (hazard ratio 4.249; 95% CI 1.798–10.04; P<0.001).

Conclusions: The timing of the first ambulation was associated with the incidence of HAD. Promoting early mobilization may reduce the risk of HAD after TAVI.

Background: Recurrence after ablation for atrial fibrillation (AF) may occur in patients in whom atrial remodeling progresses. Atrial conduction time is a marker of remodeling. This study investigated whether atrial conduction time is related to postoperative recurrence.

Methods and Results: This study enrolled 441 patients with AF (median age 69 years; 144 women; paroxysmal/non-paroxysmal AF=231/210) who underwent initial radiofrequency catheter ablation at Mie University Hospital between January 2018 and December 2022. The interval from the earliest potential in the right atrium (RA) to the latest potential in the coronary sinus (CS) was measured using a BeeAT catheter during sinus rhythm after ablation. The primary endpoint was AF recurrence or atrial tachycardia lasting >30 s in the 1 year after ablation. Recurrence was observed in 44 patients. Patients were categorized into 2 groups according to recurrence. The RA-CS interval was significantly longer in the recurrence group (122.5±17.7 vs. 98.5±17.7 ms; P<0.001). In Cox regression analysis, the RA-CS interval was independently associated with recurrence (hazard ratio 1.05; 95% confidence interval [CI] 1.03–1.07; P<0.001). The cut-off value for the RA-CS interval was 111 ms (area under the curve=0.845; 95% CI 0.785–0.905). The recurrence rate was significantly higher in patients with an RA-CS interval ≥111 vs. <111 ms.

Conclusions: The RA-CS interval time was an independent predictor of recurrence after AF ablation.

Recently, some clinicians have been diagnosing and treating arrhythmias on the basis of electrocardiogram (ECG) devices with low accuracy. In Europe and the US, several statements on the use of ECGs have already been published by related academic societies. In addition, with the relaxation of regulations on media advertising ambulatory/wearable ECG devices, the frequency of use of simple ECG devices by the general public will increase in the future. Therefore, this statement describes the functions and features of non-invasive ambulatory or wearable ECG devices that have been approved as medical devices in Japan (and that can record ECGs remotely), as well as points to note when using them; provides an overview of data storage and security for ambulatory/wearable ECG devices and implantable loop recorders (ILRs), as well as discussing differences between their use and the use of non-invasive ambulatory/wearable ECG devices; and provides classes of recommendation for the use of these devices and their evaluation for each arrhythmia type or condition. We describe lead-based ambulatory ECG devices (classical 24-h Holter ECG monitoring), handheld ECG devices, handheld-based ECG devices using a smartphone, wearable ECG devices (smartwatch and garment ECG devices), and patch ECG devices. In addition, we provide information on methods that are not based on the original ECG, such as photoplethysmography and oscillometric blood pressure measurement, and describe the limitations of their use. We hope that the publication of this statement will lead to the appropriate use of ambulatory/wearable ECG devices in Japan.

Background: Although tricuspid regurgitation (TR) is no longer considered a negligible disease, its detailed status in real-world heart failure (HF) patients remains unknown.

Methods and Results: From the KUNIUMI registry, we evaluated data for 1,646 consecutive HF patients. The primary endpoint was all-cause mortality over a median follow-up period of 3.0 years (interquartile range 1.4–3.0 years). Of the 1,646 HF patients, 369 (22.4%) had moderate or greater TR; the mean (±SD) age of these patients was 82.0±8.5 years. Atrial functional TR was the most common etiology of TR in HF patients with moderate or greater TR (70.7%), and was more common in HF patients with severe than moderate TR (75.5% vs. 65.3%; P=0.032). The mortality rate was high in HF patients with severe and moderate TR (27.1% and 17.0%, respectively). During follow-up, 33.1% of HF patients with moderate TR progressed to severe TR, and showed unfavorable all-cause mortality compared with those with unchanged TR. Atrial functional TR was a more common etiology in HF patients with moderate TR and worsened TR than in those with unchanged TR (84.6% vs. 59.5%; P=0.004). Right atrial enlargement was independently correlated with worsened TR.

Conclusions: Moderate or greater TR was prevalent in 22.4% of the real-world super-aged HF population. Even HF patients with moderate TR had poor outcomes, with right atrial remodeling a key factor for worsened TR.

Background: There are few studies regarding the predictors of stent underexpansion (SUE) in post-debulking calcified lesions. We investigated predictors of SUE in severely calcified lesions after debulking using optical coherence tomography-guided rotational atherectomy (RA) or orbital atherectomy (OA).

Methods and Results: As a post hoc analysis of the DIRO trial, we compared various parameters, including calcium and lipid parameters (lipid-rich plaque, thin cap fibroatheroma [TCFA], maximum lipid arc, mean lipid arc, lipid length, and lipid volume index), between groups with adequate stent expansion (ASE) and SUE. To find predictors of SUE, multivariable analysis was performed using significant factors from the univariable analysis. We also evaluated adverse events 8 months after the procedure. The SUE group consisted of 57 (65.5%) patients. After suitable debulking of severely calcified lesions using RA or OA, there was no correlation between calcium parameters and SUE; however, the lipid parameters of maximum lipid arc ≥224° and TCFA were significantly and independently correlated with SUE Approximately 45% of severely calcified lesions contained lipid-rich plaques. Adverse events occurred more frequently in the SUE than ASE group.

Conclusions: The role of calcium parameters in predicting SUE in severely calcified lesions after suitable debulking using RA or OA is weak; however, maximum lipid arc and TCFA are important predictors of SUE.

Background: The long-term effects of cumulative resting heart rate (cumRHR) on the incidence of cardiovascular events and all-cause mortality in older (age ≥60 years) hypertensive populations remain unclear. Therefore, the aim of this study was to investigate the association between cumRHR and cardiovascular events and all-cause mortality.

Methods and Results: This post hoc analysis used data from the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial of 7,517 patients in whom resting heart rate (RHR) was measured at 0, 3, 6, 9, and 12 months. “cumRHR” refers to the weighted mean of the RHR for each time interval. Participants were divided into quartiles (Q1–Q4) based on cumRHR. After adjustment for potential confounders and using Q3 (72.19–75.88 [beats/min] × year) as the reference, patients in Q4 (75.94–109.44 [beats/min] × year) had higher risks of the primary outcome (a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, and death from any cardiovascular cause) (hazard ratio [HR] 2.21; 95% confidence interval [CI] 1.42–3.43; P<0.001), major adverse cardiovascular events (HR 1.93; 95% CI 1.18–3.16; P=0.009), and stroke (HR 3.55; 95% CI 1.42–8.86; P=0.007) and those in Q1 (44.50–68.44 [beats/min] × year) had an increased risk of the primary outcome (HR 1.71; 95% CI 1.08–2.71; P=0.02). No such trends were observed for all-cause mortality. A U-shaped relationship was observed with the primary outcome, with higher risk for both very low or very high cumRHR levels compared with midrange values.

Conclusions: Both low and high cumRHR levels were associated with higher risk of cardiovascular events in older patients with hypertension.

Background: Cardiovascular emergencies often require intensive care unit (ICU) management, but there is limited data comparing outcomes based on the admission ward.

Methods and Results: We analyzed data from the Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination (JROAD-DPC) database (2016–2020) for 715,054 patients (mean age, 75.4±14.2 years, 58.4% male) admitted with acute myocardial infarction (N=175,974), unstable angina (N=45,308), acute heart failure (N=179,871), acute aortic dissection (N=58,597), pulmonary embolism (N=17,009), or post-cardiac arrest (N=184,701). Patients were categorized into 4 groups: intensive care add-ons 1/2, 3/4 (ICU 1/2, 3/4), high-care unit (HCU), and general wards. Comparisons included patient characteristics, hospitalization duration, mortality rates, and rates of defibrillation or cardiopulmonary resuscitation (CPR) defined by chest compression. General ward patients were the oldest and with shortest hospitalization durations. Additionally, mortality rates were the highest in general wards for acute heart failure, myocardial infarction, and aortic dissection. Defibrillation rates were 7.0%, 5.6%, 3.1%, and 4.3%, for ICU 1/2, 3/4, HCU, and general ward, respectively, with corresponding mortality rates of 40.4%, 44.1%, 44.6%, and 79.3%. CPR rates were 10.1%, 9.5%, 6.2%, and 30.8%, with mortality rates of 71.0%, 73.9%, 78.4%, and 97.7%, respectively.

Conclusions: High mortality rates in general wards highlight the importance of ICU management, particularly for acute myocardial infarction and aortic emergencies. These findings support prioritizing ICU admission for these critical conditions.

Background: Idiopathic pericarditis generally has a favorable prognosis, but contemporary data on treatment patterns and outcomes remain limited.

Methods and Results: Using a nationwide Japanese database, we analyzed 8,020 pericarditis patients hospitalized between April 2016 and March 2021, and identified 3,963 (49%) patients with idiopathic pericarditis after excluding those with infectious, autoimmune or other causes. During the study period, the median age increased from 62 to 68 years (P_trend<0.001), and prescription rates of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, and the simultaneous administration of NSAIDs and colchicine increased over time (from 65.9 to 72.6% [P=0.049], from 17.4 to 44.3% [P<0.001], and from 8.0 to 22.7% [P<0.001], respectively). The mean incidence of in-hospital death and rehospitalization for recurrence was 1.4% and 5.7%, respectively; neither changed over time. The mean length of hospitalization increased from 8 to 10 days and the cost of hospitalization increased from JPY 417,000 to JPY 525,000. Multivariable analysis showed that age and steroid use were significant predictors of in-hospital death, whereas cardiac tamponade was not (adjusted odds ratio 1.32; 95% confidence interval 0.56–3.14).

Conclusions: Among hospitalized patients with idiopathic pericarditis, prescription rates of medications recommended by European Society of Cardiology guidelines have increased, although the concurrent use of NSAIDs and colchicine remains uncommon; there have been no changes in the incidence of in-hospital death. Prospective studies, including outpatients, are needed to clarify the prognosis and recurrence rate of idiopathic pericarditis.

Background: Genetic testing for long QT syndrome (LQTS) is useful for diagnosis, risk stratification, and therapeutic strategies. This study investigated the clinical impact of genetic testing for LQTS patients.

Methods and Results: Total 3,851 patients (proband: 2,316 [60%]; female: 2,283 [59%]; median age: 14 years [interquartile range 9–36 years]) diagnosed with LQTS (LQTS score ≥3.5, QTc ≥500 ms, pathogenic variants in LQTS-associated genes, or unexplored syncope with QTc 480–499 ms) were enrolled in this study. Of these patients, 1,146 (29.8%) experienced syncope and 322 (8.5%) experienced ventricular fibrillation (VF) or cardiopulmonary arrest (CPA) at ≤70 years of age. Genetic testing using a next-generation sequencing panel and/or Sanger sequencing was performed for 3,770 (98%) patients, genotype was then identified in the following LQTS-associated genes: KCNQ1 (45%), KCNH2 (34%), SCN5A (8%), KCNE1 (0.1%), KCNE2 (0.03%), KCNJ2 (2.7%), CACNA1C (1.2%), and CALM1,2 (0.3%). Forty-seven (1.2%) patients had double or compound heterozygous variants in LQTS-associated genes, whereas the genotype remained unknown in 220 (5.8%) patients. When comparing phenotype with genotype, QTc was significantly longer in CALM1,2 patients than in others except for CACNA1C, whereas QTc was almost normal in KCNJ2 patients. The incidence of the first cardiac event (syncope, VF/CPA) differed among the genotypes, and prognosis was significantly worse for CALM1,2 patients.

Conclusions: Comprehensive genetic testing, including non-major LQTS genes, is important for diagnosis and risk stratification of LQTS.

Background: With aging of the population, atherosclerotic diseases have increased in Japan, with acute coronary syndrome (ACS) a significant cause of morbidity and mortality. In Kagoshima Prefecture, ACS mortality rates exceed the national average, reflecting challenges in lipid management and access to care.

Methods and Results: The Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry, initiated in April 2022, enrolled 2,328 ACS patients across Kagoshima. This study evaluated the impact of a standardized lipid management pathway, the “Kagoshima Style,” on low-density lipoprotein cholesterol (LDL-C) control and guideline adherence, as well as the regional profile of ACS in Kagoshima. The pathway was implemented at all percutaneous coronary intervention facilities to optimize lipid management and secondary prevention. LDL-C levels decreased significantly (P<0.0001) from admission to discharge and at 3 months (113.3±39.9, 74.6±28.0, and 69.2±25.9 mg/dL, respectively), with no difference according to place of residence. The proportion of patients with LDL-C <70 mg/dL increased from 12% at admission to 59% at 3 months. Maximum tolerated doses of high-intensity statin use increased from 7% at baseline to 9.3% after pathway implementation. Geographic disparities were evident, with patients from isolated islands experiencing delayed treatment access.

Conclusions: The Kagoshima Style pathway improved lipid management, reducing LDL-C and enhancing guideline adherence. This interim analysis provides insights into lipid management and regional disparities in patients with ACS across Kagoshima prefecture.

Background: Transcatheter atrial septal defect (ASD) closure is the first treatment option for secundum ASD, but parameters for optimal device selection have not been established. We compared outcomes between occluders with a wire frame and metal mesh devices.

Methods and Results: This study included secundum ASD patients implanted with a wire frame occluder (GORE^®CARDIOFORM ASD occluder [GCA]; W.L. Gore & Associates) or metal mesh devices (Amplatzer septal occluder device [Abbott] and Occlutech Figulla Flex II device [Occlutech]). The presence of residual shunt and B-type natriuretic peptide (BNP) levels after implantation were compared. Of the 970 patients with either GCA (n=48) or a metal mesh device (n=922; control), 42 patients from each group were analyzed after propensity score matching. The prevalence of residual shunt was significantly lower in the GCA group 1 day and 1 month after implantation (P<0.001 and P=0.017, respectively), whereas there was no significant difference between the 2 groups 6 months later (P=0.088). BNP levels at 1 month were significantly higher in the GCA group (ratio of change 1.36; 95% confidence interval [CI] 1.01–1.83), but did not differ significantly between the 2 groups at 6 months (ratio of change 1.04; 95% CI 0.65–1.65).

Conclusions: Patients implanted with a wire frame occluder had a lower prevalence of residual shunt and a greater increase in BNP levels in the early period after implantation.

Background: Anthracyclines are widely used in cancer treatment, yet their potential for anthracycline-induced cardiotoxicity (AIC) limits their clinical utility. Despite the significant anatomical relevance of pericardial adipose tissue (PeAT) to cardiovascular disease, its response to anthracycline exposure remains poorly understood.

Methods and Results: Male New Zealand White rabbits (n=17) received weekly doxorubicin injections and underwent magnetic resonance imaging (MRI) scans biweekly for 10 weeks. PeAT volumes (total, left paraventricular, right paraventricular) were measured together with ventricular function. Histopathological evaluations were also conducted. A mixed linear model identified the earliest timeframe for detectable changes in PeAT volume and left ventricular function. Total PeAT volume decreased from the 6th week (1.17±0.06, P<0.05) and continued to decrease until the 8th week (0.96±0.06, P<0.05) and left paraventricular adipose tissue volume decreased significantly, but no changes were observed in right paraventricular adipose tissue volume. The volume of PeAT exhibited a positive correlation with left ventricular ejection fraction (LVEF) (r=0.43, P<0.05), which declined below 50% by the 8th week, and a negative correlation with myocardial cell injury scores (r=−0.595, P<0.05).

Conclusions: Anthracycline administration led to an early reduction in PeAT volume, particularly in the left paraventricular region, detectable by MRI as early as the 6th week. Changes in PeAT volume preceded alterations in LVEF and were associated with declines in cardiac function and myocardial cell damage.

Background: The early repolarization pattern (ERP) is associated with cardiovascular death, but its connection with arrhythmias remains unknown. This study evaluated relationships between ERP and incident arrhythmias, including ventricular arrhythmias, bradyarrhythmias, and atrial fibrillation (AF)/flutter (Afl).

Methods and Results: We analyzed 14,679 middle-aged (45–64 years) participants from the Atherosclerosis Risk in Communities cohort, a prospective population-based study in the US. Participants were monitored for ERP status at baseline and at 3 subsequent follow-up visits. We examined associations between incident arrhythmias and baseline ERP, time-varying ERP, time-updated ERP, and changes in ERP over time using Cox models to estimate hazard ratios (HRs) adjusted for potential confounders. Over a 20-year follow-up, there were 1,252 ventricular arrhythmias, 890 bradyarrhythmias, and 2,202 cases of AF. Time-updated ERP was associated with increased HRs for ventricular arrhythmias (1.55; 95% confidence interval [CI] 1.35–1.77), bradyarrhythmias (1.76; 95% CI 1.48–2.08), and AF (1.25; 95% CI 1.10–1.43). Time-varying ERP also showed associations with these outcomes. Compared with individuals with consistently normal electrocardiogram results, those with new-onset or persistent ERP had increased risks of incident arrhythmias. In subjects with time-updated ERP, anterior leads and J wave amplitudes ≥0.2 mV were associated with a higher incidence of arrhythmias.

Conclusions: Several types of ERP, including time-varying, time-updated, new-onset, and consistent, are associated with the incidence of arrhythmias in the middle-aged biracial (Black and White) population.

Background: Vericiguat, an oral soluble guanylate cyclase stimulator, is a novel therapeutic agent for patients with heart failure with reduced ejection fraction; however, the detailed cardioprotective mechanism remains unclear. We aimed to explore the mechanism of the effect of vericiguat on the myocardium, particularly focusing on oxidative stress, using in vivo and in vitro experiments.

Methods and Results: Male 8-week-old mice were divided into a control group, angiotensin II (AngII) infusion group, and AngII infusion with low- or high-dose vericiguat treatment group. After 14 days of treatment, vericiguat did not affect the systolic or diastolic blood pressure increase caused by AngII infusion. AngII-induced cardiac hypertrophy and fibrosis in the left ventricle (LV) were significantly ameliorated by high-dose vericiguat treatment. AngII-induced O₂⁻overproduction and upregulation of messenger RNA levels of Nppa, Nppb, Myh7, Col1a1, Col3A1, and Tgfb1 in the LV were significantly attenuated by vericiguat in a dose-dependent manner. Incubation of neonatal rat cardiomyocytes using vericiguat and AngII revealed that preceding incubation with vericiguat directly reduced AngII-induced cardiomyocyte O₂⁻production and cardiac hypertrophy-associated gene expression. In addition, AngII-induced phosphorylation of ERK 1/2 or p38 MAPK was significantly attenuated by the incubation with vericiguat.

Conclusions: Our study demonstrated that vericiguat suppresses myocardial oxidative stress via the regulation of ERK 1/2 or p38 MAPK signaling, leading to antihypertrophic/fibrotic effects.

Background: Changes in left ventricular (LV) remodeling, especially in relation to the duration of therapy, are poorly understood in patients with hypertrophic non-obstructive cardiomyopathy (HNCM).

Methods and Results: This study included 254 consecutive patients with HNCM. Patients were divided into 3 groups according to the length of chronic cibenzoline therapy (CCT): Group I (n=104), CCT ≥10 years; Group II (n=85), 5 years≤CCT<10 years; and Group III (n=65), 1 year ≤CCT<5 years. SV1+RV5 and the maximum depth of precordial negative T waves were measured on electrocardiograms (ECG). In addition to routine echocardiographic indices, we measured the distance between the mitral valve and the apex (i.e., the “LV long distance” [LVLD]). After CCT, ECG indices and LV wall thicknesses were decreased in all 3 groups. LV dimensions and LV fractional shortening were preserved, and did not differ significantly among the groups. Left atrial dimension and the E/A ratio also did not differ among the groups, whereas the E/early diastolic annular velocity (Ea) ratio was decreased in Groups I and II. After CCT, LVLD was increased in all groups (all P<0.0001). These improvements were greater in Group I than in Groups II and III.

Conclusions: CCT preserved LV systolic function and reduced LV hypertrophy in patients with HNCM. The E/Ea ratio was improved in Groups I and II. Thus, CCT aids in treating patients with HNCM.

Background: Both underweight and overweight are recognized as important factors influencing outcomes in patients undergoing cardiovascular surgery. This study investigated the effects of body mass index (BMI) on hospital-associated disability (HAD) and hospitalization costs in patients undergoing elective cardiovascular surgery (coronary artery bypass grafting, valve surgery, aortic surgery) by analyzing data from the Japanese Registry of All Cardiac and Vascular Diseases – Diagnosis Procedure Combination (JROAD-DPC) database.

Methods and Results: All patients in the JROAD-DPC database were categorized into 5 groups according to the World Health Organization BMI criteria for Asians. HAD was defined as a decrease of ≥5 points in the Barthel Index from admission to discharge. The primary outcome was the prevalence of HAD, and the secondary outcome was hospitalization costs. Among the 228,891 patients included in the study, the median BMI was 23.2 kg/m². The prevalence of HAD was 8.7%, with a U-shaped relationship between BMI and HAD, indicating that both extremely low and high BMIs were associated with a higher incidence of HAD. Hospitalization costs also showed a U-shape relationship with BMI, with higher costs for patients with HAD.

Conclusions: Low BMI in any age group was associated with HAD, and older people with a BMI considered too high also had HAD. BMI could be an important risk stratification tool for functional outcomes and economic burden in patients undergoing elective cardiovascular surgery.

Background: We previously reported that a high level of small dense low-density lipoprotein cholesterol (sdLDL-C) calculated by the Sampson equation was independently associated with the development of ischemic heart disease (IHD), but it remains unclear whether the effect depends on the level of low-density lipoprotein cholesterol (LDL-C).

Methods and Results: We investigated the associations of new onset of IHD with categorized groups of high (H-) and low (L-) levels of estimated sdLDL-C and LDL-C using 25^thpercentile levels of sdLDL-C level (25.2 mg/dL) and LDL-C (100 mg/dL) as cutoff values in 17,963 Japanese individuals (men/women: 11,508/6,455, mean age: 48 years) who underwent annual health checkups. During a 10-year follow-up period, 570 subjects (men/women: 449/121) had new development of IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, smoking habit, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) [95% confidence interval (CI)] for new onset of IHD was significantly higher in subjects with H-sdLDL-C/H-LDL-C (1.49 [1.06–2.08]) and subjects with H-sdLDL-C/L-LDL-C (1.49 [1.00–2.22]) than in subjects with L-sdLDL-C/L-LDL-C as the reference.

Conclusions: A high level of sdLDL-C estimated by the Sampson equation was a predominant predictor for the development of IHD, regardless of the level of LDL-C, in a general Japanese population.

Background: The EMPA-REG OUTCOME trial confirmed empagliflozin reduced mortality and heart failure hospitalization risk. These findings raised the possibility that empagliflozin may modulate cardiac autonomic function in patients with type 2 diabetes (T2D).

Methods and Results: The EMPYREAN study was a prospective randomized open-label assessor-blinded multicenter investigation of patients with T2D without prior antidiabetic therapy with sodium-glucose cotransporter 2 or dipeptidyl peptidase 4 inhibitors. Electrocardiographic monitoring was performed at study onset and after 12 and 24 weeks of treatment. Heart rate variability was analyzed using the MemCalc method. The primary endpoint was the change in the low frequency (LF; 0.04–0.15 Hz)/high frequency (HF; 0.15–0.4 Hz) ratio from baseline to 24 weeks. In all, 113 patients were randomized. The median age in the empagliflozin and sitagliptin groups was 60 and 63 years, respectively. There were no significant differences in serial changes in the LF/HF ratio (0.52, 95% confidence interval [CI] −0.15 to 1.19, P=0.126) or HF (16.13, 95% CI −11.58 to 43.84, P=0.251) between the 2 groups. In time domain analysis, serial changes in root mean square successive difference (1.90, 95% CI −0.56 to 4.38, P=0.12) and percent of difference between adjacent normal RR intervals >50 ms (1.04, 95% CI −0.32 to 2.41, P=0.13) were not significantly different.

Conclusions: The effects of empagliflozin and sitagliptin on autonomic nerve activity did not differ significantly in patients with T2D.

Background: The aim of this was to develop an atrial fibrillation (AF) risk score using items usually included in Japanese governmental health check-ups.

Methods and Results: We analyzed data from 6,476 Japanese participants registered in the Suita Study. At baseline, the participants were aged ≥30 years and were free from AF. Cox regression analysis was used to identify AF risk factors, and a 0–100 score was developed to predict AF events within 10 years. Within a median follow-up of 14.6 years, 278 participants developed AF. The risk score incorporated age [<50 years (16 points for men, 0 for women), 50–59 years (26 points for men, 14 for women), 60–69 years (41 points for men, 37 for women), ≥70 years (54 points for men, 51 for women)], current smoking with a smoking index >500 (7 points), heavy alcohol consumption (8 points), body mass index ≥25 kg/m²(6 points), hypertension (7 points), urinary proteins (4 points), glutamic-pyruvic transaminase >50 IU/dL (4 points), and cardiovascular disease history (10 points). The 10-year AF event probabilities were 7.1%, 8.4%, 10.8%, and 15.9% for scores of 47–54, 55–58, 59–69, and ≥70, respectively.

Conclusions: The new risk score to predict AF uses items similar to those used in Japanese governmental health check-ups.

Background: Hemodialysis (HD) is associated with adverse cardiovascular events after percutaneous coronary intervention (PCI). Although the ultrathin strut biodegradable polymer sirolimus-eluting stent (ultrathin strut BP-SES) has had better results in patients undergoing PCI compared with other drug-eluting stents (DES), its usefulness in HD patients is unknown.

Methods and Results: This study involved 286 lesions in 162 HD patients who underwent PCI with a DES between January 2018 and June 2022. The incidence of clinically driven target lesion revascularization (TLR), target vessel failure (TVF: cardiac death, target vessel MI and clinically driven target vessel revascularization [TVR]) was assessed. During a median 636 days, clinically driven TLR occurred in 32 lesions. Clinically driven TLR at 2 years was significantly lower in the ultrathin strut BP-SES group than in the other DES group (2.9% vs. 17.3%, log-rank P=0.028). TVF occurred in 43 patients. The cumulative incidence of TVF was not different between two groups; however, clinically driven TVR was significantly lower in patients treated with the ultrathin strut BP-SES than with other DES (4.5% vs. 25.7%, log-rank P=0.027). In the quantitative coronary angiography analysis, late lumen loss at follow-up was significantly smaller in the ultrathin strut BP-SES group (0.13±0.40 vs. 0.67±1.02 mm, P<0.001).

Conclusions: In patients on HD undergoing PCI, the incidence of clinically driven TLR was significantly lower in ultrathin strut BP-SES compared to other DES.

Background: Patients with atrial fibrillation (AF) often present with symptoms similar to acute coronary syndrome (ACS), including chest pain and elevated levels of high-sensitivity cardiac troponin (hs-cTn). The 0/1-hour algorithm using hs-cTn is a rapid diagnostic tool endorsed by the European Society of Cardiology to rule out myocardial infarction (MI). However, because its effectiveness in patients with AF remains unclear, in this study we assessed the diagnostic accuracy of the 0/1-hour algorithm in patients with and without AF presenting with chest pain in the emergency department.

Methods and Results: We conducted a secondary analysis of the DROP-ACS cohort, including 1,333 patients from Japan and Taiwan, with AF in 10.3% of cases. We examined the algorithm’s negative predictive value (NPV), sensitivity, positive predictive value (PPV), and specificity for ruling MI in or out. Patients with AF were more frequently placed in the observe group (54% vs. 34.9%, P<0.05) and less often in the rule-out group (24.1% vs. 44.6%, P<0.05). The NPV and sensitivity for ruling out MI were 100%, while the PPV and specificity were lower in patients with AF (60% and 89.7%, respectively).

Conclusions: The 0/1-hour algorithm effectively ruled out MI in patients with AF, with high safety and accuracy. However, patients with AF are more likely to be stratified into the observe group, requiring further examination for final diagnosis.

Background: The effect of paced-QRS (p-QRS) duration on long-term outcomes is unclear, so we assessed the association between p-QRS duration and cardiac events.

Methods and Results: We enrolled 187 patients (103 males, mean age: 77±12 years) who underwent pacemaker implantation between 2018 and 2021. During the median follow-up period of 972 days (761–1,292 days), 18 patients experienced cardiac events (1 cardiac death, 17 heart failure hospitalizations). The p-QRS duration was longer in the cardiac event group than in the noncardiac event group (162±17 vs. 148±17 ms, P=0.005). Receiver operating characteristic curve analysis identified 149 ms as the optimal cutoff value for predicting cardiac events (area under the curve, 0.72). Kaplan-Meier analysis showed better outcomes for mid-range p-QRS duration (≤149 ms, n=89) compared with long p-QRS duration (>149 ms, n=98) (P=0.005). Multivariate Cox hazard analysis indicated a good outcome with mid-range p-QRS duration (hazard ratio: 0.28, 95% confidence interval: 0.06–0.88, P=0.029).

Conclusions: A p-QRS duration of ≤149 ms was associated with a reduction in cardiac events. Therefore, it may serve as a target index of success in right ventricular pacing.

Background: The prevalence of congenital long QT syndrome (LQTS) (1 : 2,000) is based on genetic testing and ECG data, but the prevalence of electrocardiographically determined prolonged corrected QT interval (pQTc) in infants is unclear.

Methods and Results: Subjects were 10,282 1-month-old infants who participated in 2 prospective ECG screening studies performed in 2010–2011 and 2014–2016. Infants with a QTc ≥0.45 using Bazett’s formula [QTc(B)] at 1-month medical checks were re-examined. pQTc was defined as QTc ≥0.46 on 2 different ECGs in early infancy. Infants with QTc ≥0.50 or progressive prolongation of QTc to 0.50 were defined as at high risk. The prevalence of infants with a pQTc was 11/10,282 (1 : 935; 95% confidence interval, 1 : 588–1 : 2,283). Five infants were diagnosed as at high risk, and all infants had an abrupt increase in QTc(B) values in early infancy, mostly at 6–11 weeks after birth and when medication was started. No infants with a pQTc experienced LQTS-related symptoms. Statistical analysis showed that a cutoff QTc(B) ≥0.45 was optimal for screening infants with a pQTc.

Conclusions: The prevalence of ECG-determined pQTc is approximately 1 : 1,000. An abrupt increase in QTc(B) values occurs in infants at high risk, mostly at 6–11 weeks after birth. A cutoff QTc(B) value ≥0.45 may be appropriate for 1-month-old screening in this population.

Background: Pulmonary valvular regurgitation in postoperative patients with repaired tetralogy of Fallot (rTOF) significantly impairs exercise capacity and causes right heart failure. Quantitative evaluation of the pulmonary valvular regurgitation fraction (PRF) by cardiac magnetic resonance (CMR) is commonly used to determine the indication for surgical or catheter interventions, but less commonly using echocardiography.

Methods and Results: We retrospectively investigated the feasibility and validation of vector flow mapping (VFM) for the quantification of PRF (VFM-PRF) in 34 pediatric patients with rTOF, comparing it to CMR-derived PRF (CMR-PRF) and other qualitative or semiquantitative echocardiographic indices. Each predictive value for CMR-PRF ≥40% was assessed using receiver operating characteristic curves. VFM-PRF and CMR-PRF showed good agreement, with a correlation coefficient of 0.90 and the highest predictive value for CMR-PRF ≥40%, resulting in an area under the curve of 0.93. Other conventional echocardiographic parameters demonstrated poor predictive accuracy.

Conclusions: This is the first report to demonstrate the accurate quantification of PRF by echocardiography using VFM in pediatric patients with rTOF, showing good agreement with CMR results. Particularly in children, VFM may be clinically useful in determining the indication for reintervention for pulmonary valve replacement, offering a possible alternative to CMR, which often requires deep sedation and general anesthesia.

The World Health Organization recognizes digital health as a key driver for sustainable health systems. Digital health is broad concept that refers to the use of digital technologies to improve health and healthcare. Mobile health is part of digital health and refers to the use of mobile devices such as smartphones, tablets, and wearable gadgets to deliver health-related services. By proactively utilizing personal health records from mHealth, in conjunction with electronic health records, advanced medical practices can be achieved. This integration facilitates app-based patient education and encouragement, lifestyle modification, and efficient sharing of medical information between hospitals. Beyond emergency care, information sharing enables patients to visit multiple healthcare facilities without redundant tests or unnecessary referrals, reducing the burden on both patients and healthcare providers.

Background: The Revised Cardiac Risk Index (RCRI) has been incorporated into preoperative assessment guidelines and is used for simple preoperative screening; however, validation studies within large populations are limited. Moreover, although sex differences in perioperative risk are recognized, their effect on the performance of the RCRI remains unclear. Therefore, in this study we evaluated whether sex differences exist in the risks within the strata classified by the RCRI.

Methods and Results: The Japan Medical Data Center database based on claim and health examination data in Japan between January 2005 and April 2021 was used. A total of 161,359 noncardiac surgeries performed during hospitalization were analyzed. The main outcome was the 30-day risk of major adverse cardiovascular events. Although there was no significant sex difference among those with an RCRI ≥1, males had a significant hazard rate (1.32 [95% confidence interval, 1.03–1.68]) of postoperative events in the low-risk group with an RCRI of 0. However, this significant difference was not detected in the population excluding those who underwent breast and gynecological surgeries.

Conclusions: The RCRI achieved reasonable risk stratification in validation using Japanese real-world data regardless of sex. Although further detailed analysis is necessary to determine the sex differences, the validity of using the RCRI for screening purposes is supported at this stage.

Background: Right ventricular (RV) dysfunction negatively affects mitral valve transcatheter edge-to-edge repair (M-TEER) outcomes in patients with ventricular secondary mitral regurgitation (vSMR). However, RV dysfunction occurs in the late phase of heart failure, when it may not respond to interventions. The pulsatile component of RV afterload, pulmonary artery (PA) compliance, is a sensitive parameter that decreases before RV dysfunction occurs. We explored the utility of PA compliance in predicting cardiac events after M-TEER.

Methods and Results: We analyzed 107 patients with vSMR who underwent M-TEER and in whom right heart catheter parameters were measured in a conscious state. Twenty-four patients had a cardiac event. There were no differences in patient characteristics or echocardiographic parameters between groups with and without cardiac events. PA compliance was significantly reduced in the event group, but other RV function parameters did not differ between the 2 groups. Receiver operating characteristic curve analysis revealed an optimal prognostic cut-off value for PA compliance of 2.7 mL/mmHg. In multivariate Cox regression, reduced PA compliance (<2.7 mL/mmHg) was strongly associated with cardiac events. Kaplan-Meier analysis revealed PA compliance had significant prognostic power for the composite outcome of cardiac events (log-rank P<0.01).

Conclusions: Reduced PA compliance (hemodynamically derived in the conscious state) was a strong prognostic indicator in patients with vSMR who underwent M-TEER.

Background: The HELT-E₂S₂score, a novel risk stratification system, was developed to determine the incidence of ischemic stroke in Japanese patients with non-valvular atrial fibrillation (NVAF). It has been suggested that the HELT-E₂S₂score is more useful than the CHADS₂and CHA₂DS₂-VASc scores for Japanese patients with NVAF. This study determined the incidence of ischemic stroke in patients with NVAF and cardiac implantable electronic devices (CIEDs) and assessed the validity of the HELT-E₂S₂score in this population.

Methods and Results: We retrospectively analyzed the database of the CIED clinic of Chiba University Hospital and investigated the incidence of ischemic stroke according to the HELT-E₂S₂score. Of the 730 consecutive patients who were followed-up at the CIED clinic, those without NVAF were excluded, leaving 362 patients in this study (mean [±SD] follow-up period, 64±48 months; mean age, 73±16 years; 65% male). The mean CHADS₂and CHA₂DS₂-VASc scores were 1.8±1.2 and 2.8±1.6 points, respectively. During follow-up, 31 (8.6%) patients experienced ischemic stroke. The c-statistic for the HELT-E₂S₂score was 0.719 (95% confidence interval [CI] 0.657–0.795), which was higher than the c-statistics for the CHADS₂(0.704; 95% CI 0.647–0.768; P=0.025) and CHA₂DS₂-VASc (0.700; 95% CI:0.621–0.747; P=0.0097) scores.

Conclusions: Risk stratification for ischemic stroke using the HELT-E₂S₂score is valid in Japanese patients with NVAF and CIEDs.

Recent advances in traditional “-omics” technologies have provided deeper insights into cardiovascular diseases through comprehensive molecular profiling. Accordingly, digitalomics has emerged as a novel transdisciplinary concept that integrates multimodal information with digitized physiological data, medical imaging, environmental data, electronic health records, environmental records, and biometric data from wearables. This digitalomics-driven augmented multiomics approach can provide more precise personalized health risk assessments and optimization when combined with conventional multiomics approaches. Artificial intelligence and machine learning (AI/ML) technologies, alongside statistical methods, serve as key comprehensive analytical tools in realizing this comprehensive framework. This review focuses on two promising AI/ML applications in cardiovascular medicine: digital phonocardiography (PCG) and AI text generators. Digital PCG uses AI/ML models to objectively analyze heart sounds and predict clinical parameters, potentially surpassing traditional auscultation capabilities. In addition, large language models, such as generative pretrained transformer, have demonstrated remarkable performance in assessing medical knowledge, achieving accuracy rates exceeding 80% in medical licensing examinations, although there are issues regarding knowledge accuracy and safety. Current challenges to the implementation of these technologies include maintaining up-to-date medical knowledge and ensuring consistent accuracy of outputs, but ongoing developments in fine-tuning and retrieval-augmented generation show promise in addressing these challenges. Integration of AI/ML technologies in clinical practice, guided by appropriate validation and implementation strategies, may notably advance precision cardiovascular medicine through the digitalomics framework.

Background: Comprehensive management of acute coronary syndrome (ACS) requires seamless treatment across institutions, including intensive care centers and local clinics. However, maintaining guideline-directed medical therapy remains challenging. One promising option to improve the situation may be the implementation of regional collaborative clinical pathways. This study evaluated the prevalence and functionality of such pathways for ACS in Japan.

Methods and Results: A nationwide survey was conducted through questionnaires and web searches, targeting all 47 prefectural managers of Japanese Circulation Association (JCA) branches. The study focused on pathways managed at the prefectural or regional levels, excluding inactive or institutional pathways. In all, 18 pathways were identified: 11 (23%) prefecture wide and 4 (9%) region wide. Most pathways included risk factor targets such as low-density lipoprotein cholesterol (LDL-C), HbA1c, and blood pressure, but only 8 pathways set an LDL-C target of <70 mg/dL. Pathways updated between 2022 and 2024 and incorporating LDL-C management protocols were considered functional. In all, 45 JCA branches viewed future ACS pathways established by the government or academic societies as potentially useful resources.

Conclusions: Regional collaborative clinical pathways for ACS patients in Japan show variable implementation across prefectures, with approximately one-third of prefectures having established pathways. Future efforts should prioritize the establishment of comprehensive, sustainable, and standardized pathways to optimize ACS management and improve patient outcomes nationwide.

Background: Selecting an appropriate cannula size is crucial for achieving an adequate extracorporeal membrane oxygenation (ECMO) flow rate. However, the association between ECMO cannula size and the prognosis of patients with out-of-hospital cardiac arrest (OHCA) has not been fully elucidated. We examined the associations between ECMO cannula size and neurological outcomes and survival at discharge in patients with OHCA who received ECMO.

Methods and Results: This is a secondary analysis of the Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation in Japan (SAVE-J II study). The primary and secondary outcomes were favorable neurological outcomes and survival at discharge, respectively. In all, 918 patients were included in the analysis. There were no statistically significant differences between cannula sizes and neurological outcomes. Multivariable analysis showed that increasing body weight (BW)-adjusted sizes of arterial cannulas (odds ratio [OR] 1.04 per 0.01-Fr/kg increase; 95% confidence interval [CI] 1.01–1.07; P=0.011) and venous cannulas (OR 1.04 per 0.01-Fr/kg increase; 95% CI 1.01–1.06; P=0.005) were significantly associated with the survival rate at discharge. Increasing BW-adjusted sizes of arterial cannulas were significantly associated with cannulation site bleeding.

Conclusions: There were no significant associations between favorable neurological outcomes and cannula size, whereas larger-sized arterial and venous cannulas were significantly associated with higher survival rates at discharge in patients with OHCA who received ECMO.

Time-space network hypertension is a data science approach that connects diverse information related to hypertension within a time-space framework. This field of academic research aims to predict disease onset and direct effective, individualized, optimized treatments by integrating and analyzing the variability of multiple internal biological and external environmental signals as they relate to blood pressure variability across different time phases. By linking time series changes in blood pressure and biological distribution with multi-environmental and physiological information, enabled by advances in digital technology, the time-space network hypertension approach contributes to “digital hypertension” research. This article from Jichi Medical University provides an update on research relating to the time-space network hypertension approach, which is designed to progress hypertension management towards achieving net zero cardiovascular events.

Background: Although sudden cardiac death (SCD) generally occurs more frequently in men than in women, there are limited data on sex differences in SCD in patients with chronic heart failure (HF) across a range of left ventricular ejection fraction (LVEF).

Methods and Results: We examined sex differences in SCD incidence, timing, and risk factors in 4,683 patients with chronic HF (3,186 men, 1,497 women) from a multicenter prospective observational cohort study (CHART-2). Over a median follow-up of 8.8 years after study enrollment, there were 215 SCDs (160 in men, 55 in women). The SCD incidence rates in men and women were 6.1 and 4.6 per 1,000 person-years, respectively (P=0.088). Among women, more than half the SCDs occurred in the first 5 years of follow-up. Beyond 5 years, the SCD incidence rate was significantly lower in women than in men (3.6 vs. 5.9 per 1,000 person-years, respectively; P=0.044). After adjusting for confounders, age, increased B-type natriuretic peptide, and LVEF <50% were common prognostic factors. After 5 years of follow-up, left ventricular (LV) enlargement was a risk factor for SCD in both sexes.

Conclusions: These results indicate that there are sex differences in SCD, especially beyond 5 years of follow-up, with a lower prevalence in women. LV enlargement is a common long-term prognostic factor in both sexes, suggesting the importance of preventing LV remodeling in HF management.

Background: Selexipag, an oral prostacyclin (PGI₂) receptor agonist, is approved for adult patients with pulmonary arterial hypertension (PAH). This study evaluated the efficacy and safety of selexipag for Japanese pediatric patients with PAH.

Methods and Results: The study enrolled 6 patients who received selexipag twice daily at an individualized dose based on body weight; maintenance doses were determined for each patient by 12 weeks after starting administration. Efficacy, including pulmonary hemodynamics, was evaluated after 16 weeks, and efficacy and safety were further evaluated 52 weeks after treatment was initiated in the last enrolled patient. The mean (±SD) change in the pulmonary vascular resistance index from baseline to Week 16 (the primary endpoint of the study) was −5.55±6.88 Wood units·m²; improvements were also seen in other pulmonary hemodynamic parameters. The 6-min walk distance increased and N-terminal pro-B-type natriuretic peptide decreased up to Week 64, but the between-subject variability was large. The World Health Organization functional class was improved in 1 of 6 patients at Week 16 and in 2 of 4 patients at Week 64. No patient worsened. The major side effects of selexipag were those characteristic of PGI₂, and the safety profile of selexipag was similar to that in adult patients.

Conclusions: The efficacy and safety of selexipag in Japanese pediatric patients with PAH were demonstrated.

Background: The primary prevention of atrial fibrillation (AF), which increases mortality through complications including stroke and heart failure, is important. Excessive salt intake and low potassium intake are risk factors for cardiovascular disease; however, their association with AF remains inconclusive. This study investigated the association between sodium- and potassium-related urinary markers and AF prevalence.

Methods and Results: Data from the Tohoku Medical Megabank Project Community-based Cohort Study were used in this cross-sectional study. The urinary sodium-to-potassium (Na/K) ratio and estimated 24-h sodium and potassium excretion were calculated using spot urine samples and categorized into quartiles (Q1–Q4). The prevalence of AF was the primary outcome. Of the 26,506 participants (mean age 64.8 years; 33.2% males) included in this study, 630 (2.4%) had AF. Using Q1 as the reference group, the odds ratios for AF prevalence in Q4 were 1.35 (95% confidence interval [CI] 1.07–1.73) and 1.59 (95% CI 1.20–2.12) for 24-h estimated urinary Na/K ratio and estimated 24-h sodium excretion, respectively. Estimated 24-h potassium excretion was not associated with AF prevalence.

Conclusions: AF prevalence was positively associated with the urinary Na/K ratio and estimated 24-h urinary sodium excretion, but not with estimated 24-h urinary potassium excretion. Although further prospective studies are warranted, the findings of this study suggest that salt intake may be a modifiable risk factor for AF.

Catheter ablation is a widely used treatment modality for various cardiac tachyarrhythmias, including atrial and ventricular arrhythmias. Although it is generally considered safe, the procedure carries potential complications, with coronary artery injury being one of the most significant. The aim of this systematic review was to assess the incidence, mechanisms, contributing factors, diagnostic strategies, and preventive measures related to coronary artery injury in patients undergoing catheter ablation, including radiofrequency catheter ablation, cryoablation, and pulsed-field ablation.