Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) show a relationship through the sharing of several risk factors, and the prevalence of each disease increases in an age-related manner. Therefore, clinicians are very likely to encounter patients with both diseases. Importantly, the risk of death in patients with CVD is even greater in those with coexisting COPD. Cardiopulmonary risk, defined as “the risk of serious respiratory and/or cardiovascular events in patients with COPD,” is a concept whereby COPD exacerbations (characterized by worsening of COPD symptoms over a short period of time) and/or CVD events may increase the risk of death due to these events in patients with COPD. Lowering cardiopulmonary risk requires appropriate treatment to prevent COPD exacerbations. Inhalation therapies can prevent COPD exacerbations and may reduce mortality rates. Research to investigate whether inhaled therapies can lower cardiopulmonary risk is ongoing. There is a need for early COPD diagnosis and timely, effective treatment that prevents COPD exacerbations while also considering cardiopulmonary risk. We propose an urgent call to action for cardiology and respirology societies to address cardiopulmonary risk and reduce COPD and CVD deaths.

Background: In addition to the J-HeartMate Risk Score (J-HMRS) and HeartMate 3 Risk Score (HM3RS), the J-MACS Risk Score (J-MACS-RS) was developed to predict death after left ventricular assist device (LVAD) implantation in Japanese patients with heart failure (HF). However, the correlation between these scores, the characteristics of high-risk patients as per these scores, and the mortality stratification of these scores in HF patients regardless of LVAD implantation are still not fully understood.

Methods and Results: Hospitalized patients with HF who underwent echocardiography and right heart catheterization were included (n=269). Patients at low or medium risk per the J-HMRS or HM3RS and at high risk per the J-MACS-RS (LM_J-HMH_J-MACS and LM_HM3H_J-MACS, respectively) were compared with those at low or medium risk per both scores (LM_J-HMLM_J-MACSand LM_HM3LM_J-MACS, respectively). The J-MACS-RS was well associated with the J-HMRS (r=0.66) and HM3RS (r=0.65). Patients with LM_J-HMH_J-MACS were older and showed a higher prevalence of ischemic etiology and history of cardiac surgery than those with LM_J-HMLM_J-MACS. LM_J-HMH_J-MACS and LM_HM3H_J-MACSshowed higher serum creatinine levels and central venous pressure-to-pulmonary artery wedge pressure ratios than LM_J-HMLM_J-MACSand LM_HM3LM_J-MACS, respectively. All scores stratified the 3-year mortality in patients with HF.

Conclusions: The J-MACS-RS correlated well with the J-HMRS and HM3RS. These scores may predict 3-year mortality, even in Japanese HF patients, regardless of LVAD implantation.

Background: Japan’s heart transplantation system is characterized by an extremely long waiting period, which contributes to significant mortality on the waiting list. The current allocation system may maintain favorable post-transplant outcomes at the expense of high-risk patients, particularly those with severe heart failure or complications following left ventricular assist device (LVAD) implantation. To explore an optimal allocation system for Japan, we investigated risk factors for waiting list mortality.

Methods and Results: We analyzed 300 patients registered on the heart transplant waiting list at Osaka University between 2014 and 2024. Cox hazard analysis identified age at registration (hazard ratio [HR] 1.023) and congenital heart disease (HR 4.531) as independent risk factors for mortality. In the LVAD cohort (n=244), right heart failure (HR 4.582), stroke associated with systemic infection (HR 5.175), and sudden stroke without preceding infection (HR 3.158) were significant risk factors. Although the HeartMate 3 significantly reduced sudden stroke (P<0.001), it did not improve right heart failure or infection-related stroke. Patients with these complications had significantly lower proportions of time at home with an LVAD (P<0.001).

Conclusions: Prioritized organ allocation for patients with congenital heart disease, right heart failure, or LVAD-related infections may improve waiting list survival. Reducing hospitalizations in high-risk LVAD patients could also be beneficial from a healthcare economics perspective.

Background: With an increase in the aging population, heart failure (HF) has become a major healthcare problem. Therefore, early detection of key signals characteristic of each of the stages of HF has the potential to improve treatment and palliative care. Metabolomics profiling may be useful in identifying biomarkers of HF and improving HF treatment.

Methods and Results: This study was a retrospective subanalysis of the CURE-HF registry, a prospective observational study of patients with acute decompensated HF. Patients were divided into 3 groups: those who died within 3 months of discharge due to cardiovascular disease (CVD), those who died within 3–6 months of discharge due to CVD, and those who survived >2 years as a control group. Serum samples from 28 patients (median age 85 years [interquartile range 74–90 years]; 11 (39.3%) women) were subjected to capillary electrophoresis time-of-flight mass spectrometry. Partial least-squares (PLS) discriminant analysis showed a negative correlation between carnitine and short-term mortality (R=−0.508, P=0.006). Urea (R=−0.597, P<0.001) and symmetric dimethylarginine (R=−0.634, P<0.001) were negatively correlated with survival, while tryptophan was positively correlated with survival (R=0.548, P=0.003).

Conclusions: Carnitine, symmetric dimethylarginine, urea, and tryptophan appear to be critical biomarkers for monitoring terminal stages in HF. Our results suggest that myocardial energy metabolism and renal dysfunction are associated with changes in the metabolome.

Background: The impact of home-based cardiac rehabilitation (HBCR) during the Coronavirus Disease 2019 (COVID-19) pandemic on changes in exercise frequency and capacity according to sex and age has not been studied.

Methods and Results: This cohort study included 118 patients participating in HBCR and 149 patients participating in center-based cardiac rehabilitation (CBCR) for whom data on exercise and peak oxygen uptake (V̇O_2peak) were available at program enrollment and completion. Changes in these parameters were compared HBCR and CBCR, and according to sex and age in the HBCR group. The change in HBCR group was equivalent to or superior to CBCR group. In the HBCR group, there were no differences between males and females in the change in exercise (1.7±2.7 vs. 1.6±2.5 days/week and 18±19 vs. 19±18 min/day), or V̇O_2peak(5.5±6.5 vs. 3.8±4.5 mL/kg/min). Although there was no difference in the change in exercise between the younger and older groups (1.4±2.7 vs. 1.9±2.7 days/week and 19±19 vs. 17±18 min/day), the increase in V̇O_2peakwas greater for younger than older patients (7.1±6.1 vs. 3.2±5.3 mL/kg/min). After adjustment for potential confounders, linear regression revealed that the change in V̇O_2peakwas larger among younger patients.

Conclusions: During the COVID-19 pandemic, exercise frequency and capacity increased similarly among men and women. Younger patients showed a greater improvement in exercise capacity than older patients.

Background: Initially regarded as a benign acute cardiomyopathy, recent insights have shown that takotsubo syndrome (TTS) carries a prognosis comparable to that of acute coronary syndrome, with a notable impact of inflammatory burden. Given the seasonal variation seen in air pollution, inflammation, and coronary events, we investigated whether chronobiology and inflammation contribute to adverse outcomes.

Methods and Results: Between 2008 and 2020, all consecutive TTS patients were retrospectively included in a multicenter registry. We analyzed the impact of seasonal variation and inflammation on in-hospital events, including acute cardiac failure, cardiogenic shock, and death, as well as 30-day mortality. In-hospital events were identified in 238 (42.6%) patients. Higher rates of in-hospital events and 30-day mortality were observed during winter and spring than in summer and autumn. Multivariate analysis identified the presence of dyspnea on admission (odds ratio [OR] 4.02; 95% confidence interval [CI] 2.61–6.17; P<0.001), a neurological trigger (OR 2.58; 95% CI 1.21–5.50; P=0.014), hyperleukocytosis (OR 1.04; 95% CI 1.02–1.17; P=0.002), and left ventricular ejection fraction at admission (OR 0.98; 95% CI 0.96–1.00; P=0.011) as independent predictors of adverse outcomes.

Conclusions: In TTS, higher rates of in-hospital events and 30-day mortality were observed during winter and spring. Inflammatory burden and neurological disorders emerged as independent predictors of poor prognosis.

Background: The association between blood urea nitrogen (BUN) levels and incident heart failure (HF) in the general population is still unclear.

Methods and Results: We assessed the association of BUN level with incident HF in 14,167 ARIC participants without a history of HF at baseline (1987–1989) (mean age 54.1 years, 54.4% female, 25.2% Black). BUN levels (mg/dL) were divided into quartiles, with the highest quartile further divided into tertiles (Q1 ≤13, Q2 13–15, Q3 15–17, Q4a 17–19, Q4b 19–21, Q4c >21). HF events were identified through to December 31, 2019, using diagnostic codes on discharge records or death certificates. Hazard ratios (HRs) were estimated using multivariable Cox models. During a median follow-up of 26.2 years, 3,482 participants developed HF (incidence rate 10.7 per 1,000 person-years). In a multivariable Cox model adjusted for sociodemographic variables, the highest BUN quartile (Q4) had a HR of 1.19 (95% confidence interval [CI] 1.09, 1.31) compared with Q1. HRs for Q4a, Q4b, and Q4c were 1.14 (95% CI 1.02, 1.28), 1.11 (0.96, 1.28), and 1.42 (1.22, 1.63), respectively. After further adjustment for clinical factors, the association remained significant for Q4c (HR 1.23 [1.06, 1.43]). Associations were consistent across demographic and clinical subgroups.

Conclusions: In this community-based cohort, higher BUN levels were significantly associated with incident HF. BUN, routinely measured in clinical care, may help identify individuals at risk of HF.

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: 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: Polypharmacy, driven by guideline-directed medical therapy (GDMT) and medications for comorbidities, including potentially inappropriate medications (PIMs), is common in older adults with heart failure (HF). Although medication profiles affect survival, the effects of frailty and disability status remain underexplored.

Methods and Results: This retrospective study assessed polypharmacy (≥5 medications), the use of GDMT, and PIMs based on the Beers Criteria. Frailty and disability status were determined using Japan’s Long-term Care Insurance (LTCI) certification. Patients were stratified according to LTCI, and the prognostic impact of medication profiles was analyzed. The total medication count was correlated with both GDMT and PIM use. Among 1,264 patients, those with LTCI were older, had more severe comorbidities, higher polypharmacy and PIM use, and lower use of GDMT medications. In multivariate Cox regression analysis, regardless of LTCI, GDMT medication use was associated with a favorable prognosis (LTCI: odds ratio [OR] 0.47, 95% confidence interval [CI] 0.258–0.866, P=0.015; no LTCI: OR 0.57, 95% CI 0.400–0.799, P=0.001). PIM use was associated with a poor prognosis only in the no-LTCI group (OR 1.51; 95% CI 1.040–2.203; P=0.030).

Conclusions: Polypharmacy may have both beneficial and harmful effects, with prognostic implications potentially influenced by frailty and disability status. Although GDMT medications were consistently associated with favorable outcomes, the impact of PIMs appeared to differ depending on LTCI.

Background: We evaluated the surgical outcomes of modified right ventricle (RV) overhaul (mRVOh), implemented as part of comprehensive management for pulmonary atresia with intact ventricular septum (PA-IVS).

Methods and Results: Twenty-five mRVOh procedures were performed in 23 patients with PA-IVS without RV-dependent coronary circulation. The procedure involved RV sinus myectomy, infundibular muscle resection, and tricuspid valve (TV) and pulmonary valve (PV) repair. In addition, in neonates and young infants, Blalock-Taussig shunt or patent ductus arteriosus banding was performed simultaneously. TV and PV annulus sizes were measured using echocardiography; RV function and volume were assessed using magnetic resonance imaging (MRI) in 18 patients. The median age and body weight at the time of mRVOh were 7.0 months and 7.1 kg, respectively. Biventricular repair was performed in 19 patients, and 6 required reoperations, including 2 with redo mRVOh. After mRVOh, the mean TV and PV annulus z-scores showed a significant increase towards the normal range, from −1.91 to −1.40 (P=0.031), and from −2.23 to −1.11 (P=0.014), respectively. Serial postoperative MRI showed significant increases in RV end-diastolic and end-systolic volume indices, stroke volume index, and cardiac index (P<0.001 for all), with preserved RV function.

Conclusions: Both RV size and TV annulus showed proportionate growth after mRVOh. mRVOh may be a viable option for facilitating sustainable RV and TV growth in selected patients with PA-IVS.

Background: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) are key biomarkers used for heart failure (HF) management. Although traditional auscultation lacks objective evaluation, the SSS01-series phonocardiogram enables rapid recording of heart sounds and ECG. We developed a deep-learning model to estimate plasma BNP levels from these non-invasive dynamic physiological signals, with the aim of validating the model’s performance with an external validation dataset and assessing its feasibility for clinical application.

Methods and Results: This multicenter study evaluated the estimated BNP (eBNP) model for predicting plasma BNP levels ≥100 pg/mL using 8 s of heart sound and ECG data. Validation was performed on an external validation dataset of 140 patients, achieving an area under the receiver operating characteristic curve (AUROC) of 0.895, with sensitivity and specificity of 84.3% and 82.9%, respectively. Subgroup analysis of patients with body mass index of 18.5–25 (n=127) showed more substantial predictive capability, with an AUROC of 0.959, sensitivity of 92.5%, and specificity of 84.8%.

Conclusions: The eBNP model demonstrated strong potential for non-invasive and rapid HF screening. Its simplicity and objectivity make it ideally suited for point-of-care testing, offering a promising approach for early HF diagnosis and detection monitoring of HF exacerbations. These findings, validated on datasets independent of training, highlight the model’s robustness across diverse clinical populations.

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: 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 Japanese Circulation Society (JCS) launched a Certified Heart Failure Educator (CHFE) program in 2021. However, reports regarding this program are lacking. Here we describe the initial experience following implementation of CHFE program and assess its association with hospital quality measures.

Methods and Results: We performed a retrospective study using data from CHFE certification data for 2021–2024 and data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination in 2021. The cumulative number of CHFEs increased from 1,771 in 2021 to 6,603 in 2024. Various medical professionals joined the system, and almost all CHFEs were affiliated with hospitals. Of all 813 hospitals included, 416 (51.2%) had at least 1 CHFE in 2021, with a median number of 2 CHFEs per hospital. The group of hospitals with CHFEs had a higher proportion of JCS training hospitals and a higher number of annual heart failure (HF) hospitalizations and cardiology beds. Of 71,678 patients hospitalized for acute HF and discharged to home, 41,558 (58.0%) were hospitalized in facilities with CHFEs. After adjustment for baseline characteristics, hospital admission to a facility with a CHFE was associated with higher achievement of process measures and lower in-hospital mortality.

Conclusions: The CHFE system was successfully implemented and contributed to HF management primarily in high-quality hospitals. Our findings may provide insights for future strategies regarding this system.

Background: Although hemodialysis (HD) is a significant risk factor for infective endocarditis (IE), risks associated with peritoneal dialysis (PD) and specific types of HD access remain underexplored.

Methods and Results: This retrospective study analyzed 215,965 patients with end-stage renal disease (ESRD) and 1,076,532 age- and sex-matched individuals without ESRD from the general population (control group). ESRD patients were grouped into those undergoing HD or PD, with the HD group further subdivided by access type: arteriovenous fistula (AVF), catheter, or graft. The incidence of IE was lower in the PD than HD group; among patients on HD, the incidence of IE was lowest for those with access via an AVF.

Conclusions: PD and AVF access lower the risk of IE among patients with ESRD. Thus, the clinical use of both should be prioritized.

Background: The effects of calcium-channel blockers (CCBs) in heart failure with preserved ejection fraction (HFpEF), particularly by sex, remain unclear.

Methods and Results: We retrospectively analyzed 412 elderly hypertensive patients with HFpEF (308 women, 104 men). Female CCB users had significantly lower B-type natriuretic peptide (BNP) levels. Multivariable regression showed that CCB use was independently associated with lower BNP, higher EF, and lower tricuspid regurgitation pressure gradient in women, but not in men.

Conclusions: CCB use, particularly amlodipine, may be associated with sex-specific hemodynamic benefits in hypertensive elderly women with HFpEF, independent of blood pressure control.

Background: In aging societies, shared tools are needed to assess and communicate activities of daily living (ADL). The Barthel Index (BI) is widely used in administrative data but remains underutilized in discharge planning.

Methods and Results: We analyzed 605 older cardiovascular patients discharged from a regional hospital, classifying functional levels by BI ambulation, total score, and 6-minute walk distance. Higher levels corresponded with greater ADL independence across BI items.

Conclusions: The BI reflects structured functional tiers and serves as a common language in care coordination.