Aims: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods and results: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best-estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in-hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R2 = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per −1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140–100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per −1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in-hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62). Conclusions: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF.

Aims: To investigate the clinical significance of the modification of the kidney protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors by baseline body mass index (BMI). Methods and results: We included individuals with SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors newly prescribed for type 2 diabetes using a nationwide epidemiological cohort and performed propensity score matching (1:2). The primary outcome was the annual eGFR decline, assessed using a linear mixed-effects model, compared between individuals with SGLT2 inhibitors and DPP4 inhibitors. We investigated the interaction effect of BMI at the time of prescription using a three-knot restricted cubic spline model. We analysed 2165 individuals with SGLT2 inhibitor prescriptions and 4330 individuals with DPP4 inhibitor prescriptions. Overall, the annual decline in eGFR was less pronounced in the group treated with SGLT2 inhibitors than in those treated with DPP4 inhibitors (−1.34 mL/min/1.73 m2 vs. −1.49 mL/min/1.73 m2). The advantage of SGLT2 inhibitors in mitigating eGFR decline was augmented in the individuals with higher BMI (P-value for interaction 0.0017). Furthermore, even upon adjusting the definition of outcomes to encompass a 30 or 40% reduction in eGFR, the potential advantages of SGLT2 inhibitors over DPP4 inhibitors persisted, with a trend of augmented effects with higher BMI. This interaction effect was evident in the individuals with preserved kidney function. Conclusion: Our nationwide epidemiological study substantiated the improved kidney outcomes in the SGLT2 inhibitor users compared with the DPP4 inhibitor users across a wide range of BMI, which was pronounced for individuals with higher BMI.

Background : Hypersensitivity reaction is a classic cause of in-stent restenosis (ISR) in coronary stents, typically reported in bare-metal stents and first-generation drug-eluting stents. Biodegradable polymer sirolimus-eluting stent (BP-SES) was developed with the concept of biocompatibility, and there has been no report of ISR of BP-SES with hypersensitivity reaction. Case summary : An 81-year-old woman presented with ST-elevation acute inferior myocardial infarction. Primary percutaneous coronary intervention was performed for the culprit lesion in the left circumflex artery with a permanent polymer everolimus-eluting stent (PP-EES), followed by BP-SES implantation in the left anterior descending artery. Eight months later, coronary angiography showed total occlusion of the PP-EES and diffuse ISR in the BP-SES, treated with a paclitaxel-eluting balloon. Fluorodeoxyglucose with positron emission tomography showed increased uptake around the BP-SES, and cardiac magnetic resonance imaging revealed a late gadolinium-enhanced area around both stents. Four months later, she developed re-ISR in the BP-SES, and optical coherence tomography demonstrated diffuse-layered neointimal hyperplasia with microvascularization and peri-strut low-intensity area. She was successfully treated with coronary artery bypass grafting. Discussion : Our case demonstrated repetitive short-term ISR of the BP-SES. Observation by both intravascular and non-invasive imaging modalities suggested the presence of hypersensitivity reaction localized in the stent. Hypersensitivity to the metal may be a possible mechanism because both stents are composed of L605 cobalt–chromium alloy. This is the first report of ISR of a BP-SES with hypersensitivity reaction. Non-invasive imaging can be useful to assess this critical condition.

Aims: Cardiovascular–kidney–metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association. Methods and results: We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80–1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1–3 differed between the sexes: HR by Stage 1, 1.12 (1.04–1.21) vs. 1.12 (1.07–1.16); by Stage 2, 1.78 (1.69–1.88) vs. 1.43 (1.39–1.48); by Stage 3, 1.99 (1.89–2.10) vs. 1.82 (1.76–1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively. Conclusion: In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex.

Aims: Cancer survivors are at increased cardiovascular risk due to shared risk factors and treatment-related toxicity. The recently proposed cardiovascular-kidney-metabolic (CKM) syndrome framework provides a novel approach for cardiometabolic risk stratification, but its prognostic value in cancer patients remains unclear. In this study, we aimed to evaluate the association between CKM stages and cardiovascular outcomes in cancer patients using a large-scale nationwide dataset. Methods and results: We conducted a retrospective cohort study of 76 111 cancer patients without prior CVD from the DeSC database (2014–2023). Participants were classified into CKM stages (0–3) at baseline, with Stage 4 defined as the composite outcome of myocardial infarction, heart failure, atrial fibrillation, stroke, or peripheral artery disease. Multivariable Cox proportional hazards models were used to assess the risk of progression to Stage 4. Over a median follow-up of 2.6 years, advancing CKM stages were associated with a graded increase in cardiovascular disease (CVD) risk. Compared to Stage 0–1 (reference), adjusted hazard ratios for Stage 4 were 1.23 (95% confidence interval: 1.13–1.33) for Stage 2 and 1.47 (1.36–1.60) for Stage 3. Sensitivity analyses confirmed consistent associations across different groups stratified by age, sex, chemotherapy history, and cancer types. Furthermore, sensitivity analyses using alternative risk prediction models or expanded CVD definitions yielded similar results. Conclusion: The CKM staging system effectively stratifies cardiovascular risk in cancer patients, with higher stages predicting significantly worse outcomes. These findings advocate for integrating CKM assessment into onco-cardiologic practice to guide early intervention and improve patient outcomes.