Takao Kato

Aims: Type 2 diabetes (T2D) and chronic kidney disease (CKD) markedly increase the risk of heart failure (HF) and death. While finerenone improves outcomes in clinical trials, real-world evidence and direct comparisons with steroidal mineralocorticoid receptor antagonists (MRAs) are limited. We evaluated finerenone versus steroidal MRAs (spironolactone and eplerenone) in patients without prior HF. Methods: Using the TriNetX platform, we conducted a retrospective multi-center observational study. We identified patients aged ≥18 years with T2D and CKD without prior HF and ischemic heart disease, who initiated MRAs after receiving a sodium-glucose co-transporter 2 (SGLT2) inhibitor as first-line therapy between 2021 and 2024 (N=3,680). Of these, 724 initiated finerenone and 1,542 initiated a steroidal MRA. After propensity score matching, each group included 551 patients. The primary outcome was all-cause death during the 18-month follow-up period; the secondary outcome was new-onset HF and renal outcome (a composite of end-stage renal disease and dialysis). Results: Over 18-month, finerenone initiation was associated with lower incidence rates of all-cause death (2.1 vs 4.5 events/100 person-years; incidence rate difference, −2.41; 95% CI, −4.38 to −0.44) and new-onset HF (6.5 vs 12.9; −6.38; 95% CI, −9.75 to −3.02), whereas no significant difference was observed for the renal outcome (8.3 vs 9.1; −0.81; 95% CI, −3.99 to 2.37). Conclusions: Finerenone was associated with a lower 18-month risk of all-cause death compared with steroidal MRAs in patients aged ≥18 years with T2D and CKD without prior HF, who received an SGLT2 inhibitor as first-line therapy; however, residual confounding cannot be excluded, and these findings should be considered hypothesis-generating.

BACKGROUND: Cardiac sarcoidosis (CS) may lead to serious outcomes, but large-scale data are lacking because of its rarity, diagnostic uncertainty, and heterogeneous clinical presentations. Actual management and outcomes, including recurrence, are not well understood. This study aimed to clarify the actual management and outcomes of CS from a nationwide large-scale registry. METHODS: This multicenter retrospective registry enrolled 2366 consecutive patients with CS. Of these, 1852 patients newly diagnosed between 2012 and 2021 were analyzed. Patients were stratified into 4 groups: definite CS, probable CS, presumed systemic sarcoidosis, and presumed isolated CS based on diagnostic criteria. The primary end point was a composite of all-cause death, heart failure hospitalization, or fatal ventricular arrhythmic event. The secondary end point was recurrence of CS. RESULTS: Cardiac imaging performance rates were high (cardiac magnetic resonance: 64%, ¹⁸ F-fluorodeoxyglucose positron emission tomography: 82%), and 974 (53%) patients were diagnosed clinically without histological evidence. During a median 5.1-year follow-up, the primary outcome occurred in 519 (28%, 6.4/100 patient-years) patients, and the 4 groups exhibited different clinical presentations and prognoses; definite CS and presumed isolated CS groups showed a high incidence of the primary end point, fatal ventricular arrhythmic event, hospitalization for heart failure, and cardiovascular death. Most patients (89%) received immunosuppressive therapy, but 291 (18%, 4.1/100 patient-years) patients developed recurrence during steroid tapering, with a 5-year recurrence rate of 17.0%. Recurrence was associated with subsequent primary end point (hazard ratio, 1.38 [95% CI, 1.00–1.89]; P =0.048). CONCLUSIONS: This large-scale multicenter registry showed that clinical presentation and prognosis differ depending on the presence or absence of extracardiac lesions and histological evidence; therefore, it is necessary to recognize the characteristics of each phenotype in managing CS.

Background: Female sex has been associated with poor prognosis in hypertrophic cardiomyopathy (HCM), but the factors contributing to this disparity remain insufficiently defined. We aimed to clarify sex differences in clinical characteristics and factors associated with cardiovascular death in Japan. Methods: This multicenter, retrospective observational study of HCM was conducted between January 1, 2006, and December 31, 2018 (REVEAL‐HCM study [Multicenter Registry to Evaluate Risk Factors for Disease Progression, Sudden Cardiac Death and Adverse Clinical Outcomes in Japanese Patients With Hypertrophic Cardiomyopathy]; UMIN000046932). Patients aged ≥16 years with HCM were enrolled. Baseline characteristics and clinical outcomes including cardiovascular death were assessed. Univariable and multivariable Cox proportional hazards models were used to identify factors associated with cardiovascular death. Results: Of 3247 patients (median age, 67 years; 43% women), women were older and more symptomatic at presentation (52% New York Heart Association class II–IV versus 35% in men). Cardiovascular death was more common in women (hazard ratio [HR], 1.37 [95% CI, 1.02–1.82]; P =0.03). In multivariable analysis, older age (per 1‐year increase; HR, 1.04 [95% CI, 1.02–1.06]), advanced New York Heart Association class (HR, 1.99 [95% CI, 1.40–2.82]), history of atrial fibrillation (HR, 1.55 [95% CI, 1.10–2.18]), greater maximal wall thickness indexed to body surface area (per 1‐mm/m ² increase; HR, 1.12 [95% CI, 1.06–1.20]), and apical HCM (HR, 0.53 [95% CI, 0.32–0.88]) were independently associated with cardiovascular death, attenuating the HR for female sex. Conclusions: Sex differences in clinical characteristics and outcomes were observed. The excess cardiovascular death in women with HCM was largely explained by older age, more advanced symptoms, greater indexed wall thickness, and sex‐specific differences in both the prevalence and prognostic impact of apical HCM.

Background: The restrictive filling pattern of transmitral inflow has been shown to be associated with a poor prognosis in patients with heart failure (HF) with reduced ejection fraction or myocardial infarction. We aimed to investigate the significance of restrictive filling pattern in patients with HF with preserved ejection fraction (HFpEF). Methods: Among 4056 patients with acute decompensated HF in the Kyoto Congestive Heart Failure registry, we analysed 830 patients with HFpEF who had transmitral inflow data available in echocardiography. Patients whose early to late diastolic transmitral flow velocity (E/A ratio) ≥2 were classified as having a restrictive filling pattern of transmitral inflow. The main outcome measures were all-cause death and HF hospitalisation at 1 year. Results: Among 830 patients, a restrictive filling pattern was observed in 144 (17.3%) patients, who had higher prevalence of a history of atrial fibrillation and supranormal left ventricular ejection fraction (>65%), and higher brain natriuretic peptide level at discharge. The cumulative 1-year incidence of HF hospitalisation was significantly higher in patients with restrictive filling pattern than those without (31.0% vs 18.1%, p<0.001), while the cumulative 1-year incidence of all-cause death was not different between the two groups (14.2% vs 14.4%, p=0.93). After adjusting for confounding factors, the excess risk of restrictive filling pattern relative to non-restrictive filling pattern remained significant for HF hospitalisation (HR=1.58, 95% CI 1.10 to 2.27, p=0.01), but not for all-cause death (HR=0.92, 95% CI 0.60 to 1.42, p=0.70). Conclusions: A restrictive filling pattern of transmitral inflow was associated with an increased risk for HF hospitalisation, but not for all-cause death, in patients with acute decompensated HFpEF.

Background: The residential environment may influence access to care and prognosis in patients with heart failure (HF). Evidence on the impact of geographic factors in Japan is limited. We investigated the association of home‐to‐hospital distance and residential population density with 1‐year clinical outcomes in patients hospitalized for acute decompensated HF.Methods and Results: We used the Kyoto Congestive Heart Failure registry to analyze 3,616 patients who were discharged alive after their first hospitalization. Home‐to‐hospital distance was calculated using road travel distance and dichotomized by the median (8.0 km). Residential density was classified as urban (densely inhabited districts [DID]) or suburban (non-DID). The primary outcome was all‐cause death at 1 year, assessed using hospital‐stratified Cox proportional hazards models. The median home‐to‐hospital distance was 8.0 km (interquartile range 4.1–14.5 km); 1,797 (49.7%) patients were in the long‐distance group. The long‐distance group had a higher risk of all‐cause death than the short‐distance group (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.02, 1.39; P=0.02). As a continuous variable, each doubling of distance was associated with increased all‐cause death (HR 1.06; 95% CI 1.02, 1.10). Suburban residence was not significantly associated with the primary outcome compared with urban residence (adjusted HR 1.18; 95% CI 0.99, 1.44; P=0.06).Conclusions: In Japanese patients hospitalized for acute decompensated HF, longer home-to-hospital distance, but not residential population density, was associated with a higher risk of 1-year all-cause death.

BACKGROUND: Mitral regurgitation (MR) is a frequent comorbidity in patients with hypertrophic cardiomyopathy (HCM), which includes distinct subtypes with various characteristics. However, data on the long-term prognostic impact of MR and its progression or regression over time remain limited, particularly across individual HCM subtypes. METHODS: Patients with HCM were retrospectively included from a Japanese multicenter registry and compared by MR severity (moderate or greater versus mild or less) within each subtype: hypertrophic obstructive cardiomyopathy (HOCM), end-stage HCM (ES-HCM), and other HCM (including nonobstructive, midventricular obstruction, and apical HCM). RESULTS: Among 3602 patients (HOCM: n=837; ES-HCM: n=275; other HCM: n=2490), the prevalence of moderate or greater MR was highest in HOCM (36.3%), followed by ES-HCM (21.5%) and other HCM (8.5%). During a median follow-up of 5.3 (interquartile range, 2.1–9.3) years, the cumulative 5-year incidence of all-cause death or heart failure hospitalization was not significantly different between the moderate or greater MR and mild or less MR groups in HOCM (14.6% versus 12.4%; P =0.35) or ES-HCM (60.7% versus 54.7%; P =0.84). After adjustment for clinical covariates, no significant association was observed in either subtype (HOCM: hazard ratio, 1.13 [95% CI, 0.79–1.60], P =0.51; ES-HCM: hazard ratio, 0.84 [95% CI, 0.55–1.28], P =0.42). In contrast, in other HCM, moderate or greater MR was significantly associated with the higher 5-year cumulative incidence of all-cause death or heart failure hospitalization (34.2% versus 13.9%, P P =0.01; P _interaction =0.02). MR severity improved over time in HOCM, showed no clear change in ES-HCM, and worsened in other HCM ( P P _interaction <0.001). CONCLUSIONS: In patients with HCM, moderate or greater MR was not associated with worse outcomes in HOCM or ES-HCM, but had significant prognostic implications in other HCM subtypes, suggesting the need for HCM subtype-specific MR management.

There are limited reports on the prevalence and clinical significance of guideline-directed medical therapy (GDMT) initiation in patients with acute heart failure (HF). We analyzed 2086 patients with acute heart failure with reduced or mildly reduced ejection fraction (HFrEF or HFmrEF) in the KCHF registry. The patients were classified according to the number of GDMT classes at discharge. The primary outcome was a composite of all-cause death or HF hospitalization. There were 181 (8.7%), 508 (24.4%), 791 (37.9%), and 606 (29.1%) patients with GDMT = 0, 1, 2, and 3, respectively. Current smoker, ambulatory status, and HFrEF were associated with full GDMT, whereas age ≥ 80 years old, acute coronary syndrome, anemia, and eGFR < 30 mL/min/1.73m² were associated with absence of full GDMT. The cumulative 1-year incidence of the primary outcome was 56.3%, 40.7%, 31.9%, and 25.1% with GDMT = 0, 1, 2, and 3, respectively. The excess adjusted risk of patients with GDMT = 0 or 1, but not GDMT = 2 relative to those of GDMT = 3 remained significant for the primary outcome (HR 2.16 [1.66–2.82], 1.33 [1.07–1.66], and 1.03 [0.84–1.27]). Collectively, the greater number of GDMT classes at discharge was associated with a lower risk for all-cause death or HF hospitalization in patients with HFrEF or HFmrEF. (200 words)

Aims: Heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D) commonly coexist and are associated with poor outcomes. Although injectable semaglutide has demonstrated benefits in HFpEF, the effectiveness of oral semaglutide in this setting remains uncertain. This study compared all‐cause death and hospitalisation between oral semaglutide and sitagliptin in patients with HFpEF and T2D. Materials and Methods: Using a global healthcare data and analytics platform, the TriNetX research network, we conducted a retrospective multi‐centre observational study. We identified patients aged ≥18 years with HFpEF diagnosed before December 31, 2023 ( N = 1 731 548), of whom 812 259 had concomitant T2D. Among them, 3470 initiated oral semaglutide and 22 840 initiated sitagliptin between October 1, 2019, and December 31, 2023. After propensity score matching, each group included 3452 patients. The primary outcome was all‐cause death; the secondary outcome was hospitalisation. Results: Over 1 year, the risk for all‐cause death in patients who received oral semaglutide relative to those who received sitagliptin was significantly lower (4.3% [145/3452] vs. 7.0% [229/3452]; log‐rank p < 0.001; hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.50 to 0.75). Similarly, patients who received oral semaglutide experienced fewer hospitalisations than those who received sitagliptin (37.1% vs. 42.4%; log‐rank p < 0.001; HR, 0.83; 95% CI, 0.77 to 0.90). Conclusions: Oral semaglutide appeared to be associated with a lower 1‐year risk of all‐cause death compared with sitagliptin in patients with HFpEF and T2D.