Yu Horiuchi

Background: The prognostic value of the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score in patients undergoing mitral valve transcatheter edge‐to‐edge repair (M‐TEER) remains unclear. This study evaluated the MAGGIC score to predict outcomes after M‐TEER in patients with functional (FMR) or degenerative mitral regurgitation (DMR) and compared its performance with conventional surgical and M‐TEER–specific risk models. Methods: We analyzed 3609 patients (FMR, 71%; DMR, 29%) who underwent M‐TEER in the OCEAN (Optimized Catheter Valvular Intervention)‐Mitral registry. Patients were stratified into MAGGIC score tertiles. The primary outcome was all‐cause death at 1 and 3 years. Secondary outcomes included cardiovascular death. Predictive performance was compared with Society of Thoracic Surgeons score, European System for Cardiac Operative Risk Evaluation II, MitraScore, and COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) score. Results: The median age was 81 years, 55.3% were men, and median MAGGIC score was 30. In the FMR cohort, patients in tertile 3 had higher risks of all‐cause death (1 year: adjusted hazard ratio [HR _adj ], 4.15 [95% CI, 2.34–7.36]; 3 years: HR _adj , 1.83 [95% CI, 1.22–2.77]) and cardiovascular death (1 year: HR _adj , 2.31 [95% CI, 1.56–3.43]; 3 years: HR _adj , 1.61 [95% CI, 1.13–2.31]). In the DMR cohort, tertile 3 was associated with higher all‐cause death (1 year: HR _adj , 2.84 [95% CI, 1.18–6.86]; 3 years: HR _adj , 2.25 [95% CI, 1.07–4.73]) and cardiovascular death at 3 years (HR _adj , 3.49 [95% CI, 1.23–9.84]). The MAGGIC score demonstrated comparable or superior discrimination on the basis of the concordance index. Conclusions: The MAGGIC score independently predicted 1‐ and 3‐year all‐cause death after M‐TEER in both FMR and DMR cohorts and cardiovascular death in the FMR cohort and at 3 years in the DMR cohort. It demonstrated comparable or superior predictive performance to conventional surgical and M‐TEER–specific risk models.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2is) induce body weight and muscle loss due to the excretion of glucose in the urine, which may worsen frailty in patients with heart failure (HF). However, the impact of SGLT2is on frailty-related events in patients with HF has not been fully elucidated. Methods In this analysis of global electronic health records, patients with HF and type 2 diabetes mellitus (T2DM) who received SGLT2is were compared to those who received sitagliptin treatment from 2016 to 2021. A composite endpoint of death or new incidence of frailty-related events, including 1) mobility impairments, 2) falls and fractures, 3) pressure ulcers and weight loss, 4) incontinence, 5) dependency and caregiving, 6) dementia and delirium, and 7) anxiety and depression, was analyzed using propensity score (PS) matching. Results After PS matching, 8,148 of the 16,989 patients in the SGLT2i group were matched to 8,148 of the 18,278 patients in the sitagliptin group. The incidence of the composite endpoint and its components was lower in the SGLT2i group than in the sitagliptin group [composite endpoint, 68.1% vs. 72.6%, hazard ratio (HR) 0.85 (0.82-0.89), p <0.001; mortality, 20.4% vs. 28.2%, HR 0.69 (0.65-0.74), p <0.001; frailty-related events, 63.2% vs. 66.6%, HR 0.87 (0.84-0.91), p <0.001]. All components of frailty-related events were observed less frequently in the SGLT2i group. Conclusions SGLT2is correlated with a lower incidence of death and frailty-related events than sitagliptin in patients with HF and T2DM.

Aims: Treatment of obesity with glucagon‐like peptide‐1 (GLP‐1) receptor agonists improves cardiovascular outcomes. Tirzepatide, a dual glucose‐dependent insulinotropic polypeptide and GLP‐1 receptor agonist, achieves greater weight loss than GLP‐1 receptor agonists alone; however, direct real‐world comparisons of clinical outcomes are limited. Materials and Methods: We conducted a retrospective, active‐comparator, new‐user cohort study using the TriNetX global federated electronic health record database. Adults (≥ 18 years) without diabetes who initiated tirzepatide or semaglutide for the treatment of obesity between November 2023 and August 2024 were included. Patients with recent atherosclerotic events, prior heart failure (HF), or crossovers to the comparator were excluded. The primary outcome was major cardiovascular events including all‐cause death, acute coronary syndrome, stroke, or new‐onset HF at 12 months. Results: One‐to‐one propensity score matching yielded 35 336 pairs. Tirzepatide was associated with a lower incidence of the composite outcome compared with semaglutide (1.90% vs. 2.18%; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77–0.97; p = 0.01), driven by reduced new‐onset HF (1.04% vs. 1.29%; HR, 0.79; 95% CI, 0.68–0.92; p = 0.002), including both HF with reduced and preserved ejection fraction. No significant differences were observed in all‐cause mortality, acute coronary syndrome, or stroke. Mean weight loss was greater with tirzepatide (−9.8 kg vs. −8.0 kg; p < 0.001). Adverse event rates were comparable, with no new safety signals. Conclusions: In obese individuals without diabetes, tirzepatide was associated with a lower risk of cardiovascular events, especially incident HF, compared with semaglutide, with a similar safety profile.

Background: Loop diuretics require functioning kidney tubules to increase the excretion of sodium into urine thereby relieving congestion in patients with acute heart failure ( AHF ). Whether biomarkers of kidney tubular health are associated with the natriuretic response of loop diuretics in AHF is unknown. Methods: Spot urine sodium and 14 urine biomarkers of tubular health were measured after intravenous loop diuretic administration on the day of enrollment in 418 patients with AHF from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase–Associated Lipocalin [NGAL] Evaluation of Symptomatic Heart Failure Study). The association of each biomarker with urine sodium concentration was assessed with multivariable linear regression. Results: The mean age was 71±12 years, 64% were men, average estimated glomerular filtration rate was 56±24 mL /min per 1.73 m ² , and urine sodium was 94±48 mEq /L. Higher urine concentrations of α‐1‐microglobulin (−5.0 mEq /L [95% CI, −8.3 to −1.6 mEq /L]), insulin‐like growth factor–binding protein‐7 ( IGFBP ‐7 mEq /L; −4.1 [95% CI, −8.1 to 0.0 mEq /L]), tissue inhibitor of metalloproteinases 2 ( TIMP ‐2; −3.6 mEq /L [95% CI, −6.5 to −0.7 mEq /L]), IGFBP ‐7* TIMP ‐2 product (−5.1 mEq /L [95% CI, −6.6 to −3.7 mEq /L]), interleukin 18 (−8.2 mEq /L [95% CI, −13.2 to −3.1 mEq /L]), kidney injury molecule 1 (−2.4 mEq /L [95% CI, −4.4 to −0.3 mEq /L]), and chemokine ligand 14 (−2.3 mEq /L [95% CI, −4.0 to −0.5 mEq /L]) were associated with lower urine sodium concentration after adjustment for confounders including estimated glomerular filtration rate and urine albumin. Conclusions: Urine biomarkers of tubular health are associated with lower natriuretic response to loop diuretics in patients with AHF . Kidney tubule health may be an underappreciated contributor to diuretic responsiveness in AHF .

Background: Kidney dysfunction, defined by measures of glomerular health, in patients hospitalized with acute heart failure (HF) is associated with death and HF readmission. We aimed to determine if kidney tubule damage and dysfunction are associated with these outcomes in acute HF. Methods: In AKINESIS (Acute Kidney Injury Neutrophil Gelatinase‐Associated Lipocalin [NGAL] Evaluation of Symptomatic Heart Failure Study), 218 individuals admitted with acute HF experiencing acute kidney injury were matched with 218 individuals without acute kidney injury. Fourteen urine tubular damage and dysfunction biomarkers were measured at hospital admission in this case–control cohort. Associations between biomarkers and the composite outcome of death or HF readmission, death alone, and HF readmission alone were evaluated adjusting for confounders including kidney and cardiac biomarkers. Results: The mean age was 71±12 years, 64% were men, and mean admission estimated glomerular filtration rate was 55±23 mL/min per 1.73 m ² . There were 156 deaths or HF readmissions, 87 deaths, and 92 HF readmissions over 1 year. Each 2‐fold higher level of IGFBP‐7 (insulin‐like growth factor binding protein‐7), IGFBP‐7*TIMP‐2 (tissue inhibitor of metalloproteinases‐2) product, KIM‐1 (kidney injury molecule‐1), and MCP‐1 (monocyte chemoattractant protein‐1) was associated with a 1.36 (95% CI, 1.13–1.64), 1.08 (95% CI, 1.01–1.14), 1.12 (95% CI, 1.02–1.24), and 1.18 (95% CI, 1.03–1.34) higher risk of death or HF readmission, respectively. IGFBP‐7 was associated with death alone, whereas MCP‐1 and CCL‐14 (C‐C motif chemokine ligand‐14) were associated with HF readmission alone. Conclusions: Biomarkers of kidney tubular health are associated with risk of death and HF readmission among people admitted with acute HF independent of measures of glomerular function and cardiac risk.