Optimizing Guideline-Directed Medical Therapy During Hospitalization Improves Prognosis in Patients With Worsening Heart Failure Requiring Readmissions.

BACKGROUND: We previously demonstrated that higher simple guideline-directed medical therapy (GDMT) scores (comprising renin-angiotensin system inhibitors, ß-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter 2 inhibitors) at discharge were correlated with improved prognosis in heart failure (HF) patients. HF readmissions are linked to adverse outcomes, emphasizing the need for enhanced optimization of GDMT.Methods and Results: Using the simple GDMT score, we evaluated the effect of revising and modifying in-hospital GDMT on the prognosis of patients with HF readmissions. In this retrospective analysis of 2,100 HF patients, we concentrated on 1,222 patients with HF with reduced ejection/moderately reduced ejection fraction, excluding patients with HF with preserved ejection fraction, on dialysis, or who died in hospital. A higher current GDMT score was associated with better HF prognosis. Of the 1,222 patients in the study, we analyzed 372 cases of rehospitalization, calculating the simple GDMT scores at admission and discharge. Patients were divided into groups according to score improvement. Multivariate analysis showed a significant association between improved in-hospital simple GDMT score and the composite outcome (HF readmission+all-cause mortality; hazard ratio 0.459; 95% confidence interval 0.257-0.820; P=0.008). Even after propensity score matching to adjust for background, among rehospitalized patients, those with an improved in-hospital simple GDMT score had a better prognosis. CONCLUSIONS: Our results highlight the potential of robust interventions and score elevation during hospitalization leading to improved outcomes.

Formation of Long-Lived Dark States during Electronic Relaxation of Pyrimidine Nucleobases Studied Using Extreme Ultraviolet Time-Resolved Photoelectron Spectroscopy.

Ultrafast electronic relaxation of nucleobases from 1ππ* states to the ground state (S0) is considered essential for the photostability of DNA. However, transient absorption spectroscopy (TAS) has indicated that some nucleobases in aqueous solutions create long-lived 1nπ*/3ππ* dark states from the 1ππ* states with a high quantum yield of 0.4-0.5. We investigated electronic relaxation in pyrimidine nucleobases in both aqueous solutions and the gas phase using extreme ultraviolet (EUV) time-resolved photoelectron spectroscopy. Femtosecond EUV probe pulses cause ionization from all electronic states involved in the relaxation process, providing a clear overview of the electronic dynamics. The 1nπ* quantum yields for aqueous cytidine and uracil (Ura) derivatives were found to be considerably lower (<0.07) than previous estimates reported by TAS. On the other hand, aqueous thymine (Thy) and thymidine exhibited a longer 1ππ* lifetime and a higher quantum yield (0.12-0.22) for the 1nπ* state. A similar trend was found for isolated Thy and Ura in the gas phase: the 1ππ* lifetimes are 39 and 17 fs and the quantum yield for 1nπ* are 1.0 and 0.45 for Thy and Ura, respectively. The result indicates that single methylation to the C5 position hinders the out-of-plane deformation that drives the system to the conical intersection region between 1ππ* and S0, providing a large impact on the photophysics/photochemistry of a pyrimidine nucleobase. The significant reduction of 1nπ* yield in aqueous solution is ascribed to the destabilization of the 1nπ* state induced by hydrogen bonding.

Solvated electron formation from the conduction band of liquid methanol: Transformation from a shallow to deep trap state.

We report solvated electron (esolv -) formation dynamics from the conduction band of liquid methanol studied using femtosecond time-resolved photoelectron spectroscopy. Liquid methanol is excited with vacuum UV (9.3 eV) pump pulses, and the subsequent electron dynamics are probed with UV pulses. The photoelectron signal exhibits a short-lived component (τ = 85 fs) without spectral evolution followed by a long-lived component with continuous spectral evolution over tens of picoseconds. We ascribe the former to a superexcited state, most likely the Wannier exciton, and the latter to the ground electronic state of esolv -. In order to extract accurate energetics from the observed photoelectron spectra, we employ a spectral retrieval method to account for spectral broadening and shifting due to inelastic scattering of photoelectrons in the liquid. The electron binding energy (eBE) of the initial trap state of an electron is determined to be about 1.5 eV, and its biexponential increase up to 3.4 eV is observed with time constants of 2 and 31 ps, which are greater than 0.27 and 13 ps observed for esolv - created by the charge-transfer-to-solvent reaction from CH3O- to liquid methanol. The solvation dynamics of esolv - created by the electron trapping exhibit a pseudoisosbestic point at a pump-probe delay time of around 15 ps, and the peak energy of the eBE distribution rapidly changes around that time. These results indicate that there exist two trap states, both of which exhibit increasing eBE with time; however, the eBE of the shallow trap state increases only up to 2.1 eV, and transformation to a deep trap state at 25 ps occurs to reach an eBE of 3.4 eV.

Early Initiation of Sodium-Glucose Cotransporter 2 Inhibitor Leads to a Shorter Hospital Stay in Patients With Acute Decompensated Heart Failure.

Background: The efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with acute chronic heart failure (HF) is increasingly being reported. However, it is not clear when SGLT2i should be initiated in patients with acute decompensated HF (ADHF) after hospitalization. We retrospectively analyzed ADHF patients with newly prescribed SGLT2i. Methods and Results: Among the 694 patients hospitalized due to HF between May 2019 and May 2022, data were extracted for 168 patients with newly prescribed SGLT2i during the index hospitalization. These patients were divided into 2 groups: and early group (92 patients who started SGLT2i within 2 days of admission) and a late group (76 patients who started SGLT2i after 3 days). Clinical characteristics were comparable between the 2 groups. The date of cardiac rehabilitation initiation was significantly earlier in the early than late group (2.5±1.2 vs. 3.8±2.2 days; P<0.001). Hospital stay was significantly shorter in the early group (16.4±6.5 vs. 24.2±16.0 days; P<0.001). Although there were significantly fewer HF readmissions within 3 months in the early group (2.1% vs. 10.5%; P=0.044), the association disappeared in a multivariate analysis including clinical confounders. Conclusions: Early initiation of SGLT2i may shorten hospital stays.

A scoring evaluation for the practical introduction of guideline-directed medical therapy in heart failure patients.

AIMS: The guideline-directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced ejection fraction (HFrEF) based on the accumulating clinical evidence. However, it is difficult to implement all the trial-proven medications for every patient in the real world. METHODS AND RESULTS: A simple GDMT score was created, according to the combination of GDMT drugs (renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose transporter 2 inhibitors) administration and their dosage (0-9 points). Its impact on the prognosis of HF patients was investigated. Admitted HF patients [HFrEF and HF with mildly reduced ejection fraction (HFmrEF), n = 1054] were retrospectively analysed (excluding those with in-hospital death and dialysis). A simple GDMT score ≥5, but not the number of medications, was significantly associated with a reduction of all-cause death, HF readmission, and composite outcome (HF readmission and all-cause death) (P < 0.001). Subgroup analysis showed that almost all groups with a simple GDMT score of 5 or higher had a better prognosis. CONCLUSIONS: The developed simple GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if all four drugs cannot be introduced for some reason, a regimen with a simple GDMT score ≥5 may lead to a prognosis in HF patients.

Use of a Cutting Balloon Reduces the Incidence of Distal Embolism in Acute Coronary Syndrome Requiring Predilatation Before Stenting.

Background: Acute coronary syndrome (ACS) patients with solid lesions often require predilatation before stenting. Predilatation with high pressure may increase the risk of distal embolism, whereas direct stenting increases the risk of stent underexpansion. We recently reported that, in severely calcified lesions, using a cutting balloon (CB) can provide greater acute gain compared with other scoring balloons. Therefore, we hypothesized that predilatation with CB may reduce the incidence of distal embolism in ACS patients with solid lesions. Methods and Results: This study retrospectively analyzed data for 175 ACS patients who required predilatation, either with a conventional balloon (n=136) or CB (n=39). The occurrence of distal embolism was significantly lower in the CB than conventional balloon group (10.3% vs 32.4%, respectively; P=0.007). Multivariate analysis showed that the occurrence of distal embolism was positively associated with Thrombolysis in Myocardial Infarction (TIMI) grade and the presence of attenuated plaque, but negatively associated with the use of a CB. To support this clinical observation, we compared thrombus dispersal using a CB and non-compliant balloon in an ex vivo experimental model using a pseudo-thrombus. In this model, pseudo-thrombus dispersal was significantly smaller when a CB rather than non-compliant balloon was used (1.8±1.0% vs 2.6±1.2%, respectively; n=20, for each; P=0.002). Conclusions: In ACS patients with solid lesions that require predilatation, predilatation with a CB may reduce the incidence of distal embolism.