Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure with Malnutrition, Frailty, Sarcopenia, or Cachexia.

(1) Background: In patients with heart failure (HF) and impaired nutritional status or decreased muscle mass, sodium-glucose cotransporter-2 inhibitors (SGLT2is) may worsen these conditions and result in poor prognosis, especially worsening of frailty. We aimed to investigate the relationship between SGLT2is and clinical outcomes, including frailty-related events, in patients with HF and malnutrition, frailty, sarcopenia, or cachexia. (2) Methods: In this retrospective observational cohort study, a global federated health research network provided data on patients with HF and malnutrition, frailty, sarcopenia, or cachexia from January 2016 to December 2021. We investigated the incidence of the composite endpoint of death or frailty-related events within one year. (3) Results: Among 214,778 patients included in the analysis, 4715 were treated with SGLT2is. After propensity score matching, 4697 patients in the SGLT2is group were matched with 4697 patients in the non-SGLT2is groups. The incidence of the composite endpoint, mortality, and frailty-related events was lower in the SGLT2is group than in the non-SGLT2is group (composite endpoint, 65.6% versus 77.6%, p < 0.001; mortality, 17.4% vs. 35.5%, p < 0.001; frailty-related events, 59.4% vs. 64.3%, p < 0.001). (4) Conclusions: Patients with HF and malnutrition, frailty, sarcopenia, or cachexia had a high incidence of death and frailty-related events. SGLT2is were associated with a lower incidence of these events.

A critical period for learning and plastic changes at hippocampal CA1 synapses.

Postnatal development of hippocampal function has been reported in many mammalian species, including humans. To obtain synaptic evidence, we analyzed developmental changes in plasticity after an inhibitory avoidance task in rats. Learning performance was low in infants (postnatal 2 weeks) but clearly improved from the juvenile period (3-4 weeks) to adulthood (8 weeks). One hour after the training, we prepared brain slices and sequentially recorded miniature excitatory postsynaptic currents (mEPSCs) and inhibitory postsynaptic currents (mIPSCs) from the same hippocampal CA1 neuron. Although the training failed to affect the amplitude of either mEPSCs or mIPSCs at 2 weeks, it increased mEPSC, but not mIPSC, amplitude at 3 weeks. At 4 weeks, the training had increased the amplitude of both mEPSCs and mIPSCs, whereas mIPSC, but not mEPSC, amplitude was increased at 8 weeks. Because early-life physiological functions can affect performance, we also evaluated sensory-motor functions together with emotional state and found adequate sensory/motor functions from infancy to adulthood. Moreover, by analyzing performance of rats in multiple hippocampal-dependent tasks, we found that the developmental changes in the performance are task dependent. Taken together, these findings delineate a critical period for learning and plastic changes at hippocampal CA1 synapses.

The role of the renal resistance index in patients with heart failure with reduced or preserved ejection fraction.

BACKGROUND: Renal impairment is a common phenomenon that portends a poor prognosis of heart failure (HF). The renal arterial resistance index (RRI) can be useful for defining renal function and predicting outcomes in patients with HF. This study aimed to investigate the determining factors of the RRI in HF patients with preserved ejection fraction (HFpEF) and with reduced EF (HFrEF). METHODS: This retrospective study included 330 patients with HF. We investigated the determining factors for the RRI and the association between the RRI and 1-year composite outcome, comprising all-cause mortality and re-hospitalization for HF. RESULTS: The independent predictors of the RRI were tricuspid regurgitation peak gradient and estimated glomerular filtration rate in HFpEF, and pulse pressure and blood urea nitrogen in HFrEF. During the follow-up, 30 (9.1%) patients presented the composite outcome. Cox proportional hazard analysis revealed the association of the RRI with the composite outcome in both HFrEF (HR 1.08; 95% CI 1.03-1.14) and HFpEF (HR 1.07; 95% CI 1.03-1.12) without an interaction (p for interaction = 0.770). CONCLUSIONS: The RRI was a consistent prognosticator in patients with HFpEF and those with HFrEF, while factors defining RRI were different between these groups.