Clinical Characteristics and Prognosis of Heart Failure with Preserved Ejection Fraction Across Diverse Ejection Fraction Ranges.

Background: Recent studies have indicated that heart failure (HF) with preserved ejection fraction (HFpEF) within different left ventricular ejection fraction (LVEF) ranges presents distinct morphological and pathophysiological characteristics, potentially leading to diverse prognoses. Methods: We included chronic HF patients hospitalized in the Department of Cardiology at Hebei General Hospital from January 2018 to June 2021. Patients were categorized into four groups based on LVEF: HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%), HF with mildly reduced ejection fraction (HFmrEF, 41% ≤ LVEF ≤ 49%), low LVEF-HFpEF (50% ≤ LVEF ≤ 60%), and high LVEF-HFpEF (LVEF > 60%). Kaplan‒Meier curves were plotted to observe the occurrence rate of endpoint events (all-cause mortality and cardiovascular mortality) within a 2-year period. Cox proportional hazards regression models were employed to predict the risk factors for endpoint events. Sensitivity analyses were conducted using propensity score matching (PSM), and Fine-Gray tests were used to evaluate competitive risk. Results: A total of 483 chronic HF patients were ultimately included. Kaplan‒Meier curves indicated a lower risk of endpoint events in the high LVEF-HFpEF group than in the low LVEF-HFpEF group. After PSM, there were still statistically significant differences in endpoint events between the two groups (all-cause mortality p = 0.048, cardiovascular mortality p = 0.027). Body mass index (BMI), coronary artery disease, cerebrovascular disease, hyperlipidemia, hypoalbuminemia, and diuretic use were identified as independent risk factors for all-cause mortality in the low LVEF-HFpEF group (p < 0.05). Hyperlipidemia, the estimated glomerular filtration rate (eGFR), and ß -blocker use were independent risk factors for cardiovascular mortality (p < 0.05). In the high LVEF-HFpEF group, multivariate Cox regression analysis revealed that age, smoking history, hypoalbuminemia, and the eGFR were independent risk factors for all-cause mortality, while age, heart rate, blood potassium level, and the eGFR were independent risk factors for cardiovascular mortality (p < 0.05). After controlling for competitive risk, cardiovascular mortality risk remained higher in the low LVEF-HFpEF group than in the high LVEF-HFpEF group (Fine-Gray p < 0.01). Conclusions: Low LVEF-HFpEF and high LVEF-HFpEF represent two distinct phenotypes of HFpEF. Patients with high LVEF-HFpEF have lower risks of both all-cause mortality and cardiovascular mortality than those with low LVEF-HFpEF. The therapeutic reduction in blood volume may not be the best treatment option for patients with high LVEF-HFpEF.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Nuclear Pulposus Cells Degeneration Through the miR-145a-5p/USP31/HIF-1α Signaling Pathway.

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes possess therapeutic potential against degenerative diseases. This study aimed to investigate the effects of BMSC-derived exosomes on intervertebral disc degeneration (IVDD) and explore the underlying molecular mechanisms. Through transcriptome sequencing and histological analysis, we observed a significant increase in HIF-1α expression in degenerative nucleus pulposus (NP) tissues. The addition of HIF-1α resulted in elevated expression of inflammatory factors IL-1ß and IL-6, higher levels of matrix-degrading enzyme MMP13, and lower expression of aggrecan in NP cells. Co-culturing with BMSCs diminished the expression of HIF-1α, MMP13, IL-1ß, and IL-6 in degenerative NP cells induced by overload pressure. miRNA chip analysis and PCR validation revealed that miR-145a-5p was the primary miRNA carried by BMSC-derived exosomes. Overexpression of miR-145a-5p was effective in minimizing the expression of HIF-1α, MMP13, IL-1ß, and IL-6 in degenerative NP cells. Luciferase reporter assays confirmed USP31 as the target gene of miR-145a-5p, and the regulation of NP cells by BMSC-derived exosomes via miR-145a-5p was dependent on USP31. In conclusion, BMSC-derived exosomes alleviated IVDD through the miR-145a-5p/USP31/HIF-1α signaling pathway, providing valuable insights into the treatment of IVDD.

Meta-analysis of Serum Vitamin B12 Levels and Diabetic Retinopathy in Type 2 Diabetes.

BACKGROUND: Previous studies have shown an association between low serum vitamin B12 levels and the risk of diabetic retinopathy (DR) in type 2 diabetes, but the conclusions from various studies were inconsistent. Therefore, we collected relevant data from various databases to perform a meta-analysis and address the inconsistencies in these studies. METHODS: We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang and CQVIP for eligible studies published up to April 10, 2022, and performed a meta-analysis using Stata software to assess the association between serum vitamin B12 levels and DR. RESULTS: A total of 15 studies were included in this meta-analysis. Statistical analysis showed that serum vitamin B12 levels were significantly reduced in patients with type 2 diabetic retinopathy ,WMD 95% CI = -68.91 (-76.76, -61.06) (p <0.00001, I2 = 88.30%). In subgroup analyses by ethnicity, an association between low serum vitamin B12 levels and DR risk was found in East Asian, South Asian and mixed populations, but not in Caucasian populations. CONCLUSIONS: This meta-analysis analyzed vitamin B12 in patients with type 2 diabetic retinopathy and emphasized the importance of monitoring serum vitamin B12 levels in patients with type 2 diabetic retinopathy, but this meta-analysis still has deficiencies and limitations, and more clinical studies are needed to confirm this conclusion in the future.

Clinical characteristics, predictors, and outcomes of heart failure with improved ejection fraction.

AIMS: Improvement in ejection fraction (EF) was observed in a subset of patients with heart failure (HF) and reduced ejection fraction (HFrEF). We analyzed and compared these patients with other HF phenotypes. METHODS: Based on left ventricular ejection fraction(LVEF) at baseline and follow-up, the 561 HF patients were divided into 4 groups: HF preserved EF (HFpEF, LVEF ≥ 50% on both occasions, n = 258), HF mid-range EF (HFmrEF, fluctuating between LVEF 40 and 49% on both occasions, n = 61), HFrEF (LVEF < 40% on both occasions, n = 141), and HF improved EF (HFimpEF, defined as LVEF < 40% at baseline and LVEF ≥ 40% at follow-up with ≥10% absolute improvement, n = 101). The composite of HF readmission and all-cause mortality was considered the primary endpoint, and the secondary endpoint was all-cause mortality. RESULTS: The characteristics of HFimpEF differed from other HF phenotypes. ß-blockers and aldosterone receptor antagonists were associated with improved LVEF. Kaplan-Meier curves showed the lowest incidence of the composite endpoint (p < 0.001) and all-cause mortality (p < 0.001) in HFimpEF. The risk of cardiovascular death was lowest in HFimpEF after controlling for competing events (p < 0.001), as were competing events (p < 0.001). Valvular heart disease (VHD) (HR 8.555, 95 CI% 2.126-34.420, p = 0.003) increased the risk of all-cause death, and anemia increased the risk of all-cause death (HR 5.533, 95 CI% 1.592-19.530, p = 0.007) and cardiovascular death in HFimpEF patients (HR 5.840, 95 CI% 1.088-31.356, p = 0.040). CONCLUSIONS: HFimpEF is an independent HF phenotype with a prognosis similar to HFmrEF and superior to HFpEF and HFrEF. When HFimpEF patients had VHD and anemia, the endpoint event rate was increased.