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Hyperbaric oxygen (HBO) therapy has emerged as a potential treatment, shown to enhance blood flow and angiogenesis. However, specific effects and mechanisms of HBO on limb ischaemia responding to a hypoxic environment remain largely unknown. We aimed to investigate the therapeutic potential of HBO in the treatment of limb ischaemia. Following limb ischaemia surgery, we evaluated the angiogenic capacity in wild‐type C57BL/6J mice subjected to HBO treatment (100% oxygen at 3 ATA for 1 h/day for five consecutive days) compared to untreated controls. Notably, through laser Doppler perfusion imaging and CD31 staining mice receiving HBO postlimb ischaemia surgery exhibited significantly enhanced angiogenic capability and reduced ROS expression compared to nontreated counterparts. Additionally, in vitro experiments were conducted to investigate whether HBO could mitigate endothelial cell dysfunction and reactive oxygen species (ROS) production triggered by oxygen–glucose deprivation (OGD). HBO treatment rescued the impaired proliferation, migration and tube formation of endothelial cells following OGD. Mechanistically, HBO upregulated the expression of proangiogenic proteins, including vascular endothelial growth factor (VEGF), haem oxygenase‐1 (HO‐1), hypoxia‐inducible factor 1 (HIF‐1) and nuclear factor erythroid 2–related factor 2 (Nrf2). Collectively, HBO treatment shows promise in augmenting the endogenous angiogenic potential and suppressing ROS levels in limb ischaemia. [ABSTRACT FROM AUTHOR]

Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, is approved for treatments of patients with diabetes. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial disclosed DAPA's benefits in symptomatic heart failure, but the underlying mechanism remains largely unknown. In this longitudinal and prospective study, we investigated changes of left ventricular functions including speckle tracking in patients with diabetes who were free from symptomatic heart failure post-DAPA treatment. Using a rat model with streptozotocin-induced diabetes, we measured the effects of DAPA on myocardial function. In patients with diabetes, following 6 months of DAPA treatment, despite no significant changes in left ventricular ejection fraction, the diastolic function and longitudinal strain improved. Likewise, compared with control, the diabetic rat heart developed pronounced fibrosis and a decline in strain and overall hemodynamics, all of which were mitigated by DAPA treatment. In contrast, despite insulin exerting a glucose-lowering effect, it failed to improve myocardial function and fibrosis. In our in vitro study, under high glucose cardiomyocytes showed significant activations of apoptosis, reactive oxygen species, and endoplasmic reticulum (ER) stress-associated proteins, which were attenuated by the coincubation of DAPA. Mechanistically, DAPA suppressed ER stress, reduced myocardial fibrosis, and improved overall function. The results can lead to further improvement in management of left ventricular function in patients with diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND Inherited deficiencies in antithrombin (AT), protein C (PC), and protein S (PS) increase the risk of venous thromboembolism (VTE). The efficacy and safety of direct oral anticoagulants (DOACs) in severe VTE cases after mechanical thrombectomy are uncertain. This study aimed to evaluate the use of DOACs combined with mechanical thrombectomy in 55 patients with VTE, including 11 patients with confirmed deep vein thrombosis (DVT) and pulmonary thromboembolism (PE), 27 patients with DVT alone, and 17 with pulmonary thromboembolism alone, from a single center between January 2016 and December 2023. MATERIAL AND METHODS All patients with symptomatic VTE confirmed by computed tomography underwent mechanical thrombectomy. Fourteen patients with reduced AT (n=4), PC (n=6), and PS (n=4) function were classified as group 1, while the remaining 41 without thrombophilia were classified as group 2. The outcomes, including recurrent VTE, bleeding events, and all-cause mortality, were compared between patients with and without thrombophilia. RESULTS DOAC use was similar between the groups. One patient in the thrombophilia group switched DOACs due to bleeding, while 7 in the non-thrombophilia group changed due to bleeding or recurrent VTE. Recurrent VTE was higher in the non-thrombophilia group (7.1% vs 17.1%; P=0.664), while bleeding events were more frequent in the thrombophilia group (35.7% vs 17.1%; P=0.259); however, neither difference was statistically significant. All-cause mortality was similar between groups (7.1% vs 6.7%; P=0.903). CONCLUSIONS The study found no difference in the efficacy and safety of DOACs between VTE patients with and without inherited thrombophilia undergoing mechanical thrombectomy.

Abstract: Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin-aldosterone system inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction, its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/d), spironolactone (80 mg/kg/d), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared with that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced heart failure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel., Methods: Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes., Results: A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs., Conclusions: The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.

Background: Angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) are emerging medical treatments for decompensated heart failure (HF) with reduced ejection fraction. In clinical practice, the combination of ARNI and SGLT2i cannot be administered owing to the poor hemodynamic status in patients with HF with reduced ejection fraction (HFrEF). This study aimed to compare different strategies of HF management for ARNI first or SGLT2i first in such a population., Methods: From January 2016 to December 2021, 165 patients were diagnosed with HFrEF and New York Heart Association functional class ≥II and already received optimal medical treatment. Ninety-five patients received the ARNI-first strategy, and 70 patients received the SGLT2i-first strategy according to the physician's choice. Age, sex, hemodynamic condition, etiologies of HF, comorbidities, serum creatinine, N-terminal pro-B-type natriuretic peptide (NT-ProBNP), echocardiographic parameters, and clinical outcomes were compared between the ARNI and SGLT2i-first strategy groups., Results: In the SGLT2i-first group, the median interval between the addition of the second medication was longer (ARNI-first vs. SGLT2i-first; 74 [49-100] days vs. 112 [86-138] days; p = 0.044). Improvement in left ventricular ejection fraction (LVEF), change in left atrial dimension, and change in left ventricular end-diastolic and end-systolic volume (LVESV) did not differ between the two groups. The incidence of HF hospitalization, cardiovascular mortality, and all-cause mortality did not differ between the two groups. A non-significant trend of lower NT-proBNP levels (ARNI-first vs. SGLT2i-first; 1383 [319-2507] pg/mL vs. 570 [206-1314] pg/mL; p = 0.055) and significantly higher discontinuation rate of diuretic agents (ARNI-first vs. SGLT2i- first; 6.8% vs. 17.5%; p = 0.039) were noted in the SGLT2i-first group. When early combination (≤14D) compared to late combination (>14D), better positive remodeling of LVESV presented significantly in early combination subgroups., Conclusions: In patients with symptomatic HFrEF, SGLT2i-first strategy may provide a higher possibility of discontinuing diuretic agents than the ARNI-first strategy. Changes in LV performance, progression of renal function, and clinical outcomes did not differ between the two groups. Early combination (≤14D) provided better LV remodeling., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Background: Avoiding unnecessary radiation exposure is the main issue during coronary angiography. Herein, we aimed to investigate whether performing coronary angioplasties with monoplane or biplane imaging most effectively reduces radiation load and shortens the procedure time., Methods: We retrospectively enrolled 294 patients who required either coronary angiography or coronary angioplasty. They were divided into groups of only diagnostic angiography, one-, two- or three-vessel diseases. The fluoroscopy dose-area product (DAP), skin dose, fluoroscopy and procedure time were recorded., Results: Among the studied patients, 148 received the procedures with monoplane imaging. Compared with the radiation exposure in the monoplane group, there were significant increases in DAP and skin dose in those who received biplane imaging independently of the number of lesions. This phenomenon was also observed in the patients receiving either diagnostic angiography only or coronary interventions. In addition, there were no significant differences in contrast volume and procedure time between the monoplane and biplane groups. Notably, the average fluoroscopy time in those who received biplane imaging was significantly longer than in those who received monoplane imaging in the one- and two-vessel groups, while there were no significant differences in the diagnostic angiography only and three-vessel diseases groups., Conclusions: Our findings indicated that using monoplane imaging resulted in lesser radiation exposure and similar procedure times in coronary diagnostic and interventional settings compared to using biplane imaging. This observation should be verified in prospective randomized studies.