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Background: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and related to endothelial activation and systemic inflammation. Herein, we investigate the pathophysiological mechanisms of AF through endothelial activation and cell-cell interactions related to the development of POAF., Methods: Patients without previous AF undergoing cardiac surgery were studied. Permanent AF patients were included as positive controls. Interleukin (IL)-6, Von Willebrand factor (vWF), N-terminal pro-brain natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) were evaluated by electrochemiluminescence. Vascular cell adhesion molecule-1 (VCAM-1) and human Growth Differentiation Factor 15 (GDF-15) was assessed by ELISA. Connexins (Cxs) 40 and 43 were measured by tissue immunolabelling, and apoptosis by TUNEL assay., Results: We included 117 patients (median age 67: 27.8% female): 17 with permanent AF; 27 with POAF and 73 with non- AF. Patients with permanent AF and POAF had higher levels of NT-proBNP, hs-TnT, apoptotic nuclei and decrease Cx43 expression, compared to non-AF patients (all p-value <0.05). VCAM-1 and GDF-15 were significantly higher in permanent AF vs. non-AF (p=0.013 and p=0.035)., Conclusions: Greater endothelial activation and inflammation in AF patients compared to those without AF was found. The proinflammatory state in AF patients, in addition to the lower expression of Cx43, seems to be associated with atrial remodeling processes occurring in AF., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Thoraco-abdominal normothermic regional perfusion (TA-NRP), utilizing Extra Corporeal Membrane Oxygenation (ECMO) devices, has emerged as an effective strategy for heart recovery in donors declared dead by circulatory criteria (DCDD). After death declaration, TA-NRP restores heart activity by reperfusing the arrested heart with oxygenated blood at normothermia. Mechanical ventilation resumption in the donor enables weaning from ECMO and restores systemic circulation and oxygenation using the donor's heart and lungs. However, if pre-existing conditions prevent the donor's lungs from oxygenating blood post-cardiac activity restoration, weaning from veno-arterial ECMO may lead to systemic hypoxia, jeopardizing the restored cardiac function. Anticipating this scenario may guide planning a split ECMO circuit to facilitate earlier and more effective recovery of donor heart function post-ECMO weaning. This manuscript describes three cases of DCDD donors with hypoxic respiratory failure undergoing TA-NRP for heart recovery. By establishing a bridge in the arterial portion of the circuit, clamped out after weaning from veno-arterial ECMO, donor heart function was assessed exclusively with veno-venous ECMO support, leading to successful heart transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Royo-Villanova, Moya Sánchez, Ortín Freire, De Gea García, Rebollo Acebes, Moreno Flores, Blanco Morillo, Cánovas and Domínguez-Gil.)

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication in patients undergoing cardiac surgery with extracorporeal circulation (ECC) that increases postoperative complications and mortality. CSA-AKI develops due to a combination of patient- and surgery-related risk factors that enhance renal ischemia-reperfusion injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin reduce renal glucose reabsorption, improving tubulo-glomerular feedback, reducing inflammation and decreasing intraglomerular pressure. Preclinical studies have observed that SGLT2i may provide significant protection against renal ischemia-reperfusion injury due to their effects on inadequate mitochondrial function, reactive oxygen species activity or renal peritubular capillary congestion, all hallmarks of CSA-AKI. The VERTIGO (EValuating the Effect of periopeRaTIve empaGliflOzin) trial is a Phase 3, investigator-initiated, randomized, double-blind, placebo-controlled, multicenter study that aims to explore whether empagliflozin can reduce the incidence of adverse renal outcomes in cardiac surgery patients., Methods: The VERTIGO study (EudraCT: 2021-004938-11) will enroll 608 patients that require elective cardiac surgery with ECC. Patients will be randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg orally daily or placebo. Study treatment will start 5 days before surgery and will continue during the first 7 days postoperatively. All participants will receive standard care according to local practice guidelines. The primary endpoint of the study will be the proportion of patients that develop major adverse kidney events during the first 90 days after surgery, defined as ≥25% renal function decline, renal replacement therapy initiation or death. Secondary, tertiary and safety endpoints will include rates of AKI during index hospitalization, postoperative complications and observed adverse events., Conclusions: The VERTIGO trial will describe the efficacy and safety of empagliflozin in preventing CSA-AKI. Patient recruitment is expected to start in May 2024., Competing Interests: A.C. reports consultancy and speaker fees from Vifor Pharma and Novo Nordisk, honoraria for educational events from AstraZeneca, and grants or contracts from Alexion and LFB Biotechnologies. E.B.-M. reports grants or contracts from Alexion and LFB Biotechnologies, and travel grants from Gilead. V.F. reports honoraria for educational events from AstraZeneca and travel fees from NovoNordisk. M.F. reports grants or contracts from Alexion and LFB Biotechnologies. Á.G.-P. reports grants from Medtronic. D.P. reports consulting fees and honoraria for educational events from Edwards, Medtronic, Atricure, BBraun and Abbott. J.B.-M. reports grants or contracts from Baxter, Alexion and LFB Biotechnologies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk., (© 2023 Federation of American Societies for Experimental Biology.)

Introduction and Objectives: Surgical aortic valve replacement (SAVR) can modify the natural history of severe aortic stenosis (SAS). However, compared with the general population, these patients have a loss of life expectancy. The life expectancy of patients who undergo SAVR due to low-gradient SAS with preserved left ventricular ejection fraction (LVEF) is unknown., Methods: We included all patients between 50 and 65 years who underwent isolated SAVR in 27 Spanish centers during an 18-year period. We analyzed observed and expected survival at 18 years in patients with low-gradient SAS with preserved LVEF and all other types of SAS. We used propensity score matching to compare the life expectancy of patients with low-gradient SAS with preserved LVEF vs those with high-gradient SAS with preserved LVEF., Results: We analyzed 5084 patients, of whom 413 had low-gradient SAS with preserved LVEF. For these patients, observed survival at 10, 15 and 18 years was 86.6% (95%CI, 85.3-87.8), 75% (95%CI, 72.7-77.2), and 63.5% (95%CI, 58.8-67.8). Expected survival at 10, 15 and 18 years was 90.2%, 82.1%, and 75.7%. In the matched sample, survival of patients with low-gradient SAS with preserved LVEF was similar to that of patients with high-gradient with preserved LVEF, log-rank test, P=.95; HR=1 (95%CI, 0.7-1.4; P=.95)., Conclusions: There is a loss of life expectancy in patients with all types of SAS undergoing SAVR. This loss is higher in patients with left ventricular dysfunction and lower in patients with low-gradient or high-gradient aortic stenosis with preserved LVEF. The benefit of surgery is similar between these last 2 groups., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

The addition of reproductive fluids (RF) to the culture media has shown benefits in different embryonic traits but its long-term effects on the offspring phenotype are still unknown. We aimed to describe such effects in pigs. Blood samples and growth parameters were collected from piglets derived from in vitro-produced embryos (IVP) with or without RF added in the culture media versus those artificially inseminated (AI), from day 0 to month 6 of life. An oral glucose tolerance test was performed on day 45 of life. We show here the first comparative data of the growth of animals produced through different assisted reproductive techniques, demonstrating differences between groups. Overall, there was a tendency to have a larger size at birth and faster growth in animals derived from in vitro fertilization and embryo culture versus AI, although this trend was diminished by the addition of RFs to the culture media. Similarly, small differences in hematological indices and glucose tolerance between animals derived from AI and those derived from IVP, with a sex-dependent effect, tended to fade in the presence of RF. The addition of RF to the culture media could contribute to minimizing the phenotypical differences between the in vitro-derived and AI offspring, particularly in males.

Reproductive health underpins overall health, and thus, research in reproductive science and medicine is essential. This requires a pipeline of trained scientists and clinicians, which is challenging given the relatively small size of the field. Educational programs outside the traditional doctorate or medical degrees are needed to generate and maintain a well-trained reproductive science and medicine workforce. Master's programs have gained traction as a viable way for students to receive educational value relative to their career goals. Our hypothesis is master's degree programs in the fundamental, applied, and allied health reproductive fields broadens the workforce and increases impact. An internet web search identified 73 programs that conferred an MS degree in the areas of animal science, clinical/embryology, and reproductive health/biology. These programs are spread across the globe in Europe (47%), North America (23%), Asia (14%), South America (7%), Oceania (5%), and Africa (4%). To evaluate global exemplars, we profiled the mission and structure, curriculum, and program impact of two established master's degree programs: the Master of Science in Reproductive Science and Medicine at Northwestern University in the United States and the Biology and Technology of Reproduction in Mammals at the University of Murcia in Spain. Elements of infrastructure and support, program connectivity, and alumni networks were analyzed for their role in the success of the programs. These two programs have formally trained >375 individuals, demonstrating master's degree programs in reproductive science are an important educational mechanism. The educational best practices shared here serve as templates for expanding training programs worldwide., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction and Objectives: In young patients with severe aortic stenosis, it is unknown whether their life expectancy restored after aortic valve replacement (AVR) is unknown., Methods: We analyzed all patients aged between 50 and 65 years who underwent isolated AVR in 27 Spanish centers during an 18-year period. We compared observed and expected survival at 15 years of follow-up. We repeated all analyses for patients without complications in the postoperative period., Results: A total of 5084 patients were analyzed. For the overall sample, observed survival at 10 and 15 years was 85.3% (95%CI, 84.1%-86.4%) and 73.7% (95%CI, 71.6%-75.6%), respectively. Expected survival was 90.1% and 82.1%. Cumulative relative survival for 1, 5, 10 and 15 years of follow-up was 97.4% (95%CI, 96.9%-97.9%), 96.5% (95%CI, 95.7%-97.3%), 94.7% (95%CI, 93.3%-95.9%), and 89.8% (95%CI, 87.3%-92.1%). For patients without complications, cumulative relative survival for 1, 5, 10 and 15 years was 100.3% (95%CI, 99.8%-100.5%), 98.9% (95%CI 97.6% -99.9%), 97.3% (95%CI, 94.9%-99.4%), and 91.9% (95%CI, 86.5%-96.8%)., Conclusions: Life expectancy in young patients who have severe aortic stenosis and undergo AVR is lower than that of the general population. Life expectancy of individuals without complications during the postoperative period is also reduced. Therefore, baseline characteristics are likely the main factors that explain the reduction in life expectancy., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)