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The number of individuals referred for coronary artery bypass grafting (CABG) with preoperative atrial fibrillation (AF) is reported to be 8% to 20%. Atrial fibrillation is a known marker of high-risk patients as it was repeatedly found to negatively influence survival. Therefore, when performing surgical revascularization, consideration should be given to the concomitant treatment of the arrhythmia, the clinical consequences of the arrhythmia itself, and the selection of adequate surgical techniques. This state-of-the-art review aimed to provide a comprehensive analysis of the current understanding of, advancements in, and optimal strategies for CABG in patients with underlying AF. The following topics are considered: stroke prevention, prophylaxis and occurrence of postoperative AF, the role of surgical ablation and left atrial appendage occlusion, and an on-pump vs off-pump strategy. Multiple acute complications can occur in patients with preexisting AF undergoing CABG, each of which can have a significant effect on patient outcomes. Long-term results in these patients and the future perspectives of this scientific area were also addressed. Preoperative arrhythmia should always be considered for surgical ablation because such an approach improves prognosis without increasing perioperative risk. While planning a revascularization strategy, it should be noted that although off-pump coronary artery bypass provides better short-term outcomes, conventional on-pump approach may be beneficial at long-term follow-up. By collecting the current evidence, addressing knowledge gaps, and offering practical recommendations, this state-of-the-art review serves as a valuable resource for clinicians involved in the management of patients with AF undergoing CABG, ultimately contributing to improved outcomes and enhanced patient care., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Aortic valve-sparing aortic root replacement (VSARR) David procedure has not been routinely performed via minimally invasive access due to its complexity. Methods: We compared our results for mini-VSARR to sternotomy-VSARR from another excellence center. Results: Eighty-four patients, 62 in the sternotomy-VSARR group and 22 in the mini-VSARR group, were included. A baseline, the aneurysm dimensions were higher in the mini-VSARR group. Propensity matching resulted in 17 pairs with comparable characteristics. Aortic cross-clamp and cardiopulmonary bypass times were significantly longer in the mini-VSARR group, by 60 and 20 min, respectively ( p < 0.001). In-hospital outcomes were comparable between the groups. Drainage volumes were numerically lower, and hospital length of stay was, on average, 3 days shorter ( p < 0.001) in the mini-VSARR group. At a median follow-up of 5.5 years, there was no difference in mortality ( p = 0.230). Survival at 1, 5 and 10 years was 100%, 100%, and 95% and 95%, 87% and 84% in the mini-VSARR and sternotomy-VSARR groups, respectively. No repeat interventions on the aortic valve were documented. Echocardiographic follow-up was complete in 91% with excellent durability of repair regardless of the approach: no cases of moderate/severe aortic regurgitation were reported in the mini-VSARR group. Conclusions: The favorable outcomes, reduced drainage, and shorter hospital stays associated with the mini-sternotomy approach underscore its potential advantages expanding beyond cosmetic outcome.

Objectives: Transcatheter aortic valve implantation (TAVI) remains the preferred strategy for high-risk or elderly individuals with aortic valve (AV) stenosis who are not considered to be optimal surgical candidates. Recent evidence suggests that low-risk patients may benefit from TAVI as well. The current study evaluates midterm survival in low-risk patients undergoing elective surgical AV replacement (SAVR) versus TAVI., Methods: The Aortic Valve Replacement in Elective Patients From the Aortic Valve Multicenter Registry (AVALON) compared isolated elective transfemoral TAVI or SAVR with sternotomy or minimally invasive approach in low-risk individuals performed between 2015 and 2019. Propensity score matching was conducted to determine SAVR controls for TAVI group in a 1-to-3 ratio with 0.2 caliper., Results: A total of 2393 patients undergoing elective surgery (1765 SAVR and 629 TAVI) with median European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) score 1.81 (interquartile range [IQR], 1.36 to 2.53]) were initially included. Median follow-up was 2.72 years (IQR, 1.32-4.08; max 6.0). Propensity score matching returned 329 TAVI cases and 593 SAVR controls. Thirty-day mortality was 11 out of 329 (3.32%) in TAVI and 18 out of 593 (3.03%) in SAVR (risk ratio, 1.10; 95% CI, 0.52-2.37; P = .801) groups, respectively. At 2 years, survival curves began to diverge in favor of SAVR, which was associated with 30% lower mortality (hazard ratio, 0.70; 95% CI, 0.496-0.997; P = .048)., Conclusions: Our data did not demonstrate a survival difference between TAVI and SAVR during the first 2 postprocedure years. After that time, SAVR is associated with improved survival. Extended observations from randomized trials in low-risk patients undergoing elective surgery are warranted to confirm these findings and draw definitive conclusions., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Despite evidence suggesting the benefit of prophylactic regional antibiotic delivery (RAD) to sternal edges during cardiac surgery, it is seldom performed in clinical practice. The value of topical vancomycin and gentamicin for sternal wound infections (SWI) prophylaxis was further questioned by recent studies including randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to comprehensively assess the safety and effectiveness of RAD to reduce the risk of SWI.We screened multiple databases for RCTs assessing the effectiveness of RAD (vancomycin, gentamicin) in SWI prophylaxis. Random effects meta-analysis was performed. The primary endpoint was any SWI; other wound complications were also analysed. Odds Ratios served as the primary statistical analyses. Trial sequential analysis (TSA) was performed.Thirteen RCTs (N = 7,719 patients) were included. The odds of any SWI were significantly reduced by over 50% with any RAD: OR (95%CIs): 0.49 (0.35-0.68); p < 0.001 and consistently reduced in vancomycin (0.34 [0.18-0.64]; p < 0.001) and gentamicin (0.58 [0.39-0.86]; p = 0.007) groups (p subgroup  = 0.15). Similarly, RAD reduced the odds of SWI in diabetic and non-diabetic patients (0.46 [0.32-0.65]; p < 0.001 and 0.60 [0.44-0.83]; p = 0.002 respectively). Cumulative Z-curve passed the TSA-adjusted boundary for SWIs suggesting adequate power has been met and no further trials are needed. RAD significantly reduced deep (0.60 [0.43-0.83]; p = 0.003) and superficial SWIs (0.54 [0.32-0.91]; p = 0.02). No differences were seen in mediastinitis and mortality, however, limited number of studies assessed these endpoints. There was no evidence of systemic toxicity, sternal dehiscence and resistant strains emergence. Both vancomycin and gentamicin reduced the odds of cultures outside their respective serum concentrations' activity: vancomycin against gram-negative strains: 0.20 (0.01-4.18) and gentamicin against gram-positive strains: 0.42 (0.28-0.62); P < 0.001. Regional antibiotic delivery is safe and effectively reduces the risk of SWI in cardiac surgery patients., (© 2024. The Author(s).)

Background: Surgical ablation for atrial fibrillation at the time of isolated coronary artery bypass grafting is reluctantly attempted. Meanwhile, complete revascularization is not always possible in these patients. We attempted to counterbalance the long-term benefits of surgical ablation against the risks of incomplete revascularization., Methods: Atrial fibrillation patients undergoing isolated coronary artery bypass grafting for multivessel disease between 2012 to 2022 and included in the HEart surgery In atrial fibrillation and Supraventricular Tachycardia registry were divided into complete revascularization, complete revascularization with additional grafts, and incomplete revascularization cohorts; these were further split into surgical ablation and non-surgical ablation subgroups., Results: A total of 8,405 patients (78% men; age 69.3 ± 7.9) were included; of those, 5,918 (70.4%) had complete revascularization, and 556 (6.6%) had surgical ablation performed. Number of anastomoses was 2.7 ± 1.2. The median follow-up was 5.1 [interquartile range 2.1-8.8] years. In patients in whom complete revascularization was achieved, surgical ablation was associated with long-term survival benefit: hazard ratio 0.69; 95% confidence intervals (0.50-0.94); P = .020 compared with grafting additional lesions. Similarly, in patients in whom complete revascularization was not achieved, surgical ablation was associated with a long-term survival benefit of 0.68 (0.49-0.94); P = .019. When comparing surgical ablation on top of incomplete revascularization against complete revascularization without additional grafts or surgical ablation, there was no difference between the 2: 0.84 (0.61-1.17); P = .307, which was also consistent in the propensity score-matched analysis: 0.75 (0.39-1.43); P = .379., Conclusion: To achieve complete revascularization is of utmost importance. However, when facing incomplete revascularization at the time of coronary artery bypass grafting in a patient with underlying atrial fibrillation, concomitant surgical ablation on top of incomplete revascularization is associated with similar long-term survival as complete revascularization without surgical ablation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate in-hospital outcomes and long-term survival of patients undergoing cardiac surgery with preoperative atrial fibrillation (AF). We compared different strategies, including no-AF treatment, left atrial appendage occlusion (LAAO) alone, concomitant surgical ablation (SA) alone or both., Methods: A retrospective analysis using the KROK registry included all patients with preoperative diagnosis of AF who underwent cardiac surgery in Poland between between January 2012 and December 2022. Risk adjustment was performed using regression analysis with inverse probability weighting of propensity scores. We assessed 6-year survival with Cox proportional hazards models. Sensitivity analysis was performed based on index cardiac procedure., Results: Initially, 42 510 patients with preoperative AF were identified, and, after exclusion, 33 949 included in the final analysis. A total of 1107 (3.26%) received both SA and LAAO, 1484 (4.37%) received LAAO alone, 3921 (11.55%) SA alone and the remaining 27 437 (80.82%) had no AF-directed treatment. As compared to no treatment, all strategies were associated with survival benefit over 6-year follow-up. A gradient of treatment was observed with the highest benefit associated with SA + LAAO followed by SA alone and LAAO alone (log-rank P < 0.001). Mortality benefits were reflected when stratified by surgery type with the exception of aortic valve surgery where LAAO alone fare worse than no treatment., Conclusions: Among patients with preoperative AF undergoing cardiac surgery, surgical management of AF, particularly SA + LAAO, was associated with lower 6-year mortality. These findings support the benefits of incorporating SA and LAAO in the management of AF during cardiac surgery., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Mutations of the SCN1A gene, which encodes the voltage-dependent Na + channel's α subunit, are associated with diverse epileptic syndromes ranging in severity, even intra-family, from febrile seizures to epileptic encephalopathy. The underlying cause of this variability is unknown, suggesting the involvement of additional factors. The aim of our study was to describe the properties of mutated channels and investigate genetic causes for clinical syndromes' variability in the family of five SCN1A gene p.Arg1596Cys mutation carriers. The analysis of additional genetic factors influencing SCN1A -associated phenotypes was conducted through exome sequencing (WES). To assess the impact of mutations, we used patch clamp analysis of mutated channels expressed in HEK cells and in vivo neural excitability studies (NESs). In cells expressing the mutant channel, sodium currents were reduced. NESs indicated increased excitability of peripheral motor neurons in mutation carriers. WES showed the absence of non-SCA1 pathogenic variants that could be causative of disease in the family. Variants of uncertain significance in three genes, as potential modifiers of the most severe phenotype, were identified. The p.Arg1596Cys substitution inhibits channel function, affecting steady-state inactivation kinetics. Its clinical manifestations involve not only epileptic symptoms but also increased excitability of peripheral motor fibers. The role of Nav1.1 in excitatory neurons cannot be ruled out as a significant factor of the clinical phenotype.

Surgical intervention in the setting of cardiogenic shock (CS) is burdened with high mortality. Due to acute condition, detailed diagnoses and risk assessment is often precluded. Atrial fibrillation (AF) is a risk factor for perioperative complications and worse survival but little is known about AF patients operated in CS. Current analysis aimed to determine prognostic impact of preoperative AF in patients undergoing heart surgery in CS. We analyzed data from the Polish National Registry of Cardiac Surgery (KROK) Procedures. Between 2012 and 2021, 332,109 patients underwent cardiac surgery in 37 centers; 4852 (1.5%) patients presented with CS. Of those 624 (13%) patients had AF history. Cox proportional hazards models were used for computations. Propensity score (nearest neighbor) matching for the comparison of patients with and without AF was performed. Median follow-up was 4.6 years (max.10.0), mean age was 62 (± 15) years and 68% patients were men. Thirty-day mortality was 36% (1728 patients). The origin of CS included acute myocardial infarction (1751 patients, 36%), acute aortic dissection (1075 patients, 22%) and valvular dysfunction (610 patients, 13%). In an unadjusted analysis, patients with underlying AF had almost 20% higher mortality risk (HR 1.19, 95% CIs 1.06-1.34; P = 0.004). Propensity score matching returned 597 pairs with similar baseline characteristics; AF remained a significant prognostic factor for worse survival (HR 1.19, 95% CI 1.00-1.40; P = 0.045). Among patients with CS referred for cardiac surgery, history of AF was a significant risk factor for mortality. Role of concomitant AF ablation and/or left atrial appendage occlusion or more aggressive perioperative circulatory support should be addressed in the future., (© 2023. The Author(s).)

Objective: Preoperative atrial fibrillation (AF) increases risk of stroke, heart failure, and all-cause mortality after cardiac surgery. Despite encouraging results and guideline recommendations, surgical ablation (SA) for AF concomitant with other heart surgery remains low. In the current study we aimed to address the long-term mortality after SA concomitant with cardiac surgery., Methods: This report pertains to the HEart surgery In atrial fibrillation and Supraventricular Tachycardia (HEIST) registry. We identified 20,765 adult patients (62% male) with preoperative AF who underwent conventional sternotomy heart surgery between 2010 and 2021 in 8 tertiary centers in Poland, Netherlands, and Italy. We used Cox proportional hazards models for computations and propensity score matching to minimize differences in baseline characteristics., Results: Of included patients, 2755 (13.4%) underwent SA for AF. The highest rates of SA were observed for mitral interventions (mitral valve repair or replacement and tricuspid intervention, 25.2%), lowest for isolated coronary artery bypass grafting (6.2%). Patients in the SA group were younger (mean age 64.5 ± 9.0 years vs 68.7 ± 16.0 years; P < .001) and lower risk (mean European System for Cardiac Operative Risk Evaluation [EuroSCORE] II, 4.1 vs 5.7; P < .001). During the 11-year study period, there was a mortality reduction associated with SA (hazard ratio, 0.57; 95% CI, 0.52-0.62; P < .001). After propensity matching, 2750 pairs with similar baseline characteristics were identified. SA was associated with 16% mortality decline (hazard ratio, 0.84; 95% CI, 0.75-0.94; P = .003)., Conclusions: In this multicenter, retrospective, propensity matched study, SA concomitant with other cardiac surgery was associated with improved long-term survival regardless of baseline surgical risk., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Despite guideline recommendations, routine application of topical antibiotic agents to sternal edges after cardiac surgery is seldom done. Recent randomized controlled trials have also questioned the effectiveness of topical vancomycin in sternal wound infection prophylaxis., Methods: We screened multiple databases for observational studies and randomized controlled trials assessing the effectiveness of topical vancomycin. Random effects meta-analysis and risk-profile regression were performed, and randomized controlled trials and observational studies were analyzed separately. The primary endpoint was sternal wound infection; other wound complications were also analyzed. Risk ratios served as primary statistics., Results: Twenty studies (N = 40,871) were included, of which 7 were randomized controlled trials (N = 2,187). The risk of sternal wound infection was significantly reduced by almost 70% in the topical vancomycin group (risk ratios [95% confidence intervals]: 0.31 (0.23-0.43); P < .00001) and was comparable between randomized controlled trials (0.37 [0.21-0.64]; P < .0001) and observational studies (0.30 [0.20-0.45]; P < .00001; P subgroup  = .57). Topical vancomycin significantly reduced the risk of superficial sternal wound infections (0.29 [0.15-0.53]; P < .00001) and deep sternal wound infections (0.29 [0.19-0.44]; P < .00001). A reduction in the risk of mediastinitis and sternal dehiscence risks was also demonstrated. Risk profile meta-regression showed a significant relationship between a higher risk of sternal wound infection and a higher benefit accrued with topical vancomycin (ß-coeff. = -0.00837; P < .0001). The number needed to treat was 58.2. A significant benefit was observed in patients with diabetes mellitus (risk ratios 0.21 [0.11-0.39]; P < .00001). There was no evidence of vancomycin or methicillin resistance; on the contrary, the risk of gram-negative cultures was reduced by over 60% (risk ratios 0.38 [0.22-0.66]; P = .0006)., Conclusion: Topical vancomycin effectively reduces the risk of sternal wound infection in cardiac surgery patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Extracorporeal membrane oxygenation (ECMO) is a recognized method of support in patients with severe and refractory acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. While veno-venous (VV) ECMO is the most common type, some patients with severe hypoxemia may require modifications to the ECMO circuit. In this study, we aimed to investigate the effects of adding a second drainage cannula to the circuit in patients with refractory hypoxemia, on their gas exchange, mechanical ventilation, ECMO settings, and clinical outcomes., Methods: We conducted an observational retrospective study based on a single-center institutional registry including all consecutive cases of COVID-19 patients requiring ECMO admitted to the Centre of Extracorporeal Therapies in Warsaw between March 1, 2020 and March 1, 2022. We selected patients who had an additional drainage cannula inserted. Changes in ECMO and ventilator settings, blood oxygenation, and hemodynamic parameters, as well as clinical outcomes were assessed., Results: Of 138 VV ECMO patients, 12 (9%) patients met the inclusion criteria. Ten patients (83%) were men, and mean age was 42.2 ± 6.8. An addition of drainage cannula resulted in a significant raise in ECMO blood flow (4.77 ± 0.44 to 5.94 ± 0.81 [L/min]; p = 0.001), and the ratio of ECMO blood flow to ECMO pump rotations per minute (RPM), whereas the raise in ECMO RPM alone was not statistically significant (3432 ± 258 to 3673 ± 340 [1/min]; p = 0.064). We observed a significant drop in ventilator FiO 2 and a raise in PaO 2 to FiO 2 ratio, while blood lactates did not change significantly. Nine patients died in hospital, one was referred to lung transplantation center, two were discharged uneventfully., Conclusions: The use of an additional drainage cannula in severe ARDS associated with COVID-19 allows for an increased ECMO blood flow and improved oxygenation. However, we observed no further improvement in lung-protective ventilation and poor survival., (© 2023 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Guanfacine (an alpha-2A receptor agonist) is a commonly used drug with recognized efficacy in the treatment of attention deficit hyperactivity disorder (ADHD). This study aimed to assess the effects of guanfacine on short-lasting (interictal) epileptiform discharges in cortical neurons. Moreover, we assessed the effects of guanfacine on voltage-gated sodium currents., Methods: We conducted patch-clamp recordings in prefrontal cortex pyramidal neurons obtained from young rats. Interictal epileptiform events were evoked in cortical slices in a zero magnesium proepileptic extracellular solution with an elevated concentration of potassium ions., Results: Interictal epileptiform discharges were spontaneous depolarisations, which triggered action potentials. Guanfacine (10 and 100 µM) inhibited the frequency of epileptiform discharges. The effect of guanfacine on interictal events persisted in the presence of alpha-2 adrenergic receptor antagonist idazoxan. The tested drug inhibited neuronal excitability. Tonic NMDA currents were not influenced by guanfacine. Recordings from dispersed neurons showed that the tested drug (10 and 100 µM) inhibited persistent and fast inactivating voltage-gated sodium currents., Conclusions: This study shows that guanfacine inhibits interictal discharges in cortical neurons independently of alpha-2A adrenergic receptors. This effect may be mediated by voltage-gated sodium currents. Inhibition of interictal activity by guanfacine may be of clinical importance because interictal events often occur in patients with ADHD and may contribute to symptoms of this disease., (© 2023. The Author(s).)

Background: Transcatheter aortic valve implantation (TAVI) has become a broadly acceptable alternative to AV surgery in patients with aortic stenosis (AS). New valve designs are becoming available to address the shortcomings of their predecessors and improve clinical outcomes., Methods: A systematic review and meta-analysis was carried out to compare Medtronic's Evolut PRO, a new valve, with the previous Evolut R design. Procedural, functional and clinical endpoints according to the VARC-2 criteria were assessed., Results: Eleven observational studies involving N = 12,363 patients were included. Evolut PRO patients differed regarding age ( p < 0.001), sex ( p < 0.001) and STS-PROM estimated risk. There was no difference between the two devices in terms of TAVI-related early complications and clinical endpoints. A 35% reduction of the risk of moderate-to-severe paravalvular leak (PVL) favoring the Evolut PRO was observed (RR 0.66, 95%CI, [0.52, 0.86] p = 0.002; I 2 = 0%). Similarly, Evolut PRO-treated patients demonstrated a reduction of over 35% in the risk of serious bleeding as compared with the Evolut R (RR 0.63, 95%CI, [0.41, 0.96]; p = 0.03; I 2 = 39%), without differences in major vascular complications., Conclusions: The evidence shows good short-term outcomes of both the Evolut PRO and Evolut R prostheses, with no differences in clinical and procedural endpoints. The Evolut PRO was associated with a lower rate of moderate-to-severe PVL and major bleeding.

Background: While tackling moderate tricuspid regurgitation (TR) simultaneously with left-side heart surgery is recommended by the guidelines, the procedure is still seldom performed, especially in the minimally invasive setting. Atrial fibrillation (AF) is a known marker of both mortality and TR progression after mitral valve surgery., Aims: This study aimed to investigatev the safety of performing tricuspid intervention and minimally invasive mitral valve surgery (MIMVS) in patients with preoperative AF., Methods: We retrospectively analyzed data from the Polish National Registry of Cardiac Surgery Procedures collected between 2006 and 2021. We included all patients who underwent MIMVS (mini-thoracotomy, totally thoracoscopic, or robotic surgery) and had presented with moderate tricuspid regurgitation and AF preoperatively. The primary endpoint was death from any cause at 30 days and at the longest available follow-up after MIMVS with tricuspid intervention vs. MIMVS alone. We used propensity score (PS) matching to account for baseline differences between groups., Results: We identified 1545 patients with AF undergoing MIMVS, 54.7% were men aged 66.7 (mean [standard deviation, SD], 9.2) years. Of those, 733 (47.4%) underwent concomitant tricuspid valve intervention. At 13 years of follow-up, the addition of tricuspid intervention was associated with 33% higher mortality as compared to MIMVS alone (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05-1.69; P = 0.02). PS matching resulted in identifying 565 well-balanced pairs. Concomitant tricuspid intervention did not influence long-term follow-up (HR, 1.01; 95 CI, 0.74-1.38; P = 0.94)., Conclusions: After adjusting for baseline confounders, the addition of tricuspid intervention for moderate tricuspid regurgitation to MIMVS did not increase perioperative mortality nor influence long-term survival.

Introduction: Atrial fibrillation (AF) is a prevalent disease considerably contributing to the worldwide cardiovascular burden. For patients at high thromboembolic risk (CHA 2 DS 2 -VASc ≥3) and not suitable for chronic oral anticoagulation, owing to history of major bleeding or other contraindications, left atrial appendage occlusion (LAAO) is indicated for stroke prevention, as it lowers patient's ischaemic burden without augmentation in their anticoagulation profile., Methods and Analysis: Stand-Alone Left Atrial appendage occlusion for throMboembolism prevention in nonvalvular Atrial fibrillatioN DiseasE Registry (SALAMANDER) will be conducted in 10 heart surgery and cardiology centres across Poland to assess the outcomes of LAAO performed by fully thoracoscopic-epicardial, percutaneous-endocardial or hybrid endo-epicardial approach. The registry will include patients with nonvalvular AF at a high risk of thromboembolic and bleeding complications (CHA2DS2-VASc Score ≥2 for males, ≥3 for females, HASBLED score ≥2) referred for LAAO. The first primary outcome is composite procedure-related complications, all-cause death or major bleeding at 12 months. The second primary outcome is a composite of ischaemic stroke or systemic embolism at 12 months. The third primary outcome is the device-specific success assessed by an independent core laboratory at 3-6 weeks. The quality of life (QoL) will be assessed as well based on the QoL EQ-5D-5L questionnaire. Medication and drug adherence will be assessed as well., Ethics and Dissemination: Before enrolment, a detailed explanation is provided by the investigator and patients are given time to make an informed decision. The patient's data will be protected according to the requirements of Polish law, General Data Protection Regulation (GDPR) and hospital Standard Operating Procedures. The study will be conducted in accordance with the Declaration of Helsinki. Ethical approval was granted by the local Bioethics Committee of the Upper-Silesian Medical Centre of the Silesian Medical University in Katowice (decision number KNW/0022/KB/284/19). The results will be published in peer-reviewed journals and presented during national and international conferences., Trial Registration Number: NCT05144958., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Among patients referred for cardiac surgery, atrial fibrillation (AF) is a common comorbidity and a risk factor for postoperative arrhythmias (eg, sinus node dysfunction, atrioventricular heart block), including those requiring permanent pacemaker (PPM) implantation., Objective: The purpose of this study was to evaluate the prevalence and long-term survival of postoperative PPM implantation in patients with preoperative AF who underwent valve surgery with or without concomitant procedures., Methods: Presented analysis pertains to the HEIST (HEart surgery In atrial fibrillation and Supraventricular Tachycardia) registry. During the study period, 11,949 patients underwent valvular (aortic, mitral, or tricuspid valve replacement or repair) surgery and/or surgical ablation (SA) and were stratified according to postoperative PPM status., Results: PPM implantation after surgery was necessary in 2.5% of patients, with significant variation depending on the type of surgery (from 1.1% in mitral valve repair to 3.3% in combined mitral and tricuspid valve surgery). In a multivariate logistic regression model, tricuspid intervention (P <.001), cardiopulmonary bypass time (P = .024), and endocarditis (P = .014) were shown to be risk factors for PPM. Over long-term follow-up, PPM was not associated with increased mortality compared to no PPM (hazard ratio 0.96; 95% confidence interval 0.77-1.19; P = .679). SA was not associated with PPM implantation. However, SA improved survival regardless of PPM status (log rank P <.001)., Conclusion: In patients with preoperative AF, the need for PPM implantation after valve surgery or SA is not an infrequent outcome, with SA not affecting its prevalence but actually improving long-term survival., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Although endorsed by international guidelines, complete revascularization (CR) with Coronary Artery Bypass Grafting (CABG) remains underused. In higher-risk patients such as those with pre-operative atrial fibrillation (AF), the effects of CR are not well studied., Methods: We analyzed patients' data from the HEIST (HEart surgery In AF and Supraventricular Tachycardia) registry. Between 2012 and 2020 we identified 4770 patients with pre-operative AF and multivessel coronary artery disease who underwent isolated CABG. We divided the cohort according to the completeness of the revascularization and used propensity score matching (PSM) to minimize differences between baseline characteristics. The primary endpoint was all-cause mortality., Results: Median follow-up was 4.7 years [interquartile range (IQR) 2.3-6.9]. PSM resulted in 1,009 pairs of complete and incomplete revascularization. Number of distal anastomoses varied, accounting for 3.0 + -0.6 vs. 1.7 + -0.6, respectively. Although early (< 24 h) and 30-day post-operative mortalities were not statistically different between non-CR and CR patients [Odds Ratio (OR) and 95% Confidence Intervals (CIs): 1.34 (0.46-3.86); P = 0.593, Hazard Ratio (HR) and 95% CIs: 0.88 (0.59-1.32); P = 0.542, respectively] the long term mortality was nearly 20% lower in the CR cohort [HR (95% CIs) 0.83 (0.71-0.96); P = 0.011]. This benefit was sustained throughout subgroup analyses, yet most accentuated in low-risk patients (younger i.e., < 70 year old, with a EuroSCORE II < 2%, non-diabetic) and when off-pump CABG was performed., Conclusion: Complete revascularization in patients with pre-operative AF is safe and associated with improved survival. Particular survival benefit with CR was observed in low-risk patients undergoing off-pump CABG., 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 © 2022 Pasierski, Staromłyński, Finke, Litwinowicz, Filip, Kowalówka, Wańha, Kołodziejczak, Piekuś-Słomka, Łoś, Stefaniak, Wojakowski, Jemielity, Rogowski, Deja, Jagielak, Bartus, Mariani, Li, Matteucci, Ronco, Jiritano, Fina, Martucci, Meani, Raffa, Słomka, Malvidni, Lorusso, Zembala, Suwalski and Kowalewski.)

Capsaicin is a natural compound found in chili peppers and is used in the diet of many countries. The important mechanism of action of capsaicin is its influence on TRPV1 channels in nociceptive sensory neurons. Furthermore, the beneficial effects of capsaicin in cardiovascular and oncological disorders have been described. Many recent publications show the positive effects of capsaicin in animal models of brain disorders. In Alzheimer's disease, capsaicin reduces neurodegeneration and memory impairment. The beneficial effects of capsaicin in Parkinson's disease and depression have also been described. It has been found that capsaicin reduces the area of infarction and improves neurological outcomes in animal models of stroke. However, both proepileptic and antiepileptic effects of capsaicin in animal models of epilepsy have been proposed. These contradictory results may be caused by the fact that capsaicin influences not only TRPV1 channels but also different molecular targets such as voltage-gated sodium channels. Human studies show that capsaicin may be helpful in treating stroke complications such as dysphagia. Additionally, this compound exerts pain-relieving effects in migraine and cluster headaches. The purpose of this review is to discuss the mechanisms of the beneficial effects of capsaicin in disorders of the central nervous system.

It has been repeatedly proved that Nav1.8 tetrodotoxin (TTX)-resistant sodium currents are expressed in peripheral sensory neurons where they play important role in nociception. There are very few publications that show the presence of TTX-resistant sodium currents in central neurons. The aim of this study was to assess if functional Nav1.8 TTX-resistant sodium currents are expressed in prefrontal cortex pyramidal neurons. All recordings were performed in the presence of TTX in the extracellular solution to block TTX-sensitive sodium currents. The TTX-resistant sodium current recorded in this study was mainly carried by the Nav1.8 sodium channel isoform because the Nav1.9 current was inhibited by the -65 mV holding potential that we used throughout the study. Moreover, the sodium current that we recorded was inhibited by treatment with the selective Nav1.8 inhibitor A-803467. Confocal microscopy experiments confirmed the presence of the Nav1.8 α subunit in prefrontal cortex pyramidal neurons. Activation and steady state inactivation properties of TTX-resistant sodium currents were also assessed in this study and they were similar to activation and inactivation properties of TTX-resistant sodium currents expressed in dorsal root ganglia (DRG) neurons. Moreover, this study showed that carbamazepine (60 µM) inhibited the maximal amplitude of the TTX-resistant sodium current. Furthermore, we found that carbamazepine shifts steady state inactivation curve of TTX-resistant sodium currents toward hyperpolarization. This study suggests that the Nav1.8 TTX-resistant sodium channel is expressed not only in DRG neurons, but also in cortical neurons and may be molecular target for antiepileptic drugs such as carbamazepine., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: Atrial fibrillation (AF) is a relatively common comorbidity among patients referred for coronary artery bypass grafting (CABG) and is associated with poorer prognosis. However, little is known about how surgical technique influences survival in this population., Aim: The current analysis aimed to determine whether total arterial revascularization (TAR) is associated with improved long-term outcomes in patients with preoperative AF., Methods: We analyzed patients' data from the HEIST (HEart surgery In atrial fibrillation and Supraventricular Tachycardia) registry. The registry, to date, involves five tertiary high-volume centers in Poland. Between 2006 and 2019, 4746 patients presented with preoperative AF and multivessel coronary artery disease and underwent CABG. We identified cases of TAR and used propensity score matching to determine non-TAR controls. Median follow-up was 4.1 years (interquartile range [IQR], 1.9-6.8 years)., Results: Propensity matching resulted in 295 pairs of TAR vs. non-TAR. The mean (standard deviation [SD]) number of distal anastomoses was 2.5 (0.6) vs. 2.5 (0.6) (P = 0.94) respectively. Operative and 30-day mortality was not different between TAR and non-TAR patients (hazard ratio [HR] and 95% confidence intervals [CIs], 0.17 (0.02-1.38); P = 0.12 and 0.74 [0.40-1.35]; P = 0.33, respectively). By contrast, TAR was associated with nearly 30% improved late survival: HR, 0.72 (0.55-0.93); P = 0.01. This benefit was sustained in subgroup analyses, yet most pronounced in low-risk patients ( < 70 years old; EuroSCORE II < 2; no diabetes) and when off-pump CABG was performed., Conclusions: TAR in patients with preoperative AF is safe and associated with improved survival, with particular survival benefits in younger low-risk patients undergoing off-pump CABG.

Observational studies suggest improved outcomes with multiple (MAG) as compared to single arterial grafting (SAG) in patients with multivessel coronary artery disease and undergoing coronary artery bypass grafting (CABG). Even though around 6% of CABG patients have preoperative atrial fibrillation, previous studies did not address MAG versus SAG comparison in this setting. Data from KROK (Polish National Registry of Cardiac Surgery Procedures) were retrospectively collected. 5738 patients with multivessel coronary artery disease and AF (77.9% men, mean age 69.0 ± 8.0) undergoing isolated CABG surgery between 2006 and 2019 in 37 reference centers across Poland were analyzed. Propensity score matching was performed. Primary endpoint was mid-term survival. Median follow-up was 5 years ([IQR 1.9-7.6], max.13). One-to-three Propensity score matching included 2364 patients divided into MAG (591) and SAG (1773) subsets. Subjects were no different in terms of baseline risk and surgical characteristics. Number of distal anastomoses was 2.82 ± 0.83 versus 2.80 ± 0.75 (P = 0.516) for MAG and SAG, respectively. In-hospital outcomes and mortality risk at 1-year (hazard ratio, 95% confidence intervals: 1.13 [0.81-1.58]; P = 0.469) was unchanged with MAG. Multiple arterial grafting was associated with 20% improved mid-term survival: HR 0.80; (95% confidence intervals: 0.65-0.97); P = 0.026. Benefit was sustained in subgroup analyses, yet most appraised in low risk patients (<70-year-old; EuroSCORE <2; no diabetes) and when complete revascularization was achieved. Multiple as compared to single arterial grafting in atrial fibrillation patients undergoing CABG is safe and associated with improved mid-term survival. A particular survival benefit was observed in lower risk patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In SARS-CoV-2 patients with severe acute respiratory distress syndrome (ARDS), Veno-Venous Extracorporeal Membrane Oxygenation (V-V ECMO) was shown to provide valuable treatment with reasonable survival in large multi-centre investigations. However, in some patients, conversion to modified ECMO support forms may be needed. In this single-centre retrospective registry, all consecutive patients receiving V-V ECMO between 1 March 2020 to 1 May 2021 were included and analysed. The patient cohort was divided into two groups: those who remained on V-V ECMO and those who required conversion to other modalities. Seventy-eight patients were included, with fourteen cases (18%) requiring conversions to veno-arterial (V-A) or hybrid ECMO. The reasons for the ECMO mode configuration change were inadequate drainage (35.7%), inadequate perfusion (14.3%), myocardial infarction (7.1%), hypovolemic shock (14.3%), cardiogenic shock (14.3%) and septic shock (7.1%). In multivariable analysis, the use of dobutamine ( p = 0.007) and a shorter ICU duration ( p = 0.047) predicted the conversion. The 30-day mortality was higher in converted patients (log-rank p = 0.029). Overall, only 19 patients (24.4%) survived to discharge or lung transplantation. Adverse events were more common after conversion and included renal, cardiovascular and ECMO-circuit complications. Conversion itself was not associated with mortality in the multivariable analysis. In conclusion, as many as 18% of patients undergoing V-V ECMO for COVID-19 ARDS may require conversion to advanced ECMO support.

Aims: Because reported mortality on veno-arterial (V-A) extracorporeal life support (ECLS) substantially varies between centres, the aim of the current analysis was to assess the outcomes between units performing heart transplantation and/or implanting ventricular assist device (HTx/VAD) vs. non-HTx/VAD units in patients undergoing V-A ECLS for cardiogenic shock., Methods and Results: Systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed using PubMed/MEDLINE databases until 30 November 2019. Articles reporting in-hospital/30-day mortality and centre's HTx/VAD status were included. In-hospital outcomes and long-term survival were analysed in subgroup meta-analysis. A total of 174 studies enrolling n = 13 308 patients were included with 20 series performed in non-HTx/VAD centres (1016 patients, 7.8%). Majority of patients underwent V-A ECLS for post-cardiotomy shock (44.2%) and acute myocardial infarction (20.7%). Estimated overall in-hospital mortality was 57.2% (54.9-59.4%). Mortality rates were higher in non-HTx/VAD [65.5% (59.8-70.8%)] as compared with HTx/VAD centres [55.8% (53.3-58.2%)], P < 0.001. Estimated late survival was 61.8% (55.7-67.9%) without differences between non-HTx/VAD and HTx/VAD centres: 66.5% (30.3-1.02%) vs. 61.7% (55.5-67.8%), respectively (P = 0.797). No differences were seen with respect to ECLS duration, limb complications, and reoperations for bleeding, kidney injury, and sepsis. Yet, weaning rates were higher in HTx/VAD vs. non-HTx/VAD centres: 58.7% (56.2-61.1%) vs. 48.9% (42.0-55.9%), P = 0.010. Estimated rate of bridge to heart transplant was 6.6% (5.2-8.3%) with numerical, yet not statistically significant, difference between non-HTx/VAD [2.7% (0.8-8.3%)] as compared with HTx/VAD [6.7% (5.3-8.6%)] (P = 0.131)., Conclusions: Survival after V-A ECLS differed according to centre's HTx/VAD status. Potentially different risk profiles of patients must be taken account for before definite conclusions are drawn., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Capsaicin, a compound found in chili peppers, causes burning sensations by acting on the peripheral sensory system. However, it has also been reported to exert substantial effects on central neurons. The aim of this patch-clamp study was to test the antiepileptic potential of capsaicin in prefrontal cortical pyramidal neurons. Capsaicin at a concentration of 60 μM inhibited neuronal excitability. Moreover, later spikes in response to 50-s-long current steps were much smaller in amplitude in the presence of 60 μM capsaicin than in control solution. The tested compound did not influence the membrane potential. Voltage-clamp recordings showed that capsaicin markedly enhanced the use-dependent block of sodium channels (sodium currents were evoked at frequencies of 0,5 Hz and 10 Hz). The presence of the compound shifted the steady-state inactivation curve of sodium channels towards hyperpolarization, which suggests greater inactivation of sodium channels at rest in the presence of capsaicin. Moreover, capsaicin inhibited epileptiform events evoked in three different proepileptic solutions. Capsaicin abolished interictal-like events lasting less than 1 s recorded in zero magnesium solution with an increased potassium ion concentration. The drug also abolished long ictal events evoked in zero magnesium solution containing 4-AP. Moreover, ictal events recorded in zero magnesium solution containing picrotoxin were substantially shortened in the presence of capsaicin. We suggest that capsaicin exerts an antiepileptic effect. The important mechanism behind this phenomenon seems to be the inhibition of sodium channels, which is an effect of many antiepileptic drugs., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Frequent occurrence of paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) was the main concern with early-generation devices and focused technological improvements. Current systematic review and meta-analysis sought to compare outcomes of TAVR for severe native valve stenosis with next-generation devices: Lotus and Sapien 3., Methods: Electronic databases were screened for studies comparing outcomes of TAVR with Lotus and Sapien 3. In a random-effects meta-analysis, the pooled incidence rates of procedural, clinical and functional outcomes according to VARC-2 definitions were assessed., Results: Eleven observational studies including 2,836 patients (Lotus N=862 vs. Sapien 3 N=1,974) met inclusion criteria. No differences were observed regarding composite endpoints-device success and early safety. Similarly, 30-day mortality, major vascular complications, acute kidney injury and serious bleeding events were similar with both devices. Lotus valve demonstrated 35% reduction of the risk for mild PVL: risk ratio (RR) 0.65, 95% confidence interval (CI): 0.49-0.85, P=0.002; but there were no statistical differences with regard to moderate/severe PVL (RR 0.56, 95% CI: 0.18-1.77, P=0.320). Lotus valves produced significantly higher mean transaortic gradients: mean difference (MD) 0.88 mmHg, 95% CI, 0.24-1.53 mmHg, P=0.007; however, without translation into higher rate of prosthesis-patient mismatch (RR 1.10, 95% CI: 0.82-1.47, P=0.540). As compared to Sapien 3, Lotus device placement was associated with significantly higher rate of permanent pacemaker implantation (RR 2.30, 95% CI: 1.95-2.71, P<0.00001) and cerebrovascular events (RR 1.76, 95% CI: 1.03-2.99, P=0.040)., Conclusions: Lotus valve, as compared with Sapien 3, was associated with lower risk for PVL but higher risk for permanent pacemaker implantation and cerebrovascular events., Competing Interests: Conflicts of Interest: MK serves as the unpaid editorial board member of Journal of Thoracic Disease from Sep 2018 to Aug 2020. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Valproic acid has a long-standing reputation of effectively treating the symptoms of not only epilepsy but also psychiatric conditions. In the latter, the exact mechanism by which valproate exerts its effect remains unclear. In this study, epileptiform bursts were recorded from pyramidal neurons in the prefrontal cortex (the brain region thought to be involved in psychiatric disorders) using the patch-clamp technique. An extracellular solution with no magnesium ions and elevated potassium levels that is known to induce epileptiform activity in vitro was used. Because of their short durations, the epileptiform bursts were regarded as interictal-like epileptiform activity, which is believed to be involved in cognitive impairment. Interictal discharges occur in many neuropsychiatric disorders as well as in healthy population. Epileptic activity in prefrontal cortex pyramidal neurons was potently inhibited by two therapeutic concentrations of valproic acid (20 μM and 200 μM). Moreover, valproate suppressed spontaneous excitatory postsynaptic potentials. Epileptiform bursts were fully inhibited by NMDA receptor antagonist, which suggests that epileptiform activity is driven by NMDA receptors. The inhibition of excitability in prefrontal cortex pyramidal neurons by valproate was also shown. This study shows that it is possible to evoke NMDA-dependent epileptiform activity in prefrontal cortex pyramidal neurons in vitro. We suggest that the prefrontal cortex is a good region for studying the influence of drugs on interictal epileptiform activity., (Copyright © 2019 Elsevier B.V. All rights reserved.)