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Background and Aims: This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications., Methods: A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC., Results: The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size -0.11 (-0.36 to 0.13)] and mortality [effect size -0.07 (-0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06-0.58)]., Conclusions: In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Objectives: The evolving surgical techniques in thoracoscopic surgery necessitate the exploration of anesthesiological techniques. This study aimed to investigate whether incorporating a continuous erector spinae plane (ESP) block into a multimodal analgesia regimen is non-inferior to continuous thoracic epidural analgesia (TEA) in terms of quality of postoperative recovery for patients undergoing elective unilateral video-assisted thoracoscopic surgery., Methods: We conducted a multicenter, prospective, randomized, open-label non-inferiority trial between July 2020 and December 2022. Ninety patients were randomly assigned to receive either continuous ESP block or TEA. The primary outcome parameter was the Quality of Recovery-15 (QoR-15) score, measured before surgery as a baseline and on postoperative days 0, 1, and 2. Secondary outcome parameters included pain scores, length of hospital stay, morphine consumption, nausea and vomiting, itching, speed of mobilization, and urinary catheterization., Results: Analysis of the primary outcome showed a mean QoR-15 difference between the groups ESP block versus TEA of 1 (95% CI -9 to -12, p=0.79) on day 0, -1 (95% CI -11 to -8, p=0.81) on day 1 and -2 (95% CI -14 to -11, p=0.79) on day 2., Conclusions: The continuous ESP block is non-inferior to TEA in video-assisted thoracoscopic surgery., Trial Registration Number: Dutch Trial Register (NL6433)., Competing Interests: Competing interests: AB is a clinical consultant for Philips Research (Eindhoven, the Netherlands) since January 2016. JSHAK received a grant from Werfen BV for unrelated research. The other authors declare no potential conflict of interest., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Systemic hypothermia with bilateral antegrade selective cerebral perfusion (ASCP) is the preferred cerebral protective strategy for type A aortic dissection surgery. The optimal ASCP flow rate remains uncertain and the target flow cannot always be reached due to pressure limitations. The aim of this study was to assess the correlation between ASCP flow and regional cerebral oxygen saturation (rSO2)., Methods: A retrospective analysis was performed on 140 patients with acute type A aortic dissection who underwent surgery with moderate hypothermic circulatory arrest and bilateral ASCP between 2015 and 2021. Pearson correlation analysis was performed between ASCP flow and rSO2., Results: The median circulatory arrest duration was 46.5 (IQR:37.0-61.0) minutes. There was no significant correlation between ASCP flow and rSO2 for both the right (r = -.02, p = .851), and the left hemisphere (r = - .04, p = .618). The rSO2 values for ten patients who received > 10 mL/kg/min flow did not differ significantly from 130 patients who received 10 mL/kg/min or less for both the left hemisphere ( p = .135), and the right hemisphere ( p = .318). The ASCP flow was 5.1 (IQR:5.0- 6.5) mL/kg/min in five patients with, and 7.2 (IQR:5.8-8.3) mL/kg/min in 135 patients without a watershed infarction ( p = .098)., Conclusions: There was no correlation between ASCP flow rate and rSO2 in patients with acute type A aortic dissection. Furthermore, ASCP flow below 10 mL/kg/min was not associated with a reduction in rSO2. Definitive associations between ASCP flow and neurological outcome after type A aortic dissection surgery need further investigation., Competing Interests: Declaration of conflicting interestsThe authors received no financial support for the research, authorship and/or publication of this article.

Objectives: Aortic valve repair procedures are technically challenging, and current intraoperative evaluation methods often fail to predict the final echocardiographic result. We have developed a novel intraoperative aortic valve visualization and pressurization (AVP) device, enabling valve inspection under physiological conditions, and measuring aortic valve insufficiency (AI) during cardioplegic arrest., Methods: The AVP device is attached to the (neo)aorta, after any type of aortic valve repair, while the heart is arrested. The root is pressurized (60-80 mmHg) using a saline solution and an endoscope is introduced. The valve is inspected, and the amount of valvular leakage is measured. Postoperative 'gold standard' transesophageal echocardiogram measurements of AI are performed and compared against regurgitation volume measured., Results: In 24 patients undergoing valve-sparing root replacement, the AVP device was used. In 22 patients, postoperative echocardiographic AI was ≤ grade 1. The median leakage was 90 ml/min, IQR 60-120 ml/min. In 3 patients, additional adjustments after visual inspection was performed. In 2 patients, with complex anatomy, the valve was replaced. In one, after evaluation with the device, there was undesirable result visually and residual AI of 330 ml/min, and in another, 260 ml/min residual AI was measured and valve restriction on visual inspection., Conclusions: The novel AVP device enables intraoperative evaluation of the valve under physiological conditions, while still on arrested heart, and allows for targeted adjustments. The AVP device can be an important aid for intraoperative evaluation of the aortic valve, during valve repair and valve-sparing procedures, thereby making the operative result more predictable and the operation more efficient., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied., Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall., Methods: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue., Results: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565-nm light pulses at an intensity of 25 mW/mm 2 achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4)., Conclusion: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: The effect of an "aggressive" approach on the aortic root in acute type A aortic dissection (ATAAD) remains insufficiently explored., Methods: Retrospective analysis was conducted between 1992 and 2020 of a single-center, prospective cohort of consecutive patients aged ≥18 years diagnosed with ATAAD. Patients were divided into 2 groups: aortic root replacement (ARR; prosthetic or valve-sparing root replacement, n = 141) and conservative root approach (CRA; root sparing of partially dissected root, n = 90; and supracoronary ascending replacement in nondissected root, n = 68). Inverse probability weighting was used to compare patients with different preoperative characteristics. Mean follow-up was 5.1 (0-21) years in ARR and 7.1 (0-25) years in CRA., Results: The frequency of ARR increased over the years, with 19% and 78% of patients undergoing ARR in the earliest and most recent periods, respectively. Early mortality decreased over the years, despite a more aggressive approach, and remained lower in ARR. CRA was associated with a higher hazard of late mortality (hazard ratio, 1.38; 95% CI, 1.12-1.68; P = .001) and reintervention (hazard ratio, 2.08; 95% CI, 1.44-3.56; P = .001). After CRA, new-onset aortic valve insufficiency was a common cause of reintervention., Conclusions: Over the years, there was a gradual increase in the root replacement approach in ATAAD. Root replacement was associated with better long-term survival and fewer reinterventions compared with the conservative approach, whereas the in-hospital mortality decreased during these years. Hence, aggressive root replacement is safe and may be applied in ATAAD with good long-term clinical results, without increased hospital mortality., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Our goal was to evaluate the outcome of valve-sparing root replacement (VSRR) and to compare the outcomes to those of patients having composite valve-graft conduit aortic root replacement (CVG-ARR) in a cohort of patients with aortic root aneurysm ± valve insufficiency, without valvular stenosis. Although valve-sparing procedures are preferable in young patients, there is a lack of comparative data in comparable patients., Methods: The VSRR procedures were performed in 2005 patients, and 218 patients underwent a CVG-ARR procedure. Exclusion criteria included aortic dissection, endocarditis and valvular stenosis. Propensity score matching (3:1 ratio) was applied to compare VSRR (reimplantation 33% and remodelling 67%) and CVG-ARR., Results: We matched 218 patients with CVG-ARR to 654 patients with VSRR (median age, 56.0; median follow-up was 4 years in both groups; interquartile range 1-5 years). Early mortality was 1.1% of those who had VSRR versus 2.3% in those who had CVG-ARR. Survival was 95.4% [95% confidence interval (CI) 94-97%] at 5 years in patients who had VSRR versus 85.4% (95% CI 82-92%) in those who had CVG-ARR; P = 0.002. Freedom from reintervention at 5 years was 96.8% (95% CI 95-98%) with VSRR and 95.4% (95% CI 91-99%) with CVG-ARR (P = 0.98). Additionally, there were more thromboembolic, endocarditis and bleeding events in the patients who had CVG-ARR (P = 0.02)., Conclusions: This multicentre study shows excellent results after valve-sparing root replacement in patients with an ascending aortic aneurysm with or without valve insufficiency. Compared to composite valve-graft aortic root replacement, survival is better and valve-related events are fewer. Consequently, valve-sparing procedures should be considered whenever a durable repair is feasible. We advocate a valve-sparing strategy even in more complex cases when performed in experienced centres., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aims: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translational aspects of this strategy have remained largely unaddressed. Therefore, we investigated optogenetic termination of VTs (i) in the pathologically remodelled heart using an (ii) implantable multi-LED device for (iii) in vivo closed-chest, local illumination., Methods and Results: In order to mimic a clinically relevant sequence of events, transverse aortic constriction (TAC) was applied to adult male Wistar rats before optogenetic modification. This modification took place 3 weeks later by intravenous delivery of adeno-associated virus vectors encoding red-activatable channelrhodopsin or Citrine for control experiments. At 8-10 weeks after TAC, VTs were induced ex vivo and in vivo, followed by programmed local illumination of the ventricular apex by a custom-made implanted multi-LED device. This resulted in effective and repetitive VT termination in the remodelled adult rat heart after optogenetic modification, leading to sustained restoration of sinus rhythm in the intact animal. Mechanistically, studies on the single cell and tissue level revealed collectively that, despite the cardiac remodelling, there were no significant differences in bioelectricity generation and subsequent transmembrane voltage responses between diseased and control animals, thereby providing insight into the observed robustness of optogenetic VT termination., Conclusion: Our results show that implant-based optical cardioversion of VTs is feasible in the pathologically remodelled heart in vivo after local optogenetic targeting because of preserved optical control over bioelectricity generation. These findings add novel mechanistic and translational insight into optical ventricular cardioversion., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Study Objective: The added value of computed tomography (CT) follow-up after elective proximal aortic surgery is unclear. We evaluated the benefit of CT follow-up by assessing the incidence of aorta-related complications and reinterventions detected during routine CT follow-up., Methods: Data on 314 patients undergoing first time elective proximal aortic surgery between 2000 and 2015 were collected. The primary study end points were aorta-related complications and reinterventions, detected during routine CT follow-up. Secondary study endpoints included all aorta-related complications and reinterventions, irrespective of the mode of detection and survival., Results: Median CT follow-up time was 6.8 (IQR 4.1-9.8) years, during which a total of 1303 routine follow-up CT-scans (median 4, IQR 3-5) were performed. During CT follow-up, aorta-related complications were detected in 18 (5.7%) patients, of which 6 (1.6%) underwent reintervention. In total, 28 aorta-related complications were observed in 23 (7.3%) patients, of which 9 led to reintervention. In order to detect 1 aorta-related complication leading to reintervention, 218 routine follow-up CT-scans were required. The unadjusted and EuroSCORE II adjusted hazard ratios of not undergoing CT follow-up on mortality were 1.260 (95% CI 0.705-2.251) and 0.830 (95% CI 0.430-1.605), respectively., Conclusions: Following first time elective proximal aortic surgery, aorta-related complications are uncommon, are not always detected during CT follow-up and, if detected, often do not result in reintervention. Therefore, a more conservative CT follow-up protocol could be considered in selected patients to reduce lifetime radiation burden and health care costs., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Catheter ablation of long-standing persistent atrial fibrillation (LSPAF) remains challenging, with suboptimal success rates obtained following multiple procedures. Thoracoscopic ablation has shown effective at creating transmural lesions around the pulmonary veins and box; however, long-term rhythm follow-up data are lacking. This study aims, for the first time, to assess the long-term outcomes of thoracoscopic pulmonary vein and box ablation in LSPAF., Methods: Rhythm follow-up consisted of continuous rhythm monitoring using implanted loop recorders or 24-h Holter recordings. Rhythm status and touch-up interventions were assessed up to 5 years., Results: Seventy-seven patients with symptomatic LSPAF underwent thoracoscopic ablation in 2 centres. Freedom from atrial arrhythmias at 5 years was 50% following a single thoracoscopic procedure and 68% allowing endocardial touch-up procedures (performed in 21% of patients). The mean atrial fibrillation burden in patients with continuous monitoring was reduced from 100% preoperatively to 0.1% at the end of the blanking period and 8.0% during the second year. Antiarrhythmic drug use decreased from 49.4% preoperative to 12.1% and 14.3% at 2 and 5 years, respectively (P < 0.001). Continuous rhythm monitoring resulted in higher recurrence detection rates compared to 24-h Holter monitoring at 2-year follow-up (hazard ratio: 6.5, P = 0.003), with comparable recurrence rates at 5-year follow-up., Conclusions: Thoracoscopic pulmonary vein and box isolation are effective in long-term restoration of sinus rhythm in LSPAF, especially when complemented by endocardial touch-up procedures, as demonstrated by the 68% freedom rate at 5 years. Continuous rhythm monitoring revealed earlier, but not more numerous documentation of recurrences at 5-year follow-up., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

The lack of a scalable and robust source of well-differentiated human atrial myocytes constrains the development of in vitro models of atrial fibrillation (AF). Here we show that fully functional atrial myocytes can be generated and expanded one-quadrillion-fold via a conditional cell-immortalization method relying on lentiviral vectors and the doxycycline-controlled expression of a recombinant viral oncogene in human foetal atrial myocytes, and that the immortalized cells can be used to generate in vitro models of AF. The method generated 15 monoclonal cell lines with molecular, cellular and electrophysiological properties resembling those of primary atrial myocytes. Multicellular in vitro models of AF generated using the immortalized atrial myocytes displayed fibrillatory activity (with activation frequencies of 6-8 Hz, consistent with the clinical manifestation of AF), which could be terminated by the administration of clinically approved antiarrhythmic drugs. The conditional cell-immortalization method could be used to generate functional cell lines from other human parenchymal cells, for the development of in vitro models of human disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The epicardium, the mesothelial layer covering the heart, is a crucial cell source for cardiac development and repair. It provides cells and biochemical signals to the heart to facilitate vascularization and myocardial growth. An essential element of epicardial behavior is epicardial epithelial to mesenchymal transition (epiMT), which is the initial step for epicardial cells to become motile and invade the myocardium. To identify targets to optimize epicardium-driven repair of the heart, it is vital to understand which pathways are involved in the regulation of epiMT. Therefore, we established a cell culture model for human primary adult and fetal epiMT, which allows for parallel testing of inhibitors and stimulants of specific pathways. Using this approach, we reveal Activin A and ALK4 signaling as novel regulators of epiMT, independent of the commonly accepted EMT inducer TGFβ. Importantly, Activin A was able to induce epicardial invasion in cultured embryonic mouse hearts. Our results identify Activin A/ALK4 signaling as a modulator of epicardial plasticity which may be exploitable in cardiac regenerative medicine., 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. The handling editor declared a shared affiliation with the authors at time of review., (Copyright © 2021 Dronkers, van Herwaarden, van Brakel, Sanchez-Duffhues, Goumans and Smits.)

Rationale: In recent decades, the great potential of human epicardium-derived cells (EPDCs) as an endogenous cell source for cardiac regeneration has been recognized. The limited availability and low proliferation capacity of primary human EPDCs and phenotypic differences between EPDCs obtained from different individuals hampers their reproducible use for experimental studies., Aim: To generate and characterize inducible proliferative adult human EPDCs for use in fundamental and applied research., Methods and Results: Inducible proliferation of human EPDCs was achieved by doxycycline-controlled expression of simian virus 40 large T antigen (LT) with a repressor-based lentiviral Tet-On system. In the presence of doxycycline, these inducible EPDCs (iEPDCs) displayed high and long-term proliferation capacity. After doxycycline removal, LT expression ceased and the iEPDCs regained their cuboidal epithelial morphology. Similar to primary EPDCs, iEPDCs underwent an epithelial-to-mesenchymal transition (EMT) after stimulation with transforming growth factor β3. This was confirmed by reverse transcription-quantitative polymerase chain reaction analysis of epithelial and mesenchymal marker gene expression and (immuno) cytochemical staining. Collagen gel-based cell invasion assays demonstrated that mesenchymal iEPDCs, like primary EPDCs, possess increased invasion and migration capacities as compared to their epithelial counterparts. Mesenchymal iEPDCs co-cultured with sympathetic ganglia stimulated neurite outgrowth similarly to primary EPDCs., Conclusion: Using an inducible LT expression system, inducible proliferative adult human EPDCs were generated displaying high proliferative capacity in the presence of doxycycline. These iEPDCs maintain essential epicardial characteristics with respect to morphology, EMT ability, and paracrine signaling following doxycycline removal. This renders iEPDCs a highly useful new in vitro model for studying human epicardial properties.

Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which is often complicated by aortic valve stenosis (AoS). In tricuspid aortic valve (TAV), AoS strongly associates with coronary artery disease (CAD) with common pathophysiological factors. Yet, it remains unclear whether AoS in patients with BAV is also associated with CAD. This study investigated the association between the aortic valve morphological features and the extent of CAD. Methods and Results A single-center study was performed, including all patients who underwent an aortic valve replacement attributable to AoS between 2006 and 2019. Coronary sclerosis was graded on preoperative coronary angiographies using the coronary artery greater even than scoring method, which divides the coronaries in 28 segments and scores nonobstructive (20%-49% sclerosis) and obstructive coronary sclerosis (>49% sclerosis) in each segment. Multivariate analyses were performed, controlling for age, sex, and CAD risk factors. A total of 1296 patients (931 TAV and 365 BAV) were included, resulting in 548 matched patients. Patients with TAV exhibited more CAD risk factors (odds ratio [OR], 2.66; 95% CI, 1.79-3.96; P <0.001). Patients with BAV had lower coronary artery greater even than 20 (1.61±2.35 versus 3.60±2.79) and coronary artery greater even than 50 (1.24±2.43 versus 3.37±3.49) scores ( P <0.001), even after correcting for CAD risk factors ( P <0.001). Patients with TAV more often needed concomitant coronary revascularization (OR, 3.50; 95% CI, 2.42-5.06; P <0.001). Conclusions Patients with BAV who are undergoing surgery for AoS carry a lower cardiovascular risk profile, correlating with less coronary sclerosis and a lower incidence of concomitant coronary revascularization compared with patients with TAV.

(1) Background: The pathophysiologic basis of an acute type A aortic dissection (TAAD) is largely unknown. In an effort to evaluate vessel wall defects, we systematically studied aortic specimens in TAAD patients. (2) Methods: Ascending aortic wall specimens ( n = 58, mean age 63 years) with TAAD were collected. Autopsy tissues ( n = 17, mean age 63 years) served as controls. All sections were studied histopathologically. (3) Results: Pathomorphology in TAAD showed predominantly moderate elastic fiber fragmentation/loss, elastic fiber thinning, elastic fiber degeneration, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration. The control group showed significantly fewer signs of those histopathological features (none-mild, p = 0.00). It was concluded that the dissection plane consistently coincides with the vasa vasorum network, and that TAAD associates with a significantly thinner intimal layer p = 0.005). (4) Conclusions: On the basis of the systematic evaluation and the consistent presence of diffuse, pre-existing medial defects, we hypothesize that TAAD relates to a developmental defect of the ascending aorta and is caused by a triple-hit mechanism that involves (I) an intimal tear; and (II) a diseased media, which allows (III) propagation of the tear towards the plane of the vasa vasorum where the dissection further progresses.

Objectives: Quality assessment is an important element in providing surgical cancer care. The main objective of this study was to develop a new composite measure 'textbook outcome', to evaluate and improve quality of surgical care for patients undergoing a resection for non-small-cell lung cancer (NSCLC)., Methods: All patients undergoing an anatomical resection for NSCLC from 2012 to 2016 registered in the nationwide Dutch Lung Cancer Audit were included in an analysis to assess usefulness of a composite measure as a quality indicator. Based on expert opinion, textbook outcome was defined as having a complete resection (negative resection margins and sufficient lymph node dissection), plus no 30-day or in-hospital mortality, no reintervention in 30 days, no readmission to the intensive care unit, no prolonged hospital stay (<14 days), no hospital readmission after discharge and no major complications. The percentage of patients with a textbook outcome was calculated per hospital. Between-hospital variation in textbook outcome was analysed using case-mix adjustment models., Results: In total, 5513 patients were included in this study. Textbook outcome was achieved in 26.4% of patients. Insufficient lymph node dissection had the most substantial effect on not realizing textbook outcome. If 'sufficient lymph node dissection' was not included as a criterion, textbook outcome would be 60.7%. Case-mix adjusted textbook outcome proportions per hospitals varied between 13.2% and 37.7%., Conclusions: In contrast to focusing on a single aspect, the composite measure textbook outcome provides insight into comprehensive performance in NSCLC surgery. It can be used to evaluate both individual hospitals and national performance and provides the opportunity to give benchmarked feedback to thoracic surgeons., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Mitral valve repair in native active infective endocarditis is technically challenging. The survival benefit over valve replacement is poorly established and possibly absent because of the high risk of repair failure and reoperation. In this study, we explore the results of our structured approach in these patients., Methods: Between January 2000 and January 2017, 149 patients underwent surgery for native mitral infective endocarditis. Among them, 97 (66%) patients underwent valve repair and 52 (34%) underwent valve replacement. Our structured approach consisted of early surgery, radical resection of infected tissue, liberal use of prosthetic materials and 'patch' repair techniques. A critical assessment of expected repair durability was made intraoperatively and repair was not performed if concerns of long-term durability existed. To study the effects of valve repair on overall survival, landmark analysis was performed., Results: In-hospital mortality was 15.4% (14 repair vs 9 replacement patients; P = 0.642). There were no residual infective endocarditis cases or early reoperations. On Cox proportional hazards analysis, valve replacement was not inferior to repair within 1-year post-surgery [hazard ratio (HR) 1.134, 95% confidence interval (CI) 0.504-2.540; P = 0.76]. Beyond 1 year post-surgery, replacement was associated with decreased survival (HR 2.534, 95% CI 1.002-6.406; P = 0.049). There were no differences in freedom from recurrent infective endocarditis (P = 0.47) and mitral valve reintervention (P = 0.52)., Conclusions: Active mitral valve endocarditis remains a complex disease with significant early and late morbidity and mortality. A structured approach allows valve repair in two-thirds of patients. Clinical results could be improved by focussing on early surgery, prior to extensive valve destruction, to enable durable repairs and improve late outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Gorlin-Chaudhry-Moss syndrome (GCMS) is a rare disorder consisting of craniofacial dysostosis, hypertrichosis, underdeveloped genitalia, and ocular and dental anomalies. Recently, GCMS has been reclassified together with Fontaine syndrome as Fontaine progeroid syndrome (FPS), after a common genetic basis was found. It was previously thought that GCMS/FPS was not associated with aortopathy, but in recent years 3 patients with aortic disease have been described. We describe the fourth case, who is the oldest patient with GCMS/FPS reported in the medical literature: a 45-year-old patient who presented with acute aortic dissection. We therefore recommend screening patients previously diagnosed with GCMS/FPS for aortic pathology to aid early detection and avoid patient presentation in an acute setting., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objective: To compare clinical outcomes of clamping devices and linear nonclamping devices for isolation of the posterior left atrium (box) in thoracoscopic ablation of long-standing persistent atrial fibrillation., Methods: Eighty patients who underwent thoracoscopic pulmonary vein and box isolation using a bipolar clamping device (42 patients) or bipolar nonclamping device (38 patients) to create the roof/inferior lesions for box isolation were included from 2 centers. Follow-up consisted of 24-hour Holter at regular intervals. Freedom from AF during 1-year follow-up and catheter repeat interventions were compared between groups., Results: Acute intraoperative electrical isolation of the box compartment was significantly higher in the clamping group than in the nonclamping group (100% and 79%, respectively, P < .01). At 1-year follow-up, 91% of the clamping group and 79% of the nonclamping group were in sinus rhythm. During 1-year follow-up, recurrence rates did not significantly differ between the 2 groups (P = .08). Repeat catheter interventions were required in 10% of the clamping group and 21% of the nonclamping group (P = .15). Conduction gaps in the roof or inferior lesions were found in 1 patient (2%) in the clamping group versus 4 patients (11%) in the nonclamping group (P = .13)., Conclusions: Thoracoscopic pulmonary vein and box isolation are highly effective in restoring sinus rhythm in long-standing persistent atrial fibrillation on short-term follow-up. Comparison of clamping and nonclamping devices revealed lower rates of intraoperative exit block of the box in the nonclamping group. However, this did not translate into a significant difference in atrial fibrillation freedom at short-term (1-year) follow-up., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Rationale: After cardiac damage, excessive neurite outgrowth (sympathetic hyperinnervation) can occur, which is related to ventricular arrhythmias/sudden cardiac death. Post-damage reactivation of epicardium causes epicardium-derived cells (EPDCs) to acquire a mesenchymal character, contributing to cardiac regeneration. Whether EPDCs also contribute to cardiac re/hyperinnervation, is unknown., Aim: To investigate whether mesenchymal EPDCs influence cardiac sympathetic innervation., Methods and Results: Sympathetic ganglia were co-cultured with mesenchymal EPDCs and/or myocardium, and neurite outgrowth and sprouting density were assessed. Results showed a significant increase in neurite density and directional (i.e. towards myocardium) outgrowth when ganglia were co-cultured with a combination of EPDCs and myocardium, as compared to cultures with EPDCs or myocardium alone. In absence of myocardium, this outgrowth was not directional. Neurite differentiation of PC12 cells in conditioned medium confirmed these results via a paracrine effect, in accordance with expression of neurotrophic factors in myocardial explants co-cultured with EPDCs. Of interest, EPDCs increased the expression of nerve growth factor (NGF) in cultured, but not in fresh myocardium, possibly due to an "ischemic state" of cultured myocardium, supported by TUNEL and Hif1α expression. Cardiac tissues after myocardial infarction showed robust NGF expression in the infarcted, but not remote area., Conclusion: Neurite outgrowth and density increases significantly in the presence of EPDCs by a paracrine effect, indicating a new role for EPDCs in the occurrence of sympathetic re/hyperinnervation after cardiac damage., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The risk factors and clinical effect of elevated mitral valve (MV) gradients after valve repair for degenerative valve disease remain insufficiently understood., Methods: Between January 2004 and December 2015, a total of 484 patients underwent valve repair for degenerative disease. A true-sized full annuloplasty ring was implanted in all cases. We analysed the effect of preoperative and intraoperative factors on the postrepair gradient. Additionally, we explored the effect of postrepair gradients on long-term outcomes., Results: On linear regression analysis, postrepair MV gradients were associated with patient age (coefficient = -0.110, standard error = 0.005, P = 0.034), body surface area (coefficient = 0.905, standard error = 0.340, P = 0.008), implanted annuloplasty ring size (coefficient = -0.181, standard error = 0.018, P < 0.001) and the use of Physio I ring (coefficient = 0.414, standard error = 0.122, P = 0.001). On multivariable analysis, postrepair MV gradient was not associated with overall survival [hazard ratio (HR) 1.034, 95% confidence interval (CI) 0.889-1.203; P = 0.66] or freedom from atrial fibrillation (HR 0.849, 95% CI 0.682-1.057; P = 0.14), but did emerge as a risk factor for MV reintervention (HR 1.378, 95% CI 1.033-1.838; P = 0.029). Two out of 11 reinterventions were performed due to MV stenosis and in both patients, high postrepair gradients were seen readily on predischarge echocardiography., Conclusions: Following valve repair for degenerative MV disease, elevated gradients occur even when true-sized annuloplasty is performed. The late clinical results of valve repair with elevated postrepair gradient are impaired and further studies are needed to explore preventive measures aimed at resolving the issue., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Pneumonectomy in lung cancer treatment is associated with considerable morbidity and mortality. Its use is reserved only for patients in whom a complete oncological resection by (sleeve) lobectomy is not possible. It is unclear whether a patients' risk of receiving a pneumonectomy is equally distributed. This study examined between-hospital variation of pneumonectomy use for primary lung cancer in the Netherlands., Methods: Data from the Dutch Lung Cancer Audit for Surgery from 2012 to 2016 were used to study the use of pneumonectomy for primary lung cancer in the Netherlands. Using multivariable logistic regression, factors associated with pneumonectomy use were identified and the expected number of pneumonectomies per hospital was determined. Subsequently, the observed/expected ratio (O/E ratio) per hospital was calculated to study between-hospital differences., Results: Of the 8446 included patients, 659 (7.8%) underwent a pneumonectomy with a mean postoperative mortality of 7.1% (n = 47). Factors associated with receiving a pneumonectomy were age, gender, cardiac and pulmonary comorbidities, tumor side, size and histopathology. The pneumonectomy use in the Netherlands varied considerably between hospitals (IQR 5.5-10.1%). Three hospitals out of 51 performed significantly less pneumonectomies than expected (O/E ratio < 0.5) and three significantly more (O/E ratio > 1.7). In the latter group, severe complications were more frequent, taking other influencing factors into account (OR 1.51, 95% CI 1.05-2.19)., Conclusions: There is a considerable between-hospital variation in pneumonectomy use in lung cancer treatment. To further optimize surgical lung cancer care, we suggest center-specific feedback on pneumonectomy use and the development of a risk-adjusted pneumonectomy indicator.

Background: Up to 66% of patients show local pulmonary disease progression after pulmonary metastasectomy. Regional treatment with isolated lung perfusion (ILuP) may improve local control with minimal systemic adverse effects. The aims of this study were to evaluate local and distant control after ILuP, determine the effect on overall survival compared with historical controls, and confirm the safety and feasibility of ILuP., Methods: A total of 107 patients with resectable pulmonary metastases of colorectal carcinoma, osteosarcoma, and soft-tissue sarcoma were included in a prospective phase II study of pulmonary metastasectomy combined with ILuP with 45 mg melphalan at 37°C. Local and distant control, overall survival, lung function, and 90-day mortality and morbidity were monitored., Results: We report 0% mortality, low morbidity, and no long-term pulmonary toxicity. For colorectal carcinoma, median time to local pulmonary progression, median time to progression, and median survival time were 31, 14, and 78 months, respectively. Median time to local progression was not reached for sarcoma, whereas median time to progression and median survival time were 13 and 39 months, respectively. The 5-year disease-free rate and pulmonary progression-free rate were 26% and 44% for colorectal carcinoma and 29% and 63% for sarcoma, respectively., Conclusions: ILuP with melphalan combined with metastasectomy is feasible and safe. Compared with historical controls, favorable results were obtained in this phase II study for local control. Further evaluation of locoregional lung perfusion techniques with other chemotherapeutic drugs is warranted., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The risk factors for the development of mitral annular calcification (MAC) in degenerative mitral valve disease and the effect it may have on patient-and valve-related outcomes require further evaluation., Methods: Between January 2002 and December 2015, 627 patients underwent mitral valve operations for degenerative disease. MAC was seen in 75 patients (12%); 73 (97%) underwent valve repair (6 without annuloplasty ring implantation) and 2 (3%) underwent valve replacement after an unsuccessful repair attempt., Results: MAC was linked to patient age, female sex, and degenerative disease subtype. Early mortality was comparable between patients with and without MAC (3 of 75 [4%] vs 10 of 552 [2%], p = 0.20]. In patients with MAC, one-third of the deaths were directly related to annular decalcification and reconstruction. Early repair failure was more common in patients with MAC (8 of 75 [11%] vs 17 of 552 [3%], p = 0.006). During follow-up, no differences in overall survival or freedom from late reintervention were observed. However, at 8 years after the operation, freedom from recurrent mitral regurgitation was worse in patients with MAC. In these patients, repair failure was linked to nonuse of ring annuloplasty. For patients with MAC in whom annular decalcification and annuloplasty were performed, repair durability was comparable to patients without MAC., Conclusions: Mitral valve surgery in degenerative disease accompanied by MAC is safe. Optimal surgical strategy includes annular decalcification (when this would prevent implantation of an annuloplasty ring) and ring annuloplasty and will lead to results similar to patients without MAC. However, repair performance is hampered when the annulus is not addressed. For these patients, alternative repair techniques should be explored in the future., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Because of suboptimal therapeutic strategies, restoration of sinus rhythm in symptomatic atrial fibrillation (AF) often requires in-hospital delivery of high-voltage shocks, thereby precluding ambulatory AF termination. Continuous, rapid restoration of sinus rhythm is desired given the recurring and progressive nature of AF. Here, we present an automated hybrid bioelectronic system for shock-free termination of AF that enables the heart to act as an electric current generator for autogenous restoration of sinus rhythm. We show that local, right atrial delivery of adenoassociated virus vectors encoding a light-gated depolarizing ion channel results in efficient and spatially confined transgene expression. Activation of an implanted intrathoracic light-emitting diode device allows for termination of AF by illuminating part of the atria. Combining this newly obtained antiarrhythmic effector function of the heart with the arrhythmia detector function of a machine-based cardiac rhythm monitor in the closed chest of adult rats allowed automated and rapid arrhythmia detection and termination in a safe, effective, repetitive, yet shock-free manner. These findings hold translational potential for the development of shock-free antiarrhythmic device therapy for ambulatory treatment of AF., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Chordal replacement techniques are progressively used to treat posterior mitral valve leaflet (PMVL) prolapse while leaflet resection remains commonly in use to address excessive leaflet tissue. For excessive tissue in height, shortening neochords can be used alternatively. Use of chordal replacement techniques has been suggested to result in lower diastolic transvalvular gradients, higher freedom from reoperation and improved left ventricular function., Methods: From 1/2005 to 12/2016, 150 patients underwent valve repair for isolated PMVL prolapse with excessive tissue. Excessive tissue in height was treated by leaflet resection (N.=99) or shortening neochords (N.=51). Excessive tissue in width was always resected. Logistic regression was used to generate propensity scores for risk-adjusted comparison., Results: Two patients died postoperatively. In the Neochords group, resection of excessive tissue in width was still needed in 28 (55%) cases. Postoperative echocardiography demonstrated residual (≥2+) mitral regurgitation in 2/150 patients (Resect group). No differences in anuloplasty ring size, postoperative diastolic transvalvular gradients or left ventricular function were observed. Median clinical follow-up duration was 4.4 (IQR 2.0-7.0; 98% complete) years. There was no inter-group difference in overall survival or freedom from reintervention. Mean echocardiographic follow-up was 3.0 (IQR 1.2-5.4; 93% complete) years. In the matched population, the 6-year freedom from recurrent mitral regurgitation rates were 91.3% (95% CI: 81.9-100%) and 97.2% (95% CI: 91.9-100%) for the Resect and Neochords group, respectively (P=0.43)., Conclusions: Both leaflet resection and shortening neochords provide a valuable tool to address excessive PMVL height. Repair durability is excellent regardless of the technique utilized.

Background: In asymptomatic patients with severe degenerative mitral valve regurgitation (MR), early surgery is often performed in experienced centers. The patient- and valve-related results and the quality of life after surgery in these patients remain insufficiently explored., Methods: Between 1/2000 and 12/2015, 83 asymptomatic patients (mean age 56.6±12.6 years, 21 female) without any complications related to long-lasting MR underwent early surgery. Follow-up clinical and echocardiographic data and health-related quality of life assessment (SF-36) were studied and matched to the general population., Results: Repair rate was 100% and early mortality was 0%. Residual MR (≥grade 2+) was seen in 1 (1%) patient who underwent a successful re-repair while 4 (5%) patients needed permanent pacemaker implantation. At a median follow-up of 7.6 (IQR 4.1-11.9) years, 6 late deaths occurred. The 10-year overall survival rate was 91.5% (95% CI 84.2-98.8%) and was comparable to the general population. The health-related quality of life (84% complete) did not differ from the general population. One patient underwent late reintervention. Median echocardiography follow-up was 5.2 years (IQR 2.4-10.4; 98% complete). The 10-year freedom from recurrent MR rate (≥grade 2+) was 86.7% (95% CI 76.1-97.3%). The 10-year freedom from any atrial tachycardia rate was 68.7% (95% CI 55.2-82.2%) while 7 (8%) patients underwent late pacemaker implantation., Conclusions: Early surgical intervention in asymptomatic patients with severe MR can be performed safely and restores normal life expectancy and quality of life. However, the frequency of late arrhythmias and pacemaker implantation is high and needs further evaluation., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Purpose: The objective of this study was to assess the performance of a tissue engineering process-treated bovine pericardium patch (CardioCel, Admedus Regen Pty Ltd, Perth, Australia) in the setting of reconstructive mitral valve surgical procedures., Description: Between March 2014 and April 2016, 30 patients (57.2 ± 14.3 years of age; 27% female) underwent mitral valve leaflet repair with a CardioCel patch., Evaluation: Perioperative mortality was 7% (2 patients, non-graft related). In the 28 remaining patients, predischarge echocardiography demonstrated good repaired valve function. At a mean follow-up of 1.7 ± 0.9 years, three additional deaths occurred (two resulting from infective endocarditis and one non-cardiac related). On follow-up echocardiography (follow-up time of 1.7 ± 0.8 years; available for 26 of 28 [93%] hospital survivors), recurrent regurgitation was seen in 2 patients (both with infective endocarditis), and 1 patient underwent reoperation (no infection at the level of patch repair was observed). In the remaining patients, the most recent echocardiogram demonstrated no regurgitation or mild regurgitation and stable gradients. The thickness and echodensity of the implanted patch on follow-up echocardiograms were comparable with postoperative echocardiograms., Conclusions: Initial results with the CardioCel patch in mitral valve repair operations were satisfactory. The resistance to infection and late degeneration will need to be assessed in the future., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Surgical correction of commissural mitral valve prolapse can be challenging. Several surgical techniques, including commissural closure, leaflet resection with sliding plasty and chordal replacement, remain commonly in use. Conversely, papillary muscle head repositioning remains uncommonly utilized for the treatment of commissural prolapse., Methods: Between January 2003 and December 2015, 518 patients underwent primary mitral valve repair for severe degenerative mitral valve regurgitation at our institution. Among them, 116 patients had non-isolated commissural prolapse (14 anterolateral, 82 posteromedial and 20 bicommissural prolapse). Eighty-eight patients underwent papillary muscle head repositioning and presented the study cohort., Results: The mean patient age was 62.8 ± 12.5 years, and 32 (36%) patients were women. Postoperative echocardiography showed no residual mitral regurgitation in all but 1 (1%) patient in whom Grade 2+ regurgitation was seen. The freedom from late reintervention rates at 5 and 10 years were 96.1% [95% confidence interval (CI) 91.8-100%] and 92.7% (95% CI 86.4-99.0%), respectively. Upon reoperation, no recurrent commissural prolapse was observed. Echocardiographic follow-up demonstrated excellent valve repair durability. The freedom from Grade ≥2+ mitral regurgitation rates at 5 and 10 years were 92.6% (95% CI 86.3-98.9%) and 86.1% (95% CI 76.7-95.5%), respectively., Conclusions: Papillary muscle head repositioning for the treatment of commissural mitral valve prolapse is a reproducible and reliable technique that provides excellent long-term results.

Objective: Optimal treatment selection for patients with non-small cell lung cancer (NSCLC) depends on the clinical stage of the disease. Particularly patients with mediastinal lymph node involvement (stage IIIA-N2) should be identified since they generally do not benefit from upfront surgery. Although the standardized preoperative use of PET-CT, EUS/EBUS and/or mediastinoscopy identifies most patients with mediastinal lymph node metastasis, a proportion of these patients is only diagnosed after surgery. The objective of this study was to identify all patients with unforeseen N2 disease after surgical resection for NSCLC in a large nationwide database and to evaluate the preoperative clinical staging process., Methods: Data was derived from the Dutch Lung Surgery Audit. Patients with pathological stage IIIA NSCLC after an anatomical resection between 2013 and 2015 were evaluated. Clinical and pathological TNM-stage were compared and an analysis was performed on the diagnostic work-up of patients with unforeseen N2 disease., Results: From 3585 patients undergoing surgery for NSCLC between 2013 and 2015, a total of 527 patients with pathological stage IIIA NSCLC were included. Of all 527 patients, 254 patients were upstaged from a clinical N0 (n = 186) or N1 (n = 68) disease to a pathological N2 disease (7.1% unforeseen N2). In these 254 patients, 18 endoscopic ultrasounds, 62 endobronchial ultrasounds and 67 mediastinoscopies were performed preoperatively., Conclusions: In real world clinical practice in The Netherlands, the percentage of unforeseen N2 disease in patients undergoing surgery for NSCLC is seven percent. To further reduce this percentage, optimization of the standardized preoperative workup is necessary., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Following mitral valve repair for Barlow's disease, recurrent mitral regurgitation (MR) is believed to occur frequently and is mainly attributed to disease progression., Methods: Between January 2000 and December 2015, 180 patients (40% women, mean age 58.7 ± 13.5 years) with Barlow's disease underwent mitral valve repair. To provide a longitudinal assessment of mitral valve repair durability, a multistate model for interval-censored observations (4 states: 1, Grade 0/1+ MR; 2, Grade 2+ MR; 3, Grade 3+/4+ MR; 4, reintervention/death) was developed. The mechanism of recurrent MR was assessed echocardiographically., Results: Early mortality was 1.7%. After hospital discharge, 6 late reinterventions were performed. With death as a competing risk, the 10-year overall reintervention-free survival and reintervention rates were 79.8% (95% confidence interval 72.7-87.6%) and 4.5% (95% confidence interval 2.0-10.2%), respectively. Echocardiographic follow-up was available for 165 (93%) of hospital survivors with a total of 480 examinations. The incidence of both recurrent Grade 2+ and Grade 3+/4+ MR was relatively low up to 10 years after surgery. Grade 2+ MR did not always progress to higher regurgitation grade during the follow-up period. Grade 3+/4+ regurgitation was highly associated with valve-related morbidity and mortality. Recurrent MR (≥Grade 2+) was predominantly related to the technical aspects of valve repair., Conclusions: Despite the complex valve abnormalities observed in patients with Barlow's disease, mitral valve repair can be performed with good early and late outcomes and low rates of recurrence of MR up to 10 years after surgery. Early and late valve repair durability is good and remains stable over time, suggesting that underlying disease progression has limited clinical significance.

Background: Thoracic aortic aneurysm (TAA) is a potentially life-threatening disorder with a strong genetic component. The number of genes implicated in TAA has increased exponentially over the last decade. Approximately 20% of patients with TAA have a positive family history. As most TAA remain asymptomatic for a long time, screening of at risk relatives is warranted to prevent complications. Existing international guidelines lack detailed instructions regarding genetic evaluation and family screening of TAA patients. We aimed to develop a consensus document to provide medical guidance for all health care professionals involved in the recognition, diagnosis and treatment of patients with thoracic aortic disease and their relatives., Methods: A multidisciplinary panel of experts including cardiologists, cardiothoracic surgeons, clinical geneticists and general practitioners, convened to review and discuss the current literature, guidelines and clinical practice on genetic testing and family screening in TAA., Results: There is a lack of high-quality evidence in the literature. This consensus statement, based on the available literature and expert opinions, summarizes our recommendations in order to standardize and optimize the cardiogenetic care for patients and families with thoracic aortic disease. In particular, we provide criteria to identify those patients most likely to have a genetic predisposition, and discuss the preferred modality and frequency of screening in their relatives., Conclusions: Age, family history, aortic size and syndromic features determine who is advised to have genetic testing as well as screening of first-degree relatives. There is a need for more prospective multicenter studies to optimize current recommendations., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Barlow's disease is the most severe form of degenerative mitral valve disease, commonly characterized by bileaflet prolapse. Abnormal mitral annular dynamics is typically present and results in functional prolapse of the mitral leaflets that may be addressed with annular stabilization alone., Methods: Between January 2001 and December 2015, 128 patients with Barlow's disease and bileaflet prolapse underwent valve repair. This included anterior mitral valve leaflet (AMVL) repair in 70 patients, whereas 58 patients were identified as having functional prolapse and underwent no specific AMVL repair. During the course of the study, the proportion of patients undergoing specific AMVL repair decreased (77% in the first and 33% in the second 64 patients). Semirigid ring annuloplasty was performed in all cases. The median clinical and echocardiographic follow-up duration was 6.5 years [interquartile range (IQR) 2.9-10.5 years; 93.9% complete] and 4.7 years (IQR 2.2-10.2 years; 94.4% complete), respectively., Results: Early mortality was 1.6%. Postoperative echocardiogram demonstrated no residual mitral regurgitation in all but 1 patient (AMVL repair group). There was no significant difference in the overall survival rate at 6 years after operation between both groups. At 6 years, the freedom from recurrent ≥Grade 2+ mitral regurgitation rate was 90.7% (IQR 82.9-98.5%) and 89.1% (IQR 75.8-100%) for patients with and patients with no AMVL repair, respectively (P = 0.43). Three patients required late mitral valve reintervention, all from the AMVL repair group., Conclusions: Annular stabilization can effectively resolve the functional prolapse of the AMVL. Careful discrimination between functional and true AMVL prolapse allows for a technically less challenging operation that provides excellent repair durability.

Objectives: Native mitral valve infective endocarditis (IE) is a complicated disease with high mortality and morbidity rates. Mitral valve repair (MVRep) is feasible when limited valve destruction is present. However, recurrent valve dysfunction and reintervention are common., Methods: Between January 2000 and March 2016, 83 patients underwent surgery for isolated active native mitral valve IE. We applied an early surgery, MVRep-oriented approach with progressive utilization of patch techniques to secure a durable repair; MVRep was attempted in 67% of patients. Fifty-one (61%) patients underwent MVRep (including full-ring annuloplasty in 94%) and 32 (39%) patients underwent mitral valve replacement., Results: Early mortality was 13%. No cases of early recurrent IE occurred. Predischarge echocardiography demonstrated good MVRep function in all, except 1 patient with residual (Grade 2+) regurgitation. The mean duration of follow-up was 3.7 years (interquartile range 1.5-8.4). For hospital survivors, 8-year overall survival rates were 92.4% (95% confidence interval 84.0-100%) and 74.2% (95% confidence interval 53.8-94.6%) for the MVRep and mitral valve replacement groups, respectively. Propensity score-adjusted Cox regression analysis revealed no significant difference in survival between the 2 groups (hazard ratio 0.359, 95% confidence interval 0.107-1.200; P = 0.096). Four reinterventions occurred, 2 in each group. Echocardiographic follow-up demonstrated excellent MVRep durability; no cases of mitral regurgitation and 1 case of mitral valve stenosis were seen., Conclusions: Native mitral valve IE is linked to high mortality and morbidity rates. A durable MVRep is feasible in most patients and provides excellent mid-term durability. Mitral valve replacement is a reasonable alternative when a durable repair is not likely.

Objectives: Standardized outcome reporting is of critical importance for performance monitoring, improvement of existing techniques and introduction of novel technologies. Whether outcome reporting for surgical treatment of degenerative mitral valve disease complies with the guidelines has not been assessed to date., Methods: A systematic review of PubMed, EMBASE, Web of Science and the Cochrane Library was conducted for articles published between 1 January 2009 and 7 March 2016. Inclusion criteria were adult patient population (n ≥ 200) and surgical intervention for degenerative mitral valve disease. The quality of reported outcome was compared with the standard recommended by the guidelines on reporting morbidity and mortality after cardiac valve interventions., Results: Forty-two non-randomized clinical studies were included: 4 provided early and 38 provided early and late outcome data. Early echocardiographic outcome was reported in 49% of studies. Freedom from reintervention, the indication for reintervention and the follow-up echocardiographic outcome were reported in 97%, 59% and 79% of studies providing late outcome data, respectively. The Kaplan-Meier method was used to assess the freedom from recurrent mitral regurgitation in 60% (18/30) of studies, whereas 7% (2/30) of studies applied a longitudinal data analysis. Recurrent mitral regurgitation was most commonly defined as moderate (Grade 2+; 60%) or severe (Grade 4+; 37%) regurgitation., Conclusions: There is a significant discordance between the guidelines-based recommendations and actual reporting of outcome for surgical treatment of degenerative mitral valve disease. Better adherence to the guidelines would raise the quality and generalizability of clinical data reporting.

Objectives: Severe cases of infective endocarditis (IE) of the aortic valve can cause aortic root destruction and affect the surrounding structures, including the aortic-mitral continuity, the anterior mitral valve leaflet and the roof of the left atrium. Reconstruction after resection of all infected tissue remains challenging. We describe our surgical approach and the mid-term results., Methods: Between January 2004 and December 2015, 35 patients underwent surgery for extensive IE of the aortic valve with destruction of the aortic root, the aortic-mitral continuity and the mitral valve. Mean age was 60.4 ± 13.7; 26/35 (74%) patients had prosthetic valve endocarditis. Four patients were in critical preoperative state. Median EuroSCORE II was 18.0% [interquartile range (IQR) 11.0-26.7]., Results: Aortic root replacement was performed in 32 (91%) patients. The remaining patients underwent aortic valve replacement. Reconstruction of the aortic-mitral continuity and the roof of the left atrium were performed using a folded pericardial patch. In 28 patients (80%), mitral valve repair was performed. Postoperative mechanical circulatory support, acute kidney failure and surgical re-exploration were seen in 5 (16%), 10 (31%) and 4 (13%) patients, respectively. Early survival rate was 77% (27 patients). During a median follow-up of 29.8 months (IQR 6.4-62.9), 7 (26%) patients required reintervention (3-42 months after surgery); 4 were due to mitral incompetence, early in our experience., Conclusions: Extensive IE of the aortic root with destruction of the surrounding tissues remains a complex disease with high morbidity and mortality rates. Our technique allows native mitral valve preservation but is technically challenging., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The epicardium, a cell layer covering the heart, plays an important role during cardiogenesis providing cardiovascular cell types and instructive signals, but becomes quiescent during adulthood. Upon cardiac injury the epicardium is activated, which includes induction of a developmental gene program, epithelial-to-mesenchymal transition (EMT) and migration. However, the response of the adult epicardium is suboptimal compared to the active contribution of the fetal epicardium to heart development. To understand the therapeutic value of epicardial-derived cells (EPDCs), a direct comparison of fetal and adult sources is paramount. Such analysis has been hampered by the lack of appropriate culture systems., Methods: Human fetal and adult EPDCs were isolated from cardiac specimens obtained after informed consent. EPDCs were cultured in the presence of an inhibitor of the TGFβ receptor ALK5. EMT was induced by stimulation with 1 ng/ml TGFβ. PCR, immunofluorescent staining, scratch assay, tube formation assay and RT 2 -PCR for human EMT genes were performed to functionally characterize and compare fetal and adult EPDCs., Results: In this study, a novel protocol is presented that allows efficient isolation of human EPDCs from fetal and adult heart tissue. In vitro, EPDCs maintain epithelial characteristics and undergo EMT upon TGFβ stimulation. Although similar in several aspects, we observed important differences between fetal and adult EPDCs. Fetal and adult cells display equal migration abilities in their epithelial state. However, while TGFβ stimulation enhanced adult EPDC migration, it resulted in a reduced migration in fetal EPDCs. Matrigel assays revealed the ability of adult EPDCs to form tube-like structures, which was absent in fetal cells. Furthermore, we observed that fetal cells progress through EMT faster and undergo spontaneous EMT when TGFβ signaling is not suppressed, indicating that fetal EPDCs more rapidly respond to environmental changes., Conclusions: Our data suggest that fetal and adult EPDCs are in a different state of activation and that their phenotypic plasticity is determined by this activation state. This culture system allows us to establish the cues that determine epicardial activation, behavior, and plasticity and thereby optimize the adult response post-injury.

Objectives: Extracardiac conduits are widely used to complete a Fontan circulation in patients with univentricular hearts. Although polytetrafluoroethylene conduits have proven good long-term patency, Dacron (polyethylene terephthalate) prostheses are still infrequently applied, with, as yet, no information on the long-term patency., Methods: All patients who received an extracardiac Dacron conduit (n = 12) were retrospectively studied. The initial conduit size was 16 mm in all recipients. The mean age at Fontan completion was 3.1 ± 0.7 years. Patients with clinical symptoms and/or significant conduit stenosis (>50% of diameter) underwent reoperation., Results: Of the 12 patients, 8 underwent reoperation (75%) at a mean interval of 6.5 ± 1.8 years after the Fontan operation. All conduits were replaced by an 18-mm polytetrafluoroethylene graft. The explants showed ubiquitous tissue deposits on the inner surface, with a residual internal diameter from 8 to 11 mm. All patients survived the extracardiac conduit replacement. Recovery was uneventful, except that 1 patient experienced long-lasting pleural fluid drainage. The mean hospital stay was 10.6 ± 12.0 days., Conclusions: The incidence of extracardiac Dacron conduit stenosis in total cavopulmonary connection patients is high. These data indicate that the use of this type of conduit should be avoided. Vigilant follow-up is advised for those patients who have undergone Fontan completion with a Dacron extracardiac conduit., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Purpose: This study was conducted to investigate the degree of fibrosis in atrial appendages of patients with and without atrial fibrillation (AF) undergoing cardiac surgery. In addition, we hypothesized that areas of atrial fibrosis can be identified by electrogram fractionation and low voltage for potential ablation therapy., Methods: Interstitial fibrosis from right (RAA) and/or left atrial appendages (LAA) was studied in patients with sinus rhythm (SR, n = 8), paroxysmal (n = 21), and persistent AF (n = 20) undergoing coronary artery bypass and/or aortic or mitral valve surgery. Atrial fibrosis quantification was performed with Masson trichrome staining. Intraoperative bipolar epicardial electrophysiological measurements were performed to correlate fibrosis to electrogram fractionation, voltage, and AF cycle length., Results: The average degree of fibrosis was 11.2 ± 7.2 % in the LAA and 22.8 ± 7.6 % in the RAA (p < 0.001). Fibrosis was not significantly higher in paroxysmal AF patients compared to SR subjects (18.2 ± 8.7 versus 20.7 ± 5.3 %). Persistent AF patients had a higher degree of LAA and RAA fibrosis compared to paroxysmal AF patients (LAA 14.6 ± 8.7 versus 8.6 ± 4.7 %, p = 0.02, and RAA 28.2 ± 7.9 versus 18.2 ± 8.7 %, respectively, p = 0.04). The left atrial end diastolic volume index was higher in persistent AF patients compared to SR controls (38.3 ± 16.4 and 28 ± 11 ml/m(2), respectively, p = 0.04). No correlation between atrial fibrosis and electrogram fractionation or voltage was found., Conclusion: Patients with structural heart disease undergoing cardiac surgery have more fibrosis in the RAA than in the LAA. Furthermore, RAA fibrosis is increased in persistent AF but not paroxysmal AF patients compared to control subjects. Electrogram fractionation and low voltage did not provide accurate identification of the fibrotic substrate.

Damage to the thoracic sympathic chain is a rare complication of video-assisted thoracic surgery (VATS) pleurectomy. We report our experience with a patient who underwent parietal pleurectomy and bullectomy by VATS and postoperatively suffered from palmar anhydrosis and compensatory controlateral hyperhidrosis. The possible mechanisms of nerve damage and various techniques of performing pleurectomy are discussed.

Introduction: Intrapericardial (IPC) delivery of antiarrhythmic agents is an appealing idea to increase the therapeutic width and reduce side effects of drugs, particularly in the thin atria. The aim of this study was to determine the effects of IPC versus intravenous (IV) d,l-sotalol and flecainide infusion on transmural atrial electrophysiology and sustained atrial fibrillation (AF) in the goat., Methods and Results: Effects of IPC and IV sotalol and flecainide infusion on epi- and endocardial atrial electrophysiology, ECG, and tissue drug concentrations were studied in goats without and with persistent AF (>24 hours). Epicardial atrial refractory period (AERP, bcl 400 ms) increased after 120 minutes of 1 mg/kg/hour IPC sotalol with 61 +/- 8 ms (P = 0.02), whereas the endocardial AERP was not affected. One mg/kg/hour IPC flecainide increased the epicardial pacing threshold and the epicardial AERP with 4 +/- 0.5 mA (P = 0.003) and 33 +/- 11 ms (P = 0.05), respectively. Endocardial values were unchanged. Marked ST-elevations in the precordial ECG leads were observed after IPC flecainide. In the AF group, IPC drugs did not prolong AF cycle length to a greater extent than IV delivery. The number of cardioversions was not different between the two delivery routes. A steep transmural drug concentration gradient after IPC sotalol and flecainide was observed in all heart chambers., Conclusion: IPC sotalol and flecainide infusion in goats markedly affects epicardial atrial electrophysiology. IPC delivery, however, does not prolong AFCL or terminate AF to a greater extent than IV infusion. This suggests that the perpetuation of AF is not dominated by the epicardial and sub epicardial atrial layers.

Objectives: Atrial dilatation predisposes to atrial fibrillation. Although several animal models focus on the initiating mechanisms of atrial fibrillation in dilated atria, a model of left atrial overload resulting in persistent atrial fibrillation in nonanesthetized animals has not been presented thus far., Methods: In 24 goats a vascular shunt was implanted between the aorta and the left atrium through a left thoracotomy. In 6 animals the shunt was ligated immediately (control group). Ultrasonic crystals were implanted to monitor atrial dilatation. Bipolar electrodes were positioned epicardially on the left atrium for measurement of the atrial effective refractory period, conduction times, and atrial fibrillation duration., Results: Four weeks of overload resulted in an increase of left atrial pressure (23.1 +/- 6.8 mm Hg in the open-shunt group vs 7.0 +/- 1.9 mm Hg in the control group, P = .002) and a progressive dilatation of the left atrium (135% +/- 20% in the open-shunt group vs 98% +/- 8.0% in the control group, P = .002). Among the open-shunt group's long-term survivors (n = 12), 9 animals showed prolonged atrial fibrillation (>1 hour), and of these, 6 were in persistent atrial fibrillation (>1 week). The atrial effective refractory period increased during the first week and remained prolonged until death (182 +/- 11 ms in the open-shunt group vs 161 +/- 15 ms, P = .03). The conduction time did not change. An increase in collagen formation was noticed in both groups, without a significant difference between them., Conclusions: A chronic aortic to left atrial shunt is a feasible model in the goat. It induces progressive left atrial dilatation with an increased atrial fibrillation duration up to hours in the majority of animals. Prolonged atrial fibrillation duration could not be explained by a shortening of atrial effective refractory period or increase in fibrosis.