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Objectives: Extracorporeal membrane oxygenation (ECMO) for postcardiotomy cardiogenic shock has been increasingly used without concomitant mortality reduction. This study aims to investigate determinants of in-hospital and postdischarge mortality in patients requiring postcardiotomy ECMO in the Netherlands.Methods: The Netherlands Heart Registration collects nationwide prospective data from cardiac surgery units. Adults receiving intraoperative or postoperative ECMO included in the register from January 2013 to December 2019 were studied. Survival status was established through the national Personal Records Database. Multivariable logistic regression analyses were used to investigate determinants of in-hospital (3 models) and 12-month postdischarge mortality (4 models). Each model was developed to target specific time points during a patient's clinical course.Results: Overall, 406 patients (67.2% men, median age, 66.0 years [interquartile range, 55.0-72.0 years]) were included. In-hospital mortality was 51.7%, with death occurring in a median of 5 days (interquartile range, 2-14 days) after surgery. Hospital survivors (n = 196) experienced considerable rates of pulmonary infections, respiratory failure, arrhythmias, and deep sternal wound infections during a hospitalization of median 29 days (interquartile range, 17-51 days). Older age (odds ratio [OR], 1.02; 95% CI, 1.0-1.04) and preoperative higher body mass index (OR, 1.08; 95% CI, 1.02-1.14) were associated with in-hospital death. Within 12 months after discharge, 35.1% of hospital survivors (n = 63) died. Postoperative renal failure (OR, 2.3; 95% CI, 1.6-4.9), respiratory failure (OR, 3.6; 95% CI, 1.3-9.9), and re-thoracotomy (OR, 2.9; 95% CI, 1.3-6.5) were associated with 12-month postdischarge mortality.Conclusions: In-hospital and postdischarge mortality after postcardiotomy ECMO in adults remains high in the Netherlands. ECMO support in patients with higher age and body mass index, which drive associations with higher in-hospital mortality, should be carefully considered. Further observations suggest that prevention of re-thoracotomies, renal failure, and respiratory failure are targets that may improve postdischarge outcomes.

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.

Functional human atrial myocytes derived from foetal atrial tissue can be massively expanded via a conditional cell-immortalization method, and used in in vitro models of atrial fibrillation.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.

Contains fulltext : 248644.pdf (Publisher’s version ) (Closed access) BACKGROUND: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. METHODS: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. RESULTS: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4-1.9; P

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 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.

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 P P P 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.

Aortic valve surgery in non-elderly patients represents a very challenging patient population. The younger the patient is at the point of aortic valve intervention, the longer their anticipated life expectancy will be, with longer exposure to valve-related complications and risk for re-operation. Although the latest international guidelines recommend aortic valve repair in patients with aortic valve insufficiency, what we see in the real world is that the vast majority of these aortic valves are replaced. However, current prosthetic valves has now been shown to lead to significant loss of life expectancy for non-elderly patients up to 50% for patients in their 40s undergoing mechanical aortic valve replacement. Bioprostheses carry an even worse long-term survival, with higher rates of re-intervention. The promise of trans-catheter valve-in-valve technology is accentuating the trend of bioprosthetic implantation in younger patients, without yet the appropriate evidence. In contrast, aortic valve repair has shown excellent outcomes in terms of quality of life, freedom from re-operation and freedom from major adverse valve-related events with similar life expectancy to general population as it is also found for the Ross procedure, the only available living valve substitute. We are at a time when the paradigm of aortic valve surgery needs to change for the better. To better serve our patients, we must acquire high quality real-world evidence from multiple centers globally - this is the vision of the AVIATOR registry and our common responsibility.

(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.

Background and aim of the study This study aims to provide an overview of clinical outcome after bioprosthetic aortic root replacement and lifetime event-risk estimates of mortality and valve-related events, and the potential effect of type of prosthesis used. Methods A systematic literature search was conducted between January 2000 and August 2019. Inclusion criteria: aortic root replacement in adults. Data were pooled by inverse-variance weighting and entered a microsimulation model to calculate lifetime event-risk and (event-free) life expectancy. Results Of 2.106 publications, 31 were included (N = 5.227 patients, 74% stentless valves). Mean age was 65.4 years (74% male). Pooled early mortality was 5.5% (95% CI: 4.3-7.2%). During follow-up (mean 4.1 years, total 22.706 patient-years), late mortality was 4.8%/patient-year and reoperation 0.9%/patient-year. Linearized-occurrence-rates for thromboembolism, endocarditis, and hemorrhagic events:1.2; 0.9 and 0.5 %/patient-year; no significant difference between stented and stentless prosthesis. Translating into a 60-year-old patient, an estimated life expectancy of 14 years (general population: 22 years) and lifetime risks of thromboembolism, endocarditis and reintervention of 21%, 13%, and 8%, respectively is expected. Conclusions The study shows impaired survival and a notable lifetime risk of valve-related events after bioprosthetic aortic root replacement. The risk of thromboembolism is prominent, especially during earlier follow-up, suggesting higher risk of thromboembolism early after operation. Type of prosthesis, stented or stentless, is not associated with higher valve-related events. Moreover, this study could be used as a benchmark to compare outcome with other aortic root replacement procedures.

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.

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.

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 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.

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 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.

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.

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. (C) 2019 by The Society of Thoracic Surgeons

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.

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 degrees 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. (C) 2019 by The Society of Thoracic Surgeons

Objective: Valve-sparing aortic root replacement has gained popularity in the last decade. This report provides short-term outcome and differences between patients after valve-sparing versus valve-...

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: The nationwide Dutch Lung Surgery Audit (DLSA) started in 2012 to monitor and evaluate the quality of lung operations in The Netherlands as an improvement tool. This outline describes the establishment, structure, and organization of the audit by the Dutch Society of Lung Surgeons (NVvL) and the Dutch Society of Cardiothoracic Surgeons (NVT), in collaboration with the Dutch Institute for Clinical Auditing. In addition, the first 4-year results are presented.METHODS: The NVvL and NVT initiated a web-based registration, including weekly updated online feedback for participating hospitals. Data verification by external data managers is performed on regular basis. The audit is incorporated in national quality improvement programs, and participation in the DLSA is mandatory by health insurance organizations and the National Healthcare Inspectorate.RESULTS: Between January 1, 2012, and December 31, 2015, all hospitals performing lung operations participated, and a total of 19,557 patients were registered from which almost half comprised lung cancer patients. Nationwide the guideline adherence increased over the years, and 96.5% of lung cancer patients were discussed in preoperative multidisciplinary teams. Overall postoperative complications and mortality after non-small cell lung cancer operations were 15.5% and 2.0%, respectively.CONCLUSIONS: The audit provides reliable benchmarked information for caregivers and hospital management with potential to start local, regional, or national improvement initiatives. Currently, the audit is further completed with data from nonsurgical lung cancer patients, including treatment data from pulmonary oncologists and radiation oncologists. This will ultimately provide a comprehensive overview of lung cancer treatment in The Netherlands.

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.

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.

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.

Surgical repair in rheumatic mitral valve disease is technically challenging as the disease affects both valvular and subvalvular structures. Due to the resultant shortage of pliable valve tissue, pericardial patch techniques are progressively used to restore normal valve function. This makes mitral valve repair possible even in the most severe forms of rheumatic mitral valve disease. In this tutorial, we report a case of mitral valve repair with a bileaflet (decellularized) pericardial patch in a patient with severe rheumatic mitral valve disease.

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 KaplanMeier 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.

OBJECTIVESFollowing mitral valve repair for Barlow’s disease, recurrent mitral regurgitation (MR) is believed to occur frequently and is mainly attributed to disease progression.METHODSBetween 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.RESULTSEarly 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.CONCLUSIONSDespite 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 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 RT2-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.

Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. Plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophages in the myocardium. Compared to plain liposomes, liposomal clodronate treatment rapidly worsened left ventricular ejection function in hypertensive rats. Liposomal clodronate- treated Ren-2 rat hearts showed areas of myocyte loss with abundant inflammatory cell infiltration, predominantly comprising CD4 positive T lymphocytes. The current study showed that lack of macrophages was associated with earlier development of myocardial dysfunction in hypertensive rats. Modulation of macrophage function may be of value in the evolution of cardiomyopathy. © 2009 Sage Publications.

Aims To study the feasibility and electrophysiological efficacy of minimally invasive beating heart ablation of the pulmonary veins (PVs) via a robot-assisted single-sided approach. Background PV isolation by minimally invasive epicardial ablation may offer a new treatment for patients with lone atrial fibrillation (AF). However, complete PV isolation has been shown to be difficult to obtain. Methods and results In 14 mongrel dogs, robot-assisted epicardial microwave ablation was performed on the beating heart by a single-sided right chest approach. Isolation of all PVs was performed in two steps to study the effect of an incomplete and a complete isolation on AF. AF was studied by random and burst pacing. Incremental pacing was performed to study conduction characteristics across the lesions. Opening of the pericardial reflections, introduction of the catheter and ablation were robotically feasible by a single-sided approach in 11 dogs. The AF duration decreased from 6.6±4.1 to 1.3±0.8 s ( P =0.03) and 1.6±1.6 s ( P =0.04 compared with control) after incomplete and completed isolation of the PVs. The AF cycle length increased from 134±5 to 141±5 and 145±8 ms ( P =0.03) after incomplete and complete isolation, respectively. Several incomplete lesions showed 2 : 1 exit and/or entrance block during incremental pacing. After complete isolation, AF was no longer inducible from the PVs. Conclusion Epicardial PV isolation can be successfully performed by a single-sided robot-assisted approach. The effect of PV ablation on AF is not an all or none phenomenon. Incomplete isolation already decreases AF duration and lengthens the AF cycle length. However, complete isolation is necessary to prevent AF induction by triggering from the isolated area.

Pulmonary vein isolation is a hallmark in current surgical ablation for atrial fibrillation. However, validation of isolation remains cumbersome. We evaluated electrophysiologic and not histologic means to test isolation.In 16 mongrel dogs, robot-assisted epicardial beating-heart microwave ablation (FLEX 10) was performed around the pulmonary veins. Electrophysiologic isolation was tested by pacing at 4 times threshold values inside and outside the pulmonary veins (exit and entrance block). The histology of lesions was studied for transmurality and continuity of the lesion lines. In 5 dogs, lesions were studied at various time intervals.Histologic evaluation of the lesions showed incomplete (48% +/- 20%) circumferential myocardial damage in all dogs with acute lesions. Electrophysiologic evaluation showed completion of the box (entrance and exit block) in 8 dogs and in another 5 dogs after repeated ablation (p0.01 compared with histologic evaluation). Electrophysiologic evaluation of the dogs with chronic lesions showed completed lesions in 4 of 5 dogs directly after ablation. At follow-up (1 to 3 weeks), the isolations remained electrophysiologically complete. Histologic evaluation of the lesions 1 to 3 weeks after ablation showed complete (100%) circumferential lesions in all 4 dogs (p0.001 compared with the histology of dogs with acute lesions).Directly after treatment, ablation lesions are best evaluated electrophysiologically, because complete (transmural and circumferential) lesions are not shown by histologic evaluation in the acute stage. After 1 to 3 weeks, the histology is in accordance with the electrophysiology. To obtain a complete isolation, online electrophysiologic evaluation during pulmonary vein microwave ablation is necessary to optimize the results.

Targeting drugs to the heart by intrapericardial (i.p.c.) delivery may be a promising strategy to obtain higher drug efficiencies with lesser side effects. We examined whether i.p.c. delivery of sotalol and atenolol in rats offers advantages over intravenous (i.v.) application. Following sustained IPC infusion of sotalol or atenolol, pericardial fluid levels exceeded plasma levels 97 and 134 times respectively (P < 0.01) resulting in 3.8 and 4.7 times higher overall left ventricular tissue drug levels (P < 0.05). In a second experiment, the effects of the i.p.c. or i.v. beta-blocker infusions on nitroprusside-induced tachycardia were studied in conscious rats. For both drugs, i.p.c. infusion of 0.03 mg/kg.h produced similar antitachycardiac effects as the 1 mg/kg.h i.v. dose. In a third set of studies, dP/dt max challenged by dobutamine infusion was assessed to study ventricular contractile function after i.v. and i.p.c. sotalol in anesthetized rats. i.p.c. sotalol infusion attenuated the dobutamine response curve to a greater extent than i.v. (P < 0.01). In conclusion, i.p.c. infusion of sotalol and atenolol results in high cardiac tissue concentrations with low systemic drug levels. Similar antitachycardiac effects can be obtained at a 10- to 30-fold lower dose compared with i.v. delivery. Also, depression of ventricular contractility is acquired at a substantially lower i.p.c. sotalol dose. Thus, beta-blocking properties of sotalol and atenolol can be greatly enhanced by applying them i.p.c.

Background— Inflammatory mechanisms have been proposed to be important in heart failure (HF), and cytokines have been implicated to add to the progression of HF. However, it is unclear whether such mechanisms are already activated when hypertrophied hearts still appear well-compensated and whether such early mechanisms contribute to the development of HF. Methods and Results— In a comprehensive microarray study, galectin-3 emerged as the most robustly overexpressed gene in failing versus functionally compensated hearts from homozygous transgenic TGRmRen2-27 (Ren-2) rats. Myocardial biopsies obtained at an early stage of hypertrophy before apparent HF showed that expression of galectin-3 was increased specifically in the rats that later rapidly developed HF. Galectin-3 colocalized with activated myocardial macrophages. We found galectin-3-binding sites in rat cardiac fibroblasts and the extracellular matrix. Recombinant galectin-3 induced cardiac fibroblast proliferation, collagen production, and cyclin D1 expression. A 4-week continuous infusion of low-dose galectin-3 into the pericardial sac of healthy Sprague-Dawley rats led to left ventricular dysfunction, with a 3-fold differential increase of collagen I over collagen III. Myocardial galectin-3 expression was increased in aortic stenosis patients with depressed ejection fraction. Conclusions— This study shows that an early increase in galectin-3 expression identifies failure-prone hypertrophied hearts. Galectin-3, a macrophage-derived mediator, induces cardiac fibroblast proliferation, collagen deposition, and ventricular dysfunction. This implies that HF therapy aimed at inflammatory responses may need to be targeted at the early stages of HF and probably needs to antagonize multiple inflammatory mediators, including galectin-3.

Item does not contain fulltext 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.

Contains fulltext : 125460.pdf (Publisher’s version ) (Open Access) 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.

Contains fulltext : 117945.pdf (Publisher’s version ) (Open Access) 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.

Contains fulltext : 71486.pdf (Publisher’s version ) (Closed access) 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.

A 23-year-old woman was admitted to the hospital because of progressive shortness of breath since 2 weeks. She had a history of Blackfan-Diamond anaemia, and sagittal sinus thrombosis 3 years ago. Computed tomography pulmonary angiography (CTA) revealed bilateral pulmonary embolisms. Despite 3 weeks of coumarin treatment, symptoms increased and progression of …

Background Surgical pulmonary vein isolation has gained widespread use as a treatment modality for patients with concomitant atrial fibrillation. However, several uncertainties persist concerning the appropriate energy source, approach, and the need for lesion transmurality. In this study, we present an in-depth histologic investigation of epicardial ablation lesions in 3 patients. Methods Within a large clinical series of adjuvant epicardial beating-heart microwave isolation of the pulmonary veins, with intraoperative measurement of electrical block, 3 nonablation-related deaths allowed detailed histologic investigation of the lesions. All three patients were in sinus rhythm prior to death. Transmural histologic sections from the box lesion encircling the pulmonary veins were microscopically examined for tissue damage, lesion depth, width, and transmurality, as well as for signs of ongoing repair. Results Three out of 13 tissue samples showed transmural lesions. In three sections no histologic damage was observed and in the remaining samples transmural extent of myocardial damage ranged from 48% to 82% (mean, 64 ± 13%). Lesion depths varied between 1.2 mm and 5.7 mm (mean 2.6 ± 1.3 mm). The lesion depth did not differ significantly among patients and was not related to the thickness of the epicardial or myocardial layers. Interestingly, several sections showed clear necrosis of nerve bundles located in the epicardial tissue. Conclusions This post-mortem histologic study showed that in the majority of samples the lesions were not transmural and that the extent of myocardial damage was highly variable. Even in this validated approach of epicardial beating heart ablation with satisfactory clinical results, transmurality of lesions cannot be assumed.

Purpose: The relationship between left atrium (LA) dilatation and atrial fibrillation (AF) has been extensively proved. The aim of this study was to develop an animal model of sustained AF, induced by controlled chronic left atrial overload. Methods: In 12 goats, a left thoracotomy was performed to implant a 8ram vascular graft (gore-tex ®) between the thoracic aorta and the LA. Intra operative atrial overload was monitored by volume and invasive pressure measurements. The LA was chronically instrumented with ukrasonic crystals and bipolar sensing/pacing electrodes. LA dilatation and electrophysiology were regularly evaluated in the conscious goats and compared with a control group with a non-functional shunt. Sustained AF (1 week) was the ultimate purpose. Anew invasive LA pressure was measured ahead of sacrifice. Results: Operatively there was manifest LA overload with calculated volume augmentation of 59.34-42.2% (from 42.3 to 67.4 mm 3, p

Background: Surgical pulmonary vein isolation has established itself as an effective treatment modality for patients with concomitant atrial fibrillation (AF). However, several uncertainties persist concerning the appropriate energy source, approach and the need for transmurality of lesions. In this study, we present an in-depth histological investigation of epicardial ablation lesions in 3 patients. Methods: Within a large clinical series of adjective epicardial beating-heart microwave isolation of the pulmonary veins with intra-operative measurement of electrical block, 3 non-ablation related deaths allowed detailed histological investigation of the lesions. Two out of three patients had been in stable sinus rhythm prior to dead, one patient did show several short paroxysms of AF post-operatively. Stained sections from the box lesion encircling the pulmonary veins were microscopically examined for tissue damage, lesion depth, width, transmurality, as well as for signs of ongoing repair. Results: Three out of 13 samples showed transmural lesions. In three sections no histological damage was observed and in the remaining samples transmurality ranged from 48% to 82% (mean 64 13%). Lesions depths varied between 1.2 mm and 5.7 mm (mean 2.6 1.3 mm). The lesion depth did not differ significantly between patients and was not related to the thickness of the epicardial or myocardial layers. Interestingly, several sections showed clear necrosis of nerve branches located in the epicardial tissue. Conclusion: Even in this validated approach of epicardial beating heart ablation with satisfactory clinical results, transmurality can not be assumed. This indicates that complete histological isolation of the pulmonary veins may not be necessary for the treatment of AF. The working mechanism of epicardial pulmonary vein isolation may also involve modification of AF substrate, for instance by epicardial nerve denervation.

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.