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Context: Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging.Objective: To compare the 2 recommended lung cancer staging strategies.Design, Setting, and Patients: Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography.Intervention: Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread.Main Outcome Measures: The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications.Results: Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P = .11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P = .02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P = .47) and 94% (62/66; 95% CI, 85%-98%) (P = .02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P = .02). The complication rate was similar in both groups.Conclusions: Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies.Trial Registration: clinicaltrials.gov Identifier: NCT00432640. [ABSTRACT FROM AUTHOR]

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 present study assessed whether descending thoracic aorta growth can be measured reliably by volumetric analysis using multi-detector row computed tomography (MDCT) and whether growth influences the need for future aortic interventions in survivors of acute type A aortic dissection., Methods: A total of 51 patients (58 ± 11 years, 61% male) who underwent surgery for type A aortic dissection with ≥2 postoperative MDCT scans ≥5 months apart were included. Volumetric analysis of the descending thoracic aorta was performed with acceptable intraobserver variability. Growth of the complete, false and true lumen was estimated in ml/year and defined as slow growth (≤average growth) or fast growth (>average growth)., Results: The complete lumen volume increased from 133 ± 8 ml to 163 ± 9 ml after 3.5 years follow-up (p < 0.001), with an average growth rate of 6.1 ml/year. The false lumen volume increased from 81 ± 7 ml to 106 ± 12 ml (p = 0.018) with an average growth rate of 2.8 ml/year. The true lumen changed only slightly from 59 ± 4 ml to 65 ± 8 ml (p = 0.205). Five-year freedom from descending thoracic aorta intervention was significantly lower in patients with above-average growth of the complete lumen (80 ± 9%) compared to slow growth (100%; p = 0.003). Similar observations were made for the false lumen (fast: 74 ± 12% vs. slow: 100%; p = 0.042)., Conclusions: Increased growth of the false lumen of the descending thoracic aorta after type A aortic dissection was associated with a higher risk of secondary interventions., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: It remains unclear whether aortic valve replacement (AVR) has an effect on the aortic root dilatation rate in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The present study evaluated the pre- and postoperative annual aortic root dilatation rates in BAV and TAV., Methods: A total of 93 patients (67 ± 11 years; 71% men) who underwent AVR between 2003 and 2013 and had at least 2 pre- and postoperative echocardiographic studies 1 year or more apart were included in this retrospective observational study. The sinus of Valsalva (SOV), sinotubular junction (STJ) and ascending aorta (AAo) were measured in the parasternal long-axis view., Results: Patients with BAV (n = 22) were significantly younger and had less coronary artery disease than patients with TAV (n = 71). At all points in time, the aortic root diameters were larger in BAV compared with TAV. Preoperatively, the STJ and AAo grew significantly faster in BAV compared with TAV (STJ, 0.27 versus 0.04 mm/y; p = 0.021; AAo, 0.42 versus 0.15 mm/y; p = 0.019). After operation, there were no significant differences in aortic root dilatation rates between BAV and TAV (SOV, -0.01 versus 0.15 mm/y; p = 0.096; STJ, 0.08 versus 0.05 mm/y; p = 0.676; AAo, 0.28 versus 0.35 mm/y; p = 0.745)., Conclusions: The annual aortic root dilatation rates were significantly higher in BAV compared with TAV before AVR. However, after AVR, aortic root dilatation rates were similar in BAV and TAV, suggesting an important role of hemodynamics on aortic root dilatation in BAV., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Transapical valve-in-valve mitral valve implantation (TA-MVI) has been described as an alternative treatment option in patients with degenerated bioprostheses in the mitral position. We report the first case of prosthesis dislocation and migration into the left atrium after TA-MVI. A new prosthesis was implanted using the same approach. The dislocated prosthesis was successfully removed through the left atrial appendage through an extended anterolateral thoracotomy without the use of cardiopulmonary bypass., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The clinical stage of non-small cell lung cancer (NSCLC) determines the initial treatment, whereas the pathologic stage best determines prognosis and the need for adjuvant treatment. In an era in which stereotactic ablative radiotherapy (SABR) has become an alternative modality to surgical intervention, clinical staging is even more important, because pathologic staging is omitted in the case of SABR. The objective of this study was to determine the concordance between clinical and pathologic stage in routine clinical practice for patients with early-stage NSCLC., Methods: Prospective data were derived from the Dutch Lung Surgery Audit (DLSA) in 2013 and 2014. Patients with clinical stage I NSCLC who underwent surgical resection and had a positron emission tomography-computed tomography (PET-CT) scan in their clinical workup were selected. Clinical and pathologic TNM (cTNM and pTNM) stages were compared., Results: From a total of 1,790 patients with clinical stage I, 1,555 (87%) patients were included in this analysis. Concordance between cTNM and pTNM was 59.9%. Of the patients with clinical stage I, 22.6% were upstaged to pathologic stage II or higher. In total, 14.9% of all patients with clinical stage I had nodal metastases, and 5.5% of all patients had unforeseen N2 disease. In patients with clinical stage T2a tumors, 21.3% had nodal metastases, 14.5% being N1 and 6.7% being N2 disease., Conclusions: Concordance between clinical and pathologic stage is 59.9%. In patients with clinical stage I NSCLC, 22.6% were upstaged to pathologic stage II or higher, which is an indication for adjuvant chemotherapy. Improvement in accuracy of staging is thus needed, particularly for these patients., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Clinical staging of non-small cell lung cancer (NSCLC) determines the initial treatment offered to a patient. The similarity between clinical and pathologic staging in some studies is as low as 50%, and others publish results as high as 91%. The Dutch Lung Surgery Audit is a clinical database that registers the clinical and pathologic TNM of almost all NSCLC patients who undergo operations in the Netherlands. The objective of this study was to determine the accuracy of clinical staging of NSCLC., Methods: Prospective data were derived from the Dutch Lung Surgery Audit in 2013 and 2014. Patients were included if they had undergone a surgical resection for stage IA to IIIB NSCLC without neoadjuvant treatment and had a positron emission tomography-computed tomography scan as part of the clinical workup. Clinical (c)TNM and pathologic (p)TNM were compared, and whether discrepancy was based on tumor or nodal staging was determined., Results: From 2,834 patients identified, 2,336 (82.4%) fulfilled the inclusion criteria and had complete data. Of these 2,336, 1,276 (54.6%) were staged accurately, 707 (30.3%) were clinically understaged, and 353 (15.1%) were clinically overstaged. In the understaged group, 346 patients had a higher pN stage (14.8%), of which 148 patients had unforeseen N2 disease (6.3%). In the overstaged group, 133 patients had a cN that was higher than the pN (5.7%)., Conclusions: Accuracy of NSCLC staging in the Netherlands is low (54.6%), even in the era of positron emission tomography-computed tomography. Especially accurate nodal staging remains challenging. Future efforts should include the identification of specific pitfalls in NSCLC staging., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling., Methods: In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters., Results: Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV 25 : +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dt MAX , and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV 25 : -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia., Conclusions: Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia., Clinical Trial Registration: URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844., (© 2016 American Heart Association, Inc.)

Objective: The future promises many technological advances in the field of heart valve interventions, like tissue-engineered heart valves (TEHV). Prior to introduction in clinical practice, it is essential to perform early health technology assessment. We aim to develop a conceptual model (CM) that can be used to investigate the performance and costs requirements for TEHV to become cost-effective., Methods: After scoping the decision problem, a workgroup developed the draft CM based on clinical guidelines. This model was compared with existing models for cost-effectiveness of heart valve interventions, identified by systematic literature search. Next, it was discussed with a Delphi panel of cardiothoracic surgeons, cardiologists and a biomedical scientist (n=10)., Results: The CM starts with the valve implantation. If patients survive the intervention, they can remain alive without complications, die from non-valve-related causes or experience a valve-related event. The events are separated in early and late events. After surviving an event, patients can experience another event or die due to non-valve-related causes. Predictors will include age, gender, NYHA class, left ventricular function and diabetes. Costs and quality adjusted life years are to be attached to health conditions to estimate long-term costs and health outcomes., Conclusions: We developed a CM that will serve as foundation of a decision-analytic model that can estimate the potential cost-effectiveness of TEHV in early development stages. This supports developers in deciding about further development of TEHV and identifies promising interventions that may result in faster take-up in clinical practice by clinicians and reimbursement by payers., Competing Interests: Conflicts of Interest: None declared.

Introduction: The literature on surgical salvage, i.e. lung resections in patients who develop a local recurrence following stereotactic ablative radiotherapy (SABR), is limited. We describe our experience with salvage surgery in nine patients who developed a local recurrence following SABR for early stage non-small cell lung cancer (NSCLC)., Methods: Patients who underwent surgical salvage for a local recurrence following SABR for NSCLC were identified from two Dutch institutional databases. Complications were scored using the Dindo-Clavien-classification., Results: Nine patients who underwent surgery for a local recurrence were identified. Median time to local recurrence was 22 months. Recurrences were diagnosed with CT- and/or 18FDG-PET-imaging, with four patients also having a pre-surgical pathological diagnosis. Extensive adhesions were observed during two resections, requiring conversion from a thoracoscopic procedure to thoracotomy during one of these procedures. Three patients experienced complications post-surgery; grade 2 (N = 2) and grade 3a (N = 1), respectively. All resection specimens showed viable tumor cells. Median length of hospital stay was 8 days (range 5-15 days) and 30-day mortality was 0 %. Lymph node dissection revealed mediastinal metastases in 3 patients, all of whom received adjuvant therapy., Conclusions: Our experience with nine surgical procedures for local recurrences post-SABR revealed two grade IIIa complications, and a 30-day mortality of 0 %, suggesting that salvage surgery can be safely performed after SABR.

Aims: Extent of left ventricular (LV) reverse remodeling after aortic valve repair or replacement (AVR) may differ between patients operated for acute aortic regurgitation (AR) and chronic AR. The aim of this study was to compare changes in LV volumes and function between patients with acute and chronic AR who underwent AVR., Methods and Results: A total of 98 patients (54±15 years, 61% men) with acute (n=21) or chronic AR (n=77) were included in the present retrospective evaluation. LV volumes, LV ejection fraction, and global longitudinal strain indexed for LV end-diastolic volume (GLSi) were assessed preoperatively and after a median follow-up of 28 months (interquartile range: 17-66 months). Patients with acute AR tended to have smaller preoperative LV end-diastolic volume compared with chronic AR (156±15 vs 183±6 mL; P=.070). Both in patients with acute and chronic AR, significant LV reverse remodeling with sustained reduction in LV volumes occurred during follow-up with a significant smaller LV end-diastolic volume in acute AR compared with chronic AR (106±8 vs 128±5 mL; P=.032). Preoperative and postoperative LV ejection fractions were not significantly different between groups. In contrast, GLSi was better in patients with acute AR compared with chronic AR before AVR (-1.34±0.20 vs -0.96±0.07%/10 mL; P=.042) and during follow-up (-1.65±0.16 vs -1.29±0.07%/10 mL; P=.017)., Conclusions: After AVR, LV reverse remodeling occurs both in patients with acute and chronic AR. However, LV end-diastolic volume was more reduced and GLSi was more preserved during follow-up in acute AR than in chronic AR., (© 2016, Wiley Periodicals, Inc.)

Objectives: The objective of this study was to compare male-female differences with respect to baseline characteristics and short-term outcome in a contemporary nationwide cohort of patients who underwent isolated mitral valve (MV) surgery., Methods: All patients [N = 3411; 58% males (N = 1977)] who underwent isolated MV surgery (replacement: N = 1048, 31%; reconstruction: N = 2364, 69%) in the Netherlands between January 2007 and December 2011 were included in this study. Differences in patient and procedural characteristics and in-hospital outcome were compared between male and female patients., Results: Female patients were generally older (mean age, 64 vs 61 years, P < 0.001), presented more often with pulmonary hypertension (P = 0.03) and had higher logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) I (P < 0.001). Male patients presented more often with prior coronary artery bypass graft surgery (P < 0.001) and active endocarditis (P = 0.002). Female patients underwent MV replacement more often (P < 0.001) and, in case of replacement, received stented bioprostheses more often (P < 0.001). In-hospital mortality rates after MV replacement were 7% (n = 33) and 7% (n = 40) in male and female patients, respectively (OR 1.08, 95% CI 0.67-1.75; P = 0.75). In-hospital mortality rates after MV reconstruction were 1.4% (n = 21) and 1.3% (n = 11) in male and female patients, respectively (OR 0.88, 95% CI 0.42-1.84; P = 0.74)., Conclusions: There are substantial male-female differences in patient presentation and procedural aspects in isolated MV surgery in the Netherlands. Female patients are older, have more severe disease at the time of surgery and undergo valve repair less often. Future studies are needed to identify potentially modifiable patient factors to improve the outcome of female patients with MV disease., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Infective endocarditis of the aortic valve with local aortic root destruction requires radical resection of infected tissues and subsequent reconstruction of periannular structures and the left ventricular outflow tract (LVOT). Homografts or stentless bioprostheses are recommended for use in this specific patient group. The Freestyle stentless bioprosthesis is a porcine aortic root prosthesis, which approaches the surgical versatility of the homograft, but has the advantage of ready availability and uniform quality. We assessed clinical and echocardiographic outcome following the use of this prosthesis in extensive aortic valve endocarditis., Methods: Between June 2000 and December 2014, 55 Freestyle prostheses were implanted for aortic valve endocarditis involving the root in 54 patients (74% male). The mean age at operation was 61 ± 13 years. The mean EuroSCORE II was 20.1 ± 13.5. Twenty-nine (54%) patients had prosthetic valve endocarditis. The median follow-up time after surgery was 3.5 years, ranging from 0 to 15 years., Results: Early and late mortality were 11% (6 patients) and 14% (7 patients), respectively. Estimated overall survival at 1 and 5 years was 83 and 70%, respectively. There was no survival difference between patients with native or prosthetic valve endocarditis. One patient underwent reoperation for recurrent endocarditis 2.3 years after the initial procedure. No other prosthesis failure occurred. At a median follow-up of 3.3 years, mean gradient over the prosthesis was 4.3 ± 2.3 mmHg. No patient had more than mild aortic regurgitation., Conclusions: The Freestyle stentless bioprosthesis is a valuable option to reconstruct the LVOT after debridement in extensive aortic valve endocarditis. It is readily available with a versatility and clinical outcome comparable with that of homografts. Although early mortality remains considerable in this high-risk group of patients, late survival is good with low rates of recurrence of endocarditis, immediate local control and good haemodynamic performance on echocardiography., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Mesenchymal stromal cells (MSCs) may reduce inflammation and promote tissue repair in pulmonary emphysema., Aim: To study the safety and feasibility of bone marrow-derived autologous (BM-) MSC intravenous administration to patients with severe emphysema., Design: A phase I, prospective open-label study registered at ClinicalTrials.gov as NCT01306513 Eligible patients had lung volume reduction surgery (LVRS) on two separate occasions. During the first LVRS bone marrow was collected, from which MSCs were isolated and expanded ex vivo After 8 weeks, patients received two autologous MSC infusions 1 week apart, followed by the second LVRS procedure at 3 weeks after the second BM-MSC infusion., Methods: Up to 3 weeks after the last MSC infusion adverse events were recorded. Using immunohistochemistry and qPCR for analysis of cell and proliferation markers, emphysematous lung tissue obtained during the first surgery was compared with lung tissue obtained after the second surgical session to assess BM-MSC effects., Results: From 10 included patients three were excluded: two did not receive MSCs due to insufficient MSC culture expansion, and one had no second surgery. No adverse events related to MSC infusions occurred and lung tissue showed no fibrotic responses. After LVRS and MSC infusions alveolar septa showed a 3-fold increased expression of the endothelial marker CD31 (P  =  0.016)., Conclusions: Autologous MSC treatment in severe emphysema is feasible and safe. The increase in CD31 expression after LVRS and MSC treatment suggests responsiveness of microvascular endothelial cells in the most severely affected parts of the lung., (© The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later., Methods and Materials: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses., Results: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83)., Conclusion: Radiation therapy regimens used in BC treatment between 1989 and 2005 increased the risk of CVD, and anthracycline-based chemotherapy regimens increased the risk of CHF., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Differences in recurrence rate of aortic regurgitation (AR) and extent of left ventricular (LV) remodeling across the different surgical options in patients operated for type A aortic dissection remain unknown. The present evaluation compared the AR recurrence rate and changes in LV volumes and systolic function in valve-sparing aorta replacement (VSAR), supracoronary ascending aorta replacement (SCAR), and aortic valve and aorta replacement (AVAR). A total of 97 patients (58 ± 12 years, 62% men) with acute type A aortic dissection who underwent VSAR (n = 24), SCAR (n = 43), or AVAR (n = 30) were evaluated. Changes in LV volumes and function between postoperative and follow-up were compared using linear mixed models. Postoperative AR grades were not significantly different between groups. However, after median follow-up of 47 months, AR grade ≥2 was significantly more often observed in SCAR (55%) and VSAR (25%) compared to AVAR (0%, p <0.001). LV volumes remained stable in VSAR and AVAR but increased significantly in SCAR (LV end-diastolic volume: from 99 ± 4 to 131 ± 6 ml; p <0.001; LV end-systolic volume: from 49 ± 3 to 66 ± 5 ml; p = 0.002). In patients with recurrent AR grade ≥2 at follow-up, LV volumes increased, whereas patients without recurrent AR did not show significant LV dilatation. In conclusion, patients with acute type A aortic dissection who underwent SCAR or VSAR showed more frequently AR grade ≥2 recurrence compared to AVAR. However, only patients who underwent SCAR experienced adverse LV remodeling at follow-up. Recurrence of AR grade ≥2 was associated with adverse LV remodeling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The predictive performance of static risk prediction models such as EuroSCORE deteriorates over time. We aimed to explore different methods for continuous updating of EuroSCORE (dynamic modeling) to improve risk prediction., Methods and Results: Data on adult cardiac surgery from 2007 to 2012 (n=95 240) were extracted from the Netherlands Association for Cardio-Thoracic Surgery database. The logistic EuroSCORE predicting in-hospital death was updated using 6 methods: recalibrating the intercept of the logistic regression model; recalibrating the intercept and joint effects of the prognostic factors; re-estimating all prognostic factor effects, re-estimating all prognostic factor effects, and applying shrinkage of the estimates; applying a test procedure to select either of these; and a Bayesian learning strategy. Models were updated with 1 or 3 years of data, in all cardiac surgery or within operation subgroups. Performance was tested in the subsequent year according to discrimination (area under the receiver operating curve, area under the curve) and calibration (calibration slope and calibration-in-the-large). Compared with the original EuroSCORE, all updating methods resulted in improved calibration-in-the-large (range -0.17 to 0.04 versus -1.13 to -0.97, ideally 0.0). Calibration slope (range 0.92-1.15) and discrimination (area under the curve range 0.83-0.87) were similar across methods. In small subgroups, such as aortic valve replacement and aortic valve replacement+coronary artery bypass grafting, extensive updating using 1 year of data led to poorer performance than using the original EuroSCORE. The choice of updating method had little effect on benchmarking results of all cardiac surgery., Conclusions: Several methods for dynamic modeling may result in good discrimination and superior calibration compared with the original EuroSCORE. For large populations, all methods are appropriate. For smaller subgroups, it is recommended to use data from multiple years or a Bayesian approach., (© 2016 American Heart Association, Inc.)

Aortic valve sparing surgery for aortic regurgitation and/or aortopathy serves as an alternative to aortic valve and root replacement. One of the advantages of aortic valve sparing surgery over conventional replacement is that there is no need for life-long anticoagulation, which is particularly attractive in young patients who may receive a mechanical prosthesis otherwise. However, successful aortic valve repair requires high expertise. At present, reparability is determined intraoperatively by direct surgical inspection. Preoperative imaging techniques might improve the patient selection for aortic valve repair. The mechanism of aortic regurgitation, aortic valve morphology and calcification and aortic root dimensions are all of importance when aortic valve repair is considered. The present review focuses on the role of imaging techniques in determining aortic valve reparability.

Objectives: Selection of tubular graft size during David reimplantation technique for aortic root dilatation is based on perioperative leaflet height measurements. The present study evaluated whether transthoracic echocardiography (TTE)-based algorithms may help in selecting the graft size preoperatively., Methods: Thirty patients (52 ± 11 years old, 73% men) who underwent David reimplantation technique were evaluated. The implanted graft size was based on the David's formula. Leaflet height [diameter = 1.1 × ((2 × 2/3 × leaflet height) + 2)), leaflet length (diameter = ((2 × 2/3 × leaflet length) + 2)] and leaflet area [diameter = 0.8 × ((2 × √(total leaflet area/π)) + 2)] TTE-derived formulas were retrospectively developed. The percentage of under- or oversized implanted grafts was calculated and the association between the adequacy of graft sizing using TTE-derived formulas and the incidence of residual aortic regurgitation (AR) was evaluated retrospectively., Results: The incidence of postoperative mild residual AR was 23%. The true diameter of the inplanted graft was oversized based on leaflet height in 15 (50%) patients, based on leaflet length in 13 (43%) patients and based on leaflet area TTE-derived formula in 11 (37%) patients. The incidence of mild AR was significantly lower in undersized grafts compared with oversized grafts based on leaflet length TTE-derived formula (6 vs 46%, P = 0.032) and leaflet area TTE-derived formula (5 vs 55%, P = 0.009)., Conclusions: In patients undergoing David reimplantation technique, grafts considered undersized according to the leaflet length or leaflet area TTE-derived formula were associated with less incidence of residual AR than patients with oversized grafts., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Fibrosis increases arrhythmogenicity in myocardial tissue by causing structural and functional disruptions in the cardiac syncytium. Forced fusion of fibroblastic cells with adjacent cardiomyocytes may theoretically resolve these disruptions. Therefore, the electrophysiological effects of such electrical and structural integration of fibroblastic cells into a cardiac syncytium were studied., Methods and Results: Human ventricular scar cells (hVSCs) were transduced with lentiviral vectors encoding enhanced green fluorescent protein alone (eGFP↑-hVSCs) or together with the fusogenic vesicular stomatitis virus G protein (VSV-G/eGFP↑-hVSCs) and subsequently co-cultured (1:4 ratio) with neonatal rat ventricular cardiomyocytes (NRVMs) in confluent monolayers yielding eGFP↑- and VSV-G/eGFP↑-co-cultures, respectively. Cellular fusion was induced by brief exposure to pH = 6.0 medium. Optical mapping experiments showed eGFP↑-co-cultures to be highly arrhythmogenic [43.3% early afterdepolarization (EAD) incidence vs. 7.7% in control NRVM cultures, P < 0.0001], with heterogeneous prolongation of action potential (AP) duration (APD). Fused VSV-G/eGFP↑-co-cultures displayed markedly lower EAD incidence (4.6%, P < 0.001) than unfused co-cultures, associated with decreases in APD, APD dispersion, and decay time of cytosolic Ca(2+) waves. Heterokaryons strongly expressed connexin43 (Cx43). Also, maximum diastolic potential in co-cultures was more negative after fusion, while heterokaryons exhibited diverse mixed NRVM/hVSC whole-cell current profiles, but consistently showed increased outward Kv currents compared with NRVMs or hVSCs. Inhibition of Kv channels by tetraethylammonium chloride abrogated the anti-arrhythmic effects of fusion in VSV-G/eGFP↑-co-cultures raising EAD incidence from 7.9 to 34.2% (P < 0.001)., Conclusion: Forced fusion of cultured hVSCs with NRVMs yields electrically functional heterokaryons and reduces arrhythmogenicity by preventing EADs, which is, at least partly, attributable to increased repolarization force., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Changes in mitral valve geometry in patients with significant aortic regurgitation (AR) have not been evaluated. The aim of the present study was to assess the prevalence of significant secondary mitral regurgitation (MR; grade ≥ 2) and the geometric characteristics of the mitral valve in patients with moderate and severe AR (grade ≥ 2) undergoing aortic valve and root surgery., Methods: One-hundred twenty patients (mean age, 54 ± 15 years; 65% men) with AR grade ≥ 2 undergoing aortic valve and root surgery were retrospectively evaluated. The presence of MR grade ≥ 2 and geometry of the mitral valve were assessed on preoperative transthoracic echocardiography. Left ventricular (LV) dimensions and mitral valve geometry were compared between patients with MR grade ≥ 2 and patients without., Results: MR grade ≥ 2 was present in 28 patients (23%). Patients with MR grade ≥ 2 had higher European System for Cardiac Operative Risk Evaluation II scores and more often used β-blockers and diuretics than their counterparts. Patients with MR grade ≥ 2 had larger tenting areas (mean, 1.59 ± 0.79 vs 1.25 ± 0.41 cm(2); P = .003), larger inter-papillary muscle distances (mean, 28.4 ± 9.5 vs 24.8 ± 5.2 mm; P = .014), larger left atria (mean, 40.9 ± 13.7 vs 32.0 ± 12.2 mL/m(2); P = .002), and lower LV ejection fractions (mean, 47.3 ± 12.2% vs 54.3 ± 9.3%; P = .002) as compared to patients with MR grade < 2. However, there were no differences in indexed LV volumes. On multivariate logistic regression analysis, LV ejection fraction (odds ratio, 0.94; 95% confidence interval, 0.89-0.99; P = .018) and indexed left atrial volume (odds ratio, 1.05; 95% confidence interval, 1.01-1.10; P = .019) remained independently associated with MR grade ≥ 2 after correcting for tenting area and inter-papillary muscle distance., Conclusions: Among patients with AR grade ≥ 2 undergoing aortic valve and root surgery, the prevalence of MR grade ≥ 2 was 23%. Lower LV ejection fraction and larger left atrial volume were independently associated with MR grade ≥ 2., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) reverse remodeling after aortic valve replacement (AVR) for aortic regurgitation (AR) is associated with superior prognosis. The outcomes of valve-sparing aortic root replacement techniques on LV performance have not been compared with LV reverse remodeling in AVR. The present evaluation compared the extent of long-term LV reverse remodeling in patients with aortic root pathology and/or AR who underwent aortic valve repair (AVr) with patients who underwent AVR., Methods: A total of 226 patients (54.7 ± 14.3 years, 63% male) with AR or aortic root pathology who underwent AVr (n = 135) or AVR with the Freestyle® stentless aortic root bioprosthesis [Medtronic, Inc.; Minneapolis, Minnesota] (n = 91) were included in the present retrospective evaluation. LV volumes and ejection fraction were assessed preoperatively, postoperatively (before hospital discharge) and during follow-up., Results: Baseline characteristics were comparable between patient groups, except for higher prevalence of bicuspid aortic valve anatomy among AVR patients (38% vs. 16%, p < 0.001). In addition, patients undergoing AVR had significantly larger LV end-diastolic and end-systolic volumes than their counterparts. After a median follow-up of 46 months (interquartile range: 17 to 78 months), both groups of patients showed a significant and sustained reduction in LV end-diastolic and end-systolic volumes, with significantly larger reduction in patients undergoing AVR. Ejection fraction decreased significantly postoperatively and improved later during follow-up similarly in both groups. The incidence of significant AR at long-term follow-up was comparable among groups (AVr: 8% vs. AVR: 7%)., Conclusions: LV reverse remodeling occurs after AVR and AVr, reaching comparable LV volumes and function after a median of four years of follow-up., (© 2014 Wiley Periodicals, Inc.)

Introduction: The 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20-50%). Local recurrence rate is high (48-66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control., Methods: From 2006 to 2011, 50 patients, 28 male, median age 57 years (15-76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan-Meier method., Results: Operative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3-63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values., Conclusion: Compared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma.

Objectives: The aim was to describe procedural volumes, patient risk profile and outcomes of heart valve surgery in the past 16 years in Netherlands., Methods: The Dutch National Database for Cardio-Thoracic Surgery includes approximately 200 000 cardiac operations performed between 1995 and 2010. Information on all valve surgeries (56 397 operations) was extracted. We determined trends for changes in procedural volume, demographics, risk profile and in-hospital mortality of valve operations. Because of incomplete data in the first years of registration, the total number of operations in those years was estimated using Poisson regression. For a subset from 2007 to 2010, follow-up data were available. Survival status was obtained through linkage with the national Cause of Death Registry, and survival analysis was performed using Kaplan-Meier method. Information on discharge and readmissions was obtained from the National Hospital Discharge Registry., Results: The annual volume of heart valve operations increased by more than 100% from an estimated 2431 in 1995 to 5906 in 2010. Adjusted for population size in Netherlands, the number of operations per 100 000 adults increased from 20 in 1995 to 43 in 2010. In 2010, frequently performed valve surgery included the following: 34.6% isolated aortic valve (AoV) replacement, 21.8% AoV replacement and coronary artery bypass grafting (CABG), 14.6% isolated mitral valve surgery (repair or replacement) and 9.1% mitral valve and CABG. In AoV surgery, an increasing use of bioprostheses in all age categories is observed. In mitral valve surgery, 75.4% was performed by repair rather than replacement in 2010. In-hospital mortality for all valve surgery decreased significantly from 4.6% in 2007 to 3.6% in 2010, whereas the mean logistic EuroSCORE remained stable (median 5.8, P = 1.000). Thirty-day mortality after all valve surgery was 3.9% and 120-day mortality was 6.5%. At 1 year, survival after all valve surgery was 91.6% and a reoperation had been performed in 1.6%. The median postoperative length of stay was 7 days (interquartile range (IQR) 5-11) in the primary hospital and 11 days (IQR 8-16), including subsequent stay, in the secondary hospital., Conclusions: The results of this study provide a comprehensive overview of valve surgery trends and outcomes in Netherlands. The number of heart valve operations performed in Netherlands has increased since 1995. The significant decrease in mortality and unchanged EuroSCORE between 2007 and 2010 might reflect a general improvement of the safety of valve surgery., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Recent concerns about potential overdiagnosis and overtreatment of ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects of treatment, such as cardiovascular disease (CVD), of great importance. We studied cardiovascular morbidity and mortality in a large population-based cohort of DCIS patients., Methods: Data on all incident DCIS case patients in the Netherlands between 1989 and 2004 who were diagnosed before the age of 75 years were obtained (n = 10468). CVD data was acquired through linkage with population-based registries. Standardized mortality ratios were calculated by comparing mortality in our cohort with that in the Dutch female population, taking into account person-years of observation. Within-cohort comparisons were based on multivariable competing-risk regression., Results: Compared with the general population, 5-year survivors of DCIS had a similar risk of dying due to any cause (standardized mortality ratio [SMR] = 1.04; 95% confidence interval [CI] = 0.97 to 1.11) but a lower risk of dying of CVD (SMR = 0.77; 95% CI = 0.67 to 0.89). No difference in CVD risk was found when comparing 5-year survivors treated with radiotherapy with those treated with surgery only. Left-sided vs right-sided radiotherapy also did not increase this risk (hazard ratio [HR] = 0.94; 95% CI = 0.67 to 1.32). In a subgroup analysis of all DCIS patients diagnosed between 1997 and 2005, we were able to account for history of CVD and did not observe a risk difference between treatment groups (left-sided vs right-sided radiotherapy: HR = 0.94; 95% CI = 0.68 to 1.29)., Conclusions: After a median follow-up of 10 years, we did not find an increased risk for cardiovascular morbidity or mortality after radiotherapy for DCIS when comparing surgery and radiotherapy vs surgery only, nor when comparing radiotherapy for left-sided vs right-sided DCIS. Compared with the general population, DCIS patients have a decreased risk of cardiovascular death, independent of treatment., (© The Author 2014. Published by Oxford University Press.)

Aims: Assess and compare among Dutch cardiothoracic surgeons and cardiologists: opinion on (1) patient involvement, (2) conveying risk in aortic valve selection, and (3) aortic valve preferences., Methods and Results: A survey among 117 cardiothoracic surgeons and cardiologists was conducted. Group responses were compared using the Mann-Whitney U test. Most respondents agreed that patients should be involved in decision-making, with surgeons leaning more toward patient involvement (always: 83 % versus 50 % respectively; p < 0.01) than cardiologists. Most respondents found that ideally doctors and patients should decide together, with cardiologists leaning more toward taking the lead compared with surgeons (p < 0.01). Major risks of the therapeutic options were usually discussed with patients, and less common complications to a lesser extent. A wide variation in valve preference was noted with cardiologists leaning more toward mechanical prostheses, while surgeons more often preferred bioprostheses (p < 0.05)., Conclusion: Patient involvement and conveying risk in aortic valve selection is considered important by cardiologists and cardiothoracic surgeons. The medical profession influences attitude with regard to aortic valve selection and patient involvement, and preference for a valve substitute. The variation in valve preference suggests that in most patients both valve types are suitable and aortic valve selection may benefit from evidence-based informed shared decision-making.

Background: The underlying mechanism of aortic regurgitation and aortic valve and root characteristics are associated with the durability of surgical repair., Objective: We investigated whether multidetector CT (MDCT) identifies the characteristics of the aortic valve and root that may be associated with the ability to perform successful surgical repair., Methods: Sixty-one patients with aortic regurgitation and/or aortic root pathology who were evaluated for aortic valve or root repair and underwent clinically indicated gated or nongated MDCT of the aortic valve and aortic root were included in the present analysis. Patients with endocarditis were excluded. MDCT data of aortic valve anatomy and calcification and thoracic aorta dimensions were analyzed., Results: The aortic valve and root was successfully repaired in 36 patients (55 ± 13 years; 61% male; median EuroSCORE II, 3.8%) whereas in 25 patients (56 ± 15 years; 52% male; median EuroSCORE II, 2.5%) repair was not attempted (n = 20) or valve repair was converted to aortic valve replacement during surgery (n = 5). In patients in whom repair was considered not possible or failed, there was a higher percentage of bicuspid aortic valves (48% vs 17%; P = .019), more severe commissural calcification, and more severe annular calcification., Conclusion: The degree of commissural and annular calcification of the aortic valve determined by MDCT is inversely related to the ability to perform surgical valve repair instead of replacement. Similarly, bicuspid valve anatomy predicts failure to perform repair., (Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the accuracy of data from hospital administration databases and a national clinical cardiac surgery database and to compare the performance of the Dutch hospital standardised mortality ratio (HSMR) method and the logistic European System for Cardiac Operative Risk Evaluation, for the purpose of benchmarking of mortality across hospitals., Methods: Information on all patients undergoing cardiac surgery between 1 January 2007 and 31 December 2010 in 10 centres was extracted from The Netherlands Association for Cardio-Thoracic Surgery database and the Hospital Discharge Registry. The number of cardiac surgery interventions was compared between both databases. The European System for Cardiac Operative Risk Evaluation and hospital standardised mortality ratio models were updated in the study population and compared using the C-statistic, calibration plots and the Brier-score., Results: The number of cardiac surgery interventions performed could not be assessed using the administrative database as the intervention code was incorrect in 1.4-26.3%, depending on the type of intervention. In 7.3% no intervention code was registered. The updated administrative model was inferior to the updated clinical model with respect to discrimination (c-statistic of 0.77 vs 0.85, p<0.001) and calibration (Brier Score of 2.8% vs 2.6%, p<0.001, maximum score 3.0%). Two average performing hospitals according to the clinical model became outliers when benchmarking was performed using the administrative model., Conclusions: In cardiac surgery, administrative data are less suitable than clinical data for the purpose of benchmarking. The use of either administrative or clinical risk-adjustment models can affect the outlier status of hospitals. Risk-adjustment models including procedure-specific clinical risk factors are recommended.

In this review we discuss cardiovascular mortality, incidence and prevalence of heart disease, and cardiac interventions and surgery in the Netherlands. We combined most recently available data from various Dutch cardiovascular registries, Dutch Hospital Data (LMR), Statistics Netherlands (CBS), and population-based cohort studies, to provide a broad quantitative update. The absolute number of people dying from cardiovascular diseases is declining and cardiovascular conditions are no longer the leading cause of death in the Netherlands. However, a substantial burden of morbidity persists with 400,000 hospitalisations for cardiovascular disease involving over 80,000 cardiac interventions annually. In the Netherlands alone, an estimated 730,000 persons are currently diagnosed with coronary heart disease, 120,000 with heart failure, and 260,000 with atrial fibrillation. These numbers emphasise the continuous need for dedicated research on prevention, diagnosis, and treatment of heart disease in our country.

Objectives: The aim of our study was to investigate early mortality after cardiac surgery and to determine the most adequate follow-up period for the evaluation of mortality rates., Methods: Information on all adult cardiac surgery procedures in 10 of 16 cardiothoracic centres in Netherlands from 2007 until 2010 was extracted from the database of Netherlands Association for Cardio-Thoracic Surgery (n = 33 094). Survival up to 1 year after surgery was obtained from the national death registry. Survival analysis was performed using Kaplan-Meier and Cox regression analysis. Benchmarking was performed using logistic regression with mortality rates at different time points as dependent variables, the logistic EuroSCORE as covariate and a random intercept per centre., Results: In-hospital mortality was 2.94% (n = 972), 30-day mortality 3.02% (n = 998), operative mortality 3.57% (n = 1181), 60-day mortality 3.84% (n = 1271), 6-month mortality 5.16% (n = 1707) and 1-year mortality 6.20% (n = 2052). The survival curves showed a steep initial decline followed by stabilization after ∼60-120 days, depending on the intervention performed, e.g. 60 days for isolated coronary artery bypass grafting (CABG) and 120 days for combined CABG and valve surgery. Benchmark results were affected by the choice of the follow-up period: four hospitals changed outlier status when the follow-up was increased from 30 days to 1 year. In the isolated CABG subgroup, benchmark results were unaffected: no outliers were found using either 30-day or 1-year follow-up., Conclusions: The course of early mortality after cardiac surgery differs across interventions and continues up to ∼120 days. Thirty-day mortality reflects only a part of early mortality after cardiac surgery and should only be used for benchmarking of isolated CABG procedures. The follow-up should be prolonged to capture early mortality of all types of interventions.

Aims: Mitral valve repair in patients with functional mitral regurgitation (FMR) has been associated with beneficial left ventricular (LV) reverse remodelling. Recently, galectin-3 emerged as a marker of myocardial inflammation and fibrosis which may influence LV remodelling after surgery. The aim of the current study was to evaluate the association between pre-operative galectin-3 levels and LV reverse remodelling in heart failure patients with significant FMR who underwent mitral valve repair., Methods and Results: In total, 42 heart failure patients (66 ± 10 years, 69% male) were evaluated. Plasma galectin-3 levels were assessed pre-operatively. Two-dimensional echocardiographic parameters were measured at baseline, and at 6 and 12 months after surgery. LV reverse remodelling was defined as a decrease in LV end-systolic volume ≥15% at 6 months follow-up. In total, 57% of the patients showed LV reverse remodelling. Patients with LV reverse remodelling showed significantly lower pre-operative galectin-3 levels (17.5 ± 5.6 vs. 23.7 ± 9.9 ng/mL, P = 0.009) compared with patients without LV reverse remodelling. In addition, patients with galectin-3 ≤18.2 ng/mL had a six-fold higher probability of showing LV reverse remodelling after surgery as compared with patients with levels >18.2 ng/mL (odds ratio 6.58, 95% confidence interval 1.32-33.33, P = 0.02)., Conclusion: High pre-operative plasma galectin-3 is independently associated with the absence of LV reverse remodelling after mitral valve repair. Galectin-3 may be useful to identify heart failure patients who will need additional treatment to obtain beneficial LV reverse remodelling.

Background: Segmental dose reduction with increasing age after thoracic epidural anaesthesia (TEA) has been documented. We hypothesised that after a fixed loading dose of ropivacaine at the T3-T4 level, increasing age would result in more extended analgesic spread. In addition, other aspects of neural blockade and haemodynamic changes were studied., Methods: Thirty-five lung surgery patients were included in three age groups. Thirty-one patients received an epidural catheter at the T3-T4 interspace followed by an injection of 8-ml ropivacaine 0.75%. Analgesia was assessed with pinprick and temperature discrimination. Motor block was tested using the Bromage and epidural scoring scale for arm movements score. An arterial line was inserted for invasive measurement of blood pressure, cardiac index (CI) and stroke volume (SV)., Results: There was no influence of age on quality of TEA except for the caudal border of analgesia being somewhat lower in the middle and older age group compared with the young age group. Heart rate (6.0 ± 5.9, P < 0.001), mean arterial pressure (16.1 ± 15.6, P < 0.001), CI (0.55 ± 0.49, P < 0.001) and SV (9.6 ± 14.6, P = 0.001) decreased after TEA for the total group. Maximal reduction in heart rate after TEA was more extensive in the young age group compared with the other age groups. There was no effect of age on other cardiovascular parameters., Conclusion: We were unable to demonstrate an effect of age on the maximal number of spinal segments blocked after TEA; however, the caudad spread of analgesia increased with advancing age. In addition, reduction of heart rate was greater in the youngest group., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Several genes involved in the familial appearance of thoracic aortic aneurysms and dissections (FTAAD) have been characterized recently, one of which is SMAD3. Mutations of SMAD3 cause a new syndromic form of aortic aneurysms and dissections associated with skeletal abnormalities. We discovered a small interstitial deletion of chromosome 15, leading to disruption of SMAD3, in a boy with mild mental retardation, behavioral problems and revealed features of the aneurysms-osteoarthritis syndrome (AOS). Several family members carried the same deletion and showed features including aortic aneurysms and a dissection. This finding demonstrates that haploinsufficiency of SMAD3 leads to development of both thoracic aortic aneurysms and dissections, and the skeletal abnormalities that form part of the aneurysms-osteoarthritis syndrome. Interestingly, the identification of this familial deletion is an example of an unanticipated result of a genomic microarray and led to the discovery of important but unrelated serious aortic disease in the proband and family members., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Aims: Systemic complications after cardiac surgery are common in heart failure patients. However, the pathophysiological mechanisms, such as a different local inflammatory response of failing hearts, remain in question. This study examines whether failing hearts respond differently to cardioplegic arrest and reperfusion compared with non-failing hearts (controls)., Methods and Results: The inflammatory response was evaluated in samples collected simultaneously from the radial artery and coronary sinus, and myocardial tissue in 62 patients undergoing cardiac surgery. No myocardial release of inflammatory mediators was observed upon reperfusion in controls (n = 19). In contrast, in patients with heart failure, reperfusion was characterized by a myocardial release of several cytokines. Myocardial interleukin-6 was 115% increased in non-ischaemic heart failure (n = 18, P = 0.002) as compared with a 117% increase in patients with ischaemic heart failure (n = 25, P = 0.01). Furthermore, a myocardial release of monocyte chemoattractant protein-1 was observed in both patient groups: a 109% (P = 0.001) and 114% (P = 0.01) increase in patients with non-ischaemic heart failure and ischaemic heart failure, respectively. Post-operative myocardial damage, expression of inflammatory mediators, and p65-nuclear factor-κB activity were similar in all patient groups. Inflammatory cell content was increased in early ischaemic myocardial tissue in both heart failure groups compared with controls., Conclusion: Heart failure patients show a clear myocardial inflammatory response upon reperfusion, probably explained by degranulation of infiltrated inflammatory cells. Results in controls indicate that they better withstand cardioplegic arrest and reperfusion without an explicit myocardial inflammatory response.

External leg compression (ELC) may increase cardiac output (CO) in fluid-responsive patients like passive leg raising (PLR). We compared the hemodynamic effects of two methods of ELC and PLR measured by thermodilution (COtd), pressure curve analysis Modelflow™ (COmf) and ultra-sound HemoSonic™ (COhs), to evaluate the method with the greatest hemodynamic effect and the most accurate less invasive method to measure that effect. We compared hemodynamic effects of two different ELC methods (circular, A (n = 16), vs. wide, B (n = 13), bandages inflated to 30 cm H2O for 15 min) with PLR prior to each ELC method, in 29 post-operative cardiac surgical patients. Hemodynamic responses were measured with COtd, COmf and COhs. PLR A increased COtd from 6.1 ± 1.7 to 6.3 ± 1.8 L·min(-1) (P = 0.016), and increased COhs from 4.9 ± 1.5 to 5.3 ± 1.6 L·min(-1) (P = 0.001), but did not increase COmf. ELC A increased COtd from 6.4 ± 1.8 to 6.7 ± 1.9 L·min(-1) (P = 0.001) and COmf from 6.9 ± 1.7 to 7.1 ± 1.8 L·min(-1) (P = 0.021), but did not increase COhs. ELC A increased COtd and COmf as in PLR A. PLR B increased COtd from 5.4 ± 1.3 to 5.8 ± 1.4 L·min(-1) (P < 0.001), and COhs from 5.0 ± 1.0 to 5.4 ± 1.0 L·min(-1) (P = 0.013), but not COmf. ELC B increased COtd from 5.2 ± 1.2 to 5.4 ± 1.1 L·min(-1) (P = 0.003), but less than during PLR B (P = 0.012), while COmf and COhs did not change. Bland-Altman and polar plots showed lower limits of agreement with changes in COtd for COmf than for COhs. The circular leg compression increases CO more than bandage compression, and is able to increase CO as in PLR. The less invasive Modelflow™ can detect these changes reasonably well.

Objective: Upcoding or undercoding of risk factors could affect the benchmarking of risk-adjusted mortality rates. The aim was to investigate the effect of misclassification of risk factors on the benchmarking of mortality rates after cardiac surgery., Methods: A prospective cohort was used comprising all adult cardiac surgery patients in all 16 cardiothoracic centers in The Netherlands from January 1, 2007, to December 31, 2009. A random effects model, including the logistic European system for cardiac operative risk evaluation (EuroSCORE) was used to benchmark the in-hospital mortality rates. We simulated upcoding and undercoding of 5 selected variables in the patients from 1 center. These patients were selected randomly (nondifferential misclassification) or by the EuroSCORE (differential misclassification)., Results: In the random patients, substantial misclassification was required to affect benchmarking: a 1.8-fold increase in prevalence of the 4 risk factors changed an underperforming center into an average performing one. Upcoding of 1 variable required even more. When patients with the greatest EuroSCORE were upcoded (ie, differential misclassification), a 1.1-fold increase was sufficient: moderate left ventricular function from 14.2% to 15.7%, poor left ventricular function from 8.4% to 9.3%, recent myocardial infarction from 7.9% to 8.6%, and extracardiac arteriopathy from 9.0% to 9.8%., Conclusions: Benchmarking using risk-adjusted mortality rates can be manipulated by misclassification of the EuroSCORE risk factors. Misclassification of random patients or of single variables will have little effect. However, limited upcoding of multiple risk factors in high-risk patients can greatly influence benchmarking. To minimize "gaming," the prevalence of all risk factors should be carefully monitored., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

In 2007 The Netherlands Association for Cardio-Thoracic Surgery (Nederlandse Vereniging voor Thoraxchirurgie, NVT) instituted the Adult Cardiac Surgery Database. The dataset comprises demographic factors, type of intervention, in-hospital mortality and 18 risk factors for mortality after cardiac surgery, according to the European System for Cardiac Operative Risk Evaluation definitions. Currently, this procedural database contains over 60 000 interventions. Completeness of data is excellent and national coverage of all 16 Dutch cardio-thoracic surgery centres has been achieved since the start. The primary goal of the database is to control and maintain the quality of care by evaluation of outcomes. This is accomplished by regular feedback and comparison of outcomes. For a subset of the database (procedures from 10 out of 16 centres) longer-term follow-up has been established by means of data linkage to two national registries. This provides information on survival status, causes of death and readmissions. The database has recently been used for research, resulting in methodological papers aimed at optimizing comparison of outcomes. In future, clinical issues will also be addressed, for example survival after coronary artery bypass grafting and valve surgery.

Aims: Despite a successful surgical procedure and adherence to current recommendations, postoperative left ventricular (LV) dysfunction after mitral valve repair (MVr) for organic mitral regurgitation (MR) may still occur. New approaches are therefore needed to detect subclinical preoperative LV dysfunction. LV global longitudinal strain (GLS), assessed with speckle-tracking echocardiographic analysis, has been proposed as a novel measure to better depict latent LV dysfunction. The aim of this study was to investigate the value of GLS to predict long-term LV dysfunction after MVr., Methods and Results: A total of 233 patients (61% men, 61 ± 12 years) with moderate-severe organic MR who underwent successful MVr between 2000 and 2009 were included. Echocardiography was performed at baseline and long-term follow-up (34 ± 20 months) after MVr. LV dysfunction at follow-up was defined as LV ejection fraction (EF) <50% and was present in 29 (12%) patients. A cut-off value of -19.9% of GLS showed a sensitivity and specificity of 90 and 79% to predict long-term LV dysfunction. By univariate logistic regression analysis, baseline LVEF ≤60%, LV end-systolic diameter (ESD) ≥40 mm, atrial fibrillation, presence of symptoms, and GLS >-19.9% were predictors of long-term LV dysfunction. By multivariate analysis, GLS remained an independent predictor of LV dysfunction (odds ratio 23.16, 95% confidence interval: 6.53-82.10, P < 0.001), together with LVESD., Conclusion: In a large series of patients operated within the last decade, MVr resulted in a low incidence of long-term LV dysfunction. A GLS of >-19.9% demonstrated to be a major independent predictor of long-term LV dysfunction after adjustment for parameters currently implemented into guidelines.

Background: Heart failure is characterised as a strong risk factor for systemic failure after cardiac surgery. However, the impact has never been substantiated., Methods: Patients with heart failure (n = 48) - scheduled for elective ventricular reconstruction or external constraint device-were compared with a one-to-one matched control group of patients without heart failure undergoing cardiac surgery between 2006 and 2009., Results: As expected, patients with heart failure more frequently experienced complications definitely related to pump failure (p = 0.01). However, complications not related to their pump failure were also more often observed, such as prolonged mechanical ventilation, sepsis and vasoplegia (p = 0.01). Overall, organ dysfunction-circulatory, renal, and pulmonary failure-was often observed in heart failure patients, contributing to a prolonged stay in the intensive care unit (p < 0.001) as well as in hospital (p = 0.01)., Conclusion: The adverse postoperative course in patients with heart failure is not only directly related to circulatory failure, but merely reflects a systemic dysregulation. Our findings suggest that heart failure impacts outcome and should therefore be included in prevailing risk classification systems. Offensive perioperative treatment strategies, focused on the main complications in patients with heart failure, will lead to improved results after cardiac surgery.

Bilateral diaphragm paralysis is a serious condition causing failure to sleep in the supine position and this condition often results into severe hypercapnia leading to respiratory failure. Here we describe two cases that required mechanical ventilation, and subsequently failed to respond to intermittent non-invasive ventilation. Subjects were successfully taken from mechanical ventilation after unilateral plication of a hemidiafragm and one of them further improved after plication of the contralateral paralysed diaphragm. Remarkably, decompression of the left lower lung lobe after 20 years of lobar atelectasis resulted in rapid improvement of ventilation and gas exchange.

Objective: Remodeling of the left ventricle (LV) in ischemic cardiomyopathy frequently leads to functional mitral regurgitation (MR). The indication for correcting MR in patients undergoing LV reconstruction (LVR) is unclear. In this study, we evaluated our strategy of correcting MR≥grade 2+ by restrictive mitral annuloplasty (RMA) during LVR., Methods: We studied 92 consecutive patients (76 men, mean age 61±10 years) who underwent LVR for ischemic heart failure (IHF). RMA was performed in all patients with MR≥grade 2+ on preoperative echocardiography and in patients who showed increased MR to ≥grade 2+ immediately after LVR. Patients were attributed to a RMA and no-RMA group, depending on whether or not concomitant RMA had been performed. Mean clinical and structured echocardiographic follow-up was 47±20 months and was 100% complete., Results: In 38 out of 40 patients (95%) with preoperative MR≥grade 2+, concomitant RMA was planned and performed. In 17 out of 52 patients (33%) with MR

Background: Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell (RBC) transfusions. Whether platelet (PLT) and/or plasma transfusions are a marker for more concomitant RBC transfusions or are independently associated with complications after cardiac surgery is unknown., Study Design and Methods: Data from two randomized controlled studies were combined to analyze the effects of PLT and/or plasma transfusions on postoperative infections, length of stay in the intensive care unit (ICU), all-cause mortality, and mortality in the presence or absence of infections in the postoperative period., Results: After adjusting for confounding factors, plasma units and not RBC transfusions were associated with all-cause mortality. White blood cell (WBC)-containing RBC transfusions and PLT transfusions were associated with mortality occurring in the presence of or after infections. The number of (WBC-containing) RBC transfusions was also significantly associated with postoperative infections and with ICU stay for 4 or more days., Conclusion: Although it is difficult to separate the effects of blood components, we found that in cardiac surgery, perioperative plasma transfusions are independently associated with all-cause mortality. WBC-containing RBC transfusions and PLT transfusions are independently associated with mortality in the presence of infections in the postoperative period. Future transfusion studies in cardiac surgery should concomitantly consider the possible adverse effects of all the various transfused blood components., (© 2011 American Association of Blood Banks.)

Objective: Nonischemic dilated cardiomyopathy with functional mitral regurgitation carries a poor prognosis. Mitral valve surgery with implantation of a cardiac support device can treat mitral regurgitation and promote left ventricular reverse remodeling. This observational study evaluates clinical and echocardiographic outcomes of an individualized medico-surgical approach, focusing on mitral regurgitation recurrence and left ventricular reverse remodeling., Methods: Sixty-nine consecutive patients with heart failure (New York Heart Association class III/IV) with functional mitral regurgitation (grade 3+/4+) and left ventricular remodeling (end-diastolic volume 227 ± 73 mL, ejection fraction 26% ± 8%) underwent restrictive mitral annuloplasty (median ring size 26), with (n = 41) or without (n = 28) a cardiac support device and optimal postoperative medical treatment. Patients were clinically and echocardiographically evaluated at up to 3.1 years' median follow-up., Results: Early mortality was 5.8%. Actuarial survival at 1, 2, and 5 years was 86% ± 4%, 79% ± 5%, and 63% ± 7%. New York Heart Association class improved from 3.1 ± 0.4 to 2.0 ± 0.5 (P < .01). Cardiac support device implantation in addition to mitral valve surgery, applied in patients with more advanced left ventricular remodeling, resulted in similar clinical outcome, greater left ventricular end-diastolic volume decrease (33% vs 18%; P = .007), and in a trend toward less recurrent mitral regurgitation of grade 2+ or more (actuarial freedom at 3 years 89% ± 8% vs 63% ± 11%; P = .067)., Conclusions: An individualized medico-surgical approach to nonischemic cardiomyopathy combining restrictive mitral annuloplasty, cardiac support device implantation, and optimal medical management leads to favorable survival and improved functional status, low incidence of significant recurrent mitral regurgitation, and sustained left ventricular reverse remodeling., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: We hypothesize that concomitant tricuspid annuloplasty in patients with tricuspid annular dilatation who undergo mitral valve repair could prevent progression of tricuspid regurgitation and right ventricular remodeling., Methods: In 2002, 80 patients underwent mitral valve repair. Concomitant tricuspid annuloplasty was performed in 13 patients with grade 3 or 4 tricuspid regurgitation. In 2004, 102 patients underwent mitral valve repair. Concomitant tricuspid annuloplasty was performed in 21 patients with grade 3 or 4 tricuspid regurgitation and in 43 patients with an echocardiographically determined tricuspid annular diameter of 40 mm or greater. Patients underwent transthoracic echocardiographic analysis preoperatively and at the 2-year follow-up., Results: In the 2002 cohort right ventricular dimensions did not decrease (right ventricular long axis, 69 ± 7 vs 70 ± 8 mm; right ventricular short axis, 29 ± 7 vs 30 ± 7 mm); tricuspid regurgitation grade and gradient remained unchanged. In the 2004 cohort right ventricular reverse remodeling was observed (right ventricular long axis, 71 ± 6 vs 69 ± 9 mm; right ventricular short axis, 29 ± 5 vs 27 ± 5 mm; P < .0001); tricuspid regurgitation diminished (1.6 ± 1.0 vs 0.9 ± 0.6, P < .0001), and transtricuspid gradient decreased (28 ± 13 vs 23 ± 15 mm Hg, P = .021). Subanalysis of the 2002 cohort showed that in 23 patients without grade 3 or 4 tricuspid regurgitation but baseline tricuspid annular dilatation, the degree of tricuspid regurgitation was worse at the 2-year follow-up. Moreover, this caused right ventricular dilatation. Subanalysis of the 2004 cohort demonstrated reverse right ventricular remodeling and decreased tricuspid regurgitation in 43 patients with preoperative tricuspid annular dilatation who underwent tricuspid annuloplasty., Conclusions: Concomitant tricuspid annuloplasty during mitral valve repair should be considered in patients with tricuspid annular dilatation despite the absence of important tricuspid regurgitation at baseline because this improves echocardiographic outcome., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)