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Supplemental material, sj-docx-1-dhj-10.1177_20552076231187605 for Cardiac surgery risk prediction using ensemble machine learning to incorporate legacy risk scores: A benchmarking study by Tim Dong, Shubhra Sinha, Ben Zhai, Daniel P Fudulu, Jeremy Chan, Pradeep Narayan, Andy Judge, Massimo Caputo, Arnaldo Dimagli, Umberto Benedetto and Gianni D Angelini in DIGITAL HEALTH

Supplemental material, sj-pdf-1-prf-10.1177_02676591221091200 for Large animal model of vein grafts intimal hyperplasia: A systematic review by Oluwatomini Fashina, Riccardo G Abbasciano, Liam W McQueen, Shameem Ladak, Sarah J George, Sadeeh Suleiman, Prakash P Punjabi, Gianni D Angelini and Mustafa Zakkar in Perfusion

Supplemental material, sj-pdf-1-prf-10.1177_02676591221091200 for Large animal model of vein grafts intimal hyperplasia: A systematic review by Oluwatomini Fashina, Riccardo G Abbasciano, Liam W McQueen, Shameem Ladak, Sarah J George, Sadeeh Suleiman, Prakash P Punjabi, Gianni D Angelini and Mustafa Zakkar in Perfusion

Self-inflicted skin disorders are artefact diseases inflicted by the use of multiple different means, for various different purposes. They account for about 2% of dermatology patient visits and include disorders with a denied or hidden pathological behavior (factitious disorders) and disorders with a non-denied and non-hidden pathological behavior (compulsive disorders). In turn, factitious skin disorders are subdivided into two groups: factitious disorders without an external incentive and factitious disorders with external incentives. In addition to the general diagnostic criteria, the present work examines the clinical forms of diseases of the first group (including dermatitis artefacta, Munchausen Syndrome, Munchausen Syndrome by proxy, and Morgellons Syndrome). In this case, the subject suffers from psychological problems and generally aims to attract the attention of the people around him, and in particular of his general practitioner, or else is reacting to difficult or unfavorable environmental conditions by means of an involuntary somatization at the level of the skin. The second part of the work on self-inflicted skin disorders will comprise the factitious disorders with external incentives and the compulsive disorders.

Supplemetary Material for 2021 MiECTiS focused update on the 2016 position paper for the use of minimal invasive extracorporeal circulation in cardiac surgery by Kyriakos Anastasiadis, Polychronis Antonitsis, John Murkin, Cyril Serrick, Serdar Gunaydin, Aschraf El-Essawi, Mark Bennett, Gabor Erdoes, Andreas Liebold, Prakash Punjabi, Konstantinos C Theodoropoulos, Bob Kiaii, Alexander Wahba, Filip de Somer, Adrian Bauer, Alexander Kadner, Wim van Boven, Helena Argiriadou, Apostolos Deliopoulos, Robert Α Baker, Ingo Breitenbach, Can Ince, Pascal Starinieri, Hansjoerg Jenni, Vadim Popov, Narain Moorjani, Marco Moscarelli, Marco Di Eusanio, Alex Cale, Oz Shapira, Christophe Baufreton, Ignazio Condello, Frank Merkle, Marco Stehouwer, Christof Schmid, Marco Ranucci, Gianni Angelini, Thierry Carrel in Perfusion

Additional tables and figures

Introduction: Coronary artery bypass grafting remains one of the best therapies for advanced coronary artery disease. The most used conduit remains the great saphenous vein, which is susceptible to short-term and long-term failure, the result of acute thrombosis, intimal hyperplasia, and late superimposed atheroma. In this review, we present the current findings related to the pathophysiology of vein graft failure. Methods: A search of three databases - MEDLINE®, Web of Science™, and Cochrane Library - was undertaken for the terms “pathophysiology”, “prevention”, and “treatment” plus the term “vein graft failure”. Results: The pathophysiology of saphenous graft failure can be classified in three distinct phases - acute thrombosis, intimal hyperplasia, and accelerated atherosclerosis. All these processes start with an underlying histological predisposition of the vein and at the time of harvesting and preparation for grafting. These mechanisms are a result of localized inflammatory and prothrombotic cascades that obey different causes, but ultimately result in the stenosis or occlusion of the vein graft. Conclusion: The interaction between the different parts of the pathophysiology of vein graft failure is extremely complex and variable. Recent improvements in surgical techniques and secondary pharmaceutical prevention like early aspirin administration and long-term statin treatment have significantly reduced early and late saphenous vein graft failure. However, this continues to be a fascinating area of research with the potential for further improvement for patients and health service provision.

Supplemental material, sj-docx-1-prf-10.1177_02676591221091200 for Large animal model of vein grafts intimal hyperplasia: A systematic review by Oluwatomini Fashina, Riccardo G Abbasciano, Liam W McQueen, Shameem Ladak, Sarah J George, Sadeeh Suleiman, Prakash P Punjabi, Gianni D Angelini and Mustafa Zakkar in Perfusion

BACKGROUND: The success of coronary artery bypass grafting surgery (CABG) is dependent on long-term graft patency, which is negatively related to early wall thickening. Avoiding high-pressure distension testing for leaks and preserving the surrounding pedicle of fat and adventitia during vein harvesting may reduce wall thickening.METHODS: A single-centre, factorial randomized controlled trial was carried out to compare the impact of testing for leaks under high versus low pressure and harvesting the vein with versus without the pedicle in patients undergoing CABG. The primary outcomes were graft wall thickness, as indicator of medial-intimal hyperplasia, and lumen diameter assessed using intravascular ultrasound after 12 months.RESULTS: Ninety-six eligible participants were recruited. With conventional harvest, low-pressure testing tended to yield a thinner vessel wall compared with high-pressure (mean difference [MD; low minus high] -0.059 mm, 95% confidence interval (CI) -0.12, +0.0039, p = .066). With high pressure testing, veins harvested with the pedicle fat tended to have a thinner vessel wall than those harvested conventionally (MD [pedicle minus conventional] -0.057 mm, 95% CI: -0.12, +0.0037, p = .066, test for interaction p = .07). Lumen diameter was similar across groups (harvest comparison p = .81; pressure comparison p = .24). Low-pressure testing was associated with fewer hospital admissions in the 12 months following surgery (p = .0008). Harvesting the vein with the pedicle fat was associated with more complications during the index admission (p = .0041).CONCLUSIONS: Conventional saphenous vein graft preparation with low-pressure distension and harvesting the vein with a surrounding pedicle yielded similar graft wall thickness after 12 months, but low pressure was associated with fewer adverse events.

Supplemental material, sj-pdf-1-prf-10.1177_02676591211021935 for Minimally invasive versus transcatheter closure of secundum atrial septal defects: a systematic review and meta-analysis by Esther Goh, Haya Mohammed, Mohammad Yusuf Salmasi, Samantha Ho, Umberto Benedetto, Massimo Caputo, Gianni Angelini and Hunaid A Vohra in Perfusion

Supplemental material, sj-pdf-1-prf-10.1177_02676591211012571 for Nrf2-Keap-1 imbalance under acute shear stress induces inflammatory response in venous endothelial cells by Alexander O Ward, Graciela B Sala-Newby, Shameem Ladak, Gianni D Angelini, Massimo Caputo, M.-Saadeh Suleiman, Paul C Evans, Sarah J George and Mustafa Zakkar in Perfusion

Supplemental material, sj-pdf-1-prf-10.1177_02676591211012571 for Nrf2-Keap-1 imbalance under acute shear stress induces inflammatory response in venous endothelial cells by Alexander O Ward, Graciela B Sala-Newby, Shameem Ladak, Gianni D Angelini, Massimo Caputo, M.-Saadeh Suleiman, Paul C Evans, Sarah J George and Mustafa Zakkar in Perfusion

Supplemental material, sj-pdf-1-prf-10.1177_02676591211021935 for Minimally invasive versus transcatheter closure of secundum atrial septal defects: a systematic review and meta-analysis by Esther Goh, Haya Mohammed, Mohammad Yusuf Salmasi, Samantha Ho, Umberto Benedetto, Massimo Caputo, Gianni Angelini and Hunaid A Vohra in Perfusion

A best evidence topic was written according to a structured protocol. The question addressed was: Is the use of prophylactic, perioperative steroids associated with better clinical outcomes following heart surgery in neonates? Altogether, 194 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. One study found improved hospital survival in the group without steroids. Steroids increased infection in one large retrospective study. Incidence of hyperglycaemia was increased in the steroid group in 2 out of 5 studies. Use of steroids was associated with a shorter duration of ventilation and better oxygenation in one study. Postoperative steroid infusion was associated with reduced low cardiac output syndrome, inotrope requirement and less fluid retention in two controlled trials in which all patients received preoperative steroid. High dose steroid was associated with renal dysfunction in one study, comparing single versus double dose steroid prophylaxis. Steroid non-recipients had a shorter intensive care length of stay in 2 out of 7 studies. We conclude that use of steroids perioperatively does not unequivocally improve clinical outcome in neonatal heart surgery. A large, multicentre prospective randomized controlled trial is needed to clarify the role of steroids in paediatric heart surgery.

Supplemental Material, Supplement_Table_and_Appendix for Corticosteroids and Other Anti-Inflammatory Strategies in Pediatric Heart Surgery: A National Survey of Practice by Daniel P. Fudulu, Alvin Schadenberg, Ben Gibbison, Ian Jenkins, Stafford Lightman, Gianni D. Angelini, and Serban Stoica in World Journal for Pediatric and Congenital Heart Surgery

BACKGROUND: Whether a restrictive threshold for hemoglobin level in red-cell transfusions, as compared with a liberal threshold, reduces postoperative morbidity and health care costs after cardiac surgery is uncertain.METHODS: We conducted a multicenter, parallel-group trial in which patients older than 16 years of age who were undergoing nonemergency cardiac surgery were recruited from 17 centers in the United Kingdom. Patients with a postoperative hemoglobin level of less than 9 g per deciliter were randomly assigned to a restrictive transfusion threshold (hemoglobin level RESULTS: A total of 2007 patients underwent randomization; 4 participants withdrew, leaving 1000 in the restrictive-threshold group and 1003 in the liberal-threshold group. Transfusion rates after randomization were 53.4% and 92.2% in the two groups, respectively. The primary outcome occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% confidence interval [CI], 0.91 to 1.34; P=0.30); there was no indication of heterogeneity according to subgroup. There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67; P=0.045). Serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups.CONCLUSIONS: A restrictive transfusion threshold after cardiac surgery was not superior to a liberal threshold with respect to morbidity or health care costs. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN70923932.).

Objectives: An increasing number of octogenarians are referred to undergo mitral valve surgery for degenerative disease, and percutaneous approaches are being increasingly used in this subgroup of patients. We sought to determine the survival and its predictors after Mitral Valve Surgery in Octogenarians (MiSO) in a multicenter UK study of high-volume specialized centers. Methods: Pooled data from 3 centers were collected retrospectively. To identify the predictors of short-term composite outcome of 30 days mortality, acute kidney injury, and cerebrovascular accident, a multivariable logistic regression model was developed. Multiple Cox regression analysis was performed for late mortality. Kaplan–Meier curves were generated for long-term survival in various subsets of patients. Receiver operating characteristic analysis was done to determine the predictive power of the logistic European System for Cardiac Operative Risk Evaluation. Results: A total of 247 patients were included in the study. The median follow-up was 2.9 years (minimum 0, maximum 14 years). A total of 150 patients (60.7%) underwent mitral valve repair, and 97 patients (39.3%) underwent mitral valve replacement. Apart from redo cardiac surgery (mitral valve repair 6 [4%] vs mitral valve replacement 11 [11.3%], P =.04) and preoperative atrial fibrillation (mitral valve repair 79 [52.6%] vs mitral valve replacement 34 [35.1%], P

Pairwise comparisons of the individual studies, NMA plots and results for those outcomes not included in the main text. (DOCX 2566 kb)

Summary tables of included and excluded study characteristics [47–60]. (DOCX 87 kb)

BACKGROUND: Anomalous coronary artery from the pulmonary artery (ACAPA) is a very rare congenital anomaly that often occurs during infancy. Patients can present in a critical condition. METHODS: We analysed procedure-related data from a national audit database for the period 2000-2013. RESULTS: A total of 120 patients 30 days) were available in 102 patients and the mean follow-up time was 4.7 years. The 30-day overall mortality was 1.9%, higher for neonates (16.7% vs 1%, p=0.1) and after postoperative extracorporeal membrane oxygenation (ECMO) (20% vs 1%, p=0.09). At 10 years the survival estimate is 95.1%, freedom from coronary and mitral reintervention being 95.9% and 91.2%, respectively. Use of postoperative ECMO was a risk factor for long-term mortality (p

Cardiac fibrosis is a final common pathology in inherited and acquired heart diseases that causes cardiac electrical and pump failure. Here, we use systems genetics to identify a pro-fibrotic gene network in the diseased heart and show that this network is regulated by the E3 ubiquitin ligase WWP2, specifically by the WWP2-N terminal isoform. Importantly, the WWP2-regulated pro-fibrotic gene network is conserved across different cardiac diseases characterized by fibrosis: human and murine dilated cardiomyopathy and repaired tetralogy of Fallot. Transgenic mice lacking the N-terminal region of the WWP2 protein show improved cardiac function and reduced myocardial fibrosis in response to pressure overload or myocardial infarction. In primary cardiac fibroblasts, WWP2 positively regulates the expression of pro-fibrotic markers and extracellular matrix genes. TGFβ1 stimulation promotes nuclear translocation of the WWP2 isoforms containing the N-terminal region and their interaction with SMAD2. WWP2 mediates the TGFβ1-induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2.

Cardiac fibrosis is a final common pathology in inherited and acquired heart diseases that causes cardiac electrical and pump failure. Here, we use systems genetics to identify a pro-fibrotic gene network in the diseased heart and show that this network is regulated by the E3 ubiquitin ligase WWP2, specifically by the WWP2-N terminal isoform. Importantly, the WWP2-regulated pro-fibrotic gene network is conserved across different cardiac diseases characterized by fibrosis: human and murine dilated cardiomyopathy and repaired tetralogy of Fallot. Transgenic mice lacking the N-terminal region of the WWP2 protein show improved cardiac function and reduced myocardial fibrosis in response to pressure overload or myocardial infarction. In primary cardiac fibroblasts, WWP2 positively regulates the expression of pro-fibrotic markers and extracellular matrix genes. TGFβ1 stimulation promotes nuclear translocation of the WWP2 isoforms containing the N-terminal region and their interaction with SMAD2. WWP2 mediates the TGFβ1-induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2.

Objectives: Several randomized controlled trials have compared adrenaline (epinephrine) with alternative therapies in patients with cardiac arrest with conflicting results. Recent observational studies suggest that adrenaline might increase return of spontaneous circulation but worsen neurologic outcome. We systematically compared all the vasopressors tested in randomized controlled trials in adult cardiac arrest patients in order to identify the treatment associated with the highest rate of return of spontaneous circulation, survival, and good neurologic outcome. Design: Network meta-analysis. Patients: Adult patients undergoing cardiopulmonary resuscitation. Interventions: PubMed, Embase, BioMed Central, and the Cochrane Central register were searched (up to April 1, 2017). We included all the randomized controlled trials comparing a vasopressor with any other therapy. A network meta-analysis with a frequentist approach was performed to identify the treatment associated with the highest likelihood of survival. Measurements and Main Results: Twenty-eight studies randomizing 14,848 patients in 12 treatment groups were included. Only a combined treatment with adrenaline, vasopressin, and methylprednisolone was associated with increased likelihood of return of spontaneous circulation and survival with a good neurologic outcome compared with several other comparators, including adrenaline. Adrenaline alone was not associated with any significant difference in mortality and good neurologic outcome compared with any other comparator. Conclusions: In randomized controlled trials assessing vasopressors in adults with cardiac arrest, only a combination of adrenaline, vasopressin, and methylprednisolone was associated with improved survival with a good neurologic outcome compared with any other drug or placebo, particularly in in-hospital cardiac arrest. There was no significant randomized evidence to support neither discourage the use of adrenaline during cardiac arrest.

Objective: To compare markers of cardiac injury, inflammatory and oxidative responses, and myocardial cellular changes in the left and right ventricles of patients undergoing isolated coronary artery bypass grafting (CABG) or aortic valve replacement (AVR) using cardiopulmonary bypass (CPB) and cardioplegic arrest with or without remote ischaemic preconditioning (RIPC). Methods: Two conditions were studied for each surgical stratum (CABG or AVR): (a) no RIPC and (b) RIPC following anaesthesia and before sternotomy. The control group (no RIPC) represented standard clinical practice. Left and right ventricular biopsies were collected before CPB and at the end of ischaemic cardioplegic arrest. Blood samples were collected before, during, and after the operation. Results: Between March 2012 and April 2014, 124 patients agreed to participate in the study; 64 and 60 patients formed the CABG and AVR populations, respectively, and were randomised to receive RIPC or sham treatment. There were no differences in troponin release between groups (geometric mean ratio 0.92 (0.75,1.10), p=0.9; and 0.9 (0.35,1.44), p=0.65 CABG and AVR respectively). The postoperative course in each group was similar with no mortality. There were no significant differences in phosphorylation potential or energy charge in left and right ventricle biopsies or in circulating inflammatory markers between groups. No serious adverse events were reported. Conclusions: RIPC did not confer significant cardioprotection as measured by troponin I release. This result was possibly related to the inability of the study to stratify anaesthesia regimens. Both RIPC and Tru-Cut ventricle biopsy procedures were safe. Open Access

Background: Pulmonary dysfunction is a common complication of cardiac surgery. Pulmonary protection strategies have evolved over the years; however, their efficacy remains controversial. Objective: To compare interventions aiming at reducing pulmonary dysfunction in patients undergoing coronary artery bypass grafting. The (BiPAP) trial [ISRCTN 85570732] investigated the efficacy of NIV with BiPAP in addition to usual care, versus usual care alone. The ventilate trial [ISRCTN 34428459] investigated LFV versus usual care during cardiopulmonary bypass. Outcome measures: In the BiPAP trial, the primary outcome was time until fit for discharge. In the ventilate trial, the primary outcome was inflammation measured by NF-B p65 activation in lung biopsies pre- and post- CPB. In a sub-study, pulmonary arteries were isolated from lung biopsies, to characterise changes in structure and function related to the CPB. Results: The median duration of the hospital stay until fit-for-discharge was 5 days for the BiPAP group (IQR, 4-6) and 6 days for the usual care group with a reduced incidence of adverse events. In the ventilate trial LFV (adjusted for pre-CPB level) compared to the standard care group had no effect on NF-B p65 activation in lung biopsies. In a sub-study, the pattern of anatomical and physiological changes in pulmonary artery obtained from lung biopsy pre- and post-CPB was described. Conclusions: The BiPAP trial, improved recovery time. The ventilate trial did not significantly improve clinical or inflammatory markers. For the first time in human we describe the structural and functional changes in pulmonary arteries from lung biopsy associated with CPB. A better understanding of available modalities of lung protection and/or combinations could result in the development of customised strategies for the different cohorts of patients with the potential to maximise patient and institutional benefits. Open Access

Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) are important for limiting pain and inflammation, although many increase the risk of cardiovascular events including myocardial infarction, stroke and heart failure. However, celecoxib (a selective COX-2 inhibitor), has been associated with a more positive cardiovascular profile. We explored the hypothesis that celecoxib induces anti-oxidant and anti-inflammatory genes in the vascular endothelium via AMP kinase (AMPK), thereby limiting inflammation-mediated injury. Methods/Results: In vitro cultured human umbilical vein endothelial cells were studied. Our results indicate that celecoxib induces cytoprotective genes; including heme oxygenase-1 (HO-1) and manganese superoxide dismutase (MnSOD). Importantly, these observations were reproduced in human aortic endothelial cells. In contrast, the traditional NSAIDs (ibuprofen and naproxen) failed to reproduce the cytoprotective actions of celecoxib. Subsequently, we found celecoxib increased expression of additional cytoprotective genes (Bcl-2, FHC, DAF and TXNRD1) in vitro, and importantly, celecoxib treatment of C57BL/6 mice led to increased HO-1 and ferritin heavy chain (FHC) expression in the aortic endothelium in vivo. The actions of celecoxib were shown to be independent of COX-2 by using dimethyl-celecoxib, which lacks COX-2 inhibitory properties and reproduced celecoxib’s cytoprotective effects. Mechanistically, celecoxib led to the generation of mitochondrial reactive oxygen species, which activated AMPK leading to HO-1 and MnSOD induction. Celecoxib treatment led to AMPKα (Thr172) and CREB (Ser133) phosphorylation via a linear pathway, and the nuclear translocation of NRF-2. The effects of celecoxib were inhibited by siRNA-mediated depletion of AMPKα1, CREB-1 and NRF2. Further functional analyses revealed celecoxib to inhibit, via activation of AMPK, TNFα-mediated phosphorylation of NF-κB p65, p65 nuclear translocation, TNFα-induced VCAM-1 expression and IL-1β-induced IL-6 mRNA expression. Conclusion: Our data demonstrate that celecoxib regulates cytoprotective gene expression in ECs via a novel mtROS-AMPK-CREB-Nrf2-dependent pathway. A deeper understanding of the mechanisms of action of NSAIDs will inform clinical practice and ultimately assist the development of safer therapeutics. Open Access

Background: Cardiac surgery with cardiopulmonary bypass (CPB) can lead to a spectrum of post-operative complications as a result of activation of systemic inflammatory responses. Cellular injury can lead to the release of damage-associated molecular patterns (DAMPs) such as mitochondria DNA (mtDNA), which act as a ligand activating leukocytes and endothelial cells via innate immunity receptors such as Toll-like receptor 9 (TLR9). However, the contributions of DAMPs to inflammatory responses to CPB are unknown. Aim: This study is to identify the DAMPs and associated receptors that drive systemic inflammatory responses to surgery, which may lead to the identification of novel anti-inflammatory interventions such as TLR antagonists with subsequent translation of our findings to the clinical field. Additionally, Post-operative atrial fibrillation (POAF) is frequent complication in cardiac surgery, which may contribute to the inflammatory response. We aimed to identify a possible predictor for POAF, which may lead to its prevention or early management. Methods: Sixty-six patients undergoing CABG were recruited, 44 with on-pump and 22 with off-pump CABG (OPCAB) to compare the effect of CPB. To identify the effect of ischemic heart disease (IHD) on the mtDNA release. We recruited a separate group of 22 patients undergoing aortic valve replacement (AVR) with normal coronary angiogram. Blood samples were taken at different time-points to CPB. Quantitative PCR was generated to quantify mtDNA concentration (Chapter 3). Pro-inflammatory biomarkers such as interleukines, interferons, MAP kinases , NF-κB and other biomarkers were assessed by PCR array (Chapter 5). Both mtDNA and the proinflmmatory biomarker were preoperatively compared to assess of the development of POAF (Chapter 6). Additionally, we used different animal models experiments, to establish the effect of surgery and CPB on TLR9 signalling and to test the effect of blocking TLR9. Specifically, we performed sternotomy in mouse and rat models respectively and performed sternotomy with CPB in the pig model (Chapter 4). Results: mtDNA was significantly higher in patients with IHD than those without (p0.05). Blocking the TLR9 in mice has significantly reduced the production of proinflammatory cytokine (IL-6). INF-α and mtDNA were the only independent predictors for POAF development. Conclusion: Elevation in circulating mtDNA level is related to the extent of the IHD. CPB can influence the release of circulating mtDNA and proinflammatory cytokines production via signalling the TLR9, which may contribute to the initiation of a sterile systemic inflammatory response. The mtDNA and INF- α were independent predictors for development of POAF, which are in agreement with the inflammatory theory that relates the inflammation to the POAF development. Open Access

In patients with mitral regurgitation (MR) secondary to ischemic or non-ischemic dilated cardiomyopathy, valve repair is usually performed by means of an undersized annuloplasty. This procedure leads to symptomatic improvement and reverse left ventricular (LV) remodeling in a substantial proportion of patients. However, the failure rate of undersized annuloplasty is still high and is mainly due to inappropriate patient selection and to technical issues which have been progressively identified. Annuloplasty alone should only be carried out in the early phase of the disease before the occurrence of advanced LV remodeling and echocardiographic predictors of unfavourable outcome should be taken into account. Under certain circumstances, in particular when tethering is more pronounced, surgery should include additional procedures beside annuloplasty to enhance the durability of the repair. The edge-to-edge (EE) technique has been used in our Institution for this purpose. Herein we will report what we have learned over the years by using this method of repair as an adjunct to undersized annuloplasty in patients with functional mitral regurgitation.

none 24 si Aim We sought to determine whether theoptimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary studyoutcome was the 1- year composite risk of myocardial infarction (MI)or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MIor ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P=0.71; Pinteraction=0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MIor ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify theoptimal duration of DAPT after DES in individual patients basedon their relative ischaemic and bleeding risks. Palmerini, Tullio; Della Riva, Diego; Benedetto, Umberto; Bacchi Reggiani, Letizia; Feres, Fausto; Abizaid, Alexandre; Gilard, Martine; Morice, Marie-Claude; Valgimigli, Marco; Hong, Myeong-Ki; Kim, Byeong-Keuk; Jang, Yangsoo; Kim, Hyo-Soo; Park, Kyung Woo; Colombo, Antonio; Chieffo, Alaide; Sangiorgi, Diego; Biondi-Zoccai, Giuseppe; Généreux, Philippe; Angelini, Gianni D.; Pufulete, Maria; White, Jonathon; Bhatt, Deepak L.; Stone, Gregg W Palmerini, Tullio; Della Riva, Diego; Benedetto, Umberto; Bacchi Reggiani, Letizia; Feres, Fausto; Abizaid, Alexandre; Gilard, Martine; Morice, Marie-Claude; Valgimigli, Marco; Hong, Myeong-Ki; Kim, Byeong-Keuk; Jang, Yangsoo; Kim, Hyo-Soo; Park, Kyung Woo; Colombo, Antonio; Chieffo, Alaide; Sangiorgi, Diego; Biondi-Zoccai, Giuseppe; Généreux, Philippe; Angelini, Gianni D.; Pufulete, Maria; White, Jonathon; Bhatt, Deepak L.; Stone, Gregg W