Milan Milojevic

Causes of Death Following PCI Versus CABG in Complex CAD 5-Year Follow-Up of SYNTAX

BACKGROUND There are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI). OBJECTIVES The purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients. METHODS An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths. RESULTS In the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores. CONCLUSIONS During a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).

Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data

BACKGROUND Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies. METHODS We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics. FINDINGS We included 11 randomised trials involving 11 518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR] 1·20, 95% CI 1·06-1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09-1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19-1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86-1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87-1·33; p=0·52), regardless of diabetes status and SYNTAX score. INTERPRETATION CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies. FUNDING None.

2017 EACTS Guidelines on perioperative medication in adult cardiac surgery

Authors/Task Force Members: Miguel Sousa-Uva* (Chairperson) (Portugal), Stuart J. Head (Netherlands), Milan Milojevic (Netherlands), Jean-Philippe Collet (France), Giovanni Landoni (Italy), Manuel Castella (Spain), Joel Dunning (UK), T omas Gudbjartsson (Iceland), Nick J. Linker (UK), Elena Sandoval (Spain), Matthias Thielmann (Germany), Anders Jeppsson (Sweden) and Ulf Landmesser* (Chairperson) (Germany)

Current Practice of State-of-the-Art Surgical Coronary Revascularization.

Coronary artery bypass grafting remains one of the most commonly performed major surgeries, with well-established symptomatic and prognostic benefits in patients with multivessel and left main coronary artery disease. This review summarizes current indications, contemporary practice, and outcomes of coronary artery bypass grafting. Despite an increasingly higher-risk profile of patients, outcomes have significantly improved over time, with significant reductions in operative mortality and perioperative complications. Five- and 10-year survival rates are ≈85% to 95% and 75%, respectively. A number of technical advances could further improve short- and long-term outcomes after coronary artery bypass grafting. Developments in off-pump and no-touch procedures; epiaortic scanning; conduit selection, including bilateral internal mammary artery and radial artery use; intraoperative graft assessment; minimally invasive procedures, including robotic-assisted surgery; and hybrid coronary revascularization are discussed.

Influence of practice patterns on outcome among countries enrolled in the SYNTAX trial: 5-year results between percutaneous coronary intervention and coronary artery bypass grafting

OBJECTIVES To examine differences among participating countries in baseline characteristics, clinical practice, medication strategies and outcomes of patients randomized to coronary artery bypass grafting and percutaneous coronary intervention in the SYNTAX trial. METHODS In SYNTAX, centres in 18 different countries enrolled 1800 patients, of which 8 countries enrolled ≥80 patients, what was projected to be a large enough sample size to be included in the analysis. Baseline characteristics, practice patterns and clinical outcomes were compared between the USA (n = 245), the UK (n = 267), Italy (n = 197), France (n = 208), Germany (n = 179), Netherlands (n = 148), Belgium (n = 91) and Hungary (n = 83). The remaining patients from other participating countries were pooled together (n = 382). RESULTS Five‐year results demonstrated significantly different outcomes between countries. After adjustment, percutaneous coronary intervention patients in France had lower rates of major adverse cardiac and cerebrovascular events [hazard ratio (HR) = 0.60, 95% confidence interval (CI) 0.37‐0.98], while the incidence of repeat revascularization was higher in Hungary (HR = 1.89, 95% CI 1.14‐3.42). Coronary artery bypass grafting showed the lowest rate of repeat revascularization in the UK (HR = 0.32, 95% CI 0.12‐0.85). There were numerous differences in the risk profile of patients between participating countries, as well as marked differences in surgical practice across countries in the use of blood cardioplegia (range 3.1‐89.0%; P < 0.001), bilateral internal mammary artery usage (range 7.8‐68.2%; P < 0.001) and off‐pump procedures (range 3.9‐44.4%; P < 0.001). Variation was also found for percutaneous coronary intervention in the number of implanted stents (range 4.0 ± 2.3 to 6.1 ± 2.6; P < 0.001) as well as for the entire stents length (range 69.0 ± 45.1 to 124.1 ± 60.9; P < 0.001). Remarkable differences were observed in the prescription of post‐coronary artery bypass grafting medication in terms of acetylsalicylic acid (range 79.6‐95.0%; P = 0.004), thienopyridine (6.8‐31.1%; P < 0.001) and statins (41.3‐89.1%; P < 0.001). CONCLUSIONS Patient characteristics and clinical patterns are significantly different between countries, resulting in significantly different 5‐year outcomes. This article presents specific data that can further improve outcomes in each country. Clinical Trials Registry NCT00114972.

Clinical guidelines for the management of patients with transposition of the great arteries with intact ventricular septum

Authors/Task Force Members: George E. Sarris* (Chairperson) (Greece), Christian Balmer (Switzerland), Pipina Bonou (Greece), Juan V. Comas (Spain), Eduardo da Cruz (USA), Luca Di Chiara (Italy), Roberto M. Di Donato (United Arab Emirates), José Fragata (Portugal), Tuula Eero Jokinen (Finland), George Kirvassilis (USA), Irene Lytrivi (USA), Milan Milojevic (Netherlands), Gurleen Sharland (UK), Matthias Siepe (Germany), Joerg Stein (Austria), Emanuela Valsangiacomo Büchel (Switzerland) and Pascal R. Vouhé (France)

Annual number of candidates for transcatheter aortic valve implantation per country: current estimates and future projections

Aims The number of transcatheter aortic valve implantation (TAVI) procedures is rapidly increasing. This has a major impact on health care resource planning. However, the annual numbers of TAVI candidates per country are unknown. The aim of this study was to estimate current and future number of annual TAVI candidates in 27 European countries, the USA and Canada. Methods and results Systematic literature searches and meta-analyses were performed on aortic stenosis (AS) epidemiology and decision-making in severe symptomatic AS. The incidence rate of severe AS was determined. Findings were combined with population statistics and integrated into a model employing Monte Carlo simulations to predict the annual number of TAVI candidates. Various future scenarios and sensitivity analyses were explored. Data from 37 studies (n = 26 402) informed the model. The calculated incidence rate of severe AS was 4.4‰/year [95% confidence interval (95% CI) 3.0-6.1‰] in patients ≥65 years. AS-related symptoms were present in 68.3% (95% CI 60.8-75.9%) of patients with severe AS. Despite having severe symptomatic AS, 41.6% (95% CI 36.9-46.3%) did not undergo surgical aortic valve replacement. Of the non-operated patients, 61.7% (95% CI 42.0-81.7%) received TAVI. The model predicted 114 757 (95% CI 69 380-172 799) European and 58 556 (95% CI 35 631-87 738) Northern-American TAVI candidates annually. Conclusion Currently, approximately 180 000 patients can be considered potential TAVI candidates in the European Union and in Northern-America annually. This number might increase up to 270 000 if indications for TAVI expand to low-risk patients. These findings have major implications for health care resource planning in the 29 individual countries.

Serum cytokine profile of laryngeal squamous cell carcinoma patients

OBJECTIVES This study aimed to evaluate serum cytokine concentrations in healthy individuals and laryngeal squamous cell carcinoma patients. METHODS A total of 59 laryngeal squamous cell carcinoma patients and 44 healthy controls were included. Multiplex analysis of interleukins 2, 4, 5, 6, 10, 12, 13 and 17 and interferon-gamma with respect to the presence of laryngeal carcinoma, tumour-node-metastasis T stage, nodal involvement and larynx subsite was performed. RESULTS Statistical analysis revealed no difference in serum cytokine levels between patients and healthy controls. The serum interleukin-12 concentration was significantly higher in patients with early (T1-2) than in those with late (T3-4) stage disease and without nodal involvement (p < 0.05). Serum interleukin-10 levels were significantly higher in T3-4 stage than in T1-2 stage patients (p < 0.05). Additionally, serum interleukin 10, 12 and 13 concentrations (p < 0.05) and interleukin-6 concentration (p < 0.01) were significantly higher in patients with T1-2 stage supraglottic vs glottic tumours. CONCLUSION Serum cytokines level cannot be used as laryngeal squamous cell carcinoma markers. Progression from T1-2 to T3-4 stage is followed by decreased serum interleukin-12 levels and increased interleukin-10 levels. Nodal involvement is associated with lower serum interleukin-12 levels. In patients with early stage tumours, serum interleukin 6, 10, 12 and 13 concentrations are significantly higher in those with supraglottic vs glottic tumours.

Hierarchical testing of composite endpoints: applying the win ratio to percutaneous coronary intervention versus coronary artery bypass grafting in the SYNTAX trial

AIMS The goal of the study was to compare long-term outcomes of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG), accounting for the clinical impact of individual components in the composite endpoints and prioritising these using the win ratio (Rw). METHODS AND RESULTS The win ratio was compared with conventional methods of analyses (hazard ratio [HR] and relative risk) in the SYNTAX trial (n=1,800). For the composite of death/stroke/myocardial infarction (MI), the win ratio favoured CABG and was 1.37 (95% CI: 1.10-1.77) for matched analysis, 1.28 (95% CI: 1.11-1.53) for unmatched analysis, while the conventional HR was 1.29 (95% CI: 1.11-1.53). The largest number of winners in favour of CABG over PCI were based on MI (n=39 vs. n=19, respectively). Death was significantly reduced with CABG in matched (Rw=1.39, 95% CI: 1.04-1.86) and unmatched win ratio analyses (Rw=1.27, 95% CI: 1.01-1.42) as compared with non-significant conventional analysis (HR 1.19, 95% CI: 0.92-1.56). In subgroups, matched win ratio analyses had a larger treatment effect in favour of CABG compared with conventional analyses, especially in patients with three-vessel disease and intermediate SYNTAX scores, while unmatched win ratios had a smaller point estimate, but with narrower confidence intervals than matched analyses findings. CONCLUSIONS This re-analysis of the SYNTAX trial using the win ratio shows that the most important benefit of CABG treatment is the reduction of hard clinical endpoints such as mortality and MI. Future trials using this approach can expect to maintain similar statistical power with smaller sample sizes, and thereby reduce the cost of a trial.

Clinical guidelines for the management of patients with transposition of the great arteries with intact ventricular septum: The Task Force on Transposition of the Great Arteries of the European Association for Cardio-Thoracic Surgery (EACTS) and the Association for European Paediatric and Congenital Cardiology (AEPC)

Authors/Task Force Members: George E. Sarris* (Chairperson) (Greece), Christian Balmer (Switzerland), Pipina Bonou (Greece), Juan V. Comas (Spain), Eduardo da Cruz (USA), Luca Di Chiara (Italy), Roberto M. Di Donato (United Arab Emirates), José Fragata (Portugal), Tuula Eero Jokinen (Finland), George Kirvassilis (USA), Irene Lytrivi (USA), Milan Milojevic (Netherlands), Gurleen Sharland (UK), Matthias Siepe (Germany), Joerg Stein (Austria), Emanuela Valsangiacomo Büchel (Switzerland) and Pascal R. Vouhé (France)