Stephan Windecker

2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)

The ESC/ESH Guidelines represent the views of the ESC and ESH and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their dating.The ESC and ESH are not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the ESC/ESH Guidelines and any other official

ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).

ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

The ESC/EAS Guidelines represent the views of the ESC and EAS, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication.The ESC and EAS is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the ESC/EAS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC/EAS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the ESC/EAS Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC/EAS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Although most clinical trials of coronary stents have measured nominally identical safety and effectiveness end points, differences in definitions and timing of assessment have created confusion in interpretation.The Academic Research Consortium is an informal collaboration between academic research organizations in the United States and Europe. Two meetings, in Washington, DC, in January 2006 and in Dublin, Ireland, in June 2006, sponsored by the Academic Research Consortium and including representatives of the US Food and Drug Administration and all device manufacturers who were working with the Food and Drug Administration on drug-eluting stent clinical trial programs, were focused on consensus end point definitions for drug-eluting stent evaluations. The effort was pursued with the objective to establish consistency among end point definitions and provide consensus recommendations. On the basis of considerations from historical legacy to key pathophysiological mechanisms and relevance to clinical interpretability, criteria for assessment of death, myocardial infarction, repeat revascularization, and stent thrombosis were developed. The broadly based consensus end point definitions in this document may be usefully applied or recognized for regulatory and clinical trial purposes.Although consensus criteria will inevitably include certain arbitrary features, consensus criteria for clinical end points provide consistency across studies that can facilitate the evaluation of safety and effectiveness of these devices.

Coronary artery disease (CAD) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. This process can be modified by lifestyle adjustments, pharmacological therapies, and invasive interventions designed to achieve disease stabilization or regression. The disease can have long, stable periods but can also become unstable at any time, typically due to an acute atherothrombotic event caused by plaque rupture or erosion. However, the disease is chronic, most often progressive, and hence serious, even in clinically apparently silent periods. The dynamic nature of the CAD process results in various clinical presentations, which can be conveniently categorized as either acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). The Guidelines presented here refer to the management of patients with CCS. The natural history of CCS is illustrated in Figure 1.

99mTc : technetium-99m 201TI : thallium 201 ABCB1 : ATP-binding cassette sub-family B member 1 ABI : ankle-brachial index ACC : American College of Cardiology ACCF : American College of Cardiology Foundation ACCOMPLISH : Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension ACE : angiotensin converting enzyme ACIP : Asymptomatic Cardiac Ischaemia Pilot ACS : acute coronary syndrome ADA : American Diabetes Association ADP : adenosine diphosphate AHA : American Heart Association ARB : angiotensin II receptor antagonist ART : Arterial Revascularization Trial ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASSERT : Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial AV : atrioventricular BARI 2D : Bypass Angioplasty Revascularization Investigation 2 Diabetes BEAUTIFUL : Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction BIMA : bilateral internal mammary artery BMI : body mass index BMS : bare metal stent BNP : B-type natriuretic peptide BP : blood pressure b.p.m. : beats per minute CABG : coronary artery bypass graft CAD : coronary artery disease CAPRIE : Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events CASS : Coronary Artery Surgery Study CCB : calcium channel blocker CCS : Canadian Cardiovascular Society CFR : coronary flow reserve CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance CI : confidence interval CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease Epidemiology Collaboration CMR : cardiac magnetic resonance CORONARY : The CABG Off or On Pump Revascularization Study COURAGE : Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation COX-1 : cyclooxygenase-1 COX-2 : cyclooxygenase-2 CPG : Committee for Practice Guidelines CT : computed tomography CTA : computed tomography angiography CV : cardiovascular CVD : cardiovascular disease CXR : chest X-ray CYP2C19*2 : cytochrome P450 2C19 CYP3A : cytochrome P3A CYP3A4 : cytochrome P450 3A4 CYP450 : cytochrome P450 DANAMI : Danish trial in Acute Myocardial Infarction DAPT : dual antiplatelet therapy DBP : diastolic blood pressure DECOPI : Desobstruction Coronaire en Post-Infarctus DES : drug-eluting stents DHP : dihydropyridine DSE : dobutamine stress echocardiography EACTS : European Association for Cardiothoracic Surgery EECP : enhanced external counterpulsation EMA : European Medicines Agency EASD : European Association for the Study of Diabetes ECG : electrocardiogram Echo : echocardiogram ED : erectile dysfunction EF : ejection fraction ESC : European Society of Cardiology EXCEL : Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization FAME : Fractional Flow Reserve vs. Angiography for Multivessel Evaluation FDA : Food & Drug Administration (USA) FFR : fractional flow reserve FREEDOM : Design of the Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease GFR : glomerular filtration rate HbA1c : glycated haemoglobin HDL : high density lipoprotein HDL-C : high density lipoprotein cholesterol HR : hazard ratio HRT : hormone replacement therapy hs-CRP : high-sensitivity C-reactive protein HU : Hounsfield units ICA : invasive coronary angiography IMA : internal mammary artery IONA : Impact Of Nicorandil in Angina ISCHEMIA : International Study of Comparative Health Effectiveness with Medical and Invasive Approaches IVUS : intravascular ultrasound JSAP : Japanese Stable Angina Pectoris KATP : ATP-sensitive potassium channels LAD : left anterior descending LBBB : left bundle branch block LIMA : Left internal mammary artery LDL : low density lipoprotein LDL-C : low density lipoprotein cholesterol LM : left main LMS : left main stem LV : left ventricular LVEF : left ventricular ejection fraction LVH : left ventricular hypertrophy MACE : major adverse cardiac events MASS : Medical, Angioplasty, or Surgery Study MDRD : Modification of Diet in Renal Disease MERLIN : Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes MERLIN-TIMI 36 : Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes: Thrombolysis In Myocardial Infarction MET : metabolic equivalents MI : myocardial infarction MICRO-HOPE : Microalbuminuria, cardiovascular and renal sub-study of the Heart Outcomes Prevention Evaluation study MPI : myocardial perfusion imaging MRI : magnetic resonance imaging NO : nitric oxide NSAIDs : non-steroidal anti-inflammatory drugs NSTE-ACS : non-ST-elevation acute coronary syndrome NYHA : New York Heart Association OAT : Occluded Artery Trial OCT : optical coherence tomography OMT : optimal medical therapy PAR-1 : protease activated receptor type 1 PCI : percutaneous coronary intervention PDE5 : phosphodiesterase type 5 PES : paclitaxel-eluting stents PET : positron emission tomography PRECOMBAT : Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease PTP : pre-test probability PUFA : polyunsaturated fatty acid PVD : peripheral vascular disease QoL : quality of life RBBB : right bundle branch block REACH : Reduction of Atherothrombosis for Continued Health RITA-2 : Second Randomized Intervention Treatment of Angina ROOBY : Veterans Affairs Randomized On/Off Bypass SAPT : single antiplatelet therapy SBP : systolic blood pressure SCAD : stable coronary artery disease SCORE : Systematic Coronary Risk Evaluation SCS : spinal cord stimulation SES : sirolimus-eluting stents SIMA : single internal mammary artery SPECT : single photon emission computed tomography STICH : Surgical Treatment for Ischaemic Heart Failure SWISSI II : Swiss Interventional Study on Silent Ischaemia Type II SYNTAX : SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery TC : total cholesterol TENS : transcutaneous electrical neural stimulation TERISA : Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina TIME : Trial of Invasive vs. Medical therapy TIMI : Thrombolysis In Myocardial Infarction TMR : transmyocardial laser revascularization TOAT : The Open Artery Trial WOEST : What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing Guidelines summarize and evaluate all evidence available, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well …

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

The ESC/EACTS Guidelines represent the views of the ESC and the EACTS and were arrived at after careful consideration of the available evidence at the time they were written.Health professionals are encouraged to take them fully into account when exercising their clinical judgement.The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient and, where appropriate and necessary, the patient's guardian or carer.It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

The Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication.The ESC and EASD are not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American–Australian–African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association ANDROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d. for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid (ASA) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospective, randomized, double-blind, Active-controlled, superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die (twice daily) b.p.m. : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled)-Vascular disease, Age 65–74, Sex category (female) CHADS2 : Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke (doubled) CI : confidence interval CRAFT : Controlled Randomized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : Randomized Double blind trIal to evaluate efficacy and safety of drOnedarone (400 mg b.i.d.) vs . amiodaroNe (600 mg q.d. for 28 daYS, then 200 mg qd thereafter) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v. : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d. : omni die (every day) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of standard therapy PCI : percutaneous coronary intervention PREVAIL : Prospective Randomized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : Randomized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d. : ter in die (three times daily) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on …

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

Guidelines and Expert Consensus Documents summarize and evaluate all available evidence with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome and the risk–benefit ratio of diagnostic or therapeutic means. Guidelines are no substitutes for textbooks and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s). The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). Members of this Task Force were selected by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) to represent all physicians involved with the medical and surgical care of patients with coronary artery disease (CAD). A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for society are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The members of the Task Force have provided disclosure statements of all relationships that might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at European Heart House, headquarters of the ESC. Any changes in conflict of interest that arose during the writing period were notified to the ESC. The Task Force report received its entire financial support from the ESC and EACTS, without any involvement of the pharmaceutical, device, or surgical industry. ESC …

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk.

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

### Abbreviations 1st AV : First-degree atrioventricular block AF : atrial fibrillation AT : atrial tachyarrhythmia ATP : Anti-tachycardia pacing AV : atrioventricular BBB : bundle branch block CHF : congestive heart failure CI : confidence interval CPG : Committee for Practice Guidelines CRT : cardiac resynchronization therapy CRT-D : cardiac resynchronization therapy and defibrillator CRT-P : cardiac resynchronization therapy and pacemaker ECG : electrocardiogram EDMD : Emery-Dreifuss muscular dystrophy EF : ejection fraction EPS : electrophysiological study ESC : European Society of Cardiology HCM : hypertrophic cardiomyopathy HF : heart failure HR : hazard ratio HV : His-ventricular ICD : implantable cardioverter defibrillator ILR : implantable loop recorder IVCD : intraventricular conduction delay LBBB : left bundle branch block LQTS : long QT syndrome LV : left ventricular LVEF : left ventricular ejection fraction LVSD : left ventricular systolic dysfunction MR : mitral regurgitation MRI : magnetic resonance imaging NYHA : New York Heart Association PM : pacemaker OR : odds ratio QALY : quality-adjusted life year RBBB : right bundle branch block RCT : randomized controlled trial RV : right ventricular SB : sinus bradycardia SNRT : sinus node recovery time SR : sinus rhythm SSS : sick sinus syndrome TAVI : transcatheter aortic valve implantation VF : ventricular fibrillation VT : ventricular tachycardia VV : interventricular (delay) ### Acronyms of the trials referenced in the recommendations or reported in the tables ADEPT : ADvanced Elements of Pacing Randomized Controlled Trial ADOPT : Atrial Dynamic Overdrive Pacing Trial AOPS : Atrial Overdrive Pacing Study APAF : Ablate and Pace in Atrial Fibrillation ASSERT : ASymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial ATTEST : ATrial Therapy Efficacy and Safety Trial AVAIL CLS/CRT : AV Node Ablation with CLS and CRT Pacing Therapies for Treatment of AF trial B4 : Bradycardia detection in Bundle Branch Block BELIEVE : Bi vs. Left Ventricular Pacing: an International Pilot Evaluation on Heart Failure Patients with Ventricular Arrhythmias BIOPACE : Biventricular pacing for atrioventricular block to prevent cardiac desynchronization BLOCK-HF : Biventricular versus right ventricular pacing in patients with AV block B-LEFT : Biventricular versus LEFT Univentricular Pacing with ICD Back-up in Heart Failure Patients CARE-HF : CArdiac REsynchronization in Heart Failure CLEAR : CLinical Evaluation on Advanced Resynchronization COMBAT : COnventional vs. Biventricular Pacing in Heart Failure and Bradyarrhythmia COMPANION : COmparison of Medical Therapy, Pacing and Defibrillation in Heart Failure DANPACE : DANish Multicenter Randomized Trial on Single Lead Atrial PACing vs. Dual Chamber Pacing in Sick Sinus Syndrome DECREASE-HF : The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure FREEDOM : Optimization Study Using the QuickOpt Method GREATER-EARTH : Evaluation of Resynchronization Therapy for Heart Failure in Patients with a QRS Duration GREATER Than 120 ms LESSER-EARTH : Evaluation of Resynchronization Therapy for Heart Failure in Patients with a QRS Duration Lower Than 120 ms HOBIPACE : HOmburg BIventricular PACing Evaluation IN-CHF : Italian Network on Congestive Heart Failure ISSUE : International Study on Syncope of Unexplained Etiology MADIT : Multicenter Automatic Defibrillator Trial MIRACLE : Multicenter InSync RAndomized CLinical Evaluation MOST : MOde Selection Trial in Sinus-Node Dysfunction MUSTIC : MUltisite STimulation In Cardiomyopathies OPSITE : Optimal Pacing SITE PACE : Pacing to Avoid Cardiac Enlargement PAVE : Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation PATH-CHF : PAcing THerapies in Congestive Heart Failure II Study Group PIPAF : Pacing In Prevention of Atrial Fibrillation Study PIRAT : Prevention of Immediate Reinitiation of Atrial Tachyarrhythmias POT : Prevention Or Termination Study PREVENT-HF : PREventing VENTricular Dysfunction in Pacemaker Patients Without Advanced Heart Failure PROSPECT : PRedictors Of Response to Cardiac Resynchronization Therapy RAFT : Resynchronization–Defibrillation for Ambulatory Heart Failure Trial RethinQ : Cardiac REsynchronization THerapy IN Patients with Heart Failure and Narrow QRS REVERSE : REsynchronization reVErses Remodelling in Systolic left vEntricular dysfunction SAFARI : Study of Atrial Fibrillation Reduction SCD HeFT : Sudden Cardiac Death in Heart Failure Trial SMART-AV : The SMARTDelay Determined AV Optimization: a Comparison with Other AV Delay Methods Used in Cardiac Resynchronization Therapy SYDIT : The SYncope DIagnosis and Treatment SYNPACE : Vasovagal SYNcope and PACing TARGET : TARgeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy THEOPACE : Effects of Oral THEOphylline and of Permanent PACEmaker on the Symptoms and Complications of Sick Sinus Syndrome VASIS-PM : VAsovagal Syncope International Study on PaceMaker therapy V-HeFT : Vasodilator in HEart Failure Trial VPSII : Second Vasovagal Pacemaker Study (VPS II) Additional references are mentioned with ‘w’ in the main text and can be found on the online addenda along with 5 figures (1, 6, 7, 9, 11, 12) and 10 tables (3, 4, 5, 9, 11, 12, 19, 21, 22, 23). They are available on the ESC website only at http://www.escardio.org/guidelines-surveys/esc-guidelines/Pages/cardiac-pacing-and-cardiac-resynchronisation-therapy.aspx Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a …

European Journal of Heart FailureVolume 14, Issue 8 p. 803-869 ESC GuidelineFree Access ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC Authors/Task Force Members, Authors/Task Force MembersSearch for more papers by this authorJohn J.V. McMurray, Corresponding Author John J.V. McMurray Chairperson UKCorresponding author. Chairperson: Professor John J.V. McMurray, University of Glasgow G12 8QQ, UK. Tel: +44 141 330 3479, Fax: +44 141 330 6955, Email: [email protected]Search for more papers by this authorStamatis Adamopoulos, Stamatis Adamopoulos GreeceSearch for more papers by this authorStefan D. Anker, Stefan D. Anker GermanySearch for more papers by this authorAngelo Auricchio, Angelo Auricchio SwitzerlandSearch for more papers by this authorMichael Böhm, Michael Böhm GermanySearch for more papers by this authorKenneth Dickstein, Kenneth Dickstein NorwaySearch for more papers by this authorVolkmar Falk, Volkmar Falk SwitzerlandSearch for more papers by this authorGerasimos Filippatos, Gerasimos Filippatos GreeceSearch for more papers by this authorCândida Fonseca, Cândida Fonseca PortugalSearch for more papers by this authorMiguel Angel Gomez-Sanchez, Miguel Angel Gomez-Sanchez SpainSearch for more papers by this authorTiny Jaarsma, Tiny Jaarsma SwedenSearch for more papers by this authorLars Køber, Lars Køber DenmarkSearch for more papers by this authorGregory Y.H. Lip, Gregory Y.H. Lip UKSearch for more papers by this authorAldo Pietro Maggioni, Aldo Pietro Maggioni ItalySearch for more papers by this authorAlexander Parkhomenko, Alexander Parkhomenko UkraineSearch for more papers by this authorBurkert M. Pieske, Burkert M. Pieske AustriaSearch for more papers by this authorBogdan A. Popescu, Bogdan A. Popescu RomaniaSearch for more papers by this authorPer K. Rønnevik, Per K. Rønnevik NorwaySearch for more papers by this authorFrans H. Rutten, Frans H. Rutten The NetherlandsSearch for more papers by this authorJuerg Schwitter, Juerg Schwitter SwitzerlandSearch for more papers by this authorPetar Seferovic, Petar Seferovic SerbiaSearch for more papers by this authorJanina Stepinska, Janina Stepinska PolandSearch for more papers by this authorPedro T. Trindade, Pedro T. Trindade SwitzerlandSearch for more papers by this authorAdriaan A. Voors, Adriaan A. Voors The NetherlandsSearch for more papers by this authorFaiez Zannad, Faiez Zannad FranceSearch for more papers by this authorAndreas Zeiher, Andreas Zeiher GermanySearch for more papers by this authorESC Committee for Practice Guidelines (CPG), ESC Committee for Practice Guidelines (CPG)Search for more papers by this authorJeroen J. Bax, Jeroen J. Bax CPG Chairperson The NetherlandsSearch for more papers by this authorHelmut Baumgartner, Helmut Baumgartner GermanySearch for more papers by this authorClaudio Ceconi, Claudio Ceconi ItalySearch for more papers by this authorVeronica Dean, Veronica Dean FranceSearch for more papers by this authorChristi Deaton, Christi Deaton UKSearch for more papers by this authorRobert Fagard, Robert Fagard BelgiumSearch for more papers by this authorChristian Funck-Brentano, Christian Funck-Brentano FranceSearch for more papers by this authorDavid Hasdai, David Hasdai IsraelSearch for more papers by this authorArno Hoes, Arno Hoes The NetherlandsSearch for more papers by this authorPaulus Kirchhof, Paulus Kirchhof Germany UKSearch for more papers by this authorJuhani Knuuti, Juhani Knuuti FinlandSearch for more papers by this authorPhilippe Kolh, Philippe Kolh BelgiumSearch for more papers by this authorTheresa McDonagh, Theresa McDonagh UKSearch for more papers by this authorCyril Moulin, Cyril Moulin FranceSearch for more papers by this authorBogdan A. Popescu, Bogdan A. Popescu RomaniaSearch for more papers by this authorŽeljko Reiner, Željko Reiner CroatiaSearch for more papers by this authorUdo Sechtem, Udo Sechtem GermanySearch for more papers by this authorPer Anton Sirnes, Per Anton Sirnes NorwaySearch for more papers by this authorMichal Tendera, Michal Tendera PolandSearch for more papers by this authorAdam Torbicki, Adam Torbicki PolandSearch for more papers by this authorAlec Vahanian, Alec Vahanian FranceSearch for more papers by this authorStephan Windecker, Stephan Windecker SwitzerlandSearch for more papers by this authorDocument Reviewers, Document ReviewersSearch for more papers by this authorTheresa McDonagh, Theresa McDonagh CPG Co-Review Coordinator UKSearch for more papers by this authorUdo Sechtem, Udo Sechtem CPG Co-Review Coordinator GermanySearch for more papers by this authorLuis Almenar Bonet, Luis Almenar Bonet SpainSearch for more papers by this authorPanayiotis Avraamides, Panayiotis Avraamides CyprusSearch for more papers by this authorHisham A. Ben Lamin, Hisham A. Ben Lamin LibyaSearch for more papers by this authorMichele Brignole, Michele Brignole ItalySearch for more papers by this authorAntonio Coca, Antonio Coca SpainSearch for more papers by this authorPeter Cowburn, Peter Cowburn UKSearch for more papers by this authorHenry Dargie, Henry Dargie UKSearch for more papers by this authorPerry Elliott, Perry Elliott UKSearch for more papers by this authorFrank Arnold Flachskampf, Frank Arnold Flachskampf SwedenSearch for more papers by this authorGuido Francesco Guida, Guido Francesco Guida ItalySearch for more papers by this authorSuzanna Hardman, Suzanna Hardman UKSearch for more papers by this authorBernard Iung, Bernard Iung FranceSearch for more papers by this authorBela Merkely, Bela Merkely HungarySearch for more papers by this authorChristian Mueller, Christian Mueller SwitzerlandSearch for more papers by this authorJohn N. Nanas, John N. Nanas GreeceSearch for more papers by this authorOlav Wendelboe Nielsen, Olav Wendelboe Nielsen DenmarkSearch for more papers by this authorStein Ørn, Stein Ørn NorwaySearch for more papers by this authorJohn T. Parissis, John T. Parissis GreeceSearch for more papers by this authorPiotr Ponikowski, Piotr Ponikowski PolandSearch for more papers by this author Authors/Task Force Members, Authors/Task Force MembersSearch for more papers by this authorJohn J.V. McMurray, Corresponding Author John J.V. McMurray Chairperson UKCorresponding author. Chairperson: Professor John J.V. McMurray, University of Glasgow G12 8QQ, UK. Tel: +44 141 330 3479, Fax: +44 141 330 6955, Email: [email protected]Search for more papers by this authorStamatis Adamopoulos, Stamatis Adamopoulos GreeceSearch for more papers by this authorStefan D. Anker, Stefan D. Anker GermanySearch for more papers by this authorAngelo Auricchio, Angelo Auricchio SwitzerlandSearch for more papers by this authorMichael Böhm, Michael Böhm GermanySearch for more papers by this authorKenneth Dickstein, Kenneth Dickstein NorwaySearch for more papers by this authorVolkmar Falk, Volkmar Falk SwitzerlandSearch for more papers by this authorGerasimos Filippatos, Gerasimos Filippatos GreeceSearch for more papers by this authorCândida Fonseca, Cândida Fonseca PortugalSearch for more papers by this authorMiguel Angel Gomez-Sanchez, Miguel Angel Gomez-Sanchez SpainSearch for more papers by this authorTiny Jaarsma, Tiny Jaarsma SwedenSearch for more papers by this authorLars Køber, Lars Køber DenmarkSearch for more papers by this authorGregory Y.H. Lip, Gregory Y.H. Lip UKSearch for more papers by this authorAldo Pietro Maggioni, Aldo Pietro Maggioni ItalySearch for more papers by this authorAlexander Parkhomenko, Alexander Parkhomenko UkraineSearch for more papers by this authorBurkert M. Pieske, Burkert M. Pieske AustriaSearch for more papers by this authorBogdan A. Popescu, Bogdan A. Popescu RomaniaSearch for more papers by this authorPer K. Rønnevik, Per K. Rønnevik NorwaySearch for more papers by this authorFrans H. Rutten, Frans H. Rutten The NetherlandsSearch for more papers by this authorJuerg Schwitter, Juerg Schwitter SwitzerlandSearch for more papers by this authorPetar Seferovic, Petar Seferovic SerbiaSearch for more papers by this authorJanina Stepinska, Janina Stepinska PolandSearch for more papers by this authorPedro T. Trindade, Pedro T. Trindade SwitzerlandSearch for more papers by this authorAdriaan A. Voors, Adriaan A. Voors The NetherlandsSearch for more papers by this authorFaiez Zannad, Faiez Zannad FranceSearch for more papers by this authorAndreas Zeiher, Andreas Zeiher GermanySearch for more papers by this authorESC Committee for Practice Guidelines (CPG), ESC Committee for Practice Guidelines (CPG)Search for more papers by this authorJeroen J. Bax, Jeroen J. Bax CPG Chairperson The NetherlandsSearch for more papers by this authorHelmut Baumgartner, Helmut Baumgartner GermanySearch for more papers by this authorClaudio Ceconi, Claudio Ceconi ItalySearch for more papers by this authorVeronica Dean, Veronica Dean FranceSearch for more papers by this authorChristi Deaton, Christi Deaton UKSearch for more papers by this authorRobert Fagard, Robert Fagard BelgiumSearch for more papers by this authorChristian Funck-Brentano, Christian Funck-Brentano FranceSearch for more papers by this authorDavid Hasdai, David Hasdai IsraelSearch for more papers by this authorArno Hoes, Arno Hoes The NetherlandsSearch for more papers by this authorPaulus Kirchhof, Paulus Kirchhof Germany UKSearch for more papers by this authorJuhani Knuuti, Juhani Knuuti FinlandSearch for more papers by this authorPhilippe Kolh, Philippe Kolh BelgiumSearch for more papers by this authorTheresa McDonagh, Theresa McDonagh UKSearch for more papers by this authorCyril Moulin, Cyril Moulin FranceSearch for more papers by this authorBogdan A. Popescu, Bogdan A. Popescu RomaniaSearch for more papers by this authorŽeljko Reiner, Željko Reiner CroatiaSearch for more papers by this authorUdo Sechtem, Udo Sechtem GermanySearch for more papers by this authorPer Anton Sirnes, Per Anton Sirnes NorwaySearch for more papers by this authorMichal Tendera, Michal Tendera PolandSearch for more papers by this authorAdam Torbicki, Adam Torbicki PolandSearch for more papers by this authorAlec Vahanian, Alec Vahanian FranceSearch for more papers by this authorStephan Windecker, Stephan Windecker SwitzerlandSearch for more papers by this authorDocument Reviewers, Document ReviewersSearch for more papers by this authorTheresa McDonagh, Theresa McDonagh CPG Co-Review Coordinator UKSearch for more papers by this authorUdo Sechtem, Udo Sechtem CPG Co-Review Coordinator GermanySearch for more papers by this authorLuis Almenar Bonet, Luis Almenar Bonet SpainSearch for more papers by this authorPanayiotis Avraamides, Panayiotis Avraamides CyprusSearch for more papers by this authorHisham A. Ben Lamin, Hisham A. Ben Lamin LibyaSearch for more papers by this authorMichele Brignole, Michele Brignole ItalySearch for more papers by this authorAntonio Coca, Antonio Coca SpainSearch for more papers by this authorPeter Cowburn, Peter Cowburn UKSearch for more papers by this authorHenry Dargie, Henry Dargie UKSearch for more papers by this authorPerry Elliott, Perry Elliott UKSearch for more papers by this authorFrank Arnold Flachskampf, Frank Arnold Flachskampf SwedenSearch for more papers by this authorGuido Francesco Guida, Guido Francesco Guida ItalySearch for more papers by this authorSuzanna Hardman, Suzanna Hardman UKSearch for more papers by this authorBernard Iung, Bernard Iung FranceSearch for more papers by this authorBela Merkely, Bela Merkely HungarySearch for more papers by this authorChristian Mueller, Christian Mueller SwitzerlandSearch for more papers by this authorJohn N. Nanas, John N. Nanas GreeceSearch for more papers by this authorOlav Wendelboe Nielsen, Olav Wendelboe Nielsen DenmarkSearch for more papers by this authorStein Ørn, Stein Ørn NorwaySearch for more papers by this authorJohn T. Parissis, John T. Parissis GreeceSearch for more papers by this authorPiotr Ponikowski, Piotr Ponikowski PolandSearch for more papers by this author First published: 18 February 2014 https://doi.org/10.1093/eurjhf/hfs105Citations: 1,653 Other ESC entities having participated in the development of this document: Associations: European Association for Cardiovascular Prevention & Rehabilitation (EACPR), European Association of Echocardiography (EAE), European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) Working Groups: Acute Cardiac Care, Cardiovascular Pharmacology and Drug Therapy, Cardiovascular Surgery, Grown-up Congenital Heart Disease, Hypertension and the Heart, Myocardial and Pericardial Diseases, Pulmonary Circulation and Right Ventricular Function, Thrombosis, Valvular Heart Disease Councils: Cardiovascular Imaging, Cardiovascular Nursing and Allied Professions, Cardiology Practice, Cardiovascular Primary Care The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC. Disclaimer. The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription. The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abbreviations and acronyms ACE angiotensin-converting enzyme ACHD adult congenital heart disease AF atrial fibrillation AF-CHF Atrial Fibrillation and Congestive Heart Failure AHF acute heart failure AIRE Acute Infarction Ramipril Efficacy ARB angiotensin receptor blocker ARR absolute risk reduction ATLAS Assessment of Treatment with Lisinopril And Survival AV atrioventricular AVP arginine vasopressin BEAUTIFUL MorBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction BEST Beta-Blocker Evaluation of Survival Trial BiVAD bi-ventricular assist device BNP B-type natriuretic peptide b.p.m. beats per minute BTC bridge to candidacy BTD bridge to decision BTR bridge to recovery BTT bridge to transplantation CABG coronary artery bypass graft CAD coronary artery disease CARE-HF Cardiac Resynchronization in Heart Failure Study CCB calcium-channel blocker CHA2DS2-VASc Cardiac failure, Hypertension, Age ≥75 (Doubled), Diabetes, Stroke (Doubled)-Vascular disease, Age 65–74 and Sex category (Female) CHARM Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity CIBIS II Cardiac Insufficiency Bisoprolol Study II CMR cardiac magnetic resonance COMET Carvedilol or Metoprolol European Trial COMPANION Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure CONSENSUS Cooperative North Scandinavian Enalapril Survival Study COPD chronic obstructive pulmonary disease COPERNICUS Carvedilol Prospective Randomized Cumulative Survival CORONA Controlled Rosuvastatin Multinational Trial in Heart Failure CPAP continuous positive airway pressure CRT cardiac resynchronization therapy CRT-D cardiac resynchronization therapy-defibrillator CRT-P cardiac resynchronization therapy-pacemaker CT computed tomography DEFINITE Defibrillators in Non-ischemic Cardiomyopathy Treatment Evaluation DIG Digitalis Investigation Group DT destination therapy ECG electrocardiogram ECMO extracorporeal membrane oxygenation EF ejection fraction eGFR estimated glomerular filtration rate ELITE II Second Evaluation of Losartan in the Elderly Trial EMPHASIS-HF Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure GFR glomerular filtration rate GISSI-HF Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico-heart failure H-ISDN hydralazine and isosorbide dinitrate HAS-BLED Hypertension, Abnormal renal/liver function (1 point each), Stroke, Bleeding history or predisposition, Labile INR, Elderly (>65), Drugs/alcohol concomitantly (1 point each) HEAAL Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan HF heart failure HF-ACTION Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training HF-PEF heart failure with 'preserved' ejection fraction HF-REF heart failure with reduced ejection fraction I-PRESERVE Irbesartan in heart failure with preserved systolic function i.v. intravenous IABP intra-aortic balloon pump ICD implantable cardioverter-defibrillator LA left atrial LBBB left bundle branch block LV left ventricular LVAD left ventricular assist device LVEF left ventricular ejection fraction MADIT-II Multicenter Automatic Defibrillator Implantation Trial II MCS mechanical circulatory support MDCT multi-detector computed tomography MERIT-HF Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure MRA mineralocorticoid receptor antagonist MR-proANP mid-regional atrial (or A-type) natriuretic peptide MUSTIC Multisite Stimulation in Cardiomyopathies NIPPV non-invasive positive pressure ventilation NNT number needed to treat NSAID non-steroidal anti-inflammatory drug NYHA New York Heart Association OPTIMAAL Optimal Therapy in Myocardial infarction with the Angiotensin II Antagonist Losartan PEP-CHF Perindopril for Elderly People with Chronic Heart failure PET positron emission tomography PUFA polyunsaturated fatty acid RAFT Resynchronization/Defibrillation for Ambulatory Heart Failure Trial RALES Randomised Aldactone Evaluation Study RCT randomized controlled trial RRR relative risk reduction SAVE Survival and Ventricular Enlargement SCD-HeFT Sudden Cardiac Death in Heart Failure Trial SENIORS Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure SHIFT Systolic Heart failure treatment with the If inhibitor ivabradine Trial SOLVD Studies of Left Ventricular Dysfunction SPECT single-photon emission computed tomography STICH Surgical Treatment for Ischemic Heart Failure TAPSE tricuspid annular plane systolic excursion TDI tissue Doppler imaging TOE transoesophageal echocardiography TRACE TRAndolapril Cardiac Evaluation Val-HeFT Valsartan Heart Failure Trial VALIANT Valsartan In Acute myocardial infarction VO2 maximal oxygen consumption 1. Preamble Guidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes, but are complements, for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible physician(s). A large number of Guidelines have been issued in recent years by the ESC as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for diagnosis, management, and/or prevention of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2. Table 1. Classes of recommendations Table 2. Levels of evidence The experts of the writing and reviewing panels filled in declarations of interest forms of all relationships which might be perceived as real or potential sources of conflicts of interest. These forms were compiled into one file and can be found on the ESC website (http://www.escardio.org/guidelines). Any changes in declarations of interest that arise during the writing period must be notified to the ESC and updated. The Task Force received its entire financial support from the ESC without any involvement from the healthcare industry. The ESC CPG supervises and coordinates the preparation of new Guidelines produced by Task Forces, expert groups, or consensus panels. The Committee is also responsible for the endorsement process of these Guidelines. The ESC Guidelines undergo extensive review by the CPG and external experts. After appropriate revisions, it is approved by all the experts involved in the Task Force. The finalized document is approved by the CPG for publication in the European Heart Journal. The task of developing ESC Guidelines covers not only the integration of the most recent research, but also the creation of educational tools and implementation programmes for the recommendations. To implement the guidelines, condensed pocket guidelines versions, summary slides, booklets with essential messages, and an electronic version for digital applications (smartphones, etc.) are produced. These versions are abridged and, thus, if needed, one should always refer to the full text version which is freely available on the ESC website. The National Societies of the ESC are encouraged to endorse, translate, and implement the ESC Guidelines. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations. Surveys and registries are needed to verify that real-life daily practice is in keeping with what is recommended in the guidelines, thus completing the loop between clinical research, writing of guidelines, and implementing them into clinical practice. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and, where appropriate and necessary, the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription. 2. Introduction The aim of this document is to provide practical, evidence-based guidelines for the diagnosis and treatment of heart failure (HF). The principal changes from the 2008 guidelines1 relate to: an expansion of the indication for mineralocorticoid (aldosterone) receptor antagonists (MRAs); a new indication for the sinus node inhibitor ivabradine; an expanded indication for cardiac resynchronization therapy (CRT); new information on the role of coronary revascularization in HF; recognition of the growing use of ventricular assist devices; and the emergence of transcatheter valve interventions. There are also changes to the structure and format of the guidelines. Therapeutic recommendations now state the treatment effect supported by the class and level of recommendation in tabular format; in the case of chronic heart failure due to left ventricular (LV) systolic dysfunction, the recommendations focus on mortality and morbidity outcomes. Detailed summaries of the key evidence supporting generally recommended treatments have been provided. Practical guidance is provided for the use of the more important disease-modifying drugs and diuretics. When possible, other relevant guidelines, consensus statements, and position papers have been cited to avoid unduly lengthy text. All tables should be read in conjunction with their accompanying text and not read in isolation. 3. Definition and diagnosis Definition of heart failure Heart failure can be defined as an abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues, despite normal filling pressures (or only at the expense of increased filling pressures).1 For the purposes of these guidelines, HF is defined, clinically, as a syndrome in which patients have typical symptoms (e.g. breathlessness, ankle swelling, and fatigue) and signs (e.g. elevated jugular venous pressure, pulmonary crackles, and displaced apex beat) resulting from an abnormality of cardiac structure or function. The diagnosis of HF can be difficult (see Section 3.6). Many of the symptoms of HF are non-discriminating and, therefore, of limited diagnostic value.2–6 Many of the signs of HF result from sodium and water retention and resolve quickly with diuretic therapy, i.e. may be absent in patients receiving such treatment. Demonstration of an underlying cardiac cause is therefore central to the diagnosis of HF (see Section 3.6). This is usually myocardial disease causing systolic ventricular dysfunction. However, abnormalities of ventricular diastolic function or of the valves, pericardium, endocardium, heart rhythm, and conduction can also cause HF (and more than one abnormality can be present) (see Section 3.5). Identification of the underlying cardiac problem is also crucial for therapeutic reasons, as the precise pathology determines the specific treatment used (e.g. valve surgery for valvular disease, specific pharmacological therapy for LV systolic dysfunction, etc.). Terminology related to left ventricular ejection fraction The main terminology used to describe HF is historical and is based on measurement of LV ejection fraction (EF). Mathematically, EF is the stroke volume (which is the end-diastolic volume minus the end-systolic volume) divided by the end-diastolic volume. In patients with reduced contraction and emptying of the left ventricle (i.e. systolic dysfunction), stroke volume is maintained by an increase in end-diastolic volume (because the left ventricle dilates), i.e. the heart ejects a smaller fraction of a larger volume. The more severe the systolic dysfunction, the more the EF is reduced from normal and, generally, the greater the end-diastolic and end-systolic volumes. The EF is considered important in HF, not only because of its prognostic importance (the lower the EF the poorer the survival) but also because most clinical trials selected patients based upon EF (usually measured using a radionuclide technique or echocardiography). The major trials in patients with HF and a reduced EF (HF-REF), or 'systolic HF', mainly enrolled patients with an EF ≤35%, and it is only in these patients that effective therapies have been demonstrated to date. Other, more recent, trials enrolled patients with HF and an EF >40–45% and no other causal cardiac abnormality (such as valvular or pericardial disease). Some of these patients did not have an entirely normal EF (generally considered to be >50%) but also did not have a major reduction in systolic function either. Because of this, the term HF with 'preserved' EF (HF-PEF) was created to describe these patients. Patients with an EF in the range 35–50% therefore represent a 'grey area' and most probably have primarily mild systolic dysfunction. The diagnosis of HF-PEF is more difficult than the diagnosis of HF-REF because it is largely one of exclusion, i.e. potential non-cardiac causes of the patient's symptoms (such as anaemia or chronic lung disease) must first be discounted (Table 3).7,8 Usually these patien

<h2>Summary</h2><h3>Background</h3> Stent thrombosis is a safety concern associated with use of drug-eluting stents. Little is known about occurrence of stent thrombosis more than 1 year after implantation of such stents. <h3>Methods</h3> Between April, 2002, and Dec, 2005, 8146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3823) or paclitaxel-eluting stents (PES; n=4323) at two academic hospitals. We assessed data from this group to ascertain the incidence, time course, and correlates of stent thrombosis, and the differences between early (0–30 days) and late (>30 days) stent thrombosis and between SES and PES. <h3>Findings</h3> Angiographically documented stent thrombosis occurred in 152 patients (incidence density 1·3 per 100 person-years; cumulative incidence at 3 years 2·9%). Early stent thrombosis was noted in 91 (60%) patients, and late stent thrombosis in 61 (40%) patients. Late stent thrombosis occurred steadily at a constant rate of 0·6% per year up to 3 years after stent implantation. Incidence of early stent thrombosis was similar for SES (1·1%) and PES (1·3%), but late stent thrombosis was more frequent with PES (1·8%) than with SES (1·4%; p=0·031). At the time of stent thrombosis, dual antiplatelet therapy was being taken by 87% (early) and 23% (late) of patients (p<0·0001). Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2·28, 95% CI 1·29–4·03) and diabetes (2·03, 1·07–3·83). <h3>Interpretation</h3> Late stent thrombosis was encountered steadily with no evidence of diminution up to 3 years of follow-up. Early and late stent thrombosis were observed with SES and with PES. Acute coronary syndrome at presentation and diabetes were independent predictors of stent thrombosis.

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints.This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavours of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, the Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiography recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints.This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

Table 1. Classes of recommendation Table 2. Levels of evidence Table 3. Estimated fetal and maternal effective doses for various diagnostic and interventional radiology procedures Table 4. Predictors of maternal cardiovascular events and risk score from the CARPREG study Table 5. Predictors of maternal cardiovascular events identified in congential heart diseases in the ZAHARA and Khairy study Table 6. Modified WHO classification of maternal cardiovascular risk: principles Table 7. Modified WHO classification of maternal cardiovascular risk: application Table 8. Maternal predictors of neonatal events in women with heart disease Table 9. General recommendations Table 10. Recommendations for the management of congenital heart disease Table 11. Recommendations for the management of aortic disease Table 12. Recommendations for the management of valvular heart disease Table 13. Recommendations for the management of coronary artery disease Table 14. Recommendations for the management of cardiomyopathies and heart failure Table 15. Recommendations for the management of arrhythmias Table 16. Recommendations for the management of hypertension Table 17. Check list for risk factors for venous thrombo-embolism Table 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancy Table 19. Risk groups according to risk factors: definition and preventive measures Table 20. Recommendations for the prevention and management of venous thrombo-embolism in pregnancy and puerperium Table 21. Recommendations for drug use ABPM : ambulatory blood pressure monitoring ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AHA : American Heart Association aPTT : activated partial thromboplastin time ARB : angiotensin receptor blocker AS : aortic stenosis ASD : atrial septal defect AV : atrioventricular AVSD : atrioventricular septal defect BMI : body mass index BNP : B-type natriuretic peptide BP : blood pressure CDC : Centers for Disease Control CHADS : congestive heart failure, hypertension, age (>75 years), diabetes, stroke CI : confidence interval CO : cardiac output CoA : coarction of the aorta CT : computed tomography CVD : cardiovascular disease DBP : diastolic blood pressure DCM : dilated cardiomyopathy DVT : deep venous thrombosis ECG : electrocardiogram EF : ejection fraction ESC : European Society of Cardiology ESH : European Society of Hypertension ESICM : European Society of Intensive Care Medicine FDA : Food and Drug Administration HCM : hypertrophic cardiomyopathy ICD : implantable cardioverter-defibrillator INR : international normalized ratio i.v. : intravenous LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction LVOTO : left ventricular outflow tract obstruction MRI : magnetic resonance imaging MS : mitral stenosis NT-proBNP : N-terminal pro B-type natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulant PAH : pulmonary arterial hypertension PAP : pulmonary artery pressure PCI : percutaneous coronary intervention PPCM : peripartum cardiomyopathy PS : pulmonary valve stenosis RV : right ventricular SBP : systolic blood pressure SVT : supraventricular tachycardia TGA : complete transposition of the great arteries TR : tricuspid regurgitation UFH : unfractionated heparin VSD : ventricular septal defect VT : ventricular tachycardia VTE : venous thrombo-embolism WHO : World Health Organization Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the …

Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents.We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation.Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021).The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

2D : two-dimensional 3D : three-dimensional ABI : ankle–brachial index ACAS : Asymptomatic Carotid Atherosclerosis Study ACCF : American College of Cardiology Foundation ACE : angiotensin-converting enzyme ACS : acute coronary syndrome ACST : Asymptomatic Carotid Surgery Trial ALI : acute limb ischaemia ASTRAL : Angioplasty and Stenting for Renal Artery Lesions trial BASIL : Bypass versus Angioplasty in Severe Ischaemia of the Leg BOA : Dutch Bypass Oral Anticoagulants or Aspirin CABG : coronary artery bypass grafting CAD : coronary artery disease CAPRIE : Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events CAPTURE : Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events CARP : Coronary Artery Revascularization Prophylaxis CAS : carotid artery stenting CASPAR : Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease CASS : Coronary Artery Surgery Study CAVATAS : CArotid and Vertebral Artery Transluminal Angioplasty Study CEA : carotid endarterectomy CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance CI : confidence interval CLEVER : Claudication: Exercise Versus Endoluminal Revascularization CLI : critical limb ischaemia CORAL : Cardiovascular Outcomes in Renal Atherosclerotic Lesions COURAGE : Clinical Outcomes Utilization Revascularization and Aggressive Drug Evaluation CPG : Committee for Practice Guidelines CREST : Carotid Revascularization Endarterectomy vs. Stenting Trial CT : computed tomography CTA : computed tomography angiography CVD : cardiovascular disease DECREASE-V : Dutch Echocardiographic Cardiac Risk Evaluation DRASTIC : Dutch Renal Artery Stenosis Intervention Cooperative Study DSA : digital subtraction angiography DUS : duplex ultrasound/duplex ultrasonography EACTS : European Association for Cardio-Thoracic Surgery EAS : European Atherosclerosis Society ECST : European Carotid Surgery Trial EPD : embolic protection device ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EUROSCORE : European System for Cardiac Operative Risk Evaluation EVA-3S : Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis EXACT : Emboshield and Xact Post Approval Carotid Stent Trial GALA : General Anaesthesia versus Local Anaesthesia for Carotid Surgery GFR : glomerular filtration rate GRACE : Global Registry of Acute Coronary Events HbA1c : glycated haemoglobin HDL : high-density lipoprotein HOPE : Heart Outcomes Prevention Evaluation HR : hazard ratio IC : intermittent claudication ICSS : International Carotid Stenting Study IMT : intima–media thickness ITT : intention to treat LDL : low-density lipoprotein LEAD : lower extremity artery disease MACCEs : major adverse cardiac and cerebrovascular events MDCT : multidetector computed tomography MONICA : Monitoring of Trends and Determinants in Cardiovascular Disease MRA : magnetic resonance angiography MRI : magnetic resonance imaging NASCET : North American Symptomatic Carotid Endarterectomy Trial ONTARGET : Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial OR : odds ratio PAD : peripheral artery diseases PARTNERS : Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival PCI : percutaneous coronary intervention PET : positron emission tomography PRO-CAS : Predictors of Death and Stroke in CAS PTA : percutaneous transluminal angioplasty RAAS : renin–angiotensin–aldosterone system RADAR : Randomized, Multicentre, Prospective Study Comparing Best Medical Treatment Versus Best Medical Treatment Plus Renal Artery Stenting in Patients With Haemodynamically Relevant Atherosclerotic Renal Artery Stenosis RAS : renal artery stenosis RCT : randomized controlled trial REACH : Reduction of Atherothrombosis for Continued Health RR : risk ratio SAPPHIRE : Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy SCAI : Society for Cardiovascular Angiography and Interventions SIR : Society of Interventional Radiology SPACE : Stent-Protected Angioplasty versus Carotid Endarterectomy SPARCL : Stroke Prevention by Aggressive Reduction in Cholesterol Levels Study STAR : Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function SSYLVIA : Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries SVMB : Society for Vascular Medicine and Biology TASC : TransAtlantic Inter-Society Consensus TIA : transient ischaemic attack UEAD : upper extremity artery disease VA : vertebral artery Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the ESC Core Curriculum topics. Guidelines and recommendations should help the physicians to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible physician(s). A large number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for diagnosis, management, and/or prevention of a given condition according to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic and therapeutic procedures was performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations were included, where data exist. The level of evidence and the strength of recommendation of particular treatment options were weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . …

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI)clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, the Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints.This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavours of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose.A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk.The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61-0·85) in the derivation cohort, and 0·70 (0·65-0·74) in the PLATO trial validation cohort and 0·66 (0·61-0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group.The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration.None.

The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy.We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population.The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56).Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT00166257.).

Stent thrombosis may occur late after drug-eluting stent (DES) implantation, and its cause remains unknown. The present study investigated differences of the stented segment between patients with and without very late stent thrombosis with the use of intravascular ultrasound.Since January 2004, patients presenting with very late stent thrombosis (> 1 year) after DES implantation underwent intravascular ultrasound. Findings in patients with very late stent thrombosis were compared with intravascular ultrasound routinely obtained 8 months after DES implantation in 144 control patients, who did not experience stent thrombosis for > or = 2 years. Very late stent thrombosis was encountered in 13 patients at a mean of 630+/-166 days after DES implantation. Compared with DES controls, patients with very late stent thrombosis had longer lesions (23.9+/-16.0 versus 13.3+/-7.9 mm; P<0.001) and stents (34.6+/-22.4 versus 18.6+/-9.5 mm; P<0.001), more stents per lesion (1.6+/-0.9 versus 1.1+/-0.4; P<0.001), and stent overlap (39% versus 8%; P<0.001). Vessel cross-sectional area was similar for the reference segment (cross-sectional area of the external elastic membrane: 18.9+/-6.9 versus 20.4+/-7.2 mm2; P=0.46) but significantly larger for the in-stent segment (28.6+/-11.9 versus 20.1+/-6.7 mm2; P=0.03) in very late stent thrombosis patients compared with DES controls. Incomplete stent apposition was more frequent (77% versus 12%; P<0.001) and maximal incomplete stent apposition area was larger (8.3+/-7.5 versus 4.0+/-3.8 mm2; P=0.03) in patients with very late stent thrombosis compared with controls.Incomplete stent apposition is highly prevalent in patients with very late stent thrombosis after DES implantation, suggesting a role in the pathogenesis of this adverse event.

In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial.

Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed.To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves.Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves.Survival, stroke, and New York Heart Association functional class.Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008).In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

abdominal aorta aneurysm ankle-brachial index Asymptomatic Carotid Atherosclerosis Study angiotensin-converting enzyme inhibitors acute coronary syndrome asymptomatic carotid atherosclerosis risk of stroke Asymptomatic Carotid Surgery Trial Asymptomatic Carotid Trial atrial fibrillation Aggressive detection and Management of the Extension of atherothrombosis in high Risk coronary patients In comparison with standard of Care for coronary Atherosclerosis angiotensin-receptor blockers absolute risk reduction angioplasty and stenting for renal artery lesions bypass versus angioplasty in severe ischaemia of the leg Best Endovascular vs. Best Surgical Therapy in Patients with Critical Limb Ischaemia best medical therapy blood pressure coronary artery bypass grafting coronary artery disease Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events Carotid ACCULINK/ACCUNET Post-Approval Trial to Uncover Rare Events Clopidogrel and Aspirin for the Reduction of Emboli in Symptomatic carotid Stenosis Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial disease carotid artery stenting common carotid artery carotid endarterectomy common femoral artery Congestive heart failure, Hypertension, Age ≥75 (2 points), Diabetes mellitus, Stroke or TIA (2 points), Vascular disease, Age 65–74 years, Sex category Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance confidence interval chronic kidney disease Claudication: exercise versus endoluminal revascularization Chronic limb-threatening ischaemia chronic mesenteric ischaemia Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter Cardiovascular Outcomes in Renal Atherosclerotic Lesions cardiopulmonary bypass Committee for Practice Guidelines Carotid Revascularization Endarterectomy versus Stenting Trial computed tomography angiography cardiovascular dual antiplatelet therapy drug eluting stent digital subtraction angiography duplex ultrasound electrocardiogram European Carotid Surgery Trial embolus protection device European Society of Cardiology European Stroke Organisation European Society of Vascular Surgery Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease Endarterectomy vs Stenting in Patients with Symptomatic Severe Carotid Stenosis endovascular therapy exercise therapy fibromuscular dysplasia great saphenous vein high-density lipoprotein cholesterol Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training high-intensity transient signal Heart Outcomes Prevention Trial hazard ratio intermittent claudication internal carotid artery implantable cardioverter defibrillator International Carotid Stenting Study international normalized ratio INternational VErapamil-SR/Trandolapril Study low-density lipoprotein cholesterol lower extremity artery disease left ventricular major adverse cardiovascular event myocardial infarction magnetic resonance angiography MultiCenter Randomized Clinical Trial of Ischemic Stroke in the Netherlands magnetic resonance imaging multisite artery disease maximal walking distance North American Symptomatic Carotid Endarterectomy Trial number needed to harm number needed to treat non-vitamin K oral anticoagulant oral anticoagulation Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial odds ratio peripheral arterial diseases percutaneous coronary intervention Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 PROlonging Dual antiplatelet treatment after Grading stent-induced intimal hYperplasia study percutaneous transluminal angioplasty quality of life renin–angiotensin–aldosterone system renal artery disease renal artery stenosis randomized clinical trial Reduction of Atherothrombosis for Continued Health Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation relative risk renal resistive index Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy single antiplatelet therapy systolic blood pressure superficial femoral artery Stent Protected Angioplasty versus Carotid Endarterectomy Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function Efficacy and Safety of XRP0038/NV1FGF in Critical Limb Ischaemia Patients With Skin Lesions transcatheter aortic valve implantation toe-brachial index transcutaneous oxygen pressure transient ischaemic attack transthoracic echocardiography upper extremity artery disease vertebral artery Vertebral Artery Stenting Trial valvular heart disease vitamin K antagonist walking distance wound, ischaemia and foot infection Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. A great number of guidelines have been issued in recent years by the European Society of Cardiology (ESC), by the European Society of Vascular Surgery (ESVS) and by the European Stroke Organization (ESO), as well as by other societies and organisations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC Website (https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. Members of this Task Force were selected by the ESC, including representation from the ESVS and ESO to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for management of a given condition according to ESC Committee for Practice Guidelines (CPG) policy and approved by the ESVS and ESO. A critical evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk–benefit ratio. The level of evidence and the strength of the recommendation of particular management options were weighed and graded according to predefined scales, as outlined in Table 1, Table 2.Table 1Classes of recommendations.Table 2Levels of evidence.Level of evidence AData derived from multiple randomized clinical trials or meta-analyses.Level of evidence BData derived from a single randomized clinical trial or large non-randomized studies.Level of evidence CConsensus of opinion of the experts and/or small studies, retrospective studies, registries. Open table in a new tab The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. These forms were compiled into one file and can be found on the ESC Website (http://www.escardio.org/guidelines). Any changes in declarations of interest that arise during the writing period were notified to the ESC and updated. The Task Force received its entire financial support from the ESC and ESVS without any involvement from the healthcare industry. The ESC CPG supervises and coordinates the preparation of new Guidelines. The Committee is also responsible for the endorsement process of these Guidelines. The ESC Guidelines undergo extensive review by the CPG and external experts, and in this case by ESVS- and ESO-appointed experts. After appropriate revisions the Guidelines are approved by all the experts involved in the Task Force. The finalized document is approved by the CPG and ESVS for publication in the European Heart Journal and in the European Journal of Vascular and Endovascular Surgery. The Guidelines were developed after careful consideration of the scientific and medical knowledge and the evidence available at the time of their dating. The task of developing ESC Guidelines in collaboration with ESVS also includes the creation of educational tools and implementation programmes for the recommendations including condensed pocket guideline versions, summary slides, booklets with essential messages, summary cards for non-specialists and an electronic version for digital applications (smartphones, etc.). These versions are abridged and thus, if needed, one should always refer to the full text version, which is freely available via the ESC Website and hosted on the EHJ Website. The National Societies of the ESC are encouraged to endorse, translate and implement all ESC Guidelines. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations. Surveys and registries are needed to verify that real-life daily practice is in keeping with what is recommended in the guidelines, thus completing the loop between clinical research, writing of guidelines, disseminating them and implementing them into clinical practice. Health professionals are encouraged to take the ESC Guidelines developed in collaboration with ESVS fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies. However, the ESC Guidelines do not override in any way whatsoever the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient or the patient's caregiver where appropriate and/or necessary. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.

Objectives: The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials.In addition, this document is intended to expand the understanding of patient risk stratification and case selection.Background: A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI.However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.Methods and Results: Two in-person meetings (held in September 2011 in Washington, DC, and in February 2012 in Rotterdam, The Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and noninterventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived.This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies.Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized.Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function.Definitions for the quality of life assessments are also reported.These endpoints formed the basis for several recommended composite endpoints.Conclusions: This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement.This initiative and document can furthermore be used as a model during current endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).(

To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health. Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials. The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the U.S. Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included: 1) respect for the historical legacy of surgical valve guidelines; 2) identification of pathophysiological mechanisms associated with clinical events; 3) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended. Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.

To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval.Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%.The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer).We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220.We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26).Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes.Biosensors Europe SA, Switzerland.

New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration.In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months.At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events.At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.)

The ESC/EACTS Guidelines represent the views of the ESC and the EACTS and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC and the EACTS are not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC/EACTS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC/EACTS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC/EACTS Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC/EACTS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

Sirolimus-eluting stents and paclitaxel-eluting stents, as compared with bare-metal stents, reduce the risk of restenosis. It is unclear whether there are differences in safety and efficacy between the two types of drug-eluting stents.

Background We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. Findings Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75–1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78–1·20]; p=0·77). Interpretation Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Funding AstraZeneca, Biosensors, and The Medicines Company.

Atrioventricular (AV) conduction disturbances requiring permanent pacemaker (PPM) implantation may complicate transcatheter aortic valve replacement (TAVR). Available evidence on predictors of PPM is sparse and derived from small studies. The objective of this study was to provide summary effect estimates for clinically useful predictors of PPM implantation after TAVR. We performed a systematic search for studies that reported the incidence of PPM implantation after TAVR and that provided raw data for the predictors of interest. Data on study, patient, and procedural characteristics were abstracted. Crude risk ratios (RRs) and 95% confidence intervals for each predictor were calculated by use of random effects models. Stratified analyses by type of implanted valve were performed. We obtained data from 41 studies that included 11,210 TAVR patients, of whom 17% required PPM implantation after intervention. The rate of PPM ranged from 2% to 51% in individual studies (with a median of 28% for the Medtronic CoreValve Revalving System [MCRS] and 6% for the Edwards SAPIEN valve [ESV]). The summary estimates indicated increased risk of PPM after TAVR for men (RR: 1.23; p < 0.01); for patients with first-degree AV block (RR: 1.52; p < 0.01), left anterior hemiblock (RR: 1.62; p < 0.01), or right bundle branch block (RR: 2.89; p < 0.01) at baseline; and for patients with intraprocedural AV block (RR: 3.49; p < 0.01). These variables remained significant predictors when only patients treated with the MCRS bioprosthesis were considered. The data for ESV were limited. Unadjusted estimates indicated a 2.5-fold higher risk for PPM implantation for patients who received the MCRS than for those who received the ESV. Male sex, baseline conduction disturbances, and intraprocedural AV block emerged as predictors of PPM implantation after TAVR. This study provides useful tools to identify high-risk patients and to guide clinical decision making before and after intervention.

Atrial fibrillation (AF) confers a substantial risk of mortality and morbidity from stroke and thrombo-embolism, and this common cardiac arrhythmia represents a major healthcare burden in Europe.1 Stroke prevention is central to the management of AF patients, with the 2012 focused update of the European Society of Cardiology (ESC) guidelines2 recommending oral anticoagulation (OAC) using well-controlled adjusted dose vitamin K antagonists (VKAs, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, previously referred to as new or novel OACs3) for patients with AF and ≥1 stroke risk factor(s). Also, these guidelines strongly advocate a clinical practice shift so that the initial decision step now is the identification of ‘truly low risk’ patients, essentially those aged <65 years without any stroke risk factor (both male and female), who do not need any antithrombotic therapy.2 The ESC guidelines also recommend the use of the CHA2DS2-VASc score4 for stroke risk assessment, and define ‘low-risk’ patients as those with a CHA2DS2-VASc score = 0 (males) or score = 1 (females). Subsequent to this initial step of identifying the low-risk patients, effective stroke prevention (which is essentially OAC) can then be offered to AF patients with ≥1 stroke risk factor(s), with treatment decisions made in consultation with patients and incorporating their preferences. In everyday clinical practice, over 80% of all patients with AF have an indication for OAC, and vascular disease co-exists in ∼30% of them.5–7 With an estimated prevalence of AF of 1–2% and ∼20% of these requiring percutaneous cardiovascular interventions over time,8 ∼1–2 million AF patients in Europe who are …

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

We sought to determine the risk of late stent thrombosis (ST) during long-term follow-up beyond 3 years, searched for predictors, and assessed the impact of ST on overall mortality.Late ST was reported to occur at an annual rate of 0.6% up to 3 years after drug-eluting stent (DES) implantation.A total of 8,146 patients underwent percutaneous coronary intervention with a sirolimus-eluting stent (SES) (n=3,823) or paclitaxel-eluting stent (PES) (n=4,323) and were followed up to 4 years after stent implantation. Dual antiplatelet treatment was prescribed for 6 to 12 months.Definite ST occurred in 192 of 8,146 patients with an incidence density of 1.0/100 patient-years and a cumulative incidence of 3.3% at 4 years. The hazard of ST continued at a steady rate of 0.53% (95% confidence interval [CI]: 0.44 to 0.64) between 30 days and 4 years. Diabetes was an independent predictor of early ST (hazard ratio [HR]: 1.96; 95% CI: 1.18 to 3.28), and acute coronary syndrome (HR: 2.21; 95% CI: 1.39 to 3.51), younger age (HR: 0.97; 95% CI: 0.95 to 0.99), and use of PES (HR: 1.67; 95% CI: 1.08 to 2.56) were independent predictors of late ST. Rates of death and myocardial infarction at 4 years were 10.6% and 4.6%, respectively.Late ST occurs steadily at an annual rate of 0.4% to 0.6% for up to 4 years. Diabetes is an independent predictor of early ST, whereas acute coronary syndrome, younger age, and PES implantation are associated with late ST.

No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of recovered vasomotion of the scaffolded vessel.The ABSORB II trial is a prospective, randomised, active-controlled, single-blind, parallel two-group, multicentre clinical trial. We enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients (2:1) to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. At 3 year follow-up, the primary endpoint was superiority of the Absorb bioresorbable scaffold versus the Xience metallic stent in angiographic vasomotor reactivity after administration of intracoronary nitrate. The co-primary endpoint is the non-inferiority of angiographic late luminal loss. For the endpoint of vasomotion, the comparison was tested using a two-sided t test. For the endpoint of late luminal loss, non-inferiority was tested using a one-sided asymptotic test, against a non-inferiority margin of 0·14 mm. The trial is registered at ClinicalTrials.gov, number NCT01425281.Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the Absorb group (335 patients, 364 lesions) or the Xience group (166 patients, 182 lesions). The vasomotor reactivity at 3 years was not statistically different (Absorb group 0·047 mm [SD 0·109] vs Xience group 0·056 mm [0·117]; psuperiority=0·49), whereas the late luminal loss was larger in the Absorb group than in the Xience group (0·37 mm [0·45] vs 0·25 mm [0·25]; pnon-inferiority=0·78). This difference in luminal dimension was confirmed by intravascular ultrasound assessment of the minimum lumen area (4·32 mm2 [SD 1·48] vs 5·38 mm2 [1·51]; p<0·0001). The secondary endpoints of patient-oriented composite endpoint, Seattle Angina Questionnaire score, and exercise testing were not statistically different in both groups. However, a device-oriented composite endpoint was significantly different between the Absorb group and the Xience group (10% vs 5%, hazard ratio 2·17 [95% CI 1·01-4·70]; log-rank test p=0·0425), mainly driven by target vessel myocardial infarction (6% vs 1%; p=0·0108), including peri-procedural myocardial infarction (4% vs 1%; p=0·16).The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non-inferior late luminal loss for the Absorb bioresorbable scaffold with respect to the metallic stent, which was found to have significantly lower late luminal loss than the Absorb scaffold. A higher rate of device-oriented composite endpoint due to target vessel myocardial infarction, including peri-procedural myocardial infarction, was observed in the Absorb group. The patient-oriented composite endpoint, anginal status, and exercise testing, were not statistically different between both devices at 3 years. Future studies should investigate the clinical impact of accurate intravascular imaging in sizing the device and in optimising the scaffold implantation. The benefit and need for prolonged dual antiplatelet therapy after bioresorbable scaffold implantation could also become a topic for future clinical research.Abbott Vascular.

The aim was to study the prognostic value of plasma ceramides (Cer) as cardiovascular death (CV death) markers in three independent coronary artery disease (CAD) cohorts. Corogene study is a prospective Finnish cohort including stable CAD patients (n = 160). Multiple lipid biomarkers and C-reactive protein were measured in addition to plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1). Subsequently, the association between high-risk ceramides and CV mortality was investigated in the prospective Special Program University Medicine—Inflammation in Acute Coronary Syndromes (SPUM-ACS) cohort (n = 1637), conducted in four Swiss university hospitals. Finally, the results were validated in Bergen Coronary Angiography Cohort (BECAC), a prospective Norwegian cohort study of stable CAD patients. Ceramides, especially when used in ratios, were significantly associated with CV death in all studies, independent of other lipid markers and C-reactive protein. Adjusted odds ratios per standard deviation for the Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio were 4.49 (95% CI, 2.24–8.98), 1.64 (1.29–2.08), and 1.77 (1.41–2.23) in the Corogene, SPUM-ACS, and BECAC studies, respectively. The Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio improved the predictive value of the GRACE score (net reclassification improvement, NRI = 0.17 and ΔAUC = 0.09) in ACS and the predictive value of the Marschner score in stable CAD (NRI = 0.15 and ΔAUC = 0.02). Distinct plasma ceramide ratios are significant predictors of CV death both in patients with stable CAD and ACS, over and above currently used lipid markers. This may improve the identification of high-risk patients in need of more aggressive therapeutic interventions.

Background— Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. Methods and Results— The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020±283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2±2.4 mm 2 and evidence of vessel remodeling (index, 1.6±0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263±149 white blood cells per high-power field) and eosinophils (DES, 20±24 eosinophils per high-power field; sirolimus-eluting stents, 34±28; paclitaxel-eluting stents, 6±6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20±24) than in those from spontaneous acute myocardial infarction (7±10), early bare-metal stent ST (1±1), early DES ST (1±2), and late bare-metal stent ST (2±3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm 2 increase in ISA cross-sectional area. Conclusions— Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition.

Patients with a patent foramen ovale (PFO) and paradoxical embolism are at risk for recurrent thromboembolic events. This study investigated the long-term risk of recurrent thromboembolic events in patients with PFO and paradoxical embolism after percutaneous PFO closure.Since 1994, a total of 80 patients with PFO and at least 1 paradoxical embolic event (transient ischemic attack [TIA], cerebrovascular accident [CVA], peripheral embolism) have undergone percutaneous PFO closure with 5 different devices. There were 30 women and 50 men, with a mean age of 52+/-12 years. Sixty patients had only a PFO, whereas 20 patients had both a PFO and an atrial septal aneurysm. The implantation procedure was successful in 78 patients (98%). During 5 years of follow-up (mean, 1.6+/-1.4 years; range, 0.1 to 5.0 years), the actuarial annual risk to suffer a recurrent thromboembolic event was 2.5% for TIA, 0% for CVA, 0.9% for peripheral emboli, and 3.4% for the combined end point of TIA, CVA, or peripheral embolism. A postprocedural shunt was a predictor of recurrent paradoxical embolism (RR, 4.2; 95% CI, 1.1 to 17.8; P=0.03). The risk for recurrent thromboembolic events in patients with both atrial septal aneurysm and PFO was not significantly increased compared with patients with only PFO (RR, 1.0; 95% CI, 0.2 to 4.7; P=0.95).Percutaneous PFO closure appears to be a promising technique in the prevention of recurrent systemic thromboembolism in patients with a PFO after a first event. Prospective studies comparing percutaneous PFO closure with antithrombotic medications or surgery must define its therapeutic value.

The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified.Quantitative coronary angiography, intravascular ultrasound with analysis of radiofrequency backscattering, and as an optional assessment, optical coherence tomography (OCT) were performed at baseline and at a 6-month follow-up. Forty-five patients successfully received a single bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3 patients declined recatheterization, 42 patients had quantitative coronary angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT. Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in-segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen with the first generation of bioresorbable everolimus drug-eluting vascular scaffold at 6 months, the backscattering of the polymeric struts did not decrease over time, the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up that 96.8% of the struts were covered and that malapposition of at least 1 strut, initially observed in 12 scaffolds, was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by OCT between and on top of the polymeric struts equaled 1.25 mm(2), or 16.6% of the scaffold area.Modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of this new generation of drug-eluting scaffold to become comparable to those of current drug eluting stents.URL: http://clinicaltrials.gov. Unique identifier: NCT00856856.

The aim of this study was to provide a quantitative appraisal of the effects on clinical outcomes of radial access for coronary interventions in patients with coronary artery disease (CAD). Randomized trials investigating radial versus femoral access for percutaneous coronary interventions have provided conflicting evidence. No comprehensive quantitative appraisal of the risks and benefits of each approach is available across the whole spectrum of patients with stable or unstable CAD. The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for randomized trials comparing radial versus femoral access for coronary interventions. Data were pooled by meta-analysis using a fixed-effects or a random-effects model, as appropriate. Pre-specified subgroup analyses according to clinical presentation, in terms of stable CAD, non–ST-segment elevation acute coronary syndromes, or ST-segment elevation myocardial infarction were performed. Twenty-four studies enrolling 22,843 participants were included. Compared with femoral access, radial access was associated with a significantly lower risk for all-cause mortality (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.87; p = 0.001, number needed to treat to benefit [NNTB] = 160), major adverse cardiovascular events (OR: 0.84; 95% CI: 0.75 to 0.94; p = 0.002; NNTB = 99), major bleeding (OR: 0.53; 95% CI: 0.42 to 0.65; p < 0.001; NNTB = 103), and major vascular complications (OR: 0.23; 95% CI: 0.16 to 0.35; p < 0.001; NNTB = 117). The rates of myocardial infarction or stroke were similar in the 2 groups. Effects of radial access were consistent across the whole spectrum of patients with CAD for all appraised endpoints. Compared with femoral access, radial access reduces mortality and MACE and improves safety, with reductions in major bleeding and vascular complications across the whole spectrum of patients with CAD.

Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear.We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns.After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53).In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

The purpose of the present study was to assess coronary vasomotor response to exercise after sirolimus-eluting stent (SES) implantation.Sirolimus-eluting stents have been shown to markedly reduce the incidence of angiographic and clinical restenosis. However, long-term effects of sirolimus on endothelial function are unknown.Coronary vasomotion was evaluated with biplane quantitative coronary angiography at rest and during supine bicycle exercise in 25 patients with coronary artery disease. Eleven patients were treated with a bare-metal stent (BMS) (control group) and 14 patients underwent SES implantation (sirolimus group) for de novo coronary artery lesions. Both groups were studied 6 +/- 1 month after the intervention. Minimal luminal diameter; stent diameter; and proximal, distal, and reference vessel diameter were determined.The reference vessel showed exercise-induced vasodilation (+13 +/- 4%) in both groups. Vasomotion within the stented vessel segments was abolished. In controls, the adjacent segments proximal and distal to the stent showed exercise-induced vasodilation (+15 +/- 3% and +17 +/- 4%, respectively). In contrast, there was exercise-induced vasoconstriction of the proximal and distal vessel segments adjacent to SESs (-12 +/- 4% and -15 +/- 6%, respectively; p < 0.001 vs. corresponding segments of controls). Sublingual nitroglycerin was associated with maximal vasodilation of the proximal and distal vessel segments in both groups.Implantation of a BMS does not affect physiologic response to exercise proximal and distal to the stent. However, SESs are associated with exercise-induced paradoxic coronary vasoconstriction of the adjacent vessel segments, although vasodilatory response to nitroglycerin is maintained. These observations suggest (drug-induced) endothelial dysfunction as the underlying mechanism.

Early-generation drug-eluting stents releasing sirolimus (SES) or paclitaxel (PES) are associated with increased risk of very late stent thrombosis occurring >1 year after stent implantation. It is unknown whether the risk of very late stent thrombosis persists with newer-generation everolimus-eluting stents (EES).We assessed the risk of stent thrombosis in a cohort of 12 339 patients with unrestricted use of drug-eluting stents (3819 SES, 4308 PES, 4212 EES). Results are incidence rates per 100 person-years after inverse probability of treatment weighting to adjust for group differences. During follow-up of up to 4 years, the overall incidence rate of definite stent thrombosis was lower with EES (1.4 per 100 person-years) compared with SES (2.9; hazard ratio, 0.41; 95% confidence interval, 0.27-0.62; P<0.0001) and PES (4.4; hazard ratio, 0.33; 95% confidence interval, 0.23-0.48; P<0.0001). The incidence rate per 100 person-years of early (0-30 days), late (31 days-1 year), and very late stent thrombosis amounted to 0.6, 0.1, and 0.6 among EES-treated patients; 1.0, 0.3, and 1.6 among SES-treated patients; and 1.3, 0.7, and 2.4 among PES-treated patients. Differences in favor of EES were most pronounced beyond 1 year, with a hazard ratio of 0.33 (EES versus SES; P=0.006) and 0.34 (EES versus PES; P<0.0001). There was a lower risk of cardiac death or myocardial with EES compared with PES (hazard ratio, 0.65; 95% confidence interval, 0.56-0.75; P<0.0001), which was directly related to the lower risk of stent thrombosis-associated events (EES versus PES: hazard ratio, 0.36; 95% confidence interval, 0.23-0.57).Current treatment with EES is associated with a lower risk of very late stent thrombosis compared with early-generation drug-eluting stents.

Background The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. Methods We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. Findings 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios [RR] 0·81, 95% CI 0·66–1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35–1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06–0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51–1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive (pinteraction=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41–1·80) during the first year and 0·17 (0·04–0·78) during subsequent years (pinteraction=0·049). Interpretation Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. Funding Biosensors Europe SA, Switzerland.

Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown.We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts. In the Cleveland Cohort, comprised of sequential subjects (n = 530) presenting to the Emergency Department (ED) with chest pain of suspected cardiac origin, an elevated plasma TMAO level at presentation was independently associated with risk of major adverse cardiac events (MACE, including myocardial infarction, stroke, need for revascularization, or death) over the ensuing 30-day (4th quartile (Q4) adjusted odds ratio (OR) 6.30, 95% confidence interval (CI), 1.89-21.0, P < 0.01) and 6-month (Q4 adjusted OR 5.65, 95%CI, 1.91-16.7; P < 0.01) intervals. TMAO levels were also a significant predictor of the long term (7-year) mortality (Q4 adjusted HR 1.81, 95%CI, 1.04-3.15; P < 0.05). Interestingly, TMAO level at initial presentation predicted risk of incident MACE over the near-term (30 days and 6 months) even among subjects who were initially negative for troponin T (< 0.1 ng/mL) (30 days, Q4 adjusted OR 5.83, 95%CI, 1.79-19.03; P < 0.01). The prognostic value of TMAO was also assessed in an independent multicentre Swiss Cohort of ACS patients (n = 1683) who underwent coronary angiography. Trimethylamine N-oxide again predicted enhanced MACE risk (1-year) (adjusted Q4 hazard ratios: 1.57, 95% CI, 1.03-2.41; P <0.05).Plasma TMAO levels among patients presenting with chest pain predict both near- and long-term risks of incident cardiovascular events, and may thus provide clinical utility in risk stratification among subjects presenting with suspected ACS.

To determine the ranges of pre-test probability (PTP) of coronary artery disease (CAD) in which stress electrocardiogram (ECG), stress echocardiography, coronary computed tomography angiography (CCTA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance (CMR) can reclassify patients into a post-test probability that defines (>85%) or excludes (<15%) anatomically (defined by visual evaluation of invasive coronary angiography [ICA]) and functionally (defined by a fractional flow reserve [FFR] ≤0.8) significant CAD.A broad search in electronic databases until August 2017 was performed. Studies on the aforementioned techniques in >100 patients with stable CAD that utilized either ICA or ICA with FFR measurement as reference, were included. Study-level data was pooled using a hierarchical bivariate random-effects model and likelihood ratios were obtained for each technique. The PTP ranges for each technique to rule-in or rule-out significant CAD were defined. A total of 28 664 patients from 132 studies that used ICA as reference and 4131 from 23 studies using FFR, were analysed. Stress ECG can rule-in and rule-out anatomically significant CAD only when PTP is ≥80% (76-83) and ≤19% (15-25), respectively. Coronary computed tomography angiography is able to rule-in anatomic CAD at a PTP ≥58% (45-70) and rule-out at a PTP ≤80% (65-94). The corresponding PTP values for functionally significant CAD were ≥75% (67-83) and ≤57% (40-72) for CCTA, and ≥71% (59-81) and ≤27 (24-31) for ICA, demonstrating poorer performance of anatomic imaging against FFR. In contrast, functional imaging techniques (PET, stress CMR, and SPECT) are able to rule-in functionally significant CAD when PTP is ≥46-59% and rule-out when PTP is ≤34-57%.The various diagnostic modalities have different optimal performance ranges for the detection of anatomically and functionally significant CAD. Stress ECG appears to have very limited diagnostic power. The selection of a diagnostic technique for any given patient to rule-in or rule-out CAD should be based on the optimal PTP range for each test and on the assumed reference standard.

The purpose of this study was to compare the efficacy of medical treatment with percutaneous closure of patent foramen ovale (PFO). Patients with cryptogenic stroke and PFO are at risk for recurrent cerebrovascular events. We compared the risk of recurrence in 308 patients with cryptogenic stroke and PFO, who were treated either medically (158 patients) or underwent percutaneous PFO closure (150 patients) between 1994 and 2000. Patients undergoing percutaneous PFO closure had a larger right-to-left shunt (p < 0.001; 95% confidence interval [CI] 1.38 to 3.07) and were more likely to have suffered more than one cerebrovascular event (p = 0.03; 95% CI 1.04 to 2.71). At four years of follow-up, percutaneous PFO closure resulted in a non-significant trend toward risk reduction of death, stroke, or transient ischemic attack (TIA) combined (8.5% vs. 24.3%; p = 0.05; 95% CI 0.23 to 1.01), and of recurrent stroke or TIA (7.8% vs. 22.2%; p = 0.08; 95% CI 0.23 to 1.11) compared with medical treatment. Patients with more than one cerebrovascular event at baseline and those with complete occlusion of PFO were at lower risk for recurrent stroke or TIA after percutaneous PFO closure compared with medically treated patients (7.3% vs. 33.2%; p = 0.01; 95% CI 0.08 to 0.81, and 6.5% vs. 22.2%; p = 0.04; 95% CI 0.14 to 0.99, respectively). Percutaneous PFO closure appears at least as effective as medical treatment for prevention of recurrent cerebrovascular events in cryptogenic stroke patients with PFO. It might be more effective than medical treatment in patients with complete closure and more than one cerebrovascular event.

Our purpose was to make a synthesis of the available evidence on the relative efficacy and safety of 2 drug-eluting stents (DES)—sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES)—in patients with coronary artery disease. It is not known whether there are differences in late outcomes between the 2 most commonly used DES: SES and PES. Sixteen randomized trials of SES versus PES with a total number of 8,695 patients were included in this meta-analysis. A full set of individual outcome data from 5,562 patients was also available. Mean follow-up period ranged from 9 to 37 months. The primary efficacy end point was the need for reintervention (target lesion revascularization). The primary safety end point was stent thrombosis. Secondary end points were death and recurrent myocardial infarction (MI). No significant heterogeneity was found across trials. Compared with PES, SES significantly reduced the risk of reintervention (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 to 0.87, p < 0.001) and stent thrombosis (HR 0.66; 95% CI 0.46 to 0.94, p = 0.02) without significantly impacting on the risk of death (HR 0.92; 95% CI 0.74 to 1.13, p = 0.43) or MI (HR 0.84; 95% CI 0.69 to 1.03, p = 0.10). Sirolimus-eluting stents are superior to PES in terms of a significant reduction of the risk of reintervention and stent thrombosis. The risk of death was not significantly different between the 2 DES, but there was a trend toward a higher risk of MI with PES, especially after the first year from the procedure.

Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients.The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.78-0.99], P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes [HR 0.81 (95% CI 0.68-0.98), P = 0.028]. Surgical aortic valve replacement was associated with a lower risk of major vascular complications [HR 1.99 (95% CI 1.34-2.93), P = 0.001] and permanent pacemaker implantations [HR 2.27 (95% CI 1.47-3.64), P < 0.001] compared to TAVI.Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.

Tricuspid regurgitation is associated with increased rates of heart failure (HF) and mortality. Transcatheter tricuspid valve interventions (TTVI) are promising, but the clinical benefit is unknown. The purpose of this study was to investigate the potential benefit of TTVI over medical therapy in a propensity score matched population. The TriValve (Transcatheter Tricuspid Valve Therapies) registry collected 472 patients from 22 European and North American centers who underwent TTVI from 2016 to 2018. A control cohort formed by 2 large retrospective registries enrolling medically managed patients with ≥ moderate tricuspid regurgitation in Europe and North America (n = 1,179) were propensity score 1:1 matched (distance ± 0.2 SD) using age, EuroSCORE II, and systolic pulmonary artery pressure. Survival was tested with Cox regression analysis. Primary endpoint was 1-year mortality or HF rehospitalization or the composite. After matching, 268 adequately matched pairs of patients were identified. Compared with control subjects, TTVI patients had lower 1-year mortality (23 ± 3% vs. 36 ± 3%; p = 0.001), rehospitalization (26 ± 3% vs. 47 ± 3%; p < 0.0001), and composite endpoint (32 ± 4% vs. 49 ± 3%; p = 0.0003). TTVI was associated with greater survival and freedom from HF rehospitalization (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.46 to 0.79; p = 0.003 unadjusted), which remained significant after adjusting for sex, New York Heart Association functional class, right ventricular dysfunction, and atrial fibrillation (HR: 0.39; 95% CI: 0.26 to 0.59; p < 0.0001) and after further adjustment for mitral regurgitation and pacemaker/defibrillator (HR: 0.35; 95% CI: 0.23 to 0.54; p < 0.0001). In this propensity-matched case-control study, TTVI is associated with greater survival and reduced HF rehospitalization compared with medical therapy alone. Randomized trials should be performed to confirm these results.

Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery disease, the risk of a composite of death from any cause or severe renal failure leading to renal-replacement therapy at 30 days was found to be lower with percutaneous coronary intervention (PCI) of the culprit lesion only than with immediate multivessel PCI. We evaluated clinical outcomes at 1 year.

This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. The LEADERS trial is the first randomized study to evaluate biodegradable polymer–based drug-eluting stents (DES) against durable polymer DES. The LEADERS trial was a 10-center, assessor-blind, noninferiority, “all-comers” trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority = 0.069). The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death, any MI, and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI: 0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19 [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a significant reduction in ST-associated clinical events (primary endpoint) over the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to 0.71], p = 0.005). The safety benefit of the biodegradable polymer BES, compared with the durable polymer SES, was related to a significant reduction in very late ST (>1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220)

The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication.The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies.Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient and, where appropriate and/or necessary, the patient's caregiver.Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations.It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

This study evaluated Multidimensional Geriatric Assessment (MGA) as predictor of mortality and major adverse cardiovascular and cerebral events (MACCE) after transcatheter aortic valve implantation (TAVI). Currently used global risk scores do not reliably estimate mortality and MACCE in these patients. This prospective cohort comprised 100 consecutive patients ≥70 years undergoing TAVI. Global risk scores (Society of Thoracic Surgeons [STS] score, EuroSCORE) and MGA-based scores (cognition, nutrition, mobility, activities of daily living [ADL], and frailty index) were evaluated as predictors of all-cause mortality and MACCE 30 days and 1 year after TAVI in regression models. In univariable analyses, all predictors were significantly associated with mortality and MACCE at 30 days and 1 year, except for the EuroSCORE at 30 days and instrumental ADL at 30 days and 1 year. Associations of cognitive impairment (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.07 to 8.31), malnutrition (OR: 6.72, 95% CI: 2.04 to 22.17), mobility impairment (OR: 6.65, 95% CI: 2.15 to 20.52), limitations in basic ADL (OR: 3.63, 95% CI: 1.29 to 10.23), and frailty index (OR: 3.68, 95% CI: 1.21 to 11.19) with 1-year mortality were similar compared with STS score (OR: 5.47, 95% CI: 1.48 to 20.22) and EuroSCORE (OR: 4.02, 95% CI: 0.86 to 18.70). Similar results were found for 30-day mortality and MACCE. Bivariable analyses, including STS score or EuroSCORE suggested independent associations of MGA-based scores (e.g., OR of frailty index: 3.29, 95% CI: 1.06 to 10.15, for 1-year mortality in a model including EuroSCORE). This study provides evidence that risk prediction can be improved by adding MGA-based information to global risk scores. Larger studies are needed for the development and validation of improved risk prediction models.

Background— The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified. Methods and Results— Quantitative coronary angiography, intravascular ultrasound with analysis of radiofrequency backscattering, and as an optional assessment, optical coherence tomography (OCT) were performed at baseline and at a 6-month follow-up. Forty-five patients successfully received a single bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3 patients declined recatheterization, 42 patients had quantitative coronary angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT. Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in-segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen with the first generation of bioresorbable everolimus drug-eluting vascular scaffold at 6 months, the backscattering of the polymeric struts did not decrease over time, the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up that 96.8% of the struts were covered and that malapposition of at least 1 strut, initially observed in 12 scaffolds, was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by OCT between and on top of the polymeric struts equaled 1.25 mm 2 , or 16.6% of the scaffold area. Conclusion— Modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of this new generation of drug-eluting scaffold to become comparable to those of current drug eluting stents. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00856856.

To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus.Collaborative network meta-analysis.Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data.Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point.35 trials in 3852 people with diabetes and 10,947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes.In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).To compare stents eluting biolimus from a biodegradable polymer with bare-metal stents in primary PCI.A prospective, randomized, single-blinded, controlled trial of 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19, 2009, and January 25, 2011. Clinical follow-up was performed at 1 and 12 months.Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582).Primary end point was the rate of major adverse cardiac events, a composite of cardiac death, target vessel-related reinfarction, and ischemia-driven target-lesion revascularization at 1 year.Major adverse cardiac events at 1 year occurred in 24 patients (4.3%) receiving biolimus-eluting stents with biodegradable polymer and 49 patients (8.7%) receiving bare-metal stents (hazard ratio [HR], 0.49; 95% CI, 0.30-0.80; P = .004). The difference was driven by a lower risk of target vessel-related reinfarction (3 [0.5%] vs 15 [2.7%]; HR, 0.20; 95% CI, 0.06-0.69; P = .01) and ischemia-driven target-lesion revascularization (9 [1.6%] vs 32 [5.7%]; HR, 0.28; 95% CI, 0.13-0.59; P < .001) in patients receiving biolimus-eluting stents compared with those receiving bare-metal stents. Rates of cardiac death were not significantly different (16 [2.9%] vs 20 [3.5%], P = .53). Definite stent thrombosis occurred in 5 patients (0.9%) treated with biolimus-eluting stents and 12 patients (2.1%; HR, 0.42; 95% CI, 0.15-1.19; P = .10) treated with bare-metal stents.Compared with a bare-metal stent, the use of biolimus-eluting stents with a biodegradable polymer resulted in a lower rate of the composite of major adverse cardiac events at 1 year among patients with STEMI undergoing primary PCI.clinicaltrials.gov Identifier: NCT00962416.

The prognostic relevance of the collateral circulation is still controversial. The goal of this study was to assess the impact on survival of quantitatively obtained, recruitable coronary collateral flow in patients with stable coronary artery disease during 10 years of follow-up.Eight-hundred forty-five individuals (age, 62+/-11 years), 106 patients without coronary artery disease and 739 patients with chronic stable coronary artery disease, underwent a total of 1053 quantitative, coronary pressure-derived collateral measurements between March 1996 and April 2006. All patients were prospectively included in a collateral flow index (CFI) database containing information on recruitable collateral flow parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as follows: CFI = (P(occl) - CVP)/(P(ao) - CVP) where P(occl) is mean coronary occlusive pressure, P(ao) is mean aortic pressure, and CVP is central venous pressure. Patients were divided into groups with poorly developed (CFI < 0.25) or well-grown collateral vessels (CFI > or = 0.25). Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 10-year survival rates in relation to all-cause deaths and cardiac deaths were 71% and 88%, respectively, in patients with low CFI and 89% and 97% in the group with high CFI (P=0.0395, P=0.0109). Through the use of Cox proportional hazards analysis, the following variables independently predicted elevated cardiac mortality: age, low CFI (as a continuous variable), and current smoking.A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease. Depending on the exact amount of collateral flow recruitable during a brief coronary occlusion, long-term cardiac mortality is reduced to one fourth compared with the situation without collateral supply.

Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction.This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%.In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

There are limited data on coronary obstruction following transcatheter valve-in-valve (ViV) implantation inside failed aortic bioprostheses. The objectives of this study were to determine the incidence, predictors, and clinical outcomes of coronary obstruction in transcatheter ViV procedures. A total of 1612 aortic procedures from the Valve-in-Valve International Data (VIVID) Registry were evaluated. Data were subject to centralized blinded corelab computed tomography (CT) analysis in a subset of patients. The virtual transcatheter valve to coronary ostium distance (VTC) was determined. A total of 37 patients (2.3%) had clinically evident coronary obstruction. Baseline clinical characteristics in the coronary obstruction patients were similar to controls. Coronary obstruction was more common in stented bioprostheses with externally mounted leaflets or stentless bioprostheses than in stented with internally mounted leaflets bioprostheses (6.1% vs. 3.7% vs. 0.8%, respectively; P < 0.001). CT measurements were obtained in 20 (54%) and 90 (5.4%) of patients with and without coronary obstruction, respectively. VTC distance was shorter in coronary obstruction patients in relation to controls (3.24 ± 2.22 vs. 6.30 ± 2.34, respectively; P < 0.001). Using multivariable analysis, the use of a stentless or stented bioprosthesis with externally mounted leaflets [odds ratio (OR): 7.67; 95% confidence interval (CI): 3.14–18.7; P < 0.001] associated with coronary obstruction for the global population. In a second model with CT data, a shorter VTC distance predicted this complication (OR: 0.22 per 1 mm increase; 95% CI: 0.09–0.51; P < 0.001), with an optimal cut-off level of 4 mm (area under the curve: 0.943; P < 0.001). Coronary obstruction was associated with a high 30-day mortality (52.9% vs. 3.9% in the controls, respectively; P < 0.001). Coronary obstruction following aortic ViV procedures is a life-threatening complication that occurred more frequently in patients with prior stentless or stented bioprostheses with externally mounted leaflets and in those with a short VTC.

The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear.One month after they had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.Among the 4434 patients in the per-protocol population, net adverse clinical events occurred in 165 patients (7.5%) in the abbreviated-therapy group and in 172 (7.7%) in the standard-therapy group (difference, -0.23 percentage points; 95% confidence interval [CI], -1.80 to 1.33; P<0.001 for noninferiority). A total of 133 patients (6.1%) in the abbreviated-therapy group and 132 patients (5.9%) in the standard-therapy group had a major adverse cardiac or cerebral event (difference, 0.11 percentage points; 95% CI, -1.29 to 1.51; P = 0.001 for noninferiority). Among the 4579 patients in the intention-to-treat population, major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group (difference, -2.82 percentage points; 95% CI, -4.40 to -1.24; P<0.001 for superiority).One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; abbreviated therapy also resulted in a lower incidence of major or clinically relevant nonmajor bleeding. (Funded by Terumo; MASTER DAPT ClinicalTrials.gov number, NCT03023020.).

In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the spectrum of risk and in important subgroups.Trials comparing TAVI vs. SAVR were identified through Medline, Embase, and Cochrane databases. The primary outcome was death from any cause at 2 years. We performed random-effects meta-analyses to combine the available evidence and to evaluate the effect in different subgroups. This systematic review and meta-analysis is registered with PROSPERO (CRD42016037273). We identified four eligible trials including 3806 participants, who were randomly assigned to undergo TAVI (n = 1898) or SAVR (n = 1908). For the primary outcome of death from any cause, TAVI when compared with SAVR was associated with a significant 13% relative risk reduction [hazard ratio (95% CI): 0.87 (0.76-0.99); P = 0.038] with homogeneity across all trials irrespective of TAVI device (Pinteraction = 0.306) and baseline risk (Pinteraction = 0.610). In subgroup analyses, TAVI showed a robust survival benefit over SAVR for patients undergoing transfemoral access [0.80 (0.69-0.93); P = 0.004], but not transthoracic access [1.17 (0.88-1.56); P = 0.293] (Pinteraction = 0.024) and in female [0.68 (0.50-0.91); P = 0.010], but not male patients [0.99 (0.77-1.28); P = 0.952] (Pinteraction = 0.050). Secondary outcomes of kidney injury, new-onset atrial fibrillation, and major bleeding favoured TAVI, while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation favoured SAVR.Compared with SAVR, TAVI is associated with a significant survival benefit throughout 2 years of follow-up. Importantly, this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients, and is particularly pronounced among patients undergoing transfemoral TAVI and in females.

Limited information exists describing the results of transcatheter aortic valve (TAV) replacement in patients with bicuspid aortic valve (BAV) disease (TAV-in-BAV). This study sought to evaluate clinical outcomes of a large cohort of patients undergoing TAV-in-BAV. We retrospectively collected baseline characteristics, procedural data, and clinical follow-up findings from 12 centers in Europe and Canada that had performed TAV-in-BAV. A total of 139 patients underwent TAV-in-BAV with the balloon-expandable transcatheter heart valve (THV) (n = 48) or self-expandable THV (n = 91) systems. Patient mean age and Society of Thoracic Surgeons predicted risk of mortality scores were 78.0 ± 8.9 years and 4.9 ± 3.4%, respectively. BAV stenosis occurred in 65.5%, regurgitation in 0.7%, and mixed disease in 33.8% of patients. Incidence of type 0 BAV was 26.7%; type 1 BAV was 68.3%; and type 2 BAV was 5.0%. Multislice computed tomography (MSCT)-based TAV sizing was used in 63.5% of patients (77.1% balloon-expandable THV vs. 56.0% self-expandable THV, p = 0.02). Procedural mortality was 3.6%, with TAV embolization in 2.2% and conversion to surgery in 2.2%. The mean aortic gradient decreased from 48.7 ± 16.5 mm Hg to 11.4 ± 9.9 mm Hg (p < 0.0001). Post-implantation aortic regurgitation (AR) grade ≥2 occurred in 28.4% (19.6% balloon-expandable THV vs. 32.2% self-expandable THV, p = 0.11) but was prevalent in only 17.4% when MSCT-based TAV sizing was performed (16.7% balloon-expandable THV vs. 17.6% self-expandable THV, p = 0.99). MSCT sizing was associated with reduced AR on multivariate analysis (odds ratio [OR]: 0.19, 95% confidence intervals [CI]: 0.08 to 0.45; p < 0.0001). Thirty-day device safety, success, and efficacy were noted in 79.1%, 89.9%, and 84.9% of patients, respectively. One-year mortality was 17.5%. Major vascular complications were associated with increased 1-year mortality (OR: 5.66, 95% CI: 1.21 to 26.43; p = 0.03). TAV-in-BAV is feasible with encouraging short- and intermediate-term clinical outcomes. Importantly, a high incidence of post-implantation AR is observed, which appears to be mitigated by MSCT-based TAV sizing. Given the suboptimal echocardiographic results, further study is required to evaluate long-term efficacy.

Percutaneous coronary intervention (PCI) with drug-eluting stents is the standard of care for treatment of native coronary artery stenoses, but optimum treatment strategies for bare metal stent and drug-eluting stent in-stent restenosis (ISR) have not been established. We aimed to compare and rank percutaneous treatment strategies for ISR.We did a network meta-analysis to synthesise both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomised controlled trials published up to Oct 31, 2014, of different PCI strategies for treatment of any type of coronary ISR. The primary outcome was percent diameter stenosis at angiographic follow-up. This study is registered with PROSPERO, number CRD42014014191.We deemed 27 trials eligible, including 5923 patients, with follow-up ranging from 6 months to 60 months after the index intervention. Angiographic follow-up was available for 4975 (84%) of 5923 patients 6-12 months after the intervention. PCI with everolimus-eluting stents was the most effective treatment for percent diameter stenosis, with a difference of -9·0% (95% CI -15·8 to -2·2) versus drug-coated balloons (DCB), -9·4% (-17·4 to -1·4) versus sirolimus-eluting stents, -10·2% (-18·4 to -2·0) versus paclitaxel-eluting stents, -19·2% (-28·2 to -10·4) versus vascular brachytherapy, -23·4% (-36·2 to -10·8) versus bare metal stents, -24·2% (-32·2 to -16·4) versus balloon angioplasty, and -31·8% (-44·8 to -18·6) versus rotablation. DCB were ranked as the second most effective treatment, but without significant differences from sirolimus-eluting (-0·2% [95% CI -6·2 to 5·6]) or paclitaxel-eluting (-1·2% [-6·4 to 4·2]) stents.These findings suggest that two strategies should be considered for treatment of any type of coronary ISR: PCI with everolimus-eluting stents because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer.None.

The pathomechanisms underlying very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography, we investigated potential causes of this adverse event.Between August 2010 and December 2014, 64 patients were investigated at the time point of VLST as part of an international optical coherence tomography registry. Optical coherence tomography pullbacks were performed after restoration of flow and analyzed at 0.4 mm. A total of 38 early- and 20 newer-generation drug-eluting stents were suitable for analysis. VLST occurred at a median of 4.7 years (interquartile range, 3.1-7.5 years). An underlying putative cause by optical coherence tomography was identified in 98% of cases. The most frequent findings were strut malapposition (34.5%), neoatherosclerosis (27.6%), uncovered struts (12.1%), and stent underexpansion (6.9%). Uncovered and malapposed struts were more frequent in thrombosed compared with nonthrombosed regions (ratio of percentages, 8.26; 95% confidence interval, 6.82-10.04; P<0.001 and 13.03; 95% confidence interval, 10.13-16.93; P<0.001, respectively). The maximal length of malapposed or uncovered struts (3.40 mm; 95% confidence interval, 2.55-4.25; versus 1.29 mm; 95% confidence interval, 0.81-1.77; P<0.001), but not the maximal or average axial malapposition distance, was greater in thrombosed compared with nonthrombosed segments. The associations of both uncovered and malapposed struts with thrombus were consistent among early- and newer-generation drug-eluting stents.The leading associated findings in VLST patients in descending order were malapposition, neoatherosclerosis, uncovered struts, and stent underexpansion without differences between patients treated with early- and new-generation drug-eluting stents. The longitudinal extension of malapposed and uncovered stent was the most important correlate of thrombus formation in VLST.

Acute coronary syndromes Bare-metal stents Coronary artery bypass grafting Coronary artery disease Drug-eluting stents EuroSCORE Guidelines Heart Team Myocardial infarction Myocardial ischaemia Myocardial revascularization Medical therapy Percutaneous coronary intervention Recommendation Revascularisation Risk stratification Stents Stable angina Stable coronary artery disease ST-segment elevation myocardial infarction SYNTAX score

The interest in rotational atherectomy (RA) has increased over the past decade as a consequence of more complex and calcified coronary stenoses being attempted with percutaneous coronary interventions. Yet adoption of RA is hampered by several factors: amongst others, by the lack of a standardised protocol. This European expert consensus document stems from the awareness of the large heterogeneity in the protocols adopted to perform rotational atherectomy. The objective of the present document is to provide some points of consensus among highly experienced operators on the most controversial steps of RA in an attempt to build the basis of a standardised and universally accepted protocol.

A large, prospective international registry was developed to evaluate the initial clinical applications of transcatheter tricuspid valve intervention (TTVI) with different devices. TTVI for native tricuspid valve dysfunction has been emerging during the last few years as an alternative therapeutic option to serve a large high-risk population of patients with severe symptomatic tricuspid regurgitation (TR). The TriValve Registry included 312 high-risk patients with severe TR (76.4 ± 8.5 years of age; 57% female; EuroSCORE II 9 ± 8%) at 18 centers. Interventions included repair at the level of the leaflets (MitraClip, Abbott Vascular, Santa Clara, California; PASCAL Edwards Lifesciences, Irvine, California), annulus (Cardioband, Edwards Lifesciences; TriCinch, 4tech, Galway, Ireland; Trialign, Mitraling, Tewksbury, Massachusetts), or coaptation (FORMA, Edwards Lifesciences) and replacement (Caval Implants, NaviGate, NaviGate Cardiac Structures, Lake Forest, California). Clinical outcomes were prospectively determined during mid-term follow-up. A total of 108 patients (34.6%) had prior left heart valve intervention (84 surgical and 24 transcatheter, respectively). TR etiology was functional in 93%, and mean annular diameter was 46.9 ± 9 mm. In 75% of patients the regurgitant jet was central (vena contracta 1.1 ± 0.5; effective regurgitant orifice area 0.78 ± 0.6 cm2). Pre-procedural systolic pulmonary artery pressure was 41 ± 14.8 mm Hg. Implanted devices included: MitraClip in 210 cases, Trialign in 18 cases, TriCinch first generation in 14 cases, caval valve implantation in 30 cases, FORMA in 24 cases, Cardioband in 13 cases, NaviGate in 6 cases, and PASCAL in 1. In 64% of the cases, TTVI was performed as a stand-alone procedure. Procedural success (defined as the device successfully implanted and residual TR ≤2+) was 72.8%. Greater coaptation depth (odds ratio: 24.1; p = 0.002) was an independent predictor of reduced device success. Thirty-day mortality was 3.6% and was significantly lower among patients with procedural success (1.9% vs. 6.9%; p = 0.04); Actuarial survival at 1.5 years was 82.8 ± 4% and was significantly higher among patients who had procedural success achieved. TTVI is feasible with different technologies, has a reasonable overall procedural success rate, and is associated with low mortality and significant clinical improvement. Mid-term survival is favorable in this high-risk population. Greater coaptation depth is associated with reduced procedural success, which is an independent predictor of mortality.

Despite major improvements in transcatheter aortic valve replacement (TAVR) periprocedural complications in recent years, the occurrence of conduction disturbances has not decreased over time and remains the most frequent complication of the procedure. Additionally, there has been an important lack of consensus on the management of these complications, which has indeed translated into a high degree of uncertainty regarding the most appropriate treatment of a large proportion of such patients along with major differences between centers and studies in pacemaker rates post-TAVR. There is therefore an urgent need for a uniform strategy regarding the management of conduction disturbances after TAVR. The present expert consensus scientific panel document has been formulated by a multidisciplinary group of interventional cardiologists, electrophysiologists, and cardiac surgeons as an initial attempt to provide a guide for the management of conduction disturbances after TAVR based on the best available data and group expertise.

The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations. This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI. The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding. Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21). Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938)

Incomplete endothelialization has been found to be associated with late stent thrombosis, a rare but devastating phenomenon, more frequent after drug-eluting stent implantation. Optical coherence tomography (OCT) has 10 times greater resolution than intravascular ultrasound and thus appears to be a valuable modality for the assessment of stent strut coverage. The LEADERS trial was a multi-centre, randomized comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer. This study sought to evaluate tissue coverage and apposition of stents using OCT in a group of patients from the randomized LEADERS trial.Fifty-six consecutive patients underwent OCT during angiographic follow-up at 9 months. OCT images were acquired using a non-occlusive technique at a pullback speed of 3 mm/s. Data were analysed using a Bayesian hierarchical random-effects model, which accounted for the correlation of lesion characteristics within patients and implicitly assigned analytical weights to each lesion depending on the number of struts observed per lesion. Primary outcome was the difference in percentage of uncovered struts between BESs and SESs. Twenty patients were included in the analysis in the BES group (29 lesions with 4592 struts) and 26 patients in the SES group (35 lesions with 6476 struts). A total of 83 struts were uncovered in the BES group and 407 out of 6476 struts were uncovered in the SES group [weighted difference -1.4%, 95% confidence interval (CI) -3.7 to 0.0, P = 0.04]. Results were similar after adjustment for pre-procedure lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap. There were three lesions in the BES group and 15 lesions in the SES group that had > or =5% of all struts uncovered (difference -33.1%, 95% CI -61.7 to -10.3, P < 0.01).Strut coverage at an average follow-up of 9 months appears to be more complete in patients allocated to BESs when compared with SESs. The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determined.