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Aims Recent studies have suggested that corticosteroid injections into the knee may harm the joint resulting in cartilage loss and possibly accelerating the progression of osteoarthritis (OA). The aim of this study was to assess whether patients with, or at risk of developing, symptomatic osteoarthritis of the knee who receive intra-articular corticosteroid injections have an increased risk of requiring arthroplasty. Methods We used data from the Osteoarthritis Initiative (OAI), a multicentre observational cohort study that followed 4,796 patients with, or at risk of developing, osteoarthritis of the knee on an annual basis with follow-up available up to nine years. Increased risk for symptomatic OA was defined as frequent knee symptoms (pain, aching, or stiffness) without radiological evidence of OA and two or more risk factors, while OA was defined by the presence of both femoral osteophytes and frequent symptoms in one or both knees. Missing data were imputed with multiple imputations using chained equations. Time-dependent propensity score matching was performed to match patients at the time of receving their first injection with controls. The effect of corticosteroid injections on the rate of subsequent (total and partial) knee arthroplasty was estimated using Cox proportional-hazards survival analyses. Results After removing patients lost to follow-up, 3,822 patients remained in the study. A total of 249 (31.3%) of the 796 patients who received corticosteroid injections, and 152 (5.0%) of the 3,026 who did not, had knee arthroplasty. In the matched cohort, Cox proportional-hazards regression resulted in a hazard ratio of 1.57 (95% confidence interval (CI) 1.37 to 1.81; p < 0.001) and each injection increased the absolute risk of arthroplasty by 9.4% at nine years’ follow-up compared with those who did not receive injections. Conclusion Corticosteroid injections seem to be associated with an increased risk of knee arthroplasty in patients with, or at risk of developing, symptomatic OA of the knee. These findings suggest that a conservative approach regarding the treatment of these patients with corticosteroid injections should be recommended. Cite this article: Bone Joint J 2020;102-B(5):586–592.

Contains fulltext : 248579.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To determine the cost-effectiveness of auditory brainstem response prior to MRI (ABR-MRI) compared to standalone MRI to diagnose vestibular schwannoma. DESIGN: A state transition model was developed to simulate costs and effects (quality-adjusted life years [QALY]) for both diagnostic strategies for patients suspected of a vestibular schwannoma. Model input was derived from literature, hospital databases and expert opinions. Scenario and sensitivity analyses addressed model uncertainty. RESULTS: Over a lifetime horizon, ABR-MRI resulted in a limited cost-saving of €68 or €98 per patient (dependent on MRI sequence) and a health loss of 0.005 QALYs over standalone MRI. ABR-MRI, however, did miss patients with other important pathology (2% of the population) that would have been detected when using standalone MRI. In total, €14 203 or €19 550 could be saved per lost QALY if ABR-MRI was used instead of standalone MRI. The results were sensitive to the detection rate of vestibular schwannoma and health-related quality of life of missed patients. CONCLUSION: The cost-saving with ABR-MRI does not seem to outweigh the number of missed patients with VS and other important pathologies that would have been detected when using standalone MRI.

Objectives: To determine the cost-effectiveness of auditory brainstem response prior to MRI (ABR-MRI) compared to standalone MRI to diagnose vestibular schwannoma. Design: A state transition decision-analytic model was developed to simulate costs and effects (quality-adjusted life years) for both treatment strategies for patients suspected of a vestibular schwannoma. Model input was derived from literature, hospital databases, and expert opinions. Scenario and sensitivity analyses addressed model uncertainty. Results: Over a lifetime horizon, ABR-MRI resulted in a limited cost-saving of \euro68 or \euro98 per patient (dependent on MRI sequence) and a health loss of 0.005 QALYs over standalone MRI. ABR-MRI, however, did miss patients with other important pathology (2% of the population) that would have been detected when using standalone MRI. Calculating the incremental cost-effectiveness ratio resulted in \euro14,203 or \euro19,550 saved per lost QALY if ABR-MRI was used instead of standalone MRI. The results were sensitive to the detection rate of vestibular schwannoma and health-related quality of life of missed patients. Conclusion: The cost-saving with ABR-MRI does not seem to outweigh the number of missed patients with VS and other important pathologies that would have been detected when using standalone MRI.

Objective. To assess the cost-effectiveness of sentinel lymph node mapping compared to risk factor assessment and routine full lymph node dissection for the assessment of lymph nodes in patients with low-and intermediate-risk endometrioid endometrial cancer.Methods. A decision-analytic model was designed to compare three lymph node assessment strategies in terms of costs and effects: 1) sentinel lymph node mapping; 2) post-operative risk factor assessment (adjuvant therapy based on clinical and histological risk factors); 3) full lymph node dissection. Input data were derived from systematic literature searches and expert opinion. QALYs were used as measure of effectiveness. The model was built from a healthcare perspective and the impact of uncertainty was assessed with sensitivity analyses.Results. Base-case analysis showed that sentinel lymph node mapping was the most effective strategy for lymph node assessment in patients with low-and intermediate-risk endometrial cancer. Compared to risk factor assessment it was more costly, but the incremental cost effectiveness ratio stayed below a willingness-to-pay threshold of epsilon 20,000 with a maximum of epsilon 9637/QALY. Sentinel lymph node mapping was dominant compared to lymph node dissection since it was more effective and less costly. Sensitivity analyses showed that the outcome of the model was robust to changes in input values. With a willingness-to-pay threshold of epsilon 20,000 sentinel lymph node mapping remained cost-effective in at least 74.3% of the iterations.Conclusion. Sentinel lymph node mapping is the most cost-effective strategy to guide the need for adjuvant therapy in patients with low and intermediate risk endometrioid endometrial cancer.(c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Front-of-package food labeling (FoPFL) is increasingly advocated as an effective intervention to facilitate behavior changes toward healthier food purchasing and consumption, particularly in relation to products with added sugar. The present study assessed the potential caries-related impacts of FoPFL, using Germany as an example. The outcomes of interest were caries lesions prevented, dental treatment costs avoided, productivity loss reductions, and disability-adjusted life years (DALYs) averted. The baseline consumption of added sugar was derived from the German National Nutrition Survey. The reduction in sugar intake due to FoPFL was modeled according to estimates from a recent meta-analysis. Microsimulations were performed for 500,000 individuals and over a time horizon of 10 y. Deterministic and probabilistic sensitivity analyses were performed to check the robustness of results. For the period from 2017 to 2027, FoPFL was identified to prevent 2,370,715 (95% confidence interval [CI], 2,062,730–2,678,700) caries lesions and avert 677.62 (95% CI, 589.59–765.65) DALYs. Treatment cost savings amounted to €175.67 million (95% CI, €152.85–€198.49), and productivity losses reduced by €27.33 million (95% CI, €23.78–€30.88). Sensitivity analyses showed that the magnitude of the effects is highly dependent on consumers’ response to FoPFL. Our findings suggest that FoPFL has the potential to substantially reduce caries increment, caries-related morbidity, and economic burden. In addition, our study allows for the inclusion of oral health estimates in overall health estimates for sugar-related food labeling. Before prioritizing a strategy to tackle sugar consumption, decision makers should carefully consider all relevant context-specific factors and implementation costs.

IntroductionArthroscopic partial meniscectomy (APM) after degenerative meniscus tears is one of the most frequently performed surgeries in orthopaedics. Although several randomised controlled trials (RCTs) have been published that showed no clear benefit compared with sham treatment or non-surgical treatment, the incidence of APM remains high. The common perception by most orthopaedic surgeons is that there are subgroups of patients thatdoneed APM to improve, and they argue that each study sample of the existing trials is not representative for the day-to-day patients in the clinic. Therefore, the objective of this individual participant data meta-analysis (IPDMA) is to assess whether there are subgroups of patients with degenerative meniscus lesions who benefit from APM in comparison with non-surgical or sham treatment.Methods and analysisAn existing systematic review will be updated to identify all RCTs worldwide that evaluated APM compared with sham treatment or non-surgical treatment in patients with knee symptoms and degenerative meniscus tears. Time and effort will be spent in contacting principal investigators of the original trials and encourage them to collaborate in this project by sharing their trial data. All individual participant data will be validated for missing data, internal data consistency, randomisation integrity and censoring patterns. After validation, all datasets will be combined and analysed using a one-staged and two-staged approach. The RCTs’ characteristics will be used for the assessment of clinical homogeneity and generalisability of the findings. The most important outcome will be the difference between APM and control groups in knee pain, function and quality of life 2 years after the intervention. Other outcomes of interest will include the difference in adverse events and mental health.Ethics and disseminationAll trial data will be anonymised before it is shared with the authors. The data will be encrypted and stored on a secure server located in the Netherlands. No major ethical concerns remain. This IPDMA will provide the evidence base to update and tailor diagnostic and treatment protocols as well as (international) guidelines for patients for whom orthopaedic surgeons consider APM. The results will be submitted for publication in a peer-reviewed journal.PROSPERO registration numberCRD42017067240.

ObjectivesWith the increasing interest in personalised medicine, the use of subgroup analyses is likely to increase. Subgroup analyses are challenging and often misused, possibly leading to false interpretations of the effect. It remains unclear to what extent key organisations warn for such pitfalls and translate current methodological research to detect these effects into research guidelines. The aim of this scoping review is to determine and evaluate the current guidance used by organisations for exploring, confirming and interpreting subgroup effects.DesignScoping review.Eligibility criteriaWe identified four types of key stakeholder organisations: industry, health technology assessment organisations (HTA), academic/non-profit research organisations and regulatory bodies. After literature search and expert consultation, we identified international and national organisations of each type. For each organisation that was identified, we searched for official research guidance documents and contacted the organisation for additional guidance.ResultsTwenty-seven (45%) of the 60 organisations that we included had relevant research guidance documents. We observed large differences between organisation types: 18% (n=2) of the industry organisations, 64% (n=9) of the HTA organisations, 38% (n=8) of academic/non-profit research organisations and 57% (n=8) of regulatory bodies provided guidance documents. The majority of the documents (n=33, 63%) mentioned one or more challenges in subgroup analyses, such as false positive findings or ecological bias with variations across the organisation types. Statistical recommendations were less common (n=19, 37%) and often limited to a formal test of interaction.ConclusionsAlmost half of the organisations included in this scoping review provided guidance on subgroup effect research in their guidelines. However, there were large differences between organisations in the amount and level of detail of their guidance. Effort is required to translate and integrate research findings on subgroup analysis to practical guidelines for decision making and to reduce the differences between organisations and organisation types.

ACCF : American College of Cardiology Foundation ACS : acute coronary syndrome AHA : American Heart Association CAD : coronary artery disease CABG : coronary artery bypass grafting CKMB : creatine kinase MB isoform cTn : cardiac troponin CT : computed tomography CV : coefficient of variation ECG : electrocardiogram ESC : European Society of Cardiology FDG : fluorodeoxyglucose h : hour(s) HF : heart failure LBBB : left bundle branch block LV : left ventricle LVH : left ventricular hypertrophy MI : myocardial infarction mIBG : meta-iodo-benzylguanidine min : minute(s) MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease) MPS : myocardial perfusion scintigraphy MRI : magnetic resonance imaging mV : millivolt(s) ng/L : nanogram(s) per litre Non-Q MI : non-Q wave myocardial infarction NSTEMI : non-ST-elevation myocardial infarction PCI : percutaneous coronary intervention PET : positron emission tomography pg/mL : pictogram(s) per millilitre Q wave MI : Q wave myocardial infarction RBBB : right bundle branch block sec : second(s) SPECT : single photon emission computed tomography STEMI : ST elevation myocardial infarction ST–T : ST-segment –T wave URL : upper reference limit WHF : World Heart Federation WHO : World Health Organization Myocardial infarction (MI) can be recognised by clinical features, including electrocardiographic (ECG) findings, elevated values of biochemical markers (biomarkers) of myocardial necrosis, and by imaging, or may be defined by pathology. It is a major cause of death and disability worldwide. MI may be the first manifestation of coronary artery disease (CAD) or it may occur, repeatedly, in patients with established disease. Information on MI rates can provide useful information regarding the burden of CAD within and across populations, especially if standardized data are collected in a manner that …

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 …

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 …