Search

Clinicians accept that there are many unknowns when we make diagnostic and therapeutic decisions. Acceptance of uncertainty is essential for the pursuit of the profession: bedside decisions must often be made on the basis of incomplete evidence. Over the years, physicians sometimes even do not realize anymore which the fundamental gaps in our knowledge are. As clinical scientists, however, we have to halt and consider what we do not know yet, and how we can move forward addressing those unknowns. The European Heart Rhythm Association (EHRA) believes that scanning the field of arrhythmia / cardiac electrophysiology to identify knowledge gaps which are not yet the subject of organized research, should be undertaken on a regular basis. Such a review (White Paper) should concentrate on research which is feasible, realistic, and clinically relevant, and should not deal with futuristic aspirations. It fits with the EHRA mission that these White Papers should be shared on a global basis in order to foster collaborative and needed research which will ultimately lead to better care for our patients. The present EHRA White Paper summarizes knowledge gaps in the management of atrial fibrillation, ventricular tachycardia/sudden death and heart failure.

Aims We sought to determine whether peri-infarct pacing prevents left ventricular (LV) remodelling and improves functional and clinical outcomes in patients with large first myocardial infarction (MI). Methods and results A total of 126 patients at 27 international sites within 10 days of onset of anterior or non-anterior MI with creatine phosphokinase >3000 U/L and QRS duration ≤120 ms were randomized 1:1:1 to dual-site biventricular pacing vs. single-site LV only pacing vs. non-implanted control. The primary endpoint was the echocardiographic core laboratory-assessed change in LV end-diastolic volume (ΔLVEDV) from baseline to 18 months between the pooled pacing therapy groups and the control group. ΔLVEDV increased by 15.3 ± 28.6 mL in the control group and by 16.7 ± 30.5 mL in the pooled pacing groups during follow-up (adjusted mean difference (95% CI) = 0.6 (−12.3, 13.5) mL, P = 0.92). There were also no significant between-group differences in the change in LV end-systolic volume or ejection fraction over time. Quality of life, as assessed by the Minnesota Living with Heart Failure (HF) and European Quality of Life-5 Dimension questionnaires and New York Heart Association class, was also similar between groups during 18-month follow-up. Six-minute walk distance improved during follow-up to an equal degree between groups, and there were no significant differences in the 18-month rates of death or HF hospitalization between the pooled pacing therapy vs. control groups (17.4 vs. 21.7% respectively, P = 0.59). Conclusions In the present multicentre, randomized trial, peri-infarct pacing did not prevent LV remodelling or improve functional or clinical outcomes during 18-month follow-up in patients with large first MI. ClinicalTrials.gov identifier NCT01213251.

Background— Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. Methods and Results— To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL ( expression quantitative trait loci ) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13–1.23; P =6.5×10 −16 ), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06–1.14; P =2.2×10 −8 ), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08–1.16; P =5.7×10 −11 ), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06–1.14; P =9.8×10 −9 ). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26–1.39; P =2.0×10 −25 ) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08–1.16; P =3.9×10 −9 ). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 ( P =2.6×10 −19 ), GJA1 ( P =2.66×10 −6 ), and TBX5 ( P =1.36×10 −5 ). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). Conclusions— We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.

BACKGROUND: -Atrial fibrillation (AF) affects over 30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: -To identify new AF-related genes, we utilized a multifaceted approach, combining large-scale genotyping in two ethnically distinct populations, cis-eQTL mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501, RR=1.18, 95%CI 1.13 - 1.23, p=6.5x10(-16)), GJA1 (rs13216675, RR=1.10, 95%CI 1.06 - 1.14, p=2.2x10(-8)), TBX5 (rs10507248, RR=1.12, 95%CI 1.08 - 1.16, p=5.7x10(-11)), and CAND2 (rs4642101, RR=1.10, 95%CI 1.06 - 1.14, p=9.8x10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555, RR=1.32, 95%CI 1.26-1.39, p=2.0x10(-25)) and CUX2 (rs6490029, RR=1.12, 95%CI 1.08-1.16, p=3.9x10(-9)). The top SNPs or their proxies were identified as cis-eQTLs for the genes CAND2 (p=2.6x10(-19)), GJA1 (p=2.66x10(-6)), and TBX5 (p=1.36x10(-05)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). CONCLUSIONS: -We have identified five novel loci for AF. Our results further expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation.

The aim of this European Heart Rhythm Association (EHRA) survey was to provide an insight into the current practice of work-up and management of patients with syncope among members of the EHRA electrophysiology research network. Responses were received from 43 centres. The majority of respondents (74%) had no specific syncope unit and only 42% used a standardized assessment protocol or algorithm. Hospitalization rates varied from 10% to 25% (56% of the centres) to >50% (21% of the centres). The leading reasons for hospitalization were features suggesting arrhythmogenic syncope (85% of respondents), injury (80%), structural heart disease (73%), significant comorbidities (54%), and older age (41%). Most widely applied tests were electrocardiogram (ECG), echocardiography, and Holter monitoring followed by carotid sinus massage and neurological evaluation. An exercise test, tilt table test, electrophysiological study, and implantation of a loop recorder were performed only if there was a specific indication. The use of a tilt table test varied widely: 44% of respondents almost always performed it when neurally mediated syncope was suspected, whereas 37% did not perform it when there was a strong evidence for neurally mediated syncope. Physical manoeuvres were the most widely (93%) applied standard treatment for this syncope form. The results of this survey suggest that there are significant differences in the management of patients with syncope across Europe, specifically with respect to hospitalization rates and indications for tilt table testing in neurally mediated syncope. The majority of centres reported using ECG, echocardiography, and Holter monitoring as their main diagnostic tools in patients with syncope, whereas a smaller proportion of centres applied specific assessment algorithms. Physical manoeuvres were almost uniformely reported as the standard treatment for neurally mediated syncope. © 2013 The Author.

The purpose of this EP wire survey was to assess clinical practice in relation to the use of left atrial appendage occlusion (LAAO) devices for stroke prevention in atrial fibrillation (AF) among members of the European Heart Rhythm Association research network. The average number of performed LAAO was 10.6 per year and most (73%) centres performed ≤10 procedures per year. We found that LAAO was being performed for stroke prevention in AF, for the most common indication being 'the patient has absolute contraindication to long term oral anticoagulants'. Among survey respondents, LAAO procedures are most often performed by interventional cardiologists. Experience varied widely, and this was reflected in the wide range of thromboembolic and procedural (tamponade, bleeding) complications reported by the respondents to this EP wire survey. © The Author 2012.

The aims of this survey was to provide insight into treatment activity, the strategy of treatment, and risk stratification of patients with asymptomatic and symptomatic ventricular pre-excitation across Europe. Fifty-eight centres, members of the European Heart Rhythm Association EP research network, covering 20 countries answered the survey questions. All centres were high-volume ablation centres. A younger person with asymptomatic Wolff-Parkinson-White (WPW) pattern has a higher likelihood of being risk-stratified or receiving ablation therapy compared with an older subject. Two-thirds of centres report that they have observed a decline in the number of patients ablated for an accessory pathway during the last 10 years. Pre-excited atrial fibrillation is rarely seen. Discontinuation of a scheduled WPW ablation due to close vicinity of the accessory pathway to the AV node happens very rarely. Patients with a first episode of pre-excited atrial fibrillation would immediately be referred for catheter ablation to be performed within weeks by 80.4% of the centres. A significant proportion of responders (50.9%) would use electrical cardioversion to restore sinus rhythm in a patient with pre-excited atrial fibrillation. With respect to the choice of antiarrhythmic medication for a patient with pre-excited AF, the majority (80.0%) would choose class 1C antiarrhytmic drugs while waiting for a catheter ablation. A patient seen in the emergency room with a second episode of orthodromic atrioventricular reentry tachycardia would be referred for immediate ablation by 79.2-90.6% of centres depending on the presence of pre-excitation. The volume of paediatric ablations performed on children younger than 12 years was low (46.4%: 0 patients per year; 46.4%: 1-9 patients per year). The majority of responding centres (61-69%) report that their country lack national guidelines dealing with clinical strategies related to WPW. There is a need for national guidelines dealing with clinical strategy in patients with WPW syndrome. Older individuals with asymptomatic WPW pattern have a higher risk of not receiving risk stratification or curative therapy with ablation compared with younger patients, despite the higher risk of developing atrial fibrillation. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved.

AimCurrent practice with regard to transvenous lead extraction among European implanting centres was analysed by this survey.Methods and resultsAmong all contacted centres, 164, from 30 countries, declared that they perform transvenous lead extraction and answered 58 questions with a compliance rate of 99.9. Data from the survey show that there seems to be an overall increasing experience of managing various techniques of lead extraction and a widespread involvement of cardiac centres in this treatment. Results and complication rates seem comparable with those of main international registries.ConclusionThis survey gives an interesting snapshot of lead extraction in Europe today and gives some clues for future research and prospective European registries. © The Author 2012.

AimsThe purpose of this EP Wire is to compare indications, techniques, implant strategy, and follow-up regarding cardiac resynchronization therapy (CRT) in several countries across Europe. Methods and resultsForty-one centres, members of the EHRA-EP Research Network, responded to this survey and completed the questions. Thirty-two per cent of the responding centres always use CRT in heart failure (HF) patients with New York Heart Association functional class II and QRS width >120 ms, and 55 of the responding centres demand additional criteria when indicating CRT, most often QRS width >150 ms (49) and echocardiographic criteria of asynchrony (34). Only 10 of centres indicate CRT in all HF patients with QRS >120 ms and right bundle branch block, and 51 demand additional criteria, most frequently echocardiographic asynchrony parameters. The vast majority of centres also indicate CRT in patients with atrial fibrillation and standard criteria for CRT. In 24 of the centres, biventricular pacemaker (CRT-P) is implanted in all situations, unless there is an indication for secondary prevention of sudden cardiac death, while 10 always choose to implant a biventricular defibrillator (CRT-D). There are no clear evidence-based recommendations concerning the implant procedure and follow-up in patients treated with CRT; therefore, the chosen strategies vary widely from one centre to another. ConclusionThis EP Wire survey shows a wide variation not only as far as CRT indications are concerned, but especially in techniques, implant strategy, and follow-up across the European countries. © The 2012 Author.

Background: Infections of cardiac implantable devices (CIEDI) have poor outcomes despite improvement in lead extraction (TLE) procedures. Methods: To explore the influence of CIEDI on the outcomes of TLE and the differences between patients with systemic (Sy) vs. local (Lo) CIEDI, we performed a sub-analysis of the EORP ELECTRa (European Lead Extraction ConTRolled) Registry. Results: Among 3555 patients enrolled by 73 centers in 19 Countries, the indication for TLE was CIEDI in 1850: 1170 with Lo-CIEDI and 680 with Sy-CIEDI. Patients with CIEDI had a worse in-hospital prognosis in terms of major complications (3.57% vs. 1.71%; p = 0.0007) and mortality (2.27% vs. 0.49%; p < 0.0001). Sy-CIEDI was an independent predictor of in-hospital death (H.R. 2.14; 95%CI 1.06–4.33. p = 0.0345). Patients with Sy-CIEDI more frequently had an initial CIED implant and a higher prevalence of comorbidities, while subjects with Lo-CIEDI had a higher prevalence of previous CIED procedures. Time from signs of CIEDI and TLE was longer for Lo-CIEDI despite a shorter pre-TLE antibiotic treatment. Conclusions: Patients with CIEDI have a worse in-hospital prognosis after TLE, especially for patients with Sy-CIEDI. These results raise the suspicion that in a relevant group of patients CIEDI can be systemic from the beginning without progression from Lo-CIEDI. Future research is needed to characterize this subgroup of patients.