Isabelle C. Van Gelder

Strategic Programming of Detection and Therapy Parameters in Implantable Cardioverter-Defibrillators Reduces Shocks in Primary Prevention Patients: Results From the PREPARE (Primary Prevention Parameters Evaluation) Study

OBJECTIVESnOur purpose was to demonstrate that strategically chosen implantable cardioverter-defibrillator (ICD) ventricular tachycardia (VT) or ventricular fibrillation (VF) detection and therapy parameters can reduce the combined incidence of device-delivered shocks, arrhythmic syncope, and untreated sustained symptomatic VT/VF (morbidity index).nnnBACKGROUNDnStrategically chosen ICD VT/VF detection and therapy parameters have been shown in previous studies to reduce the number of shocked episodes. In the PREPARE (Primary Prevention Parameters Evaluation) study, these prior strategies were combined with additional strategies specific to primary prevention patients.nnnMETHODSnThe PREPARE study was a prospective, cohort-controlled study that analyzed 700 patients (biventricular [Bi-V] ICD and non-Bi-V ICD) with primary prevention indications for an ICD from 38 centers followed for 1 year. VT/VF was detected for rates > or =182 beats/min that were maintained for at least 30 of 40 beats. Antitachycardia pacing was programmed as the first therapy for regular rhythms with rates of 182 to 250 beats/min, and supraventricular tachycardia discriminators were used for rhythms < or =200 beats/min. The control cohort consisted of 689 primary prevention patients from the EMPIRIC (Comparison of Empiric to Physician-Tailored Programming of Implantable Cardioverter Defibrillators Trial) (non-Bi-V ICD, physician arm only) and MIRACLE ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation) (Bi-V ICD) trials for whom VT/VF detection and therapy programming were not controlled.nnnRESULTSnThe PREPARE programming significantly reduced the morbidity index incidence density (0.26 events/patient-year for PREPARE study patients vs. 0.69 control cohort, p = 0.003). The PREPARE study patients were less likely to receive a shock in the first year compared with control patients (9% vs. 17%, p < 0.01). The incidence of untreated VT and arrhythmic syncope was similar between the PREPARE study patients and the control cohort.nnnCONCLUSIONSnStrategically chosen VT/VF detection and therapy parameters can safely reduce shocks and other morbidities associated with ICD therapy in patients receiving an ICD for primary prevention indications. (PREPARE-Primary Prevention Parameters Evaluation; NCT00279279).

Sudden Cardiac Death in Adult Congenital Heart Disease

Background— Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. Methods and Results— We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5–7.9; P=0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.4; P=0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.2; P=0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10–1.34; P=0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22–1.48; P=0.008). Conclusions— The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options-a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.

New risk factors for atrial fibrillation: causes of 'not-so-lone atrial fibrillation'

Atrial fibrillation (AF) is a prevalent arrhythmia in patients with cardiovascular disease. The classical risk factors for developing AF include hypertension, valvular disease, (ischaemic) cardiomyopathy, diabetes mellitus, and thyroid disease. In some patients with AF, no underlying (cardiovascular) pathology is present and the aetiology remains unknown. This condition is known as lone AF. However, in recent years, other factors playing a role in the genesis of AF have gained attention, including obesity, sleep apnoea, alcohol abuse and other intoxications, excessive sports practice, latent hypertension, genetic factors, and inflammation. In this review, we address these new risk factors (i.e. as opposed to the classical risk factors) and the mechanisms by which they lead to AF.

Implementation of device therapy (cardiac resynchronization therapy and implantable cardioverter defibrillator) for patients with heart failure in Europe: changes from 2004 to 2008

Heart failure (HF) patients increasingly receive device therapy, either an implantable cardioverter defibrillator (ICD) or a biventricular pacemaker, also called cardiac resynchronization therapy (CRT), or a CRT device with an ICD (CRT‐D). However, epidemiological data on the use of device therapy in Europe are limited.

Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene

BACKGROUNDnDesmin-related myopathy is a clinically heterogenous group of disorders encompassing myopathies, cardiomyopathies, conduction disease, and combinations of these disorders. Mutations in the gene encoding desmin (DES), a major intermediate filament protein, can underlie this phenotype.nnnOBJECTIVEnThe purpose of this study was to investigate the clinical and pathologic characteristics of 27 patients from five families with an identical mutation in the head domain region (p.S13F) of desmin.nnnMETHODS/RESULTSnAll 27 carriers or obligate carriers of a p.S13F DES founder mutation demonstrated a fully penetrant yet variable phenotype. All patients demonstrated cardiac involvement characterized by high-grade AV block at young ages and important right ventricular (RV) involvement. RV predominance was demonstrated by the presence of right bundle branch block in 10 patients (sometimes as a first manifestation) and by RV heart failure in 6 patients, including 2 patients who fulfilled the diagnostic criteria for arrhythmogenic RV cardiomyopathy. Because of this clinical overlap with desmosome cardiomyopathies, we also studied the organization of the intercalated disks, particularly the distribution of desmosomal proteins. Normal amounts of the major desmosomal proteins were found, but the intercalated disks were more convoluted and elongated and had a zigzag appearance.nnnCONCLUSIONnIn this largest series to date of individuals with a single head domain DES mutation, patients show a variable yet predominantly cardiologic phenotype characterized by conduction disease at an early age and RV involvement including right bundle branch block and/or RV tachycardias and arrhythmogenic RV cardiomyopathy phenocopies. A localized effect of desmin on the structure of the cardiac intercalated disks might contribute to disease pathogenesis.

Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.

Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT.

Background ASSERT demonstrated that subclinical atrial fibrillation (SCAF) is common in pacemaker patients without prior AF and is associated with increased risk of ischemic stroke or systemic embolism. SCAF episodes vary in duration and little is known about the incidence of different durations of SCAF, or their prognosis. Methods and results ASSERT followed 2580 patients receiving a pacemaker or ICD, aged >65 years with hypertension, without prior AF. The effect of SCAF duration on subsequent risk of ischemic stroke or embolism was evaluated with time-dependent covariate Cox models. Patients in whom the longest SCAF wasu2009⩽6u2009min were excluded from the analysis (n=125). Among 2455 patients during mean follow-up of 2.5 years, the longest single episode of SCAF lasted >6u2009min to 6u2009h in 462 patients (18.8%), >6–24u2009h in 169 (6.9%), and >24u2009h in 262 (10.7%). SCAF duration >24u2009h was associated with a significant increased risk of subsequent stroke or systemic embolism (adjusted hazard ratio [HR] 3.24, 95% confidence interval [CI] 1.51–6.95, P=0.003). The risk of ischemic stroke or systemic embolism in patients with SCAF between 6u2009min and 24u2009h was not significantly different from patients without SCAF. Conclusions SCAF >24u2009h is associated with an increased risk of ischemic stroke or systemic embolism.

Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Desmoglein-2 and Desmocollin-2 Mutations in Dutch Arrhythmogenic Right Ventricular Dysplasia/Cardiomypathy Patients Results From a Multicenter Study

Background— This study aimed to evaluate the prevalence and type of mutations in the major desmosomal genes, Plakophilin-2 (PKP2), Desmoglein-2 (DSG2), and Desmocollin-2 (DSC2), in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients. We also aimed to distinguish relevant clinical and ECG parameters. Methods and Results— Clinical evaluation was performed according to the Task Force Criteria (TFC). We analyzed the genes in (a) 57 patients who fulfilled the ARVD/C TFC (TFC+), (b) 28 patients with probable ARVD/C (1 major and 1 minor, or 3 minor criteria), and (c) 31 patients with 2 minor or 1 major criteria. In the TFC+ ARVD/C group, 23 patients (40%) had PKP2 mutations, 4 (7%) had DSG2 mutations, and 1 patient (2%) carried a mutation in DSC2, whereas 1 patient (2%) had a mutation in both DSG2 and DSC2. Among the DSG2 and DSC2 mutation-positive TFC+ ARVD/C probands, 2 carried compound heterozygous mutations and 1 had digenic mutations. In probable ARVD/C patients and those with 2 minor or 1 major criteria for ARVD/C, mutations were less frequent and they were all heterozygous. Negative T waves in the precordial leads were observed more (P<0.002) among mutation carriers than noncarriers and in particular in PKP2 mutation carriers. Conclusions— Mutations in DSG2 and DSC2 are together less prevalent (10%) than PKP2 mutations (40%) in Dutch TFC+ ARVD/C patients. Interestingly, biallelic or digenic DSC2 and/or DSG2 mutations are frequently identified in TFC+ ARVD/C patients, suggesting that a single mutation is less likely to cause a full-blown ARVD/C phenotype. Negative T waves on ECG were prevalent among mutation carriers (P<0.002).