The National Institute for Health and Care Excellence (NICE) guidelines present a synopsis of extensive internal evidence and technology reviews, with a particular focus on clinical efficacy and ...cost-effectiveness within the NHS in England. This approach has delivered a novel perspective on arrhythmia management, with important distinctions from other policymakers' recommendations. For example, when compared with the European Society of Cardiology (ESC) and the American Heart Association (AHA)/Heart Rhythm Society (HRS)/American College of Cardiology (ACC) guidelines on atrial fibrillation (AF), NICE advocates unique strategies regarding arrhythmia detection, stroke and bleeding risk stratification, and rhythm control (NICE CG 196). Likewise, for patients at risk of sudden cardiac death, NICE TA314 not only recommends device therapy based on New York Heart Association class and ECG findings, but also incorporates quality-adjusted life year data from analysis of key randomised controlled trials.This review examines the NICE guidelines, together with those from the AHA/HRS/ACC and ESC, on the management of AF and ventricular arrhythmias and highlights the key common features and discrepancies between these important documents.
The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to defibrillate ventricular arrhythmias, avoiding drawbacks of transvenous leads. The global EFFORTLESS S-ICD (Evaluation ...oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD) registry is collecting outcomes in 985 patients during a 5-year follow-up.
The primary goal of the EFFORTLESS registry is to determine the safety of the S-ICD by evaluating complications and inappropriate shock rate.
This is the first report on the full patient cohort and study endpoints with follow-up ≥1 year. The predefined endpoints are 30- and 360-day complications, and shocks for atrial fibrillation or supraventricular tachycardia.
Patients were followed for 3.1 ± 1.5 years and 82 completed the study protocol 5-year visit. Average age was 48 years, 28% were women, ejection fraction was 43 ± 18%, and 65% had a primary prevention indication. The S-ICD system and procedure complication rate was 4.1% at 30 days and 8.4% at 360 days. The 1-year complication rate trended toward improvement from the first to last quartile of enrollment (11.3% quartile 1) to 7.8% quartile 2, 6.6% quartile 3, and 7.4% quartile 4; quartile 1 vs. quartiles 2 to 4; p = 0.06). Few device extractions occurred due to need for antitachycardia (n = 5), or biventricular (n = 4) or bradycardia pacing (n = 1). Inappropriate shocks occurred in 8.1% at 1 year and 11.7% after 3.1 years. At implant, 99.5% of patients had a successful conversion of induced ventricular tachycardia or ventricular fibrillation. The 1- and 5-year rates of appropriate shock were 5.8% and 13.5%, respectively. Conversion success for discrete spontaneous episodes was 97.4% overall.
This registry demonstrates that the S-ICD fulfills predefined endpoints for safety and efficacy. Midterm performance rates on complications, inappropriate shocks, and conversion efficacy were comparable to rates observed in transvenous implantable cardioverter-defibrillator studies. (Evaluation oF Factors ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD The EFFORTLESS S-ICD Registry; NCT01085435).
The heart rate (HR) response to exercise provides useful information about the autonomic function and has prognostic value, but its reproducibility over a long period of time, a critical requirement ...for using it as a clinical biomarker, is undetermined.
To determine the intra-individual reproducibility of HR dynamics during sub-maximum exercise and one minute recovery.
1187 individuals from the Cardio physical fitness assessment test of the UK Biobank repeated a standard exercise stress test twice (recall time 34.2 ± 2.8 months) and were prospectively studied.
821 individuals complied with inclusion criteria for reproducibility analysis, including peak workload differences between assessments ≤10 W. Intra-individual correlation between HR profile during the first and the second assessment was very high and higher than inter-individual correlation (0.92±0.08 vs 0.87±0.11, p<0.01). Intra-individual correlation of indices describing HR dynamics was: ρ = 0.81 for maximum HR during exercise; ρ = 0.71 for minimum HR during recovery; ρ = 0.70 for HR changes during both exercise and recovery; Intra-individual correlation was higher for these indices of HR dynamics than for resting HR (ρ = 0.64). Bland-Altman plots demonstrated good agreement between HR indices estimated during the first and second assessment. A small but consistent bias was registered for all repeated measurements. The intra-individual consistency of abnormal values was about 60-70%.
The HR dynamics during exercise and recovery are reproducible over a period of 3 years, with moderate to strong intra-individual reproducibility of abnormal values.
The restitution of the action potential duration (APDR) and conduction velocity (CVR) are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the ...vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood.
This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves) undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed.
This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was as high as 250 ms. Heterogeneity in conduction velocity restitution can translate into both activation and repolarization dispersion and increase cardiac instability. The proposed mathematical formulation shows an excellent agreement with the experimental data (correlation coefficient r = 0.94) and provides a useful tool for the understanding of the complex interactions between activation and repolarization restitution properties as well as between their measurements.
Abstract
Ventricular arrhythmias in cardiac channelopathies are linked to autonomic triggers, which are sub-optimally targeted in current management strategies. Improved molecular understanding of ...cardiac channelopathies and cellular autonomic signalling could refine autonomic therapies to target the specific signalling pathways relevant to the specific aetiologies as well as the central nervous system centres involved in the cardiac autonomic regulation.
This review summarizes key anatomical and physiological aspects of the cardiac autonomic nervous system and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes. Proarrhythmogenic autonomic effects and potential therapeutic targets in defined conditions including the Brugada syndrome, early repolarization syndrome, long QT syndrome, and catecholaminergic polymorphic ventricular tachycardia will be examined. Pharmacological and interventional neuromodulation options for these cardiac channelopathies are discussed.
Promising new targets for cardiac neuromodulation include inhibitory and excitatory G-protein coupled receptors, neuropeptides, chemorepellents/attractants as well as the vagal and sympathetic nuclei in the central nervous system. Novel therapeutic strategies utilizing invasive and non-invasive deep brain/brain stem stimulation as well as the rapidly growing field of chemo-, opto-, or sonogenetics allowing cell-specific targeting to reduce ventricular arrhythmias are presented.
Cryoballoon ablation (Cryoballoon) has emerged as a new alternative for the treatment of symptomatic drug-refractory atrial fibrillation (AF). Whether the results of Cryoballoon are more reproducible ...than those of radiofrequency (RF) ablation remains to be proved.
A total of 860 consecutive patients undergoing a first ablation procedure for paroxysmal AF (467 treated with RF and 393 treated with Cryoballoon) were selected from a prospective multicentre survey of AF ablation (FrenchAF). Radiofrequency and Cryoballoon were compared regarding mid-term efficacy and safety. During a median follow-up of 14 months (interquartile range 8-23), patients treated with Cryoballoon displayed similar rates of freedom from atrial arrhythmia relapse in centres performing this technique (68-80% at 18 months). However, in centres performing RF, a greater heterogeneity in procedural results was observed (46-79% were free from atrial arrhythmia relapse at 18 months). On multivariate analysis, Cryoballoon (HR = 0.47, 95% CI 0.35-0.65, P < 0.001) and annual AF ablation caseload (HR = 0.87 per every 100 AF ablation procedures per year; 95% CI 0.80-0.96, P = 0.003) were independent predictors of procedural success. However, on sensitivity analysis, according to the ablation method, annual AF ablation caseload predicted only sinus rhythm maintenance in the subgroup of patients treated with RF. Analysis of interoperator results with Cryoballoon and RF confirmed lower reproducibility of RF, but suggested that besides caseload, other operator-related factors may play a role.
Cryoballoon seems to be less operator-dependent and more reproducible than RF in the setting of paroxysmal AF ablation.
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