A multi-faceted approach to atrial fibrillation: from lifestyle factors to invasive therapies

© 2019 Dr. Aleksandr VoskoboinikAtrial fibrillation (AF) is a leading epidemic of cardiovascular disease in developed countries, owing to an ageing population and the Western lifestyle. In addition to effects on quality of life and economic burden on the health system, AF is associated with heart failure, stroke and a higher risk of mortality. The focus of AF management over the last decade has shifted from anticoagulation and rate control to a more a more holistic and multi-faceted approach. This encompasses attention to potentially modifiable lifestyle factors and adoption of novel invasive strategies such as catheter ablation to maintain rhythm control. The aim of this thesis is to explore these emerging strategies in AF management, with a focus on rhythm control. Initially, we assess the impact of lifestyle related factors on AF and cardiovascular disease. The emphasis initially is on the effects of habitual alcohol consumption on the atria and ventricles and the impact of abstinence in the AF population. We explore novel strategies for cardioversion of persistent AF, focussing on improving success rates in obese patients. Finally, we explore the evolution of catheter ablation as an increasingly utilized rhythm control strategy. Chapter 1 details our evolving understanding of AF pathogenesis, and the impact of common lifestyle factors on arrhythmogenesis, with a focus on alcohol, caffeine, diet and obesity. We then explore the evidence base for rhythm control strategies, including role of anti-arrhythmics, cardioversion and catheter ablation. Chapter 2 and 3 explore the impact of regular alcohol consumption on the atrium to determine whether there is an association with electrical and structural remodelling. Chapter 2 is a prospective observational study of 75 patients undergoing novel high-density electroanatomical mapping of their left atria at the time of AF ablation. We compare non-drinkers, mild drinkers and moderate drinkers to determine whether there are differences in voltage and conduction properties between the three groups. Chapter 3 is a prospective observational study of 160 AF patients comparing atrial size, mechanical and reservoir function based on degree of alcohol intake utilizing high-definition cardiac magnetic resonance imaging (CMR). We conclude that moderate-to-heavy levels of consumption are associated with adverse atrial remodelling, characterised by reduction in voltage, slowing of atrial conduction, atrial dilatation and impaired mechanical function suggestive of progressive fibrosis. Chapter 4 is a randomized controlled trial of 140 moderate habitual drinkers with a history of AF. We examine the impact of 6 months of abstinence on risk of AF recurrence, AF burden, symptom scores, blood pressure, weight and atrial structure / function. Key findings include reduction in AF recurrence rates, with small but significant reductions in systolic blood pressure and weight. This is the first randomized trial to demonstrate the benefits of abstinence from alcohol in the AF population. Chapter 5 examines the paradox between adverse effects of moderate alcohol consumption on the atrium and AF with widely reported benefits of light-to-moderate habitual alcohol consumption with respect to cardiovascular disease, heart failure and mortality. We undertook a cross-sectional study of 165 stable outpatients comprising of lifelong non-drinkers and regular drinkers. Participants underwent cardiac MRI T1 mapping, a novel imaging sequence that examines markers of ventricular fibrosis. Interestingly, light-to-moderate drinkers displayed lower markers of fibrosis. The clinical implications of this finding require further investigation. Chapter 6 focusses on novel and improved treatment strategies for persistent AF in obese patients. We undertook a randomized controlled trial of 125 obese patients undergoing cardioversion for AF (as well as an observational sub-study of morbidly obese patients). Key findings included higher success rates with the use of hand-held paddles, manual pressure augmentation and higher energies (up to 360 Joules biphasic). Chapter 7 also focuses on improving outcomes for cardioversion in persistent AF, looking at the strategy of early presentation for cardioversion in the emergency department. We report a retrospective cohort study of 150 patients and conclude that compared to (delayed) elective cardioversion, earlier restoration of sinus rhythm prevented adverse atrial remodelling, delaying onset of next AF recurrence and improving quality of life. Chapter 8 examines our evolving understanding of ablation strategies for persistent AF. Recent studies highlight that adjunctive substrate modification beyond pulmonary vein isolation (PVI) may not offer additional benefit and may in fact be pro-arrhythmic. We perform a meta-analysis of 14 studies reporting outcomes from PVI alone in this patient population. We conclude that with current technology, acceptable arrhythmia-free survival can be achieved without additional substrate modification. Chapters 9 and 10 report observational data from our institution with the aim of critically assessing key performance measures for catheter ablation of AF over time. Chapter 9 demonstrates a significant reduction in radiation exposure over time for both operator and patient, and examines the factors responsible. Chapter 10 focuses on procedural safety over time through the prism of increasing patient complexity, greater operator experience and technological advances over time. We conclude that at a high-volume centre, catheter ablation is an acceptable strategy that can be performed safely in a large majority of patients

Arrhythmias Utilizing Concealed Nodoventricular or His-Ventricular Pathways: A Structured Approach to Diagnosis and Management

This study sought to describe the electrophysiologic characteristics, diagnostic maneuvers, and treatment of a series of arrhythmias using concealed nodoventricular (cNV) or His-ventricular (cHV) pathways. Confirming the presence and participation of cNV or cHV pathways in tachyarrhythmias is challenging. We present 4 cases of tachycardias with a participatory cNV or cHV pathway. The first patient had a narrow complex tachycardia with ventriculoatrial dissociation. Findings of an entrainment pacing from the right ventricle and fused premature ventricular complexes suggested cNV pathway involvement. The second patient had nonsustained narrow complex tachycardia with more ventricular than atrial complexes. The tachycardia exhibited an anterograde His-right bundle (RB) activation sequence and normal His-ventricular (HV) interval and consistently terminated with fused ventricular extra stimuli, suggesting cNV pathway participation. The third patient had a wide complex tachycardia (WCT) with either a right or left bundle branch block pattern. The WCT showed an eccentric His-RB activation sequence and short HV interval and terminated with fused premature ventricular complexes, suggesting a cHV (or concealed fasciculoventricular) pathway involvement. The fourth patient had a WCT with alternating bundle branch block morphologies with a short HV interval. Entrainment from the basal right ventricle demonstrated fusion and a short postpacing interval, suggesting cHV (or fasciculoventricular) pathway involvement. Ablation at the proximal RB rendered the tachycardia noninducible. A structured approach can help diagnose and treat cNV or cHV pathways. We emphasize the importance of evaluating both the His-RB activation pattern and HV interval during sinus rhythm and tachycardia as well as the ventricular pacing study

Identifying Patients at High Risk of Left Atrial Appendage Thrombus Before Cardioversion: The CLOTS‐AF Score

Background Transesophageal echocardiography–guided direct cardioversion is recommended in patients who are inadequately anticoagulated due to perceived risk of left atrial appendage thrombus (LAAT); however, LAAT risk factors remain poorly defined. Methods and Results We evaluated clinical and transthoracic echocardiographic parameters to predict LAAT risk in consecutive patients with atrial fibrillation (AF)/atrial flutter undergoing transesophageal echocardiography before cardioversion between 2002 and 2022. Regression analysis identified predictors of LAAT, combined to create the novel CLOTS‐AF risk score (comprising clinical and echocardiographic LAAT predictors), which was developed in the derivation cohort (70%) and validated in the remaining 30%. A total of 1001 patients (mean age, 62±13 years; 25% women; left ventricular ejection fraction, 49.8±14%) underwent transesophageal echocardiography, with LAAT identified in 140 of 1001 patients (14%) and dense spontaneous echo contrast precluding cardioversion in a further 75 patients (7.5%). AF duration, AF rhythm, creatinine, stroke, diabetes, and echocardiographic parameters were univariate LAAT predictors; age, female sex, body mass index, anticoagulant type, and duration were not (all P>0.05). CHADS2VASc, though significant on univariate analysis (P1.5 mg/dL, Left ventricular ejection fraction 34 mL/m2), Tricuspid Annular Plane Systolic Excursion (TAPSE) <17 mm, Stroke, and AF rhythm). The unweighted risk model had excellent predictive performance with an area under the curve of 0.820 (95% CI, 0.752–0.887). The weighted CLOTS‐AF risk score maintained good predictive performance (AUC, 0.780) with an accuracy of 72%. Conclusions The incidence of LAAT or dense spontaneous echo contrast precluding cardioversion in patients with AF who are inadequately anticoagulated is 21%. Clinical and noninvasive echocardiographic parameters may identify patients at increased risk of LAAT better managed with a suitable period of anticoagulation before undertaking cardioversion

Complex Re-Entrant Arrhythmias Involving the His-Purkinje System

This study sought to characterize the presentations, electrophysiological features and diagnostic maneuvers for a series of unique arrhythmias involving the HPS. By virtue of its unique anatomy and ion channel composition, the His-Purkinje system (HPS) is prone to a variety of arrhythmic perturbations. The authors present a collaborative multicenter case series of 6 patients with HPS-related arrhythmias. All patients underwent electrophysiological studies using standard multipolar catheters. In 3 patients, both typical and reverse bundle branch re-entry were seen, with 1 patient demonstrating “figure of 8” re-entry likely involving the septal fascicle. One patient presented with systolic dysfunction associated with a high premature ventricular complex burden, with the mechanism being bundle-to-bundle re-entrant beats masquerading as dual response to a single sinus impulse. Two patients were diagnosed with interfascicular re-entry. Diagnosis was aided by careful assessment of HV interval in sinus rhythm and ventricular tachycardia, multipolar catheters to assess the activation sequence of the His-right bundle branch, and fascicles and entrainment of different components of the HPS. Cure of the arrhythmia was achieved by ablation of the right bundle branch block in 3 patients, the left septal fascicle in 2 patients, and the left posterior fascicle in 1 patient. Proper diagnosis of re-entrant arrhythmias involving the HPS may prove challenging. We emphasize a structured approach for diagnosis and effective therapy. [Display omitted

Endocardial-epicardial phase mapping of prolonged persistent atrial fibrillation recordings: high prevalence of dissociated activation patterns

Background - Endocardial-epicardial dissociation (EED) and focal breakthroughs in humans with atrial fibrillation (AF) have been recently demonstrated using activation mapping of short 10-second AF segments. In the current study we used simultaneous endo-epi phase mapping to characterise endo-epi activation patterns on long segments of human persistent AF (PeAF). Methods - Simultaneous intra-operative mapping of endo- and epicardial lateral RA wall was performed in patients with PeAF using two high-density grid catheters (16 electrodes, 3mm spacing). Filtered unipolar and bipolar electrograms (EGM's) of continuous 2-min AF recordings and electrodes locations were exported for phase analyses. We defined EED as phase difference of ≥20ms between paired endo-epi electrodes. Wavefronts (WF) were classified as rotations, single WF (SWF), focal waves or disorganised activity as per standard criteria. Endo-Epi WF patterns were simultaneously compared on dynamic phase maps. Complex fractionated EGM's were defined as bipolar EGM's with ≥5 directional changes occupying at least 70% of sample duration. Results - Fourteen patients with PeAF undergoing cardiac surgery were included. EED was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganised activity (Endo:41.3% vs Epi:46.8%, p=0.0194) and SWF (Endo:31.3% vs Epi:28.1%, p=0.129) were the dominant patterns. Transient rotations (Endo:22% vs Epi:19.2%, p=0.169; mean duration: 590±140ms) and non-sustained focal waves (Endo:1.2% vs Epi:1.6%, p=0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. EGM fractionation was significantly higher in the epicardium than endocardium (61.2% vs 51.6%,