Anthony Chow

Characterization of Left Atrial Activation in the Intact Human Heart

Background—The patterns of activation of the human left atrium (LA), how they relate to atrial myocardial architecture, and their role in arrhythmogenesis remain largely unknown. Methods and Results—Left atrial endocardial activation was mapped in 19 patients with a percutaneous noncontact mapping system. Earliest endocardial breakthrough during sinus rhythm (SR) occurred more frequently in the septal (63%, principally posteroseptal) than anterosuperior (37%) LA and varied little with isoproterenol or high right atrial pacing rate. Regardless of site of breakthrough, LA activation was characterized in all patients by propagation around a variably complete line of functional conduction block, descending on the posterior wall from the roof, passing between the ostia of the superior and then inferior pulmonary veins (PVs) before turning septally, passing below the oval fossa, and merging further anteriorly with the septal mitral annulus. Examination of the myocardial architecture in 10 normal adult postmortem hearts revealed an abrupt change in subendocardial fiber orientation along a line following the same course. During episodes of focal initiation of atrial fibrillation (AF), interaction was observed between wavefronts entering the LA from PVs and this functional line of conduction block that resulted in LA macroreentry or formation of daughter wavefronts. Conclusions—The LA endocardium has complex but characteristic patterns of activation during sinus rhythm, pacing, and AF initiation by PV ectopy that are determined largely by the functional properties of atrial musculature. These findings have important implications for both pacing and ablative strategies for the prevention of initiation of AF.

Haemodynamic effects of changes in atrioventricular and interventricular delay in cardiac resynchronisation therapy show a consistent pattern: analysis of shape, magnitude and relative importance of atrioventricular and interventricular delay

Objective: To assess the haemodynamic effect of simultaneously adjusting atrioventricular (AV) and interventricular (VV) delays. Method: 35 different combinations of AV and VV delay were tested by using digital photoplethysmography (Finometer) with repeated alternations to measure relative change in systolic blood pressure (SBPrel) in 15 patients with cardiac resynchronisation devices for heart failure. Results: Changing AV delay had a larger effect than changing VV delay (range of SBPrel 21 v 4.2 mm Hg, p < 0.001). Each had a curvilinear effect. The curve of response to AV delay fitted extremely closely to a parabola (average R2  =  0.99, average residual variance 0.8 mm Hg2). The response to VV delay was significantly less curved (quadratic coefficient 67 v 1194 mm Hg/s2, p  =  0.003) and therefore, although the residual variance was equally small (0.8 mm Hg2), the R2 value was 0.7. Reproducibility at two months was good, with the SD of the difference between two measurements of SBPrel being 2.5 mm Hg for AV delay (2% of mean systolic blood pressure) and 1.5 mm Hg for VV delay (1% of mean systolic blood pressure). Conclusions: Changing AV and VV delays results in a curvilinear acute blood pressure response. This shape fits very closely to a parabola, which may be valuable information in developing a streamlined clinical protocol. VV delay adjustment provides an additional, albeit smaller, haemodynamic benefit to AV optimisation.

Maintenance of sinus rhythm with an ablation strategy in patients with atrial fibrillation is associated with a lower risk of stroke and death

Objective To investigate whether catheter ablation of atrial fibrillation (AF) reduces stroke rate or mortality. Methods An international multicentre registry was compiled from seven centres in the UK and Australia for consecutive patients undergoing catheter ablation of AF. Long-term outcomes were compared with (1) a cohort with AF treated medically in the Euro Heart Survey, and (2) a hypothetical cohort without AF, age and gender matched to the general population. Analysis of stroke and death was carried out after the first procedure (including peri-procedural events) regardless of success, on an intention-to-treat basis. Results 1273 patients, aged 58±11 years, 56% paroxysmal AF, CHADS2 score 0.7±0.9, underwent 1.8±0.9 procedures. Major complications occurred in 5.4% of procedures, including stroke/TIA in 0.7%. Freedom from AF following the last procedure was 85% (76% off antiarrhythmic drugs) for paroxysmal AF, and 72% (60% off antiarrhythmic drugs) for persistent AF. During 3.1 (1.0–9.6) years from the first procedure, freedom from AF predicted stroke-free survival on multivariate analysis (HR=0.30, CI 0.16 to 0.55, p<0.001). Rates of stroke and death were significantly lower in this cohort (both 0.5% per patient-year) compared with those treated medically in the Euro Heart Survey (2.8% and 5.3%, respectively; p<0.0001). Rates of stroke and death were no different from those of the general population (0.4% and 1.0%, respectively). Conclusion Restoration of sinus rhythm by catheter ablation of AF is associated with lower rates of stroke and death compared with patients treated medically.

High-Density Substrate Mapping in Brugada Syndrome. Combined Role of Conduction and Repolarization Heterogeneities in Arrhythmogenesis

Background— Two principal mechanisms are thought to be responsible for Brugada syndrome (BS): (1) right ventricular (RV) conduction delay and (2) RV subepicardial action potential shortening. This in vivo high-density mapping study evaluated the conduction and repolarization properties of the RV in BS subjects. Methods and Results— A noncontact mapping array was positioned in the RV of 18 BS patients and 20 controls. Using a standard S1-S2 protocol, restitution curves of local activation time and activation recovery interval were constructed to determine local maximal restitution slopes. Significant regional conduction delays in the anterolateral free wall of the RV outflow tract of BS patients were identified. The mean increase in delay was 3-fold greater in this region than in control (P=0<0.001). Local activation gradient was also maximally reduced in this area: 0.33±0.1 (mean±SD) mm/ms in BS patients versus 0.51±0.15 mm/ms in controls (P<0.0005). The uniformity of wavefront propagation as measured by the square of the correlation coefficient, r2, was greater in BS patients versus controls (0.94±0.04 versus 0.89±0.09 [mean±SD]; P<0.05). The odds ratio of BS hearts having any RV segment with maximal restitution slope >1 was 3.86 versus controls. Five episodes of provoked ventricular tachycardia arose from wave breaks originating from RV outflow tract slow-conduction zones in 5 BS patients. Conclusions— Marked regional endocardial conduction delay and heterogeneities in repolarization exist in BS. Wave break in areas of maximal conduction delay appears to be critical in the initiation and maintenance of ventricular tachycardia. These data indicate that further studies of mapping BS to identify slow-conduction zones should be considered to determine their role in spontaneous ventricular arrhythmias.

Prediction and prevention of sudden cardiac death in heart failure

The definition of sudden cardiac death (SCD) remains controversial. Many such deaths are not witnessed, and without cardiac monitoring at the time of death the assumption of an underlying arrhythmic cause is speculative. Nevertheless, it has been estimated that SCD accounts for 300 000 to 400 000 deaths annually in the USA.1 The degeneration of monomorphic ventricular tachycardia (VT) into ventricular fibrillation (VF) accounts for the majority of sudden arrhythmic deaths.w1 Despite considerable advances in the treatment of heart failure over the past 20 years, morbidity and mortality remain high with a four year survival of less than 50% in population based studies (fig 1). Ventricular arrhythmias (including non-sustained VT) have been documented in up to 85% of patients with severe congestive heart failure.2 Figure 1  Cumulative survival of 552 incident (new) cases of heart failure identified in the London heart failure studies 1995 to 1998. Kaplan-Meier estimates with 95% point wise confidence bands (authors’ own data). The implantable cardioverter-defibrillator (ICD) is highly effective at terminating life threatening ventricular tachyarrhythmia (fig 2). In selected high risk patients ICDs have proven to be a cost effective method of reducing mortality. At present, 1–2% of the population has heart failure and numbers continue to increase,3 but the ICD remains expensive. The challenge lies in identifying patients with heart failure who are at significant risk of arrhythmia and who would benefit from an ICD in addition to other antiarrhythmic strategies. Figure 2  Implantable cardioverter-defibrillator (ICD) data showing an episode of ventricular fibrillation terminated by a 21 J shock delivered by the device. Intracardiac electrograms are recorded from the right atrium (A) and right ventricle (V) along with a surface ECG. Sensed intracardiac intervals are shown at the bottom of the figure. Following cardioversion, ventricular fibrillation is terminated and bradycardia is seen requiring atrioventricular …

Predictors of recurrence following radiofrequency ablation for persistent atrial fibrillation.

AIMS To establish clinical factors affecting success in persistent atrial fibrillation (AF) ablation. METHODS AND RESULTS Wide area circumferential ablation with linear and electrogram-based left atrial (LA) ablation was performed in 191 consecutive patients for persistent AF. After mean follow-up of 13.0 ± 8.9 months, overall success was 64% requiring a mean of 1.5 procedures. Single procedure success rate was 32%. Left atrial size was a univariate predictor of recurrence after a single procedure (P =0.04). Only LA size [hazard ratio (HR) 1.05/mm with 95% confidential interval (CI) 1.02-1.08] was an independent predictor of recurrence after a single procedure. Only LA size was a univariate predictor of recurrence after multiple procedures (P < 0.01). Left atrial size (HR 1.07/mm with 95% CI 1.02-1.11) and hypertrophic cardiomyopathy (HCM; HR 2.42 with 95% CI 1.06-5.55) were independent predictors of recurrence after multiple procedures. Ablation strategy did not affect success after a single procedure. Left atrial size of <43 mm predicted long-term success with a sensitivity of 92%, specificity 52%, positive predictive value 49%, and negative predictive value 93%. With LA size >43 mm, HCM (HR 3.09 with 95% CI 1.70-7.5) and AF duration (HR 1.07/year with 95% CI 1.00-1.13) were independent predictors of recurrence. CONCLUSION Left atrial size is the major independent determinant of AF recurrence after ablation for persistent AF. This has important implications for patient selection for persistent AF ablation and the evaluation of AF ablation clinical trial results.

Incidence of left atrial thrombus prior to atrial fibrillation ablation: is pre-procedural transoesophageal echocardiography mandatory?

AIMS The exact role of transoesphageal echo (TOE) prior to atrial fibrillation (AF) ablation remains unclear. This study examines the incidence and predictors of left atrial (LA) thrombus in patients undergoing AF ablation. METHODS AND RESULTS Patients were treated with warfarin for at least 4 weeks prior to ablation. This was substituted with therapeutic dalteparin 3 days before the procedure. All patients underwent TOE to exclude LA thrombus. Six clinical risk factors for thrombus were defined, known to be risk factors for stroke in AF: age>75, diabetes, hypertension, valve disease, prior stroke, or transient ischaemic attack and cardiomyopathy. A total of 635 procedures were performed. The incidence of thrombus was 12/635 (1.9%) despite therapeutic anti-coagulation. Patients with thrombus had larger LA diameter, mean 50.6+/-6.2 mm vs. 44.2+/-7.6 (P=0.006). In univariate analysis, persistent AF [odds ratio (OR)=10.4 with 95% CI 1.8-19.1], hypertension [OR=11.7 with 95% CI 2.5-54.1], age>75 (OR=4.5 with 95% CI 1.2-17.2), and cardiomyopathy (OR 5.9 with 95% CI 1.8-19.1) were significantly associated with thrombus. In multivariate analysis, hypertension (OR=14.2 with 95% CI 2.6-77.5), age>75 (OR=8.1, 95% CI 1.5-44.9), and cardiomyopathy (OR=10.5 with 95% CI 2.6-77.5) were independently associated with thrombus. There was no thrombus in patients without clinical risk factors. CONCLUSION In patients presenting for AF ablation, LA thrombus is only seen in those with clinical risk factors. TOE is indicated in this group but may be unnecessary in patients without clinical risk factors.

Selection and optimisation of biventricular pacing: the role of echocardiography

The quantification of ventricular dyssynchrony is a key factor in identifying patients with severe heart failure who may benefit from cardiac resynchronisation with biventricular pacing (BVP). Echocardiographic techniques appear to offer superior sensitivity and specificity than the ECG in selecting these patients. This paper reviews the scope of current echocardiographic techniques for guiding both patient selection and optimisation of device programming following implantation.

A randomized double-blind crossover trial of triventricular versus biventricular pacing in heart failure

A significant proportion of patients implanted with biventricular (BiV) devices fail to respond. Clinical response may be improved by additional ventricular stimulation sites. This single‐centre, double‐blinded randomized crossover trial aimed to determine whether long‐term multisite ventricular pacing is superior to conventional BiV pacing in heart failure patients.

Effect of biventricular pacing on symptoms and cardiac remodelling in patients with end‐stage hypertrophic cardiomyopathy

Biventricular (BiV) pacing is an established therapy for heart failure in ischaemic and dilated cardiomyopathy. Its effects in end‐stage hypertrophic cardiomyopathy (HCM) are unknown.