Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation: a prospective, randomized, multi-centre, open label trial.

AIMS: There is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF. METHODS AND RESULTS: We recruited 321 patients with symptomatic paroxysmal AF to a prospective randomized, multi-centre, open label trial at 13 UK hospitals. Patients were randomized 1:1:1 to cryo-balloon ablation without electrical mapping with patients discharged same day [Ablation Versus Anti-arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent (AVATAR) protocol]; optimization of drug therapy; or cryo-balloon ablation with confirmation of pulmonary vein isolation and overnight hospitalization. The primary endpoint was time to any hospital episode related to treatment for atrial arrhythmia. Secondary endpoints included complications of treatment and quality-of-life measures. The hazard ratio (HR) for a primary endpoint event occurring when comparing AVATAR protocol arm to drug therapy was 0.156 (95% CI, 0.097-0.250; P < 0.0001 by Cox regression). Twenty-three patients (21%) recorded an endpoint event in the AVATAR arm compared to 76 patients (74%) within the drug therapy arm. Comparing AVATAR and conventional ablation arms resulted in a non-significant HR of 1.173 (95% CI, 0.639-2.154; P = 0.61 by Cox regression) with 23 patients (21%) and 19 patients (18%), respectively, recording primary endpoint events (P = 0.61 by log-rank test). CONCLUSION: The AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but conventional cryoablation was not superior to the AVATAR protocol. This could have wide-ranging implications on how demand for AF symptom control is met. TRIAL REGISTRATION: Clinical Trials Registration: NCT02459574.

Characterization of the arrhythmogenic substrate in patients with arrhythmogenic right ventricular cardiomyopathy undergoing ventricular tachycardia ablation.

AIMS: Arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) is associated with ventricular arrhythmias, even without RV structural disease. We aimed to characterize the RV substrate using electroanatomical mapping and to define outcomes following ventricular tachycardia (VT) ablation in patients with and without RV structural abnormalities. METHODS AND RESULTS: Twenty-nine patients with definite or suspected ARVC undergoing VT ablation were classified as 'electrical' and 'structural' cardiomyopathy based on the absence or presence of major structural criteria. Right ventricular (RV) endocardial and epicardial mapping with assessment of bipolar and unipolar voltages, distribution of late potentials (LPs), and inducible VT morphologies were performed. The endpoints for VT ablation were VT non-inducibility and LP abolition. Fourteen patients were categorized as electrical RV cardiomyopathy and 15 were categorized as structural RV cardiomyopathy. In patients with electrical cardiomyopathy, scar was limited to the epicardial surface (epicardium 13 cm2vs. endocardium 1 cm2, P < 0.05), primarily in the outflow tract, whereas patients with structural disease had greater involvement of the endocardium. During a mean follow-up of 22 ± 11 months, the VT recurrence rate was 27%, with LP abolition being a predictor of VT-free survival (HR 0.075 (0.008-0.661), P = 0.020). There was a trend towards higher recurrence rates in structural RV cardiomyopathy (40%) compared with the electrical cardiomyopathy (15%, P = 0.17). CONCLUSION: The development of RV structural disease in patients with ARVC is associated with extensive epicardial and endocardial scar. Conversely those patients without RV structural disease have identifiable epicardial scar limited to the RV outflow tract. Ventricular tachycardia (VT) ablation in both groups targeting LP abolition is effective in preventing VT recurrence.

Catheter ablation of atrial fibrillation in heart failure.

Atrial fibrillation in the presence of heart failure is an independent predictor of mortality and is associated with increased hospitalizations and worsening New York Heart Association functional class. Despite these associations, large-scale trials have not shown a benefit in rhythm restoration. However, further analysis of these trials showed that patients who remained in sinus rhythm did have improved survival rates. Studies to examine the efficacy of catheter ablation of atrial fibrillation were therefore conducted and reported efficacy rates ranging from 50% to 92% at maintaining sinus rhythm with associated improvements in left ventricular ejection fraction, quality of life, and New York Heart Association functional class.

Phrenic nerve stimulation with the quadripolar left ventricular lead not overcome by 'electronic repositioning'.

Phrenic nerve stimulation (PNS) is a frequent occurrence in patients implanted with a cardiac resynchronization therapy (CRT) device. The quadripolar left ventricular offers 10 pacing configurations which can overcome PNS in most cases. We report a rare case of significant PNS following upgrade to a CRT which was present with all 10 pacing configurations one day following implantation which required lead repositioning.

Percutaneous balloon venoplasty of pacemaker-associated superior vena cava obstruction to facilitate upgrade to a biventricular pacing system.

Superior vena cava (SVC) obstruction is an uncommon, but serious, complication of transvenous device implantation. We present a case of a 52-year-old lady admitted for upgrade to a biventricular pacemaker with significant SVC stenosis. Percutaneous balloon venoplasty of the SVC followed by insertion of biventricular pacing leads was carried out as a single procedure with no complications.

Successful catheter ablation of focal ventricular fibrillation in a patient with nonischemic dilated cardiomyopathy.

A 64-year-old man with nonischemic dilated cardiomyopathy and a biventricular defibrillator presented with recurrent ventricular fibrillation (VF) and defibrillator shocks. Evaluation of the intracardiac electrograms from his defibrillator demonstrated the consistent initiation of VF by unifocal premature ventricular complexes (PVCs). Noncontact mapping demonstrated the origin of the PVC to be near the left ventricular outflow tract toward the mitral valve ring. Several applications of radiofrequency at this position led to complete cessation of PVCs and prevented further VF. He has not had any further ventricular arrhythmias or defibrillator discharges during follow-up.

Initial experience of a cohort of patients with hypertrophic cardiomyopathy undergoing biventricular pacing.

BACKGROUND: Dual chamber pacing improves functional status and reduces left ventricular outflow tract gradients in some, but not all patients with hypertrophic cardiomyopathy (HCM) by altering ventricular depolarisation. We investigated the use of biventricular (BIV) pacing in symptomatic patients with HCM. METHOD: 8 patients aged 58±7yrs with symptomatic HCM underwent BIV pacing. 5 patients had LVOT gradients >30mmHg. Ventricular electrodes were placed in the right ventricle (RV) and a branch of the coronary sinus. An atrial electrode was inserted to achieve BIV pacing with a short AV delay. The short-term effects of different pacing modalities were assessed using 2-D and Doppler echocardiography. Symptoms and exercise tolerance were assessed after a month of each pacing mode. Long-term follow up data was available for 5 years. RESULTS: Baseline EF was 67±14% and mean QRS duration was 132±26msecs. BIV pacing reduced QRS duration compared to RV pacing (129±46 vs. 205±54msecs, p<0.005). Five of the seven patients had baseline LVOT gradients (mean 67±25mmHg) that decreased to 41±15mm Hg with RV pacing (p<0.01) and 25±15mmHg with BIV pacing (p<0.005). Improvements in exercise time with active pacing occurred in six out of eight patients (75%), three (37.5%) had optimal exercise times with RV pacing and three with BIV pacing. Of the three patients with short term improvements with BIV pacing, one died 4 years post implant, one deteriorated with LV dilatation and one had the system explanted for infection. CONCLUSION: BIV pacing showed short-term beneficial effects in some patients over and above RV pacing alone.

A New Era in Epicardial Access for the Ablation of Ventricular Arrhythmias: The Epi-Co2 Registry.

OBJECTIVES: This multicenter registry aimed to assess the reproducibility and safety of intentional coronary vein exit and carbon dioxide insufflation to facilitate subxiphoid epicardial access in the setting of ventricular tachycardia ablation. BACKGROUND: Epicardial ablation for ventricular tachycardia is not a widespread technique due to the significant potential complications associated with subxiphoid puncture. The first experience in 12 patients showed that intentional coronary vein exit and carbon dioxide insufflation was technically feasible. METHODS: A branch of the coronary sinus was cannulated by means of a diagnostic JR4 coronary catheter. Intentional perforation at the distal portion of that branch was performed with a high tip load 0.014-inch angioplasty wire. A microcatheter was advanced over the wire into the pericardial space. Carbon dioxide was then insufflated into the pericardial space, allowing direct visualization of the anterior pericardial space to facilitate subxiphoid puncture. RESULTS: Intentional coronary vein exit was attempted in 102 consecutive patients in 16 different centers and successfully completed in 101 patients. Significant pericardial adhesions were confirmed in 3 patients, preventing carbon dioxide insufflation and epicardial ablation. None of the punctures were complicated with inadvertent right ventricular puncture or damage to a coronary artery. Significant bleeding (>80 ml) due to coronary vein exit occurred in 5 patients, without hemodynamic compromise. None of the patients required surgery. CONCLUSIONS: Coronary vein exit and carbon dioxide insufflation can be safely and reproducibly achieved to facilitate subxiphoid pericardial access in the setting of ventricular tachycardia ablation.

Coronary Vein Exit and Carbon Dioxide Insufflation to Facilitate Subxiphoid Epicardial Access for Ventricular Mapping and Ablation: First Experience.

OBJECTIVES: This study assessed the feasibility of intentional coronary venous perforation and exit with subsequent pericardial carbon dioxide (CO2) insufflation as a novel method for assisting subxiphoid pericardial puncture in the setting of epicardial mapping and ablation for ventricular tachycardia. The technique required that coronary venous perforation would not lead to significant bleeding. BACKGROUND: Widespread adoption of first-line endoepicardial ventricular tachycardia ablation has not been taken up because of the risk of lacerating coronary vessels and puncturing the right ventricle with direct subxiphoid puncture. METHODS: A lateral branch of the coronary sinus was subselected using a diagnostic JR4 coronary catheter inside a steerable sheath, via femoral access, and a distal branch then perforated intentionally using a high tip load 0.014-inch angioplasty wire. Either a microcatheter or over-the-wire balloon was then passed over this into the pericardial space, allowing up to 150 ml of pericardial CO2 insufflation, which allowed direct visualization of subxiphoid anterior pericardial access using a microneedle technique. RESULTS: Intentional coronary vein exit was achieved in all 12 patients. In 1 patient, this confirmed widespread pericardial adhesions and therefore only endocardial VT ablation was undertaken. The other patients underwent successful pericardial CO2 insufflation and subxiphoid access allowing epicardial ventricular mapping and ablation. The immediate pericardial aspirate was dry or contained serous fluid in all but 1 patient. CONCLUSIONS: We report the first human transcoronary vein exit procedure. Coronary vein exit and subsequent percutaneous subxiphoid anterior access using a microneedle puncture after CO2 pericardial insufflation can be achieved reliably and safely.

Fractionation of electrograms is caused by colocalized conduction block and connexin disorganization in the absence of fibrosis as AF becomes persistent in the goat model.

BACKGROUND: Electrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear. OBJECTIVE: The aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change. METHODS: Of 12 goats, atrial burst pacemakers maintained AF in 9 goats for up to 3 consecutive 4-week periods. After each 4-week period, 3 goats underwent epicardial mapping studies of the right atrium and examination of the atrial myocardium for immunodetection of connexins 43 and 40 (Cx43 and Cx40) and quantification of connective tissue. RESULTS: Despite refractoriness returning to normal in between each 4-week period of AF, there was a cumulative increase in the prevalence of fractionated atrial electrograms during both atrial pacing (control and 1, 2, and 3 months period of AF 0.3%, 1.3% ± 1.5%, 10.6% ± 2%, and 17% ± 5%, respectively; analysis of variance, P < .05) and AF (0.3% ± 0.1%, 2.3% ± 1.2%, 14% ± 2%, and 23% ± 3%; P < .05) caused by colocalized areas of conduction block during both pacing (local conduction velocity <10 cm/s: 0.1% ± 0.1%, 0.3% ± 0.6%, 6.5% ± 3%, and 6.9% ± 4%; P < .05) and AF (1.5% ± 0.5%, 2.7% ± 1.1%, 10.1% ± 1.2%, and 13.6% ± 0.4%; P < .05), associated with an increase in the heterogeneity of Cx40 and lateralization of Cx43 (lateralization scores: 1.75 ± 0.89, 1.44 ± 0.31, 2.85 ± 0.96, and 2.94 ± 0.31; P < .02), but not associated with change in connective tissue content or net conduction velocity. CONCLUSION: Electrogram fractionation with increasing persistence of AF results from slow localized conduction or block associated with changes in atrial connexin distribution in the absence of fibrotic change.

Catheter ablation of ventricular arrhythmia in nonischemic cardiomyopathy: anteroseptal versus inferolateral scar sub-types.

BACKGROUND: The aim was to relate distinct scar distributions found in nonischemic cardiomyopathy with ventricular tachycardia (VT) morphology, late potential distribution, ablation strategy, and outcome. METHODS AND RESULTS: Eighty-seven patients underwent catheter ablation for drug-refractory VT. Based on endocardial unipolar voltage, 44 were classified as predominantly anteroseptal and 43 as inferolateral. Anteroseptal patients more frequently fulfilled diagnostic criteria for dilated cardiomyopathy (64% versus 36%), associated with more extensive endocardial unipolar scar (41 [22-83] versus 9 [1-29] cm(2); P<0.001). Left inferior VT axis was predictive of anteroseptal scar (positive predictive value, 100%) and right superior axis for inferolateral (positive predictive value, 89%). Late potentials were infrequent in the anteroseptal group (11% versus 74%; P<0.001). Epicardial late potentials were common in the inferolateral group (81% versus 4%; P<0.001) and correlated with VT termination sites (κ=0.667; P=0.014), whereas no anteroseptal patient had an epicardial VT termination (P<0.001). VT recurred in 44 patients (51%) during a median follow-up of 1.5 years. Anteroseptal scar was associated with higher VT recurrence (74% versus 25%; log-rank P<0.001) and redo procedure rates (59% versus 7%; log-rank P<0.001). After multivariable analysis, clinical predictors of VT recurrence were electrical storm (hazard ratio, 3.211; P=0.001) and New York Heart Association class (hazard ratio, 1.608; P=0.018); the only procedural predictor of VT recurrence was anteroseptal scar pattern (hazard ratio, 5.547; P<0.001). CONCLUSIONS: Unipolar low-voltage distribution in nonischemic cardiomyopathy allows categorization of scar pattern as inferolateral, often requiring epicardial ablation mainly based on late potentials, and anteroseptal, which frequently involves an intramural septal substrate, leading to a higher VT recurrence.

Persistent atrial fibrillation presenting in sinus rhythm: pulmonary vein isolation versus pulmonary vein isolation plus electrogram-guided ablation.

BACKGROUND: The classification of atrial fibrillation as paroxysmal or persistent (PsAF) is clinically useful, but does not accurately reflect the underlying pathophysiology and is therefore a suboptimal guide to selection of ablation strategy. AIM: To determine if additional substrate ablation is beneficial for a subset of patients with PsAF, in whom long periods of sinus rhythm (SR) can be maintained. METHODS: We included patients presenting with PsAF in whom continuous periods of SR>3months were documented. All patients were in SR on the day of the procedure. Electrical pulmonary vein isolation (PVI) was performed in all patients. Additional electrogram (EGM)-guided ablation was left to the discretion of the operator. Patient characteristics and follow-up were analysed with respect to presence or absence of additional EGM-guided ablation. RESULTS: Sixty-five patients (mean age 60.1±8.9years; 81.5% men) met the inclusion criteria. EGM-guided ablation was performed in 32 (49%) patients. Patients with and without EGM-guided ablation had similar baseline characteristics. Absence of EGM-guided ablation was one of the independent predictors for arrhythmia recurrences after the index procedure (hazard ratio 0.24; confidence interval 0.12-0.47). After a median follow-up of 18±10months, the number of procedures required was significantly higher in the 'PVI-only' group (2.24±0.75 vs. 1.84±0.81; P=0.04) to achieve a similar success rate (84% vs. 81%; P=0.833). CONCLUSION: The addition of EGM-guided ablation requires fewer procedures to achieve similar clinical efficacy in mid-term follow-up compared with a PVI-only strategy in patients with PsAF presenting for ablation in SR.

The importance of an ECG: back to basics.

A 48-year-old man presented to accident and emergency with syncope on a background history of 3 weeks of increasing shortness of breath. He collapsed at home prompting admission. He was a smoker with a 30-pack-year history. On examination, he was found to be tachypnoeic and hypoxic, with a raised JVP and quiet heard sounds. He was haemodynamically stable and a chest x-ray showed right upper-lobe collapse. His resting ECG demonstrated electrical alternans prompting urgent referral to the cardiologist for echocardiography. This revealed a large pericardial effusion with evidence of right ventricular diastolic collapse. In view of this, he underwent urgent pericardiocentesis. A subsequent CT scan showed bilateral pleural effusions and multiple lung nodules. Both pericardial and pleural fluid cytology were reported as metastatic non-small cell adenocarcinoma. The pericardial fluid continued to reaccumulate requiring a pericardial window. He was referred to the oncology team for palliative chemotherapy.

Adverse response to cardiac resynchronisation therapy in patients with septal scar on cardiac MRI preventing a septal right ventricular lead position.

PURPOSE: Myocardial scar is an adverse factor when considering which patients are likely to respond to cardiac resynchronisation therapy (CRT). We hypothesized that septal scarring on magnetic resonance imaging (MRI) may be associated with a poor outcome from CRT, which may relate to the inability to place the right ventricular (RV) lead in the septum. METHODS: Fifty patients (ejection fractions, 25 ± 8%; 45 men, 62.8 ± 14 years; 26 dilated cardiomyopathy; and 24 ischaemic cardiomyopathy (ICM)) receiving CRT underwent delayed enhancement cardiac MRI to assess location and burden of myocardial scar. Acute hemodynamic response (AHR) was evaluated at implant with a pressure wire in the left ventricular (LV) cavity. LV remodelling was determined by reduction in LV end-systolic volume at 6 months. RESULTS: The presence of ICM with septal scar was associated with a poor acute and chronic response to CRT. This was predominantly due to a worse response in patients with septal scar. Patients without septal scar had a better AHR with a 26.7 ± 28.9% rise in LV dP/dt (max) from baseline vs. -2.8 ± 14.5% for patients with septal scar (P = 0.01) with Biventricular (BIV) pacing. A greater proportion remodelled (56% vs. 20% (P = 0.02)). Furthermore, only 33% of patients with septal scar had an RV septal lead compared with 66% with no septal scar (P = 0.03). CONCLUSIONS: The presence of septal scar was associated with a poor acute and chronic response to CRT. This may relate to the inability to achieve a RV septal lead placement.

Effects of angiotensin receptor blockade on atrial electrical remodelling and the 'second factor' in a goat burst-paced model of atrial fibrillation.

Atrial fibrillation (AF) is self-perpetuating, via mechanisms of acute electrical remodelling and 'second factors' acting over a longer time course. Renin-angiotensin system (RAS) blockade may inhibit AF self-perpetuation. We evaluated the effects of RAS blockade with candesartan in a burst-paced goat model of lone AF in which both mechanisms are known to operate. Bioactivity of oral candesartan was demonstrated in 10 goats by inhibition of the pressor effect of angiotensin II. The effects of candesartan on electrical remodelling were assessed in 12 placebo and 12 candesartan-treated goats in a 28-day burst pacing protocol. To assess the effects of candesartan on second factors (structural remodelling), 16 goats underwent further 28-day periods of burst pacing (two periods in 16 goats, three periods in eight goats) each separated by periods of sinus rhythm sufficient for electrical remodelling to reverse. There was a progressive rise in angiotensin levels in both groups. Candesartan (0.5 mg/kg/day) achieved a 76% blunting of the pressor effect of angiotensin II and had no effect on electrical remodelling; the half time for fall of atrial effective refractory period (AERP) was 22.3 ± 4.9 h (placebo) and 22.0 ± 3.2 h (candesartan) (p = ns). Candesartan had no effect on AF stability, which progressively increased over successive 28-day periods (ANOVA p < 0.05). Candesartan had no effect on atrial electrical remodelling or the operation of 'second factors' in a goat model of lone AF. These findings suggest that any benefits of RAS blockade in patients with AF are unlikely to be due to direct effects on atrial remodelling.