Malcolm Finlay

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.

Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study

Aims Anecdotal observations suggest that sub-clinical electrophysiological manifestations of arrhythmogenic right ventricular cardiomyopathy (ARVC) develop before detectable structural changes ensue on cardiac imaging. To test this hypothesis, we investigated a murine model with conditional cardiac genetic deletion of one desmoplakin allele (DSP ±) and compared the findings to patients with non-diagnostic features of ARVC who carried mutations in desmoplakin. Methods and results Murine: the DSP (±) mice underwent electrophysiological, echocardiographic, and immunohistochemical studies. They had normal echocardiograms but delayed conduction and inducible ventricular tachycardia associated with mislocalization and reduced intercalated disc expression of Cx43. Sodium current density and myocardial histology were normal at 2 months of age. Human: ten patients with heterozygous mutations in DSP without overt structural heart disease (DSP+) and 12 controls with supraventricular tachycardia were studied by high-density electrophysiological mapping of the right ventricle. Using a standard S1–S2 protocol, restitution curves of local conduction and repolarization parameters were constructed. Significantly greater mean increases in delay were identified particularly in the outflow tract vs. controls (P< 0.01) coupled with more uniform wavefront progression. The odds of a segment with a maximal activation–repolarization interval restitution slope >1 was 99% higher (95% CI: 13%; 351%, P= 0.017) in DSP+ vs. controls. Immunostaining revealed Cx43 mislocalization and variable Na channel distribution. Conclusion Desmoplakin disease causes connexin mislocalization in the mouse and man preceding any overt histological abnormalities resulting in significant alterations in conduction–repolarization kinetics prior to morphological changes detectable on conventional cardiac imaging. Haploinsufficiency of desmoplakin is sufficient to cause significant Cx43 mislocalization. Changes in sodium current density and histological abnormalities may contribute to a worsening phenotype or disease but are not necessary to generate an arrhythmogenic substrate. This has important implications for the earlier diagnosis of ARVC and risk stratification.

Long-term efficacy of catheter ablation for atrial fibrillation: impact of additional targeting of fractionated electrograms

Objectives To investigate long-term efficacy of catheter ablation for atrial fibrillation (AF) and the impact of ablating complex or fractionated electrograms (CFEs) in addition to pulmonary vein isolation and linear lesions in persistent AF (PeAF). Methods Consecutive cases from 2002–2007 were analysed. All the patients underwent a wide-area circumferential ablation with confirmation of electrical isolation. For PeAF, linear lesions were added, with additional targeting of CFE from 2005. Data were collected in a prospective database. Attempts were made to contact all patients for follow-up. Results 285 patients underwent 530 procedures. The mean (SD) age was 57 (11) years, 75% were male, 20% had structural heart disease and 53% had paroxysmal AF (PAF). The mean number of procedures was 1.9 per patient (1.7 for PAF and 2.0 for PeAF). Procedural complications included stroke or transient ischemic attack in 0.6% and pericardial effusion requiring drainage in 1.7%. During 2.7 years (0.2 to 7.4 years) of follow-up from the last procedure, there were seven deaths (unrelated to their ablation or AF) and three strokes or transient ischemic attack (0.3% per year). Freedom from AF/atrial tachyarrhythmia was 86% for PAF and 68% for PeAF. Late recurrence was 3 per 100 years of follow-up after >3 years. The Kaplan–Meier analysis showed that CFE ablation improved the outcome for PeAF after the first cluster of procedures (p=0.049), with a trend towards improved final outcome (p=0.130). Conclusions Long-term freedom from AF is achievable in most patients with PAF and PeAF with low rates of late recurrence. Additional targeting of CFE improves outcome for PeAF. Late adverse events including stroke are few.

Catheter Ablation for Atrial Fibrillation on Uninterrupted Warfarin: Can It Be Done Without Echo Guidance?

AF Ablation on Uninterrupted Warfarin. Introduction: Catheter ablation for atrial fibrillation is an effective treatment for symptomatic patients who have failed drug therapy. Recent studies using intracardiac echocardiography have demonstrated that ablation can be performed safely on uninterrupted warfarin and may be superior to bridging low molecular weight heparin (LMWH). We sought to assess the safety of an uninterrupted warfarin protocol using a simplified ablation protocol in a prospective controlled study.

Point-by-Point Radiofrequency Ablation Versus the Cryoballoon or a Novel Combined Approach: A Randomized Trial Comparing 3 Methods of Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation (The Cryo Versus RF Trial).

Catheter ablation of paroxysmal AF using the Cryoballoon (CRYO) has yielded similar success rates to conventional wide encirclement using radiofrequency catheter ablation (RFCA), but randomized data are lacking. Pilot data suggested a high success rate with a combined approach (COMBINED) using wide encirclement with RFCA followed by 2 CRYO applications to each vein. We compared these 3 strategies in a randomized controlled trial.

Catheter ablation of atrial fibrillation in patients with heart failure: impact of maintaining sinus rhythm on heart failure status and long-term rates of stroke and death

AIMS Catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) can improve left ventricular (LV) function and HF symptoms. We aimed to investigate whether long-term maintenance of sinus rhythm impacts on hard outcomes such as stroke and death. METHODS AND RESULTS An international multicentre registry was compiled from seven centres for consecutive patients undergoing catheter ablation of AF. Long-term freedom from AF was examined in patients with and without HF. The impact of maintaining sinus rhythm on rates of stroke and death was also examined. A total of 1273 patients were included: 171 with HF and 1102 without. Median follow-up was 3.1 years (IQR 2.0-4.3). The final procedure success rate was no different for paroxysmal AF (PAF) (78.7 vs. 85.7%, P = 0.186), but significantly different for persistent AF (57.3 vs. 75.8%, P < 0.001). Multivariate analysis showed that HF independently predicted recurrent arrhythmia [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.002]. New York Heart Association class decreased from 2.3 ± 0.7 at baseline to 1.5 ± 0.8 at follow-up (P < 0.001). Left ventricular ejection fraction (LVEF) increased from 34.3 ± 9.0 to 45.8 ± 12.8% (P < 0.001). Recurrent AF was strongly predictive of stroke or death in HF patients (HR 8.33, 95% CI 1.86-37.7, P = 0.001). CONCLUSION Long-term success rates for persistent (but not paroxysmal) AF ablation are significantly lower in HF patients. Left ventricular function and HF symptoms were improved following ablation. In HF patients, recurrent arrhythmia strongly predicted stroke and death during follow-up.

Uninterrupted Warfarin for Periprocedural Anticoagulation in Catheter Ablation of Typical Atrial Flutter: A Safe and Cost‐Effective Strategy

Uninterrupted Warfarin for Periprocedural Anticoagulation in Catheter Ablation of Typical Atrial Flutter. Introduction: Many patients undergoing catheter ablation of atrial flutter (AFL) require periprocedural anticoagulation. We compared a strategy of conversion to low molecular weight heparin (LMWH) periprocedure to uninterrupted warfarinization in a nonrandomized, case‐controlled study.

The Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes Study: 5-year follow-up of revascularization with percutaneous coronary intervention versus coronary artery bypass grafting in diabetic patients with multivessel disease.

Objectives The aim of the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study was to assess percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) as treatments for multivessel coronary artery disease in diabetic patients. Background CABG is generally regarded as the treatment of choice for multivessel coronary artery disease in diabetes. PCI is an alternative therapy. The Bypass Angioplasty Revascularization in Type 1 and 2 Diabetes study compared long-term outcomes of CABG with PCI in diabetic patients treated during the bare-metal stent era. Methods We collected data prospectively on consecutive diabetic patients undergoing index angiography in a single tertiary centre from January 1998 to December 2001. Multivessel coronary artery disease was defined as more than 50% luminal stenosis in two or more vessels. Exclusion criteria included left main stem disease and previous revascularization. Results Two hundred and thirty-five eligible patients underwent CABG and 237 PCI. Median follow-up was 5.4 years. There were 46 (19%) deaths in the CABG group and 43 (18%) deaths in the PCI group (P = 0.64). Cox regression analysis revealed baseline glomerular filtration rate (hazard ratio 0.979, P = 0.001), age (hazard ratio 1.034, P = 0.033), urgent procedure (hazard ratio 1.97, P = 0.008) and myocardial infarction within 4 weeks (hazard ratio 2.494, P = 0.041) to be important predictors of outcome. At 5 years, there was no mortality difference (hazard ratio 1.0) following adjustment for baseline characteristics, and the Kaplan–Meier survival curves were similar. A subanalysis of patients with three-vessel disease revealed similar outcomes with both PCI and CABG. Conclusion In the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study, diabetic patients with multivessel coronary artery disease had similar long-term mortality whether treated with CABG or PCI, the revascularization determined by the physicians choice. This was despite the frequent use of a strategy of selective revascularization in the PCI arm. Randomized trials comparing PCI and CABG specifically in diabetes, that is, Coronary Artery Revascularization in Diabetes and Future Revascularization Evaluation in Diabetes Mellitus: Optimal Management, will show whether drug-eluting stents further enhance PCI outcomes over the long term.

A propensity matched case–control study comparing efficacy, safety and costs of the subcutaneous vs. transvenous implantable cardioverter defibrillator

BACKGROUND Subcutaneous implantable cardioverter defibrillators (S-ICD) have become more widely available. However, comparisons with conventional transvenous ICDs (TV-ICD) are scarce. METHODS We conducted a propensity matched case-control study including all patients that underwent S-ICD implantation over a five-year period in a single tertiary centre. Controls consisted of all TV-ICD implant patients over a contemporary time period excluding those with pacing indication, biventricular pacemakers and those with sustained monomorphic ventricular tachycardia requiring anti-tachycardia pacing. Data was collected on device-related complications and mortality rates. A cost efficacy analysis was performed. RESULTS Sixty-nine S-ICD cases were propensity matched to 69 TV-ICD controls. During a mean follow-up of 31±19 (S-ICD) and 32±21months (TV-ICD; p=0.88) there was a higher rate of device-related complications in the TV-ICD group predominantly accounted for by lead failures (n=20, 29% vs. n=6, 9%; p=0.004). The total mean cost for each group, including the complication-related costs was £9967±4511 (

Absence of the Regulator of G-protein Signaling, RGS4, Predisposes to Atrial Fibrillation and Is Associated with Abnormal Calcium Handling.

13,639±6173) and £12,601±1786 (