Optimum lesion set and predictors of outcome in persistent atrial fibrillation ablation: a meta-regression analysis.

AIMS: Ablation of persistent atrial fibrillation (PsAF) has been performed by many techniques with varying success rates. This may be due to ablation techniques, patient demographics, comorbidities, and trial design. We conducted a meta-regression of studies of PsAF ablation to elucidate the factors affecting atrial fibrillation (AF) recurrence. METHODS AND RESULTS: Databases were searched for prospective studies of PsAF ablation. A meta-regression was performed. Fifty-eight studies (6767 patients) were included. Complex fractionated atrial electrogram (CFAE) ablation reduced freedom from AF by 8.9% [95% confidence interval (CI) -15 to -2.3, P = 0.009). Left atrial appendage [LAA isolation (three study arms)] increased freedom from AF by 39.5% (95% CI 9.1-78.4, P = 0.008). Posterior wall isolation (PWI) (eight study arms) increased freedom from AF by 19.4% (95% CI 3.3-38.1, P = 0.017). Linear ablation or ganglionated plexi ablation resulted in no significant effect on freedom from AF. More extensive ablation increased intraprocedural AF termination; however, intraprocedural AF termination was not associated with improved outcomes. Increased left atrial diameter was associated with a reduction in freedom from AF by 4% (95% CI -6.8% to -1.1%, P = 0.007) for every 1 mm increase in diameter. CONCLUSION: Linear ablation, PWI, and CFAE ablation improves intraprocedural AF termination, but such termination does not predict better long-term outcomes. Study arms including PWI or LAA isolation in the lesion set were associated with improved outcomes in terms of freedom from AF; however, further randomized trials are required before these can be routinely recommended. Left atrial size is the most important marker of AF chronicity influencing outcomes.

Outcomes of paroxysmal atrial fibrillation ablation studies are affected more by study design and patient mix than ablation technique.

OBJECTIVE: We tested whether ablation methodology and study design can explain the varying outcomes in terms of atrial fibrillation (AF)-free survival at 1 year. BACKGROUND: There have been numerous paroxysmal AF ablation trials, which are heterogeneous in their use of different ablation techniques and study design. A useful approach to understanding how these factors influence outcome is to dismantle the trials into individual arms and reconstitute them as a large meta-regression. METHODS: Data were collected from 66 studies (6941 patients). With freedom from AF as the dependent variable, we performed meta-regression using the individual study arm as the unit. RESULTS: Success rates did not change regardless of the technique used to produce pulmonary vein isolation (PVI). Neither was adjunctive lesion sets associated with any improvement in outcome. Studies that included more males and fewer hypertensive patients were found more likely to report better outcomes. The electrocardiography method selected to assess outcome also plays an important role. Outcomes were worse in studies that used regular telemonitoring (by 23%; P < 0.001) or in patients who had implantable loop recorders (by 21%; P = 0.006), rather than those with the less thorough periodic Holter monitoring. CONCLUSIONS: Outcomes of AF ablation studies involving PVI are not affected by the technologies used to produce PVI. Neither do adjunctive lesion sets change the outcome. Achieving high success rates in these studies appears to be dependent more on patient mix and on the thoroughness of AF detection protocols. These should be carefully considered when quoting the success rates of AF ablation procedures that are derived from such studies.

Cardiac arrest in a mother and daughter and the identification of a novel RYR2 variant, predisposing to low penetrant catecholaminergic polymorphic ventricular tachycardia in a four-generation Canadian family.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia syndrome characterized by adrenergically driven ventricular arrhythmia predominantly caused by pathogenic variants in the cardiac ryanodine receptor (RyR2). We describe a novel variant associated with cardiac arrest in a mother and daughter. METHODS: Initial sequencing of the RYR2 gene identified a novel variant (c.527G > T, p.R176L) in the index case (the mother), and her daughter. Structural analysis demonstrated the variant was located within the N-terminal domain of RyR2, likely leading to a gain-of-function effect facilitating enhanced calcium ion release. Four generation cascade genetic and clinical screening was carried out. RESULTS: Thirty-eight p.R176L variant carriers were identified of 94 family members with genetic testing, and 108 family members had clinical evaluations. Twelve carriers were symptomatic with previous syncope and 2 additional survivors of cardiac arrest were identified. Thirty-two had clinical features suggestive of CPVT. Of 52 noncarriers, 11 had experienced previous syncope with none exhibiting any clinical features of CPVT. A documented arrhythmic event rate of 2.89/1000 person-years across all carriers was calculated. CONCLUSION: The substantial variability in phenotype and the lower than previously reported penetrance is illustrative of the importance of exploring family variants beyond first-degree relatives.