Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Продолжение ThermoCool AF (ThermoCool AF)
Description
Numerous small studies have demonstrated the utility of catheter ablation with pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), as compared with antiarrhythmic drug therapy (ADT). ThermoCool AF is the largest trial to study this question in patients with symptomatic paroxysmal AF, who had not improved with at least one drug.
Hypothesis
Catheter ablation would be superior to ADT in patients with symptomatic AF.
Drugs/Procedures Used
Patients were randomized in a 2:1 fashion to either catheter ablation, or a previously unused antiarrhythmic drug (AAD) (Vaughn class I or III). In the catheter ablation group, PVI was performed using the NaviStar ThermoCool Irrigated Tip Catheter, and the Carto Navigation system. Additional ablation was left to the discretion of the investigator. In the ADT arm, a previously unused Food and Drug Administration approved medication for treating AF (dofetilide, flecainide, propafenone, sotalol, quinidine) at dosages recommended by the American College of Cardiology/American Heart Association/European Society of Cardiology was used. The choice of the drug was at the discretion of the investigator.
Concomitant Medications
Warfarin for 3 months
Principal Findings
A total of 167 patients were randomized, 106 to catheter ablation, and 61 to ADT. The trial was stopped after the first 150 patients were randomized, when interim analysis suggested a strong benefit with catheter ablation. Baseline characteristics were fairly similar between the two groups. The median duration of AF was about 5.7 years. Structural heart disease was present in about 11%, hypertension was present in about 49%, and cerebrovascular accident/transient ischemic attack was noted in 3% of the patients. The mean atrial diameter was about 4.2 cm. The majority of prior AAD failures were due to propafenone (50.3%). Others included sotalol (35.2%), flecainide (27.9%), amiodarone (7.9%), and dofetilide (2.4%). The mean number of class I/III drugs at baseline was 1.3. Most patients in the ADT arm received either flecainide (36%) or propafenone (41%).

Protocol-defined treatment failure was significantly lower in the catheter ablation arm compared with the ADT arm (66% vs. 16%, hazard ratio 0.30, 95% confidence interval 0.19-0.47, p < 0.001). Freedom from symptomatic (70% vs. 19%, p < 0.001) and any (63% vs. 17%, p < 0.001) recurrent atrial arrhythmia was also improved with catheter ablation. There was a high rate of cross-over from the ADT to catheter ablation arm (77%), at a mean of 3.9 months after the onset of the effectiveness evaluation period. Quality of life and symptom severity scores were significantly better in the catheter ablation arm, as compared with the ADT arm at 3 months.

The rate of major treatment-related adverse events at 30 days was similar between the catheter ablation and ADT arms (4.9% vs. 8.8, p = NS), including one pericardial effusion in the catheter ablation arm, and two life-threatening arrhythmias in the ADT arm.
Interpretation
The results of this multicenter trial indicate that catheter ablation with PVI is associated with significantly less treatment failure at 9 months, as compared with ADT, in patients with symptomatic AF, who have failed at least one AAD. There is also a significant reduction in recurrent atrial arrhythmias, a significant improvement in quality of life, without a significant difference in major treatment-related adverse events at 30 days. One limitation of this trial is that even though more than 5,000 patients were screened, only 167 were enrolled. This raises issues with generalizability of these findings. Additionally, all investigators in this trial had extensive experience with catheter ablation, which is a technically challenging procedure. Moreover, ablation practices are not standardized, and a variety of additional ablations besides PVI were frequently employed even in this trial. Hence, outcomes at less experienced centers are likely to be less impressive. Details of rate control between the two groups are also unavailable. Long-term outcomes and cost-effectiveness analyses are also necessary. However, this trial provides supportive evidence regarding the use of catheter ablation for symptomatic AF in patients who have failed at least one AAD.
Conditions
• Arrhythmias / Atrial fibrillation
Therapies
• Electrophysiologic study
Study Design
Randomized. Parallel.
Patients Screened: 5,545
Patients Enrolled: 167
NYHA Class (% I, II, II, IV): I (87%), II (13%)
Mean Follow-Up: 9 months (with a 3-month blanking period)
Mean Patient Age: 55.7 years
% Female: 34

Mean Ejection Fraction: 62.5%
Primary Endpoints
Freedom from protocol-defined treatment failure, which included documented symptomatic paroxysmal AF during the effectiveness evaluation period
Secondary Endpoints
Major treatment-related adverse events at 30 days
Patient Population
At least three symptomatic AF episodes within 6 months prior to randomization (≥1 episode verified by electrocardiography)
Lack of response to at least one AAD (class I, class III, or atrioventricular nodal blocker)
Exclusions:
AF >30 days in duration
Age <18 years
Ejection fraction <40%
Previous catheter ablation for AF
Documented left atrial thrombus
Amiodarone therapy in the preceding 6 months
New York Heart Association class III or IV symptoms
Myocardial infarction within past 2 months, or coronary artery bypass grafting within past 6 months
Thromboembolic event within the past 12 months
Severe pulmonary disease
Prior valvular cardiac surgical procedure
Presence of implantable cardioverter defibrillator
Contraindication to ADT or anticoagulation
Life expectancy <12 months
Left atrial size >5 cm in parasternal view
References: Wilber DJ, Pappone C, Neuzil P, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA 2010;303:333-40.