TTOP”AF, the first randomised study comparing ablation therapy to traditional medical management (antiarrhythmic drugs and direct current cardioversion) showed a 90% reduction of atrial fibrillation or atrial flutter burden in 55.8% of ablation management patients. These patients were free of antiarrhythmic drug therapy at six months compared to 26.4% in the traditional medical management arm (p<0.0001), thus meeting the chronic effectiveness endpoint. While the ablation patients in the trial demonstrated a reduction in atrial fibrillation burden, the acute safety event rate in the trial was 12.3% with an upper 95% confidence interval of 19%, which did not meet the pre”defined performance goal of 16%.
Medtronic’s sponsored, TTOP”AF (Tailored treatment of permanent atrial fibrillation) clinical trial was presented at Venice Arrhythmias 2011.
The prospective multicentre, controlled clinical trial the largest to date to study the phased radiofrequency ablation technology included a total of 210 patients with persistent and long”standing persistent atrial fibrillation who were randomised in a 2:1 fashion to either receive ablation treatment (138) or traditional medical management (72). Medical management treatment failures were permitted to crossover and receive an ablation, no sooner than four months after enrolment with a target of six months.
Twenty three sites participated in the United States and one in the Netherlands. Patients in the ablation arm were allowed up to two ablations with the Phased RF ablation system (Medtronic) to achieve treatment success, and were followed at one, three and six months post”treatment. Patients in the medical management arm received antiarrhythmic drug changes and direct current cardioversions to achieve and maintain sinus rhythm, and were followed at one, three and six months.
While the ablation patients in the trial demonstrated a reduction in atrial fibrillation burden, the acute safety event rate in the trial was 12.3% with an upper 95% confidence interval of 19%, which did not meet the pre”defined performance goal of 16%. At the time the trial was designed, no benchmark for the persistent atrial fibrillation patient population existed, so the performance goal of 16% was established based on a literature review evaluating ablation procedures for right”sided and paroxysmal atrial ablation procedures. In the TTOP”AF trial, 12.3% (17) of patients experienced one or more protocol”defined procedural and/or device”related adverse events within seven days of the procedure. A total of four strokes (1.7% acute procedural stroke rate) occurred within the acute period after an ablation procedure. The stroke incidence was higher for the first few subjects undergoing an ablation procedure rather than for subjects enrolled later at each site, with three of the four strokes occurring during the first five procedures for each clinical trial centre. Two of the four patients had complete resolution of symptoms within the six-month follow”up period; the other two patients had minor residual effects from the stroke.
“Due to the advanced state of the disease and the attendant increase in the complexity of the procedure, persistent atrial fibrillation patients undergoing ablation have a higher risk than paroxysmal atrial fibrillation patients for adverse events; therefore, the acute safety findings from the TTOP”AF trial are not unexpected,” said John Hummel, director of clinical electrophysiology research at The Ohio State Medical Center. “I believe these data are promising given the reduction in atrial fibrillation burden, and therefore this ablation technology may ultimately represent an important option for drug refractory, symptomatic, persistent atrial fibrillation patients who are more difficult to treat.”
About the Phased RF ablation system
The Medtronic Phased RF ablation system is investigational in the United States and currently approved for use in regions of Europe, Asia, and Africa, as well as in Canada. The system is a percutaneous cardiac catheter and generator system that delivers customised radiofrequency energy designed to eliminate or isolate abnormal electrical impulses in the left atrium. The anatomically designed, multi”electrode catheters are intended to allow physicians to identify and selectively ablate a broader area of heart tissue without the use of current single point catheters and complex mapping and navigation equipment.