Pulmonary vein isolation alone may be best ablative procedure for persistent atrial fibrillation

BARCELONA – More extensive catheter ablation procedures offered no benefit over pulmonary vein isolation alone for persistent atrial fibrillation in the largest-ever randomized trial examining outcomes of the three most popular ablation strategies.

"This study, the STAR AF 2 trial, will force a change in thinking both in the guidelines as well as in clinical practice," Dr. Atul Verma predicted, in presenting the study findings at the annual congress of the European Society of Cardiology.

Because of a widespread belief that catheter ablation success rates are probably lower in persistent AF than in paroxysmal AF, guidelines suggest "operators should consider more ablation based on linear lesions or complex fractionated electrograms," in addition to pulmonary vein isolation, in treating patients with persistent AF (Heart Rhythm 2012;9:632-96). The guidelines noted, however, that there is little evidence to support this recommendation.

The STAR AF 2 trial was conducted to learn if more complex ablation procedures really do provide greater efficacy than pulmonary vein isolation (PVI) alone. The study included 589 patients at 48 centers in 12 countries. All patients had persistent AF refractory to at least one antiarrhythmic drug and were about to undergo their first-ever catheter ablation.

Participants were randomized 1:4:4 to PVI alone with the procedural endpoint of entrance and exit block by circular mapping catheter, or PVI plus mapping and ablation of complex fractionated electrograms during AF identified using a validated 3-D mapping system, or PVI plus a left atrial roof line and another line along the mitral valve isthmus with the endpoint of bidirectional block confirmed by prespecified pacing maneuvers.

Patients remained blinded as to which of the three treatments they received. They were prospectively followed with 24-hour Holter monitoring at 3, 6, 9, 12, and 18 months along with weekly transtelephonic monitoring transmissions or at any time they felt symptoms.

Successful PVI was achieved in 97% of patients, complex fractionated electrograms were eliminated in 80% of patients assigned to that strategy, and both target lines were blocked in 74% of patients who underwent linear ablation.

The primary outcome was freedom from a documented episode of AF lasting more than 30 seconds after one procedure with or without antiarrhythmic medication through 18 months. The rates were 59% with PVI only, 48% with PVI plus complex fractionated electrograms, and 44% with PVI and linear ablation. These rates weren’t significantly different.

There were downsides to the two more elaborate ablation strategies. Procedural times were roughly 1 hour longer. Moreover, mean fluoroscopy time was 29 minutes in the PVI-only group, compared with 41 and 42 minutes with the more complex procedures. That translates to 44% more radiation exposure for both operators and patients, with absolutely no resultant added benefit over PVI alone, noted Dr. Verma, an electrophysiologist at Southlake Regional Health Center in Newmarket, Ont.

Complication rates across the board in STAR AF 2 were among the lowest ever reported in a multicenter clinical trial of catheter ablation. Of note, however, the sole fatal complication was the result of an atrial esophageal fistula in a patient assigned to PVI plus electrogram ablation.

Discussant Dr. Jagmeet P. Singh, director of the cardiac resynchronization therapy program at Massachusetts General Hospital, Boston, called STAR AF 2 "a fantastic trial."

"This study surely advocates that less ablation is more – and less works quite well," he said, noting that the roughly 50% success rate at 18 months with PVI alone is comparable to prior published success rates in paroxysmal AF.

Discussant Dr. Paulus Kirchhof said his own recent informal survey of high-volume catheter ablation centers in the United States and Europe indicated roughly one-third do PVI alone for patients with persistent AF, one-third do PVI plus ablation of complex fractionated electrograms, and one-third do PVI plus linear ablation.

"So I would say this was a question at equipoise," added Dr. Kirchhof, professor of cardiovascular sciences at the University of Birmingham (England).

Zeroing in on the added fluoroscopy time associated with the more complex ablation procedures, he noted that observational data suggest lengthier fluoroscopy may be associated with silent, subclinical brain lesions. Based upon the STAR 2 AF results, therefore, a reasonable strategy now for persistent AF is to do PVI alone, then wait and see what happens before considering additional ablation procedures later, he said.

"More importantly, I think this study shows we have to go back to the drawing board. The time pattern of AF – its duration, whether it’s paroxysmal or persistent, the left atrial size – all these things we believe identify patients who need more therapy, they may not actually help us. We just have to accept that not all patients with AF are the same, and that the pattern of AF does not discriminate so well. I think what we can really learn from this trial moving forward is that we need a clinical classification of AF patients. We have to define the patient who would benefit before we continue to develop ever-more intensive interventional strategies," he commented.

Factors worthy of further study as potential tools for separating AF patients into subgroups for treatment purposes include markers of atrial fibrosis, whether by imaging, blood, or ECG patterns; markers of parasympathetic/sympathetic imbalance; clinical markers of abnormal calcium metabolism; or blood markers, Dr. Kirchhof added.

The STAR AF 2 trial was funded by St. Jude Medical. Dr. Verma, Dr. Singh, and Dr. Kirchhof reported receiving grant support from St. Jude Medical as well as other pharmaceutical and medical device companies. In addition, Dr. Verma and Dr. Singh have served on advisory boards for St. Jude.

bjancin@frontlinemedcom.com

BARCELONA – More extensive catheter ablation procedures offered no benefit over pulmonary vein isolation alone for persistent atrial fibrillation in the largest-ever randomized trial examining outcomes of the three most popular ablation strategies.

"This study, the STAR AF 2 trial, will force a change in thinking both in the guidelines as well as in clinical practice," Dr. Atul Verma predicted, in presenting the study findings at the annual congress of the European Society of Cardiology.

Because of a widespread belief that catheter ablation success rates are probably lower in persistent AF than in paroxysmal AF, guidelines suggest "operators should consider more ablation based on linear lesions or complex fractionated electrograms," in addition to pulmonary vein isolation, in treating patients with persistent AF (Heart Rhythm 2012;9:632-96). The guidelines noted, however, that there is little evidence to support this recommendation.

The STAR AF 2 trial was conducted to learn if more complex ablation procedures really do provide greater efficacy than pulmonary vein isolation (PVI) alone. The study included 589 patients at 48 centers in 12 countries. All patients had persistent AF refractory to at least one antiarrhythmic drug and were about to undergo their first-ever catheter ablation.

Participants were randomized 1:4:4 to PVI alone with the procedural endpoint of entrance and exit block by circular mapping catheter, or PVI plus mapping and ablation of complex fractionated electrograms during AF identified using a validated 3-D mapping system, or PVI plus a left atrial roof line and another line along the mitral valve isthmus with the endpoint of bidirectional block confirmed by prespecified pacing maneuvers.

Patients remained blinded as to which of the three treatments they received. They were prospectively followed with 24-hour Holter monitoring at 3, 6, 9, 12, and 18 months along with weekly transtelephonic monitoring transmissions or at any time they felt symptoms.

Successful PVI was achieved in 97% of patients, complex fractionated electrograms were eliminated in 80% of patients assigned to that strategy, and both target lines were blocked in 74% of patients who underwent linear ablation.

The primary outcome was freedom from a documented episode of AF lasting more than 30 seconds after one procedure with or without antiarrhythmic medication through 18 months. The rates were 59% with PVI only, 48% with PVI plus complex fractionated electrograms, and 44% with PVI and linear ablation. These rates weren’t significantly different.

There were downsides to the two more elaborate ablation strategies. Procedural times were roughly 1 hour longer. Moreover, mean fluoroscopy time was 29 minutes in the PVI-only group, compared with 41 and 42 minutes with the more complex procedures. That translates to 44% more radiation exposure for both operators and patients, with absolutely no resultant added benefit over PVI alone, noted Dr. Verma, an electrophysiologist at Southlake Regional Health Center in Newmarket, Ont.

Complication rates across the board in STAR AF 2 were among the lowest ever reported in a multicenter clinical trial of catheter ablation. Of note, however, the sole fatal complication was the result of an atrial esophageal fistula in a patient assigned to PVI plus electrogram ablation.

Discussant Dr. Jagmeet P. Singh, director of the cardiac resynchronization therapy program at Massachusetts General Hospital, Boston, called STAR AF 2 "a fantastic trial."

"This study surely advocates that less ablation is more – and less works quite well," he said, noting that the roughly 50% success rate at 18 months with PVI alone is comparable to prior published success rates in paroxysmal AF.

Discussant Dr. Paulus Kirchhof said his own recent informal survey of high-volume catheter ablation centers in the United States and Europe indicated roughly one-third do PVI alone for patients with persistent AF, one-third do PVI plus ablation of complex fractionated electrograms, and one-third do PVI plus linear ablation.

"So I would say this was a question at equipoise," added Dr. Kirchhof, professor of cardiovascular sciences at the University of Birmingham (England).

Zeroing in on the added fluoroscopy time associated with the more complex ablation procedures, he noted that observational data suggest lengthier fluoroscopy may be associated with silent, subclinical brain lesions. Based upon the STAR 2 AF results, therefore, a reasonable strategy now for persistent AF is to do PVI alone, then wait and see what happens before considering additional ablation procedures later, he said.

"More importantly, I think this study shows we have to go back to the drawing board. The time pattern of AF – its duration, whether it’s paroxysmal or persistent, the left atrial size – all these things we believe identify patients who need more therapy, they may not actually help us. We just have to accept that not all patients with AF are the same, and that the pattern of AF does not discriminate so well. I think what we can really learn from this trial moving forward is that we need a clinical classification of AF patients. We have to define the patient who would benefit before we continue to develop ever-more intensive interventional strategies," he commented.

Factors worthy of further study as potential tools for separating AF patients into subgroups for treatment purposes include markers of atrial fibrosis, whether by imaging, blood, or ECG patterns; markers of parasympathetic/sympathetic imbalance; clinical markers of abnormal calcium metabolism; or blood markers, Dr. Kirchhof added.

The STAR AF 2 trial was funded by St. Jude Medical. Dr. Verma, Dr. Singh, and Dr. Kirchhof reported receiving grant support from St. Jude Medical as well as other pharmaceutical and medical device companies. In addition, Dr. Verma and Dr. Singh have served on advisory boards for St. Jude.

bjancin@frontlinemedcom.com

BARCELONA – More extensive catheter ablation procedures offered no benefit over pulmonary vein isolation alone for persistent atrial fibrillation in the largest-ever randomized trial examining outcomes of the three most popular ablation strategies.

"This study, the STAR AF 2 trial, will force a change in thinking both in the guidelines as well as in clinical practice," Dr. Atul Verma predicted, in presenting the study findings at the annual congress of the European Society of Cardiology.

Because of a widespread belief that catheter ablation success rates are probably lower in persistent AF than in paroxysmal AF, guidelines suggest "operators should consider more ablation based on linear lesions or complex fractionated electrograms," in addition to pulmonary vein isolation, in treating patients with persistent AF (Heart Rhythm 2012;9:632-96). The guidelines noted, however, that there is little evidence to support this recommendation.

The STAR AF 2 trial was conducted to learn if more complex ablation procedures really do provide greater efficacy than pulmonary vein isolation (PVI) alone. The study included 589 patients at 48 centers in 12 countries. All patients had persistent AF refractory to at least one antiarrhythmic drug and were about to undergo their first-ever catheter ablation.

Participants were randomized 1:4:4 to PVI alone with the procedural endpoint of entrance and exit block by circular mapping catheter, or PVI plus mapping and ablation of complex fractionated electrograms during AF identified using a validated 3-D mapping system, or PVI plus a left atrial roof line and another line along the mitral valve isthmus with the endpoint of bidirectional block confirmed by prespecified pacing maneuvers.

Patients remained blinded as to which of the three treatments they received. They were prospectively followed with 24-hour Holter monitoring at 3, 6, 9, 12, and 18 months along with weekly transtelephonic monitoring transmissions or at any time they felt symptoms.

Successful PVI was achieved in 97% of patients, complex fractionated electrograms were eliminated in 80% of patients assigned to that strategy, and both target lines were blocked in 74% of patients who underwent linear ablation.

The primary outcome was freedom from a documented episode of AF lasting more than 30 seconds after one procedure with or without antiarrhythmic medication through 18 months. The rates were 59% with PVI only, 48% with PVI plus complex fractionated electrograms, and 44% with PVI and linear ablation. These rates weren’t significantly different.

There were downsides to the two more elaborate ablation strategies. Procedural times were roughly 1 hour longer. Moreover, mean fluoroscopy time was 29 minutes in the PVI-only group, compared with 41 and 42 minutes with the more complex procedures. That translates to 44% more radiation exposure for both operators and patients, with absolutely no resultant added benefit over PVI alone, noted Dr. Verma, an electrophysiologist at Southlake Regional Health Center in Newmarket, Ont.

Complication rates across the board in STAR AF 2 were among the lowest ever reported in a multicenter clinical trial of catheter ablation. Of note, however, the sole fatal complication was the result of an atrial esophageal fistula in a patient assigned to PVI plus electrogram ablation.

Discussant Dr. Jagmeet P. Singh, director of the cardiac resynchronization therapy program at Massachusetts General Hospital, Boston, called STAR AF 2 "a fantastic trial."

"This study surely advocates that less ablation is more – and less works quite well," he said, noting that the roughly 50% success rate at 18 months with PVI alone is comparable to prior published success rates in paroxysmal AF.

Discussant Dr. Paulus Kirchhof said his own recent informal survey of high-volume catheter ablation centers in the United States and Europe indicated roughly one-third do PVI alone for patients with persistent AF, one-third do PVI plus ablation of complex fractionated electrograms, and one-third do PVI plus linear ablation.

"So I would say this was a question at equipoise," added Dr. Kirchhof, professor of cardiovascular sciences at the University of Birmingham (England).

Zeroing in on the added fluoroscopy time associated with the more complex ablation procedures, he noted that observational data suggest lengthier fluoroscopy may be associated with silent, subclinical brain lesions. Based upon the STAR 2 AF results, therefore, a reasonable strategy now for persistent AF is to do PVI alone, then wait and see what happens before considering additional ablation procedures later, he said.

"More importantly, I think this study shows we have to go back to the drawing board. The time pattern of AF – its duration, whether it’s paroxysmal or persistent, the left atrial size – all these things we believe identify patients who need more therapy, they may not actually help us. We just have to accept that not all patients with AF are the same, and that the pattern of AF does not discriminate so well. I think what we can really learn from this trial moving forward is that we need a clinical classification of AF patients. We have to define the patient who would benefit before we continue to develop ever-more intensive interventional strategies," he commented.

Factors worthy of further study as potential tools for separating AF patients into subgroups for treatment purposes include markers of atrial fibrosis, whether by imaging, blood, or ECG patterns; markers of parasympathetic/sympathetic imbalance; clinical markers of abnormal calcium metabolism; or blood markers, Dr. Kirchhof added.

The STAR AF 2 trial was funded by St. Jude Medical. Dr. Verma, Dr. Singh, and Dr. Kirchhof reported receiving grant support from St. Jude Medical as well as other pharmaceutical and medical device companies. In addition, Dr. Verma and Dr. Singh have served on advisory boards for St. Jude.

bjancin@frontlinemedcom.com