Atrial fibrillation: The unknown known

For a problem that has been on the back burner for decades, the treatment of atrial fibrillation has suddenly become a "marquis" diagnosis.

Age and technology have led to an explosion of interest in this arcane cardiac problem. Advertisements for new anticoagulants and thrombin inhibitors for "A Fib" have become almost as common as those for male impotency. The aging of the world population certainly has been a major factor in its increased incidence. New technology and pharmacology has driven the increase in clinical interest and has advanced our knowledge about the disease. Epidemiology data have provided important information about the natural history of paroxysmal atrial fibrillation (AF), and its relationship to chronic AF and its adverse effects on long-term mortality.

The importance of anticoagulant therapy for the prevention of systemic emboli and stroke has been the mainstay of therapy for almost 50 years. Although we have struggled with a variety of antiarrhythmic drugs, their shortcomings have been more than apparent. Most of us now use a rate-control strategy to control the tachycardia inherent in AF. The development of new factor Xa and direct thrombin inhibitor drugs have made the logistics of providing adequate thrombus prevention much simpler, if somewhat more expensive.

The elephant in the room is the increasing use of radiofrequency catheter ablation technology that has had some success in the prevention of AF arising from the tissue in the pulmonary vein–atrial interface. Numerous small studies have reported that this technology surpasses rhythm control with antiarrhythmic agents, a hurdle not too difficult to beat. The best results have been observed in patients with recurrent paroxysmal AF where maintenance of regular sinus rhythm has been the primary outcome measurement (JAMA 2014;311:692-700). Even here, recurrence after ablation has been common. The benefit of ablation therapy in patients with initial paroxysmal AF (N. Engl. J. Med. 2012;367:1587-95) or chronic persistent AF has been uncertain at best. As a result, the AHA/ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) guidelines have given a class I (evidence level A) recommendation for ablation therapy for symptomatic paroxysmal AF and class IIa (evidence level A) and IIb (evidence level B) for symptomatic recurrent paroxysmal and longstanding persistent AF when balanced against drug tolerability, respectively (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.021]).

All of these clinical data are exciting and have led to enthusiasm for ablation technology despite the potential for nonfatal and rare fatal complication, based almost entirely on its ability to improve upon the dismal benefits of antiarrhythmic rhythm control. Even as we consider the benefit of ablation therapy, new techniques are being developed. The lack of mortality and morbidity data is a result of the short follow-up, usually limited to a year or two, and small sample size. This lack of long-term outcome data for ablation therapy should be of some concern to clinicians who have lived through the last few years. Many of my readers had not been born when we embarked on the ineffective and dangerous pharmacologic prevention of sudden death by pharmacologic suppression of ambient ventricular premature beats. Numerous surrogate measures of clinical benefit of a variety of therapeutic interventions have been disproven and disposed of in the subsequent years. The use of surrogate measures like the partial suppression of AF rather than morbidity and mortality outcomes to establish clinical benefit, have been largely discarded as a dead end.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA), which is beginning to recruit more than 2,000 patients with new-onset or undertreated paroxysmal, persistent, or longstanding AF to be followed for over 4 years may answer the question of whether radiofrequency ablation therapy, rate control, or rhythm control provides the best clinical treatment of atrial fibrillation. The primary outcome will be the composite endpoint of total mortality, disabling stroke or serious bleeding, or cardiac arrest. An important secondary endpoint will be total mortality. Until its conclusion, we should proceed cautiously with expanding radiofrequency ablation therapy for the treatment of AF.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

For a problem that has been on the back burner for decades, the treatment of atrial fibrillation has suddenly become a "marquis" diagnosis.

Age and technology have led to an explosion of interest in this arcane cardiac problem. Advertisements for new anticoagulants and thrombin inhibitors for "A Fib" have become almost as common as those for male impotency. The aging of the world population certainly has been a major factor in its increased incidence. New technology and pharmacology has driven the increase in clinical interest and has advanced our knowledge about the disease. Epidemiology data have provided important information about the natural history of paroxysmal atrial fibrillation (AF), and its relationship to chronic AF and its adverse effects on long-term mortality.

The importance of anticoagulant therapy for the prevention of systemic emboli and stroke has been the mainstay of therapy for almost 50 years. Although we have struggled with a variety of antiarrhythmic drugs, their shortcomings have been more than apparent. Most of us now use a rate-control strategy to control the tachycardia inherent in AF. The development of new factor Xa and direct thrombin inhibitor drugs have made the logistics of providing adequate thrombus prevention much simpler, if somewhat more expensive.

The elephant in the room is the increasing use of radiofrequency catheter ablation technology that has had some success in the prevention of AF arising from the tissue in the pulmonary vein–atrial interface. Numerous small studies have reported that this technology surpasses rhythm control with antiarrhythmic agents, a hurdle not too difficult to beat. The best results have been observed in patients with recurrent paroxysmal AF where maintenance of regular sinus rhythm has been the primary outcome measurement (JAMA 2014;311:692-700). Even here, recurrence after ablation has been common. The benefit of ablation therapy in patients with initial paroxysmal AF (N. Engl. J. Med. 2012;367:1587-95) or chronic persistent AF has been uncertain at best. As a result, the AHA/ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) guidelines have given a class I (evidence level A) recommendation for ablation therapy for symptomatic paroxysmal AF and class IIa (evidence level A) and IIb (evidence level B) for symptomatic recurrent paroxysmal and longstanding persistent AF when balanced against drug tolerability, respectively (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.021]).

All of these clinical data are exciting and have led to enthusiasm for ablation technology despite the potential for nonfatal and rare fatal complication, based almost entirely on its ability to improve upon the dismal benefits of antiarrhythmic rhythm control. Even as we consider the benefit of ablation therapy, new techniques are being developed. The lack of mortality and morbidity data is a result of the short follow-up, usually limited to a year or two, and small sample size. This lack of long-term outcome data for ablation therapy should be of some concern to clinicians who have lived through the last few years. Many of my readers had not been born when we embarked on the ineffective and dangerous pharmacologic prevention of sudden death by pharmacologic suppression of ambient ventricular premature beats. Numerous surrogate measures of clinical benefit of a variety of therapeutic interventions have been disproven and disposed of in the subsequent years. The use of surrogate measures like the partial suppression of AF rather than morbidity and mortality outcomes to establish clinical benefit, have been largely discarded as a dead end.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA), which is beginning to recruit more than 2,000 patients with new-onset or undertreated paroxysmal, persistent, or longstanding AF to be followed for over 4 years may answer the question of whether radiofrequency ablation therapy, rate control, or rhythm control provides the best clinical treatment of atrial fibrillation. The primary outcome will be the composite endpoint of total mortality, disabling stroke or serious bleeding, or cardiac arrest. An important secondary endpoint will be total mortality. Until its conclusion, we should proceed cautiously with expanding radiofrequency ablation therapy for the treatment of AF.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

For a problem that has been on the back burner for decades, the treatment of atrial fibrillation has suddenly become a "marquis" diagnosis.

Age and technology have led to an explosion of interest in this arcane cardiac problem. Advertisements for new anticoagulants and thrombin inhibitors for "A Fib" have become almost as common as those for male impotency. The aging of the world population certainly has been a major factor in its increased incidence. New technology and pharmacology has driven the increase in clinical interest and has advanced our knowledge about the disease. Epidemiology data have provided important information about the natural history of paroxysmal atrial fibrillation (AF), and its relationship to chronic AF and its adverse effects on long-term mortality.

The importance of anticoagulant therapy for the prevention of systemic emboli and stroke has been the mainstay of therapy for almost 50 years. Although we have struggled with a variety of antiarrhythmic drugs, their shortcomings have been more than apparent. Most of us now use a rate-control strategy to control the tachycardia inherent in AF. The development of new factor Xa and direct thrombin inhibitor drugs have made the logistics of providing adequate thrombus prevention much simpler, if somewhat more expensive.

The elephant in the room is the increasing use of radiofrequency catheter ablation technology that has had some success in the prevention of AF arising from the tissue in the pulmonary vein–atrial interface. Numerous small studies have reported that this technology surpasses rhythm control with antiarrhythmic agents, a hurdle not too difficult to beat. The best results have been observed in patients with recurrent paroxysmal AF where maintenance of regular sinus rhythm has been the primary outcome measurement (JAMA 2014;311:692-700). Even here, recurrence after ablation has been common. The benefit of ablation therapy in patients with initial paroxysmal AF (N. Engl. J. Med. 2012;367:1587-95) or chronic persistent AF has been uncertain at best. As a result, the AHA/ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) guidelines have given a class I (evidence level A) recommendation for ablation therapy for symptomatic paroxysmal AF and class IIa (evidence level A) and IIb (evidence level B) for symptomatic recurrent paroxysmal and longstanding persistent AF when balanced against drug tolerability, respectively (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.021]).

All of these clinical data are exciting and have led to enthusiasm for ablation technology despite the potential for nonfatal and rare fatal complication, based almost entirely on its ability to improve upon the dismal benefits of antiarrhythmic rhythm control. Even as we consider the benefit of ablation therapy, new techniques are being developed. The lack of mortality and morbidity data is a result of the short follow-up, usually limited to a year or two, and small sample size. This lack of long-term outcome data for ablation therapy should be of some concern to clinicians who have lived through the last few years. Many of my readers had not been born when we embarked on the ineffective and dangerous pharmacologic prevention of sudden death by pharmacologic suppression of ambient ventricular premature beats. Numerous surrogate measures of clinical benefit of a variety of therapeutic interventions have been disproven and disposed of in the subsequent years. The use of surrogate measures like the partial suppression of AF rather than morbidity and mortality outcomes to establish clinical benefit, have been largely discarded as a dead end.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA), which is beginning to recruit more than 2,000 patients with new-onset or undertreated paroxysmal, persistent, or longstanding AF to be followed for over 4 years may answer the question of whether radiofrequency ablation therapy, rate control, or rhythm control provides the best clinical treatment of atrial fibrillation. The primary outcome will be the composite endpoint of total mortality, disabling stroke or serious bleeding, or cardiac arrest. An important secondary endpoint will be total mortality. Until its conclusion, we should proceed cautiously with expanding radiofrequency ablation therapy for the treatment of AF.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.