Emerging therapies for atrial fibrillation: is the paradigm shifting?

In 1962, Thomas Kuhn popularized the term “paradigmshift” to describe a fundamental change in scientificassumptions in his book entitled “The Structure ofScientific Revolutions” [1]. While some would argue thatthe term has been overused, most would agree thatrevolutionary moments that fundamentally alter our under-standing of a condition merit this designation. Someconsider such a “paradigm shift” to have occurred inthe field of cardiac electrophysiology in 1998 withHaissaguerre’s publication in The New England Journal ofMedicine on “Spontaneous Initiation of Atrial Fibrillationby Ectopic Beats Originating in the Pulmonary Veins” [2].Over a decade later, the medical community has embracedthis mechanistic insight that the triggers of atrial fibrillation(AF) are often found in the pulmonary veins. As a result,we have added AF ablation procedures to our therapeuticarmamentarium in an effort to cure this arrhythmia. Due tothe heterogeneous nature of AF, involving multiple triggersand substrates which range from structurally normal heartsto complex congenital and acquired abnormalities, ourmechanistic knowledge remains rudimentary. While weremain in the infancy of our understanding of thisextraordinary common, yet challenging, arrhythmia, weare on the threshold of innovative ablation techniques,multiple novel antiarrhythmic agents, and alternatives tovitamin K antagonists with the emergence of directthrombin and factor Xa inhibitors [3–5]. Each has thepotential to fundamentally alter the clinical strategiestraditionally employed for restoration of normal sinusrhythm and prevention of thromboembolic events. In thisrespect, it is appropriate to evaluate these emergingtherapies and their potential impact on therapeutic strategiesfor AF over the next several years.While most of the clinical experience with AF ablationhas been with thermal lesions from radiofrequency energy,new energy sources are emerging that have the potential toimprove outcomes in AF patients. The emergence of coldas a therapeutic modality can be traced to James Arnott, awell known British physician (1797–1883). Only in recentyears, however, with the development of an over-the-wire,deflectable, balloon-based catheter design has the potentialfor the delivery of cryoenergy in the treatment of AFbecome a reality. The novelty lays not only in the energysource, cryothermal energy, rather than conventionalradiofrequency energy, but also in the approach to lesionssets, single and circumferential, as opposed to traditionalpoint-by-point ablation. A balloon-based delivery platformmay provide a more efficient means of achieving pulmo-nary vein isolation, particularly suited for patients withparoxysmal AF in whom the goal is to abolish triggers.Thus far, several European centers have demonstratedprocedure safety and short-term efficacy, achieving sinusrhythm in 74% of patients with paroxysmal AF without theuse of antiarrhythmic drug therapy [3]. The major compli-cation appears to be phrenic nerve palsy with ablation ofthe right-sided veins, whereas no significant pulmonaryvein stenosis has been noted [3, 6]. Further advances indevice configurations will likely address the issues ofvariable anatomy, and hybrid approaches will be necessaryto ablate the substrate in patients with persistent AF.Direct clinical comparisons between radiofrequency andcryoablation will expectedly follow.