20 years from demonstration of AF origin in pulmonary veins to a clincal trial with controversial results

 In 1998, Haissaguerre et al (1) described atrial ectopy or premature atrial beats within the pulmonary veins as the trigger for atrial fibrillation.It seemed to be a particularly attractive theory for the origin of paroxysmal AF (PAF) and has also been proposed as a facilitator of continuation of AF to persistent AF.

This lead to the idea that electrical isolation of the pulmonary veins by burning atrial tissue would keep the ectopy from reaching the rest of the atrium .

And so Pulmonary vein isolation (PVI) really caught on being used for not only PAF but for persistent AF as well  and ever since  the electrophysiology world has awaited a randomized clinical trial answering the question does PVI decrease mortality in atrial fibrillation (AF). It is accepted dogma,backed by considerable experience that PVI is superior to medication treatment in suppressing AF and there is general agreement that restoration of sinus rhythm improves quality of life .A  unanswered question was does PVI decrease risk of death associated with AF.

The Long-awaited CABANA trial was supposed to  or at least hoped would  provide an "Answer" to that question.

When the results of this large (2204 subjects) multi-center,multi national (https://www.acc.org/latest-in-cardiology/clinical-trials/2018/05/10/15/57/cabana) were announced there was no widespread celebration in the EP community. When the data were analyzed according to the standard statistical method used in randomized superiority clinical trials ( namely the "intention to treat" (ITT)) method), there was no difference in the primary outcome which was the combined end points of death,disabling stroke,serious bleeding or cardiac arrest  between the ablation group and the treated with drugs group.Further using ITT analysis there was no significant difference between the two treatment arms for each of the components of the combined end point .

For ablation versus drug therapy :8% vrs. 9.2%  with a hazard ratio of 0.86 (0.65-1.15, ) p=0.3 in regard to the primary endpoint.

There was no difference in death nor in serious stroke between the two arms of the study.

However looking at secondary outcomes- In regard to the category of death or cardiovascular hospitalization  there was a significant difference.

 There is more than one way to analyze data and results of the "per protocol " analysis gave  consolation to the EP cardiologists.

The per protocol analysis showed: a significant decrease in the composite primary end point with ablation  -ablation 7% versus  drug10.9 %  ( HR 0.57 , 0.50 -0.89) and decrease in all cause mortality in the ablation group , 7.5 % for drugs versus 4.4 % for ablation.

So intention to treat analysis indicated that ablation was not superior while per protocol analysis indicated that ablation was superior.Something for everyone.

Though heralded by some as a "game changer", I see nothing in the results changing any game. EP cardiologists are not likely to change their practice in any meaningful way  Just look at the final sentence in the Conclusion slide presented at the American College of Cardiology meeting in August 2018:

"Ablation is an accepted treatment strategy for treating AF with low adverse event rates even in higher risk patients."
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 Since the study confirms what other data have shown namely that ablation converts AF to sinus rhythm more often than drugs and since sinus rhythm is associated with a better "quality of life" and the results are more durable why would EP docs  change the way they are practicing ?



 1)Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Mouroux AL, Metayer PL, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med.1998;339:659