Disclamier: This program is for educational purpose only and reflects independent editorial commentary. It is not medical advice and should not replace clinical judgment or review of primary sources and guidelines. The views expressed are those of the host and contributors.
Niraj Sharma: Welcome to EP Edge Journal Watch. I am Doctor. Sharma and thank you for joining me. Before we start, a quick note on statistics, because I want this episode to work not just for electrophysiologists but also for nurses, nurse practitioners, fellows, and the broader EP team. When I say hazard ratio, think of it as a comparison of how often an event happens over time in one group versus another.
A hazard ratio of one means no difference. Above one means the event is happening more often in the study group. Below one means it is happening less often. When I mention a confidence interval, that is the range of values within which the true effect probably lies. If that range crosses one for a hazard ratio or an odds ratio, the result is less convincing statistically.
And when I say p value, that is simply the probability that the difference we saw could have happened by chance if there were really no true difference. Lower p values make the result more statistically persuasive, but they do not tell us whether the finding is large, important, or clinically useful. Let's start with cannabis and arrhythmia risk. This study was done because cannabis use is rising rapidly, while the cardiovascular conversation around it still often lags behind public perception. The investigators used a large real world TriNetX dataset from 68 U.
S. Health care organizations and compared 210,817 adult cannabis users with an equal number of propensity matched ibuprofen users. They excluded other recreational drug users, which is important because it reduces some obvious confounding. The primary outcomes were atrial fibrillation paroxysmal tachycardia, premature beats, and ventricular tachycardia The results were striking. For atrial fibrillation or flutter, the hazard ratio was one point five four nine.
In plain English, that means the cannabis group had about a fifty five percent higher rate of atrial fibrillation or flutter over follow-up than the comparison group. For paroxysmal tachycardia, the hazard ratio was 1.791, meaning about a seventy nine percent higher rate. For premature beats, the hazard ratio was 1.739, again meaning the event happened much more often in cannabis users. And the most dramatic signal was ventricular tachycardia or fibrillation, with a hazard ratio of three point zero seven eight. That means the ventricular arrhythmia rate was a little over three times higher in the cannabis group.
The confidence intervals for these hazard ratios stayed well away from one, and the p values were all less than 0.001, which makes the association statistically strong. Now, that does not prove causality. We still do not know dose, root, recency, or potency, and the exposure definition came from ICD coding rather than direct quantified exposure data. But the EP Edge take is this: the signal is broad, biologically plausible, and no longer easy to dismiss. In EP practice, cannabis should now be part of a serious arrhythmia history, especially in patients with syncope, palpitations, atrial fibrillation, ventricular arrhythmia risk, inherited channelopathy or antiarrhythmic drug exposure.
Next is the LEAF study. This paper was done because obesity and epicardial fat are linked to worse atrial fibrillation outcomes, and the investigators wanted to know whether adding liraglutide to structured risk factor modification could improve ablation results. This was a randomized study of overweight or obese patients with atrial fibrillation who had elected catheter ablation. Twenty eight patients were assigned to risk factor modification alone and thirty one were assigned to risk factor modification plus liraglutide for three months before ablation. Importantly, about eighty percent had persistent atrial fibrillation, so this was not an easy low risk population.
The primary endpoint was change in left atrial epicardial adipose tissue volume and the ablation strategy was essentially pulmonary vein isolation based. Now here is the interesting part. Overall, left atrial epicardial fat went down and weight went down, but there was no major between group difference in those early structural changes. So if you looked only at the primary mechanistic endpoint, you might think the study was underwhelming. But clinically, it was not underwhelming at all.
One year freedom from atrial fibrillation or flutter was eighty one percent in the liraglutide group and fifty four percent in the control group, with a log rank p value of 0.007. That means the separation in the recurrence curves over time was unlikely to be due to chance alone. In the persistent AF subgroup, the difference was even larger: 88% versus 50%, with a p value less than 0.001. The authors also used odds ratios in adjusted models. An odds ratio works similarly to a hazard ratio in terms of interpretation: one means no difference.
Below one means lower odds of the outcome. Above one means higher odds. In leaf, treatment with liraglutide was associated with lower twelve month recurrence with odds ratios well below one, meaning recurrence was less likely in the liraglutide arm even after accounting for other variables in the model. So what is the practical meaning of this study? The paradox is the story.
Liraglutide improved rhythm outcomes without clearly outperforming control for early weight loss or epicardial fat reduction. That opens the door to broader substrate effects possibly through inflammation, adipose biology, autonomic pathways, or what we might call pre ablation substrate stabilization. The study is small and single center, so this is not yet a blanket practice change. But the EP Edge take is that this may be the early outline of a true pharmacologic adjunct to AF ablation, especially in obese patients with persistent atrial fibrillation where substrate matters and where simply adding more lesions has so often disappointed us. Now to FARS AF2.
This paper was done because the usual clinical categories of paroxysmal versus persistent AF are often too blunt to predict who will actually do well with a pulmonary vein isolation only strategy. The investigators prospectively enrolled two nineteen patients undergoing first ablation and measured a pulmonary vein signal called FARS10, which is the average of the 10 fastest consecutive repetitive similar morphology intervals recorded in the pulmonary veins during atrial fibrillation. The primary endpoint was recurrence of AF, atrial flutter, or atrial tachycardia after a PVI only approach. The key finding was the shortest pulmonary vein, FARS 10. When that value was one hundred and fifty five milliseconds or less, recurrence was significantly lower.
The hazard ratio in the overall cohort was zero point three four. In plain language, that means the recurrence rate over follow-up was about sixty six percent lower in the fast pulmonary vein group than in the slow pulmonary vein group. In persistent AF, the hazard ratio was 0.4, meaning about a sixty percent lower recurrence rate. In paroxysmal AF, the hazard ratio was 0.18, meaning an even larger reduction in recurrence risk over time. The study also reports an area under the curve, or AUC, for cutoff of one hundred and fifty five milliseconds.
A UC tells you how well a test separates those with recurrence from those without it. An AUC of 0.5 means the test performs no better than chance. An AUC of one point zero means perfect discrimination. Here the overall AUC was modest, but the signal remained meaningful enough to suggest that pulmonary vein physiology may classify PVI only responders better than AF label alone. The EP Edge take is that this is one of the more intellectually important AF ablation papers in the issue.
It shifts the conversation away from simple category labels and toward physiologic phenotyping. We are not yet ready to build every workflow around FARS10 because it is still manual and still needs broader validation. But conceptually, this is where the field needs to go, not just paroxysmal versus persistent, but who is actually PV driven and therefore likely to respond to PVI alone. Next, the vein of Marshall ethanol infusion review. This paper ties anatomy, mechanism, and procedural together beautifully.
The reason this technique exists is that the vein of Marshall and Marshall bundle may contribute to AF through triggers, autonomic input, and epicardial substrate, particularly around the mitral isthmus. Because this region is often protected by fat and difficult to eliminate with endocardial energy alone, the vein of Marshall can be used as a vascular route for retrograde ethanol infusion. The review summarizes randomized evidence showing that in the venous trial, sinus rhythm at twelve months was forty nine point two percent with vein of Marshall ethanol infusion plus ablation versus thirty eight percent with ablation alone. That is an absolute difference of a little over eleven percent. It also highlights randomized data showing much better acute mitral isthmus block rates with vein of Marshall ethanol infusion added to radiofrequency ablation (ninety four percent versus forty three percent ).
So the EP Edge take is that this is no longer just a niche trick. It is becoming a rational substrate adjunct in persistent AF, especially when durable mitral line creation is part of the procedural goal. Now let's turn to pacing. Starting with the Qi CSP study. This was a large prospective registry from five Chinese centers, with 3,336 attempted conduction system, pacing implants, and successful implantation in three thousand one hundred and sixty seven patients.
The mean follow-up was about forty one months, which is valuable because this is no longer just acute implant performance, this is long term behavior. The investigators separated left bundle branch area pacing into true left bundle branch pacing, unclassified left bundle branch area pacing, and left ventricular septal pacing. That classification turned out to matter a great deal. Threshold rise of at least one volt at 0.5 ms occurred in just over five percent of his bundle pacing patients but only about one point eight percent of the broader left bundle branch area pacing group, and in patients with left bundle branch block and heart failure with reduced ejection fraction, the improvement in ejection fraction was much better with true conduction system capture than with left ventricular septal pacing. His pacing improved ejection fraction by about 21.9%, left bundle pacing by about 20.9%, but left ventricular septal pacing by only about twelve point one percent.
The composite of death or heart failure hospitalization in that subgroup was also much worse with left ventricular septal pacing: thirty three point three percent compared with eight point six percent for left bundle pacing and fifteen point four percent for unclassified LB pacing. The p value here was 0.004, which makes that difference statistically compelling. The EP Edge take is straightforward. Not all LB pacing is equivalent. Lead location is not the same thing as physiologic capture, and outcomes appear to depend on that distinction.
Now a very practical companion paper, Pacing site and pre implant screening for the subcutaneous ICD. This study used an ablation catheter to simulate pacing from conduction system sites and from multiple right ventricular septal sites in 30 patients, then measured S ICD screening eligibility. The baseline sinus rhythm pass rate was eighty six point seven percent. Conduction system pacing preserved that almost exactly, 86.7% for right. His pacing, 90% for leftist pacing and eighty six point seven percent for left bundle pacing.
Right ventricular septal pacing, especially apex septal pacing, performed much worse, with pass rates falling as low as ten percent in some apex positions. When you hear a p value less than 0.001 in that context, it means the differences across pacing sites were highly unlikely to be random noise. The practical EP Edge take is immediate. If S ICD compatibility matters, pacing site is not an afterthought. Conduction system pacing best preserves native like activation and native like activation best preserves native like sensing behavior.
Two final papers both highly practical. First, the study comparing chlorhexidine pocket irrigation with an antibacterial envelope for infection prevention in high risk device procedures. This was a retrospective multicenter observational study of seventeen forty nine patients with a propensity matched analysis of seven fourteen patients. The main question was simple: can a cheap and widely available chlorhexidine strategy perform similarly to a more expensive antibacterial envelope? In the full cohort, device related infection occurred in zero point eight percent versus zero point eight percent, with a hazard ratio of zero point eight nine.
That hazard ratio is so close to one that, practically speaking, it means there was no meaningful difference detected between the two strategies in this study. The confidence interval was wide, from 0.3 to 2.66, which tells you the event count was low and the precision around the estimate was limited. After matching, the results stayed essentially the same: one point one percent versus one point one percent, hazard ratio 0.97, again meaning no detectable difference. No adverse events related to chlorhexidine irrigation were reported. The strongest predictor of subsequent infection was previous device infection, with a hazard ratio of seven point zero four.
That means patients with prior device infection had about a seven fold higher rate of another infection over follow-up than those without that history. The EP Edge take is that this paper is highly operational. It does not prove equivalence in a strict randomized trial sense, but it strongly supports chlorhexidine irrigation as a pragmatic low cost strategy, especially where envelope use is limited by cost or access. Finally, the paper on NPP stimuli needed to reach a plateau post pacing interval for diagnosing reentrant atrial tachycardia. This is classic electrophysiology in the best sense, a mechanistically elegant maneuver that may simplify difficult circuit work.
The study included 43 atrial tachycardias in thirty eight patients and examined whether NPP could identify proximity to the tachycardia circuit. The results were very practical. Among sites where conventional entrainment data were available, 104 of 110 sites with NPP three had a post pacing interval minus tachycardia cycle length of thirty milliseconds or less. In other words, NPP of three usually meant you were close to or in the circuit, and all 32 sites with NPP greater than five had post pacing interval minus tachycardia cycle length greater than thirty milliseconds. That means NPP greater than five was an extremely strong signal that you were not in the circuit.
The paper also reports positive and negative predictive value. Positive predictive value tells you how often a positive test result is actually correct. Negative predictive value tells you how often a negative result is actually correct. Here, NPP three had a positive predictive value of 94% for being on the circuit, while NPP five had a negative predictive value of 100% for being out of the circuit. The EP Edge take is that this maneuver does not replace entrainment, but it gives the operator another credible tool that can be done with a single catheter and local capture without always needing the full complexity of classic entrainment validation.
So to recap briefly, this issue showed that cannabis is emerging as a real arrhythmic risk signal. Liraglutide may become a meaningful substrate, adjunct to AF ablation physiology may outperform AF labels. For selecting PVI only responders, vein of Marshall ethanol infusion is becoming a strategic tool in persistent AF. Capture classification matters in conduction system pacing. Pacing site affects S ICD eligibility.
Chlorhexidine irrigation may be a pragmatic infection strategy. NPP offers a useful new way to approach reentrant atrial tachycardia circuits. All references and graphics are available on the LinkedIn newsletter, EP Edge Journal Watch, as well as on Substack at epedge.substack.com Thank you again for listening, take care and see you till the next episode.