Dr Niraj Sharma: Hello everyone and welcome to the second issue of the EP Edge Journal Watch podcast, November 2025. I'm Doctor. Neeraj Sharma and today we'll look at six pivotal studies that are shaping the way we manage atrial fibrillation, heart failure and device therapy. We start with ARREST atrial fibrillation where structured lifestyle and risk factor management doubled freedom from AF after ablation. Then the second trial, looking at atrial fibrillation after coronary artery bypass surgery, shows that while AF is common after surgery, its burden however is remarkably low, challenging.
Continued anticoagulation. The open cabana sub analysis reminds us that ablation works best early, before non modifiable risk factors accumulate. Aquatic confirms what we have suspected: combining aspirin with a direct oral anticoagulant in AF and stable coronary artery disease adds bleeding without benefit. The DIGIT HF trial reintroduces Digitoxin, showing promise in heart failure with reduced EF, especially in patients with chronic kidney disease. Digitoxin is still used in Norway, Sweden, and Switzerland, though not available in The US.
And finally, the ICD registry analysis shows that nearly half of recipients receive life saving therapy within ten years, yet only about fifteen percent of eligible patients receive an ICD. When we deep dive into these findings, know that this is an AI conversational narration of my EP Edge Journal Watch newsletter from November issue and that every detail has been personally vetted for accuracy. Let's start.
AI 1: Welcome to the deep dive. You know, this week, you've given us a really fascinating set of sources. Basically, a curated look at some key cardiovascular studies from this past month. Covers a lot of ground. EP, heart failure, devices.
AI 2: Right. And our goal today is to really unpack these, six pivotal studies. Because when you look at them together, they seem to be pointing towards a pretty major shift in how we approach treatment, this idea of precision and proportion.
AI 1: That's a great way to put it. Yeah. Precision and proportion. I think if there's one big takeaway, even before we get into the details, it's that the trend isn't just you know, doing more interventions. It's really about doing better.
AI 2: Doing better. Meaning?
AI 1: Meaning intervening sooner, making smarter choices about who gets what therapy, and sometimes actually doing less, being more selective. We're really challenging some long held assumptions here.
AI 2: Okay, let's start with that precision idea, particularly around AF ablation. We got two studies here that suggest success isn't just about the procedure itself, but what happens beforehand. Exactly, it's about the patient's underlying state. We used to focus almost entirely on the technical aspects of the ablation but these studies highlight how much the patient's metabolic health or the stage of their disease matters.
AI 1: So first up is ARREST AF. This was an RCT, right? Took about one hundred and twenty two patients, all overweight or obese, first time AF ablation and they split them.
AI 2: Yeah, randomize them. One group got intensive physician led lifestyle and risk factor modification LRFM. The other group got, well, usual care.
AI 1: And this LRFM wasn't just casual advice, was it?
AI 2: No, no, Definitely not. It was structured. The intervention group actually achieved on average like a nine kilo weight loss and their systolic blood pressure dropped by nearly 11 points. Real measurable metabolic improvements.
AI 1: Okay. And the payoff, how did it affect the ablation success?
AI 2: Pretty dramatically, actually. Freedom from AF at one year was, over sixty one percent in the group that got the lifestyle intervention.
AI 1: Sixty one percent. And usual care.
AI 2: Only forty percent. So that's a huge difference. More than 20 percentage points. Better outcome just from optimizing their health before the procedure.
AI 1: Wow. So the take home from the source is what lifestyle changes are non negotiable?
AI 2: Pretty much. The analysis calls it mandatory procedural optimization. It's not just a nice suggestion anymore. A rest AF is the first RCT to really prove that if you invest in improving the patient's metabolic state, you directly improve the odds of the ablation working. You're prepping the heart tissue essentially.
AI 1: Okay so that's precision in preparing the patient but what about precision and timing the intervention? That brings us to the second study, the open cabana sub analysis. This one looked at factors you can't easily change.
AI 2: Right. This looked at over 2,100 people and tried to figure out if there's a point where ablation just doesn't help as much because the disease is too advanced. They use these things called non modifiable recurrence risk factors, NMRFs. NMRFs? Okay, what are those?
There are four. Having AF for more than a year, having non paroxysmulso persistent or long standing persistent AF being 65 and female sex basically markers that the atrial disease is more established, more remodeled.
AI 1: And the key finding depended on how many of these factors a patient had.
AI 2: Exactly. It was really quite striking. If patients had fewer than three of these NMRF's, they clearly benefited from ablation. Their risk of major events, death, stroke, serious bleeding, cardiac arrest was significantly lower.
AI 1: How much lower?
AI 2: The adjusted hazard ratio is 0.59. So roughly a forty percent reduction in risk. Clear benefit for earlier intervention. Good.
AI 1: What if they had three or more of those factors?
AI 2: That's where the story flips entirely. For patients with three or more NMRF, there was absolutely no benefit from ablation compared to drug therapy.
AI 1: No benefit. Or was it worse?
AI 2: Well, the adjusted hazard ratio was 1.55, suggesting if anything, a trend towards potential harm or at least certainly no advantage, maybe even higher risk in that group undergoing ablation.
AI 1: An AHR of 1.55. So for this group with more advanced risk factors, the procedure didn't help and might have even been detrimental.
AI 2: That seems to be the implication. It links back perfectly to a rest AF, you know. If you can modify the risks, like weight and blood pressure, you should. If you can't because they're fixed factors like age or a long duration of AF, then you absolutely need to intervene earlier before that extensive remodeling sets in and limits what the ablation can achieve.
AI 1: So the first big theme is be precise. Optimize the patient metabolically if you can and intervene early before the disease becomes too entrenched.
AI 2: Couldn't say it better myself.
AI 1: Okay. Let's move to the second theme then. Proportion in therapy. This idea that sometimes less is more challenging the reflex to always add more treatment.
AI 2: Yeah. This is about stepping back and asking, is this intervention truly necessary or are we adding risk without clear benefit, especially with things like blood thinners?
AI 1: Right. Like in that German study on AF after CIBG surgery, they used insertable monitors in nearly two hundred patients for a whole year after bypass.
AI 2: Uh-huh. And we know post op AF is common. Right? It often triggers long term anticoagulation plans. And sure enough, they found AF in almost half the patients, forty eight percent.
AI 1: But that wasn't the whole story, was it? The monitors showed something else.
AI 2: Exactly. They showed the burden, how much time the patients actually spent in AF. And the median burden was incredibly low, like zero point zero seven percent over the whole year. It's about three seventy minutes total per year. And critically, most of that tiny birdie happened right in the first month after surgery.
After thirty days, it was almost nothing.
AI 1: So yeah, AF happened, but it was mostly brief and early. What's the implication then for anticoagulation?
AI 2: Well it really makes you question automatically putting everyone with any post op AF on long term blood thinners. The argument from the source is that the decision should be based on the burden and duration not just the fact that it occurred. A brief flutter post op might not carry the same stroke risk as persistent AF. High incidence didn't equal high burden here.
AI 1: It's about a proportional response. Don't use the heavy artillery if it's not warranted by the actual amount of disease.
AI 2: Precisely. And that idea of de escalation of removing therapy is even stronger in the next study, aquatic, which you know, some are calling the trial of the year.
AI 1: Aquatic. Okay, set this one up for us. Who were the patients?
AI 2: These were patients who had two things going on. They had atrial fibrillation, so they were already on an oral anticoagulant, an OAC. And they had stable coronary artery disease specifically, they were at least six months out from having a stent put in, a PCI.
AI 1: Okay. AF plus stable CAD, already on an OAC. What was question?
AI 2: The question was, do these patients also need to be on aspirin? For decades, the thinking was, yes, you need the aspirin to protect the stent even long term. So they randomized about eight seventy such patients. Half got OAC plus aspirin. The other half got OAC plus placebo.
AI 1: Testing that dual therapy dogma and the results.
AI 2: The results were, frankly stunning and not in a good way for dual therapy. Adding aspirin significantly increased major bleeding. The hazard ratio was three point three five over three times the risk.
AI 1: Okay. More bleeding may be expected, but did it help with heart attacks or stent problems?
AI 2: That's the kicker, no, in fact it was the opposite. The group getting aspirin plus the OAC had more cardiovascular events overall, hazard ratio 1.53. And even more concerning, their all cause mortality was higher to (Hazard Ratio 1.7.
AI 1: Wait, so adding aspirin didn't just cause more bleeding, it led to worse cardiovascular outcomes and higher death rates in this stable group?
AI 2: Correct. It was actively harmful. Adding aspirin provided no cardiovascular benefit and significantly increased both bleeding and overall risk. It's a powerful example of disproportionate therapy adding a drug out of habit that only caused problems.
AI 1: But the conclusion for practice is
AI 2: Crystal clear. If you have a patient with AF on an OAC who's more than six months past their PCI and clinically stable, stop the aspirin. OAC monotherapy should be the standard.
AI 1: Wow. Okay. A definite case of less is more there. Alright, for our last segment, let's look at a couple of studies that kind of put things in perspective, maybe by looking at older interventions through a new lens.
AI 2: Yeah. Sometimes progress means rediscovering the value in something we already had or confirming the enduring need for established therapies.
AI 1: First, let's talk DDG HF. This one looked at Digitoxin, which sounds familiar but isn't the usual one, right?
AI 2: Digitoxin is Digoxin's older cousin, both are cardiac glycosides. This trial took over twelve hundred patients with heart failure with reduced ejection fraction meaning a weak pump who are already on all the standard modern meds the GDMT.
AI 1: So already maxed out on current therapy and they added digitoxin.
AI 2: Yep and it worked. It reduced the main outcome which was a combo of death or hospitalization for heart failure. The hazard ratio was zero point eight two, statistically significant.
AI 1: Okay. So an old drug still has legs, but why Digitoxin specifically? Why is it getting a second look now?
AI 2: It comes down to how the body handles it. The metabolism, Both digitoxin and the more common digoxin work by inhibiting the sodium potassium pump in heart cells, which helps the heart contract more strongly. But the key difference is clearance.
AI 1: How so?
AI 2: Digoxin is cleared mainly by the kidneys. Digitoxin is cleared mainly by the liver. It's hepatically metabolized.
AI 1: And why does that matter so much?
AI 2: Because a lot of patients with heart failure also have chronic kidney disease, CKD. And if your kidneys aren't working well, giving a drug like digoxin that relies on the kidneys can be risky. It can build up. Digitoxin being cleared by the liver avoids that problem.
AI 1: So it fills a niche. HFREF patients with significant CKD who need something extra beyond GDMT.
AI 2: Exactly. It offers an option for this really tricky group where digoxin might be too dangerous. Now we should add, Digitoxin fell out of favor years ago, partly because it has a really long half life, making it harder to manage and there's no quick antidote like there is for digoxin. It's not even available everywhere, mainly some European countries.
AI 1: Right. Availability is limited, especially in The US. But for that specific patient profile HFR EF plus CKD, it might be a calculated risk worth considering where it is available.
AI 2: It's precision medicine again, isn't it? Finding the right drug for the right subgroup, even if it's an older one.
AI 1: Okay, finally, let's talk about the ICD, the implantable defibrillator. With all the great new heart failure drugs and therapies, do people still need ICDs as much? Is the benefit still there?
AI 2: That's a critical question. And we got some answers from a huge analysis looked at the Medtronic CareLink database, tracking nearly a quarter million patients who got their first ICD between 2013 and 2024.
AI 1: A massive real world cohort. What did they find about therapies over time?
AI 2: They looked at the ten year cumulative incidence basically. What percentage of patients received an appropriate life saving therapy from their device within a decade? And the number is pretty substantial.
AI 1: Which was?
AI 2: Almost half. Forty eight percent of patients receive some kind of appropriate therapy.
AI 1: And breaking that down.
AI 2: About a thirty three percent received an appropriate shock for a dangerous ventricular arrhythmia and even more, forty two percent received ATP that's anti tachycardia pacing which often stops the rhythm painlessly before a shock is needed.
AI 1: So even in this modern era with better drugs, nearly one in two ICD recipients gets a potentially life saving intervention from their device within ten years.
AI 2: That's the message. Despite all the advances which are fantastic, don't get me wrong, the ICD still provides a crucial safety net against sudden cardiac death for a very large proportion of patients who meet the criteria. It confirms its sustained essential role for both primary and secondary prevention.
AI 1: Okay, so let's try and tie this all together for you. Looking back across these six studies, two big lessons seem to emerge.
AI 2: I agree. The first is clearly about precision. We saw it with ARREST AF demanding metabolic prep work before ablation and with Cabana showing we need to time that ablation before too many fixed risk factors pile up. It's about selecting the right patient and the right timing.
AI 1: And the second lesson seems to be about proportion. Doing the right amount, not necessarily the most. Aquatic screaming at us to stop unnecessary aspirin in stable patients. And the CIBG AF study suggesting we base anticoagulation on actual AF burden, not just occurrence.
AI 2: Exactly. It's about stepping down therapy, reducing risk, when the disease burden doesn't justify aggressive measures. It's a move away from just doing more reflexively.
AI 1: So the synthesis across all this research really is that shift mentioned at the start.
AI 2: Yeah, moving away from doing more towards doing better. Which means intervening sooner when needed, using smarter patient selection, and being much more selective about which interventions we apply and when to potentially de escalate.
AI 1: Which leaves us with a final thought for you, the listener, to maybe chew on. ARREST AF proved that lifestyle modification, improving metabolic health, is basically procedural optimization for AF ablation. So here's the question. Could improving metabolic health potentially change who needs other high risk interventions like an ICD? Or maybe change the threshold for needing one?
What other procedures might be fundamentally tied not just to the drugs we give but to the patient's underlying non pharmacologic health.
AI 2: Something to think about. Definitely.
AI 1: Join us next time for another deep dive.
Dr Niraj Sharma: That wraps up this issue of the EP Edge Journal Watch podcast. All the studies, references and infographics we discussed today are available on the EP Edge Journal Watch newsletter on LinkedIn, so please subscribe, follow and share. Got thoughts or questions? Send comments and feedback to epedgecast@gmail dot com and don't forget to subscribe so you never miss an episode. I am Doctor.
Neeraj Sharma, take care and bye for now.