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Niraj Sharma: Welcome back to EP Edge Journal Watch. I'm Doctor. Sharma. Thank you for the thoughtful feedback, the questions you keep sending my way. Those suggestions genuinely shape this show, including which papers make the cut, how much time we spend on the statistics, and how quickly we get to the clinical point.
This is issue 29 and it's really built around a deceptively simple question: Has the old drug first ladder in atrial fibrillation finally run out of evidence? Over the next twenty minutes or so we'll test that question from efficacy, safety, aging, disease progression, substrate, anticoagulation and the decisions that still remain after sinus rhythm returns. We're also continuing this conversation through EP Edge Journal Watch with the Heart Rhythm Society. Picture the familiar clinic visit. A patient has symptomatic AFib, you discuss rhythm control and the default sequence almost writes itself.
Try an antiarrhythmic drug, then consider ablation if the drug fails. But why is that the default? Is it because drugs work better? No. Is it because they're clearly safer?
That's becoming harder to defend. Edema and colleagues pulled together 22 randomized trials covering paroxysmal and persistent A fib, with ablation used both early and after prior treatment. Most comparisons were assessed around one year. Their question was broad: when you count recurrence, hospitalization, quality of life, mortality signals, drug intolerance, and procedural complications, which rhythm control strategy actually performs better? The headline result came from treatment naive paroxysmal Recurrence was higher with drugs, with a relative risk of one point seven six.
That means the drug group had a seventy six percent higher relative frequency of recurrence than the ablation group. It doesn't mean seventy six extra patients out of every one hundred recurred. The direction was similar in previously treated paroxysmal AFib and in persistent AFib. Atrial fibrillation related hospitalization also favored ablation. Quality of life improved in both groups, while the mortality estimates remained too imprecise to claim a survival benefit.
Here's the catch: Most of these trials had important bias from crossover and deviations from assigned treatment. Follow-up was usually short, and the ablation evidence came mainly from radiofrequency and cryoballoon procedures, not contemporary pulsed field ablation. My read is that the old ladder can't be defended by habit alone. Ablation has a concentrated procedural risk. Drug therapy has a distributed risk through recurrence, intolerance, bradycardia, organ toxicity, cardioversion, and hospitalization.
On Monday morning, I'd present those as two active strategies: not one conservative choice and one aggressive choice. The full recurrence plots and complication tables are in the EP Edge Journal Watch newsletter. Now, the harder question: even if ablation works better, is it actually safer when every serious event is counted the same way? Schalky and colleagues tackled that safety question directly. Individual trials usually aren't large enough to compare uncommon complications, so they pooled 24 randomized trials with 6,665 participants.
They compared catheter ablation with antiarrhythmic drugs over a median follow-up of twelve months and they harmonized very different safety definitions into a serious adverse event framework. The headline number was eight point eight percent with ablation versus eleven point five percent with drugs, producing a relative risk of zero point eight zero. In plain language, ablation was associated with a twenty percent lower relative risk of a serious event. The absolute gap was 2.7 percentage points, so the practical difference was about three fewer serious events for every 100 patients assigned to ablation. Unplanned hospitalization and cardiovascular events also favored ablation without a detected increase in treatment related death, stroke, major bleeding, or neurologic events.
But don't over read it, The composite mixed very different harms, reporting varied across trials, crossover blurred attribution, and pulsed field ablation wasn't represented. Randomized trials also tend to enroll selected patients in experienced centers. The accompanying editorial makes the provocative claim that ablation is moving from invasive option to safer standard. I wouldn't make that universal. I would say this: drugs no longer deserve an automatic safety advantage simply because there is no transseptal puncture.
That changes informed consent. The detailed safety categories and forest plots are available in the newsletter. Now move that conversation into an older patient. They've already tried one rhythm drug. Renal function is less forgiving.
Bradycardia is more likely polypharmacy is real. And another medication may not be the gentle option it appears to be. At the same time, procedural risk rises with age. D'Angelo et al. Used a Medicare Advantage database to compare ablation with a second antiarrhythmic drug in thirteen thousand three hundred and eleven adults aged 65 or older.
Outcomes were assessed after a ninety day blanking period through one year. Ablation was associated with a hazard ratio of zero point seven six for atrial tachyarrhythmia recurrence. A hazard ratio describes the relative rate at which events occur over time, so this translates to a twenty four percent lower adjusted recurrence rate in the ablation group during follow-up. Cardioversion, heart failure hospitalization, and ischemic stroke hospitalization also moved in the same favorable direction. The limitation is fundamental.
This was claims based observational research. Before adjustment, ablation patients were younger and healthier, and claims can't tell you frailty, atrial fibrillation burden, atrial fibrosis, functional status, or why the clinician chose one treatment. My Monday morning takeaway is straightforward: Age should modify the ablation discussion, not end it. I'd focus on frailty, function, atrial substrate, and prior drug tolerance. After one failed drug, another drug is not automatically conservative.
For the full age stratified outcomes and safety details, see the written issue. The next paper asks whether ablation changes progression of atrial fibrillation. Atrial fibrillation often moves from brief self terminating events toward persistent disease, more remodeling, more hospitalization, and a harder substrate to treat. We've known that ablation can slow that progression. What we haven't known is whether avoiding progression is actually connected to better clinical outcomes.
Lee et al. Examined eight fifty four participants with paroxysmal AFib from the CABANA trial. They compared randomized ablation with drug therapy and followed patients for a median of forty nine point seven months. The key event was the first documented transition to persistent AFib after the blanking period. Progression occurred in sixteen percent after ablation and twenty seven point seven percent with drug therapy, with an adjusted hazard ratio of zero point five two, so at any point during follow-up, the adjusted rate of progression was roughly cut in half with ablation.
The mediation analysis suggested that preventing progression explained part, but not most, of the reduction in death or cardiovascular hospitalization. The caveat is that this was a post hoc subgroup analysis with treatment crossover and no consistent continuous rhythm monitoring. Progression was documented clinically, not measured as a complete burden curve. My read is that waiting isn't always neutral. You're not simply postponing a procedure.
You may be allowing the disease to enter a stage with a different substrate and a lower chance of durable rhythm control. That doesn't mean every paroxysmal atrial fibrillation patient needs immediate ablation. It means timing belongs in the shared decision. Now consider the patient who says I feel fine and who are essentially asymptomatic. Symptom driven care assumes that no palpitations means low urgency.
But patients adapt, they walk less, normalize fatigue and call reduced function aging. The biological disease can remain active even when the patient isn't complaining. Peng et al. Analyzed fifteen thousand six hundred and three patients in the China AFib registry, including thirteen forty five classified as asymptomatic. They compared cardiovascular death or stroke over a median of five years and examined the association of rhythm control with outcomes.
The headline comparison between asymptomatic and symptomatic patients produced an adjusted hazard ratio of 0.96. Because that confidence interval crossed one, the study didn't show that asymptomatic patients had lower risk. In practical terms, silence of symptoms did not identify a safer phenotype, rhythm control was associated with better outcomes in both groups, and there wasn't convincing evidence that symptom status changed that association. But this wasn't randomized. Patients selected for rhythm control were younger, healthier, and had more favorable cardiac structure.
The very large observed benefit almost certainly includes selection bias. So no, I wouldn't use this paper to ablate every asymptomatic patient. I would use it to stop treating asymptomatic as shorthand for low risk. Recent diagnosis, remodeling, burden, heart failure and progression risk still matter. The full treatment pattern and sensitivity analyses are in the newsletter.
Persistent AFib brings us to the question operators argue about in the lab: When is more ablation actually worth it? Pulmonary vein isolation is foundational, but recurrence remains common. Low voltage areas may represent slow conduction and diseased atrial myocardium. That makes them tempting targets. The problem is that empiric substrate modification has repeatedly produced mixed results and every extra lesion can create organized atrial tachycardia or collateral injury.
The neutral parent trial raised a sharper possibility. Maybe the treatment isn't uniformly ineffective. Maybe we've been applying it to patients who don't have enough targetable substrate. Okada et al. Revisited the suppress a fib randomized trial.
Three forty one patients with persistent AFib and at least five cm2 of low voltage substrate had been assigned to pulmonary vein isolation alone or pulmonary vein isolation plus low voltage area ablation. This post hoc analysis asked whether the amount of substrate changed the treatment effect. Among patients with extensive low voltage areas, recurrence was thirty four point seven percent with additional ablation versus fifty seven point six percent with isolation alone. That's a large absolute difference within the subgroup, suggesting that more ablation mattered when substrate burden was extensive. But the overall parent trial was neutral, this analysis was post hoc, and the formal interaction narrowly missed the conventional significance threshold.
Atrial tachycardia was also numerically more frequent after substrate ablation. That trade off matters when recurrence changes from fibrillation into organized, mappable tachycardia. My take is not to ablate more, it's measure first. Limited abnormal substrate may not justify extra lesions. Extensive, potentially viable slow conduction tissue may.
The 20 square centimeter signal is a hypothesis, not a universal cutoff. The substrate curves and recurrence breakdown are laid out in the newsletter. Now shift from how much to ablate to when to ablate. You're called about a hospitalized patient with a fib, heart failure, repeated cardioversion, and poor rate control. The temptation is obvious: restore durable rhythm before discharge and avoid another admission.
But the same patient may be congested, renally unstable, hypotensive, or still recovering from the illness that brought them in. Sandhu and colleagues used the National AFib Ablation Registry to compare urgent inpatient ablation with elective procedures. The analysis included 140,051 index ablations from roughly 195 hospitals. Urgent meant the patient was already hospitalized for another reason, and the ablation was considered necessary before discharge. Urgent use had increased over time, and it was more common at higher volume centers.
These weren't comparable patients. The urgent group had far more heart failure, coronary disease, lung disease and lower ventricular function. Women, black patients and patients with Medicaid were also more heavily represented, raising an access question alongside the safety question. So the real question was whether the excess risk persisted even after adjustment. It did.
The adjusted odds ratio for a major complication with urgent ablation was two point seven zero. That means the odds were nearly three times higher than with elective ablation after accounting for measured differences. In the raw comparison, that translated to roughly two additional major complications for every 100 urgent procedures. There is a major caveat: the registry didn't tell us why the patient was hospitalized, a planned drug loading admission is not the same clinical state as decompensated heart failure or respiratory failure, residual confounding by illness severity is unavoidable, and the data largely came from the thermal ablation era. The editorial's framing is right: urgent ablation is a separate high risk pathway, not elective ablation moved on to the inpatient calendar.
Before proceeding, I'd want congestion corrected, renal and respiratory status stabilized, infection excluded, and a clear answer to whether AFib is actually driving the hospitalization. Newer energy may change some procedural risks, but it won't erase unstable physiology. The newsletter includes the complication profile and the editorial discussion on access disparities. Next comes the post ablation question almost every patient eventually asks: If the AFib is gone, why am I still taking an anticoagulant? It's a fair question.
It's also where rhythm success and stroke biology get confused. Silent recurrence can occur, atrial myopathy can persist, vascular and clinical risk factors don't disappear because the monitor is quiet. Nayak et al. Pooled 31 studies with fifty thousand three hundred and twenty seven patients who either continued or stopped oral anticoagulation after the post ablation period. Most studies were observational with only three randomized trials.
The key high risk subgroup had an odds ratio of zero point four two for stroke or transient ischemic attack with continued anticoagulation. That corresponds to fifty eight percent lower odds in patients with a stroke risk score of at least two, but this was a subgroup within a highly heterogeneous literature, and patients kept on anticoagulation were often different from those who stopped. Continuing therapy also increased major bleeding. That's the tension. The overall pooled estimate was unstable because the studies differed greatly in baseline risk, monitoring and treatment selection, but the higher risk subgroup pointed toward protection.
The accompanying editorial also warns that recent randomized trials were dominated by lower risk patients and had too few strokes to settle the question. My Monday morning approach doesn't change. After ablation, anticoagulation follows thromboembolic risk, not our emotional confidence in the procedure. A carefully selected low risk patient may stop after the appropriate period. A high risk patient needs a much stronger reason: because a quiet monitor doesn't prove the atrium or the vascular system has stopped generating thromboembolic risk.
The next paper explains why a single point on a stroke score doesn't always carry the same biological meaning. Heart failure is assigned a fixed weight in a fib stroke assessment, but age already changes baseline risk dramatically. So does heart failure add the same relative and absolute risk to a 45 year old and an 85 year old? Jalli and colleagues studied two hundred and twenty nine thousand five hundred and sixty five people with newly diagnosed AFib across Finland. They modeled age continuously and compared ischemic stroke in patients with and without heart failure over a median follow-up of 3.24.
The headline finding was remarkably practical: Heart failure added about one ischemic stroke per 100 patient years across age groups. The absolute excess stayed fairly stable. The relative effect looked much larger in younger patients because their baseline risk was lower. In the oldest patients, age already carried so much risk that the ratio moved closer to one, even though the added absolute burden remained important. The limitation is that registry coding couldn't distinguish reduced preserved ejection fraction, severity, congestion, or duration of heart failure.
My read is that this is a lesson in how we communicate risk. Relative risk tells you how sharply a factor separates groups. Absolute risk tells you how many events are actually added. For a younger patient, heart failure may be the factor that meaningfully changes the anticoagulation conversation. In an older patient, age may dominate the relative comparison, but it doesn't make added absolute burden disappear.
We'll finish the studies with a common scene. The cardioversion works, everyone is relieved, and nobody has defined what comes next. Electrical cardioversion restores sinus rhythm beautifully. It can improve how the patient feels almost immediately, but it does not create a maintenance strategy, and the relief after a successful shock can make everyone postpone the harder conversation. Thanh Zhui et al.
Reviewed three sixty one patients after successful cardioversion, tested the existing SLAC score, and developed the new SLAC score to predict recurrence within six months. The SLASH model achieved an AUC of 0.78. An AUC is not percent accuracy. It means that if you randomly choose one patient who recurred and one who didn't, the model assigns the higher risk to the recurrence patient about seventy eight percent of the time. Left atrial enlargement carried the greatest weight, alongside prior stroke, smoking, faster baseline heart rate, and the absence of postcardioversion antiarrhythmic therapy.
The caveat is substantial. This was a single center retrospective cohort. Many screened patients were excluded, the population was overwhelmingly white, monitoring was inconsistent, and validation was internal. So I wouldn't use slash to deny cardioversion, I'd use it to prevent a plan free cardioversion. If risk is high, define the maintenance drug, monitoring, risk factor treatment and ablation discussion before the shock.
The score components and risk categories are in the newsletter. Let's pull the whole issue together. The edema meta analysis says The drug first ladder is no longer self justifying. Ablation controls rhythm more effectively, and the decision should be framed as a comparison between two active treatments with different risk patterns. The Schauke safety analysis goes further.
It asks us to count delayed drug toxicity and recurrent hospitalization, with the same seriousness that we count procedural complications. When serious events and hospitalizations are counted consistently, Medication doesn't own the safety advantage. Informed consent needs to reflect the complete treatment pathway, not just the day of the procedure. The Medicare Advantage analysis reminds us that older age isn't a veto. After one failed drug, another drug may carry as much clinical burden as the procedure we're trying to avoid.
The CABANA Progression analysis makes timing matter. Waiting may allow the disease to become more persistent and the substrate less forgiving. Ablation appears to reduce the transition to persistent AFib, and part of its clinical value may come from preserving a more treatable stage of disease. The China registry study challenges symptom based gatekeeping. An asymptomatic patient isn't automatically low risk, and absence of palpitations shouldn't end a thoughtful rhythm control discussion.
The suppressed AFib analysis argues for substrate selection rather than reflexive lesion expansion. The map should help decide whether the extra lesion set has been earned. More ablation may help when low voltage disease is extensive, but limited substrate doesn't earn extra lesions. The Urgent Ablation Registry tells us that an inpatient procedure is not simply an elective case performed earlier. It's a higher risk pathway that demands optimization, explicit consent, and clarity about why the procedure can't wait.
The anticoagulation meta analysis separates sinus rhythm from stroke biology. The decision after ablation still begins with baseline thromboembolic and bleeding risk. In higher risk patients, apparent ablation success is not enough reason to stop anticoagulation. The Finnish stroke study shows why absolute and relative risk must be read together. A risk factor can look smaller as a ratio while remaining important in actual event burden.
Heart failure may be especially decisive in a younger patient even though its absolute excess remains meaningful across age. And the slash score brings us back to workflow. A successful shock should open a maintenance plan, not close the chart. Cardioversion shouldn't be a standalone event. The maintenance plan belongs before the shock, not after the recurrence.
That's issue 29. All of the references, detailed statistics, graphics, and study tables are available in the LinkedIn newsletter, EP Edge Journal Watch and on Substack at epedge. Substack dot com. Questions, suggestions or concerns can be sent to epedge Cast@gmail . com.
Thank you for spending this time with me and for continuing to make the show better with your feedback. I am Doctor. Sharma, take care.