Niraj Sharma: Welcome to EP Edge Journal Watch Issue six, January 2026. I am Doctor. Sharma and thank you for joining me for another high yield review of the most clinically relevant electrophysiology literature you need to know without the noise. This issue is anchored around left atrial appendage occlusion, long term outcomes, implant mechanics, and real world edge cases that we all wrestle with in practice. Will then broaden out into several immediately practical EP papers post TAVR conduction disease, early recurrence after persistent AF ablation, ICU anticoagulation decisions in septic shock, and a fascinating translational look at sex hormones and Torsades de Pointe.
The goal today is simple: highlight what matters, explain why it matters, acknowledge limitations, and give you an EP EDGE take you can use on rounds tomorrow. We begin with long term randomized data comparing left atrial appendage closure to oral anticoagulation, now including the OPTION trial. This meta analysis pooled over 3,000 patients from four randomized trials, with follow-up extending up to four years. The central message is nuanced but important. Thromboembolic protection was broadly similar between strategies.
There was no statistically significant difference in ischemic stroke or systemic embolism. Where the curves separate is safety. Left atrial appendage closure was associated with substantially less hemorrhagic stroke and nearly a fifty percent reduction in non procedural clinically relevant bleeding. There was also a signal toward lower cardiovascular or unexplained mortality favoring left atrial appendage closure, with a relative risk around zero point seven. Now, important caveats: These trials span different device generations, different antithrombotic regimens, and both warfarin and DOAC comparators.
Procedural bleeding is still bundled into some endpoints. EP edge takeaway: Left atrial appendage closure remains thromboembolicly competitive, consistently safer from a bleeding standpoint, and now carries a provocative not yet mechanistically explained mortality signal. Next, implant mechanics that actually change behavior. This JAK EP study examined Watchman Flex compression and peri device leak. The headline is striking higher compression, around 26%, was associated with a four fold reduction in peri device leak at follow-up.
Importantly, this did not come at the cost of higher early procedural complications. Limitations include observational design and center specific workflows, but the signal is strong. EP edge takeaway: when depth allows and you're between sizes, this supports a mindset shift. Compression may be protective, not punitive, particularly if minimizing peri device leak is your priority. Now to one of the most frontier papers in this issue.
This multicenter case series describes percutaneous aspiration thrombectomy for persistent left atrial appendage thrombus, followed immediately by no touch left atrial appendage occlusion. These were extremely high risk patients, average CHADS VASc above five, high bleeding risk, and thrombus refractory or contraindicated to further anticoagulation. Using meticulous transseptal alignment, real time imaging, aggressive embolic protection, and either manual or pump assisted aspiration. Thrombus clearance was achieved in all cases. No periprocedural strokes, no systemic embolism.
One thirty day TIA related to peri device leak. But this is not a green light for widespread adoption. Limitations are substantial: small numbers, retrospective design, technique heterogeneity, and expert centered execution. EP Edge Takeaway. This paper defines a salvage lane, not a default pathway, for the hardest left atrial appendage occlusion patients, emphasizing workflow discipline over devices.
The options sub analysis answers a question many of us hear weekly: Does left atrial appendage closure worsen AF recurrence after ablation? In over sixteen hundred randomized patients, the answer appears to be no. At three years, AF recurrence rates were similar between left atrial appendage closure and oral anticoagulation, with no difference between concomitant and stage strategies. Predictors of recurrence were what you'd expect: persistent AF and AF duration, not the device. But here's the quiet critical message: stroke and systemic embolism rates were low and similar regardless of recurrence status.
No recurrence does not equal no stroke risk. Limitations include intermittent rhythm monitoring and a binary recurrence definition EP edge takeaway. Left atrial appendage closure is rhythm neutral at scale, but rhythm success should never be used as a stroke risk off switch. This JAMA cardiology paper reframes how we think about conduction disease after TAVR. Intra procedural heart block was often transient and poor at predicting delayed high grade block.
Delayed block, on the other hand, was strongly associated with infra nodal disease, particularly post procedure HV intervals above eighty milliseconds and PR intervals exceeding three hundred milliseconds. These markers had excellent negative predictive value. Limitations include single center, physiology heavy workflows, EP edge takeaway, treat intra procedural and delayed block as different entities, and use physiology to safely de escalate when possible. Next, we revisit the CAPLA trial, this time focusing on an important secondary analysis examining early recurrence after persistent atrial fibrillation ablation. In this cohort, early recurrence during the traditional three month blanking period occurred in approximately forty four percent of patients.
But Capla moves beyond the binary concept of recurrence and looks at timing and burden. Patients with early recurrence had more than a threefold higher odds of late atrial arrhythmia recurrence with an odds ratio just over three. Timing mattered. Episodes occurring after day forty five were far more prognostic than very early events, suggesting that later recurrence reflects substrate failure rather than transient inflammation. Burden mattered as well.
Patients with more than twenty four cumulative hours of atrial arrhythmia during the blanking period had the highest likelihood of late failure, whereas very short, self terminating episodes carried substantially less risk. Importantly, the addition of posterior wall isolation did not mitigate this risk, reinforcing the concept that early recurrence in persistent AF is driven more by atrial biology than lesion set complexity. There are limitations. This was a secondary analysis. Rhythm monitoring was intermittent rather than continuous.
An ablation was performed in a radiofrequency only era. EP EDGE takeaway: In persistent atrial fibrillation, early recurrence is not a single entity. Later onset episodes and higher arrhythmia burden (particularly beyond twenty four hours) should be viewed as strong warning signals, not benign blanking period noise. Next, we turn to a clinically uncomfortable but increasingly common scenario: atrial fibrillation occurring in the setting of septic shock. This large retrospective cohort study evaluated critically ill patients with septic shock who developed atrial fibrillation and examined outcomes based on whether or not they received therapeutic anticoagulation during hospitalization.
The most striking finding was a substantial mortality signal. Patients who received therapeutic anticoagulation had an absolute reduction in in hospital mortality of nearly twenty percent, translating into a relative risk reduction of approximately thirty percent compared with those who were not anticoagulated. Importantly, this survival benefit was not accompanied by a statistically significant increase in major bleeding. Rates of ischemic stroke were low overall and did not differ meaningfully between groups, suggesting that the observed benefit may not be explained solely by embolic prevention. This raises a provocative hypothesis: anticoagulation in septic shock associated atrial fibrillation may be acting as a modifier of systemic inflammation, microvascular thrombosis, or endothelial dysfunction, rather than simply preventing left atrial appendage clot.
However, we must be cautious. This was an observational study with inherent selection bias. Patients selected for anticoagulation were likely more hemodynamically stable, had fewer contraindications, and may have received overall higher intensity care. Details regarding timing of AF onset, rhythm duration, anticoagulant class, and dosing strategies were limited, and long term outcomes beyond hospitalization were not assessed. EP Edge takeaway: New onset atrial fibrillation in septic shock should not be reflexively dismissed as a transient epiphenomenon.
While these data do not mandate anticoagulation, they strongly support individualized, physiology aware decision making and early EP input rather than a blanket avoidance strategy driven purely by bleeding fear. We close this issue with a study that quietly challenges how we think about arrhythmic risk, particularly torsades de pointes, and why it behaves so differently across sexes. This translational investigation examined patients with acquired TDP and evaluated circulating sex hormone levels alongside electrophysiologic effects in human cardiomyocyte models. The findings were striking. Men who developed TDP were found to have profound hypogonadism, with testosterone levels well below age adjusted norms.
Women, in contrast, demonstrated marked hyperestrogenism. These were not subtle differences. When patient derived hormone profiles were applied to human ventricular cardiomyocytes, both low testosterone and high estrogen directly prolonged ventricular repolarization and increased early after depolarization propensity, key mechanistic substrates for TDP. Perhaps most importantly, normalization of hormone levels reverse these electrophysiologic effects. This reframes sex hormones not as background modifiers but as active dynamic regulators of repolarization reserve.
Now some important perspective. This study does not suggest routine hormone testing for every patient with QT prolongation nor does it justify empiric hormonal manipulation. Sample sizes were modest, the population was highly selected and clinical outcomes were not driven by interventional hormone therapy. But conceptually, this is powerful. It helps explain why QT liability differs by sex, why certain patients destabilize dramatically with modest QT insults, and why one size fits all risk models often fail.
My take away: sex hormones may represent an unrecognized layer of arrhythmic vulnerability, one that intersects with drugs, electrolytes, autonomic tone, and structural disease in ways we are only beginning to understand. And that forward looking theme brings us to what's next at EP EDGE. Later this month we'll be releasing an in-depth EP EDGE deep analysis focused on pulse field ablation. We'll go beyond safety headlines to examine lesion biology, collateral tissue effects, evolving complication profiles, durability and what real world data are teaching us, sometimes uncomfortably, about where PFA truly fits in our ablation armamentarium. If you've been asking whether PFA is a revolution, an evolution, or something in between, this analysis is for you.
As always, all references and figures from today's discussion are available on my LinkedIn newsletter, EP Edge Journal Watch. I encourage you to subscribe to both the weekly journal watch and the main EP Edge newsletter where we publish deeper, extensive analyses of the topics shaping electrophysiology today. Thank you for listening. Thank you for your continued support of EP EDGE. This is Doctor.
Sharma and I'll see you in the next issue. Bye for now.