Niraj Sharma: Hi, everyone. Welcome back to EPH Journal Watch. I'm Doctor. Sharma. So what's the theme for issue 10?
It's that electrophysiology is moving from did we isolate the vein today to did we change the patient's trajectory over years, durability, phenotype specific outcomes, longitudinal impact, and the system level consequences of what we do. That's exactly how this issue is built: next generation pulsed field durability, metabolic modulation after ablation, wearable screening, we then move to the chaos in VT endpoints, precision cardioablation, mental health after ICDs, and the realities of reprocessing and sustainability. Alright, Study one: PULSAR IDE trial, a pulsed field ablation pivotal trial looking at durability of pulmonary vein isolation in paroxysmal AF. Here's the clinical problem: PFA has exploded because the safety and workflow are attractive, but multicenter durability has been variable. Non thermal energy alone doesn't automatically give you durable PVI.
Pulsar's basic hypothesis is that catheter architecture and electrode tissue contact geometry can be the lever that moves durability. Design wise, this is a multicenter, single arm pivotal IDE program, one hundred and eighty three symptomatic drug refractory paroxysmal AF patients with a roll in phase (nineteen roll in) and one hundred and sixty four in the pivotal cohort. The average age was mid-60s (about forty percent women), CHADS VASc around two. Now the device and workflow details matter. This was a 30 millimeters globular spherical array catheter with 122 individually selectable gold electrodes, integrated mapping, pacing, contact sensing, and energy delivery.
And the key concept is that energy is delivered only through electrodes in confirmed tissue contact, so you are less dependent on perfect catheter gymnastics. Endpoints The primary effectiveness endpoint was a composite: twelve month freedom from atrial arrhythmia recurrence plus freedom from procedural failure modes, like incomplete PVI, redo ablation, cardioversion, or escalation of class I or III antiarrhythmics. Safety was major adverse events within seven days. Acute PVI success was strong (about ninety four percent of veins isolated with the first application). Workflow numbers were efficient.
Mapping time around nine minutes, left atrial dwell time around sixty minutes, total procedure time about ninety six minutes. Primary effectiveness at twelve months was seventy seven point eight percent, with a 95% confidence interval of roughly 70.6-83.9. But here is the headline everyone cares about: redo durability. They assessed durability only in people who came back for redo because of recurrent AF, flutter, or atrial tachycardia. That was eleven patients total, 41 pulmonary veins evaluated with invasive PV remapping at redo, and thirty nine of 41 veins stayed isolated.
That's 95.1% redo based durability, and nine of eleven patients had all pulmonary veins durably isolated. Now two important nuances: First, redo based durability is a window, not the whole house and it is enriched for failures. Second, because it's enriched for failure, if anything, the durability estimate is likely conservative, not inflated. Safety, one major adverse event, a hemorrhagic stroke in a patient with severe hypertension, and notably no esophageal injury, no PV stenosis, no phrenic nerve injury reported. So what's the EP edge take?
Pulsar is a signal that the next jump in PFA outcomes may be less about the waveform and more about contact geometry and lesion contiguity achieved electronically. If you can make contact smart, you may not need perfect manipulation to get durable PVI. Okay, let's pivot, because the next paper asks a totally different question. What if the substrate matters more than the lesion set? Let's talk about Study two: receptor agonists in atrial fibrillation recurrence after catheter ablation.
Why it matters is pretty straightforward. Lifestyle modification is a class I recommendation in AF management, but sustained adherence is hard in real life. GLP-1R has offered durable weight loss and metabolic improvement, so the question becomes can we pharmacologically outsource risk factor modification and improve rhythm outcomes after ablation? This was a retrospective cohort analysis using the TriNetX Research Network adults with obesity, BMI over 30 undergoing AF ablation. They did one to one propensity score matching, 3,350 GLP-one RA users matched to 3,350 non users, matching across 82 demographic, clinical, and therapeutic variables, with a median follow-up of two years.
Key outcomes: AF recurrence was lower in the GLP-one RA group, hazard ratio 0.82. Progression to permanent AF was lower, hazard ratio 0.77. All cause mortality was lower, Hazard ratio 0.73. Heart failure hospitalization was lower. Hazard ratio 0.8.
And redo ablation? No significant difference. So how do we interpret that pattern? If redo rates aren't lower, the story may not be better acute ablation. It may be better substrate over time.
The proposed mechanisms are exactly in that direction: reduction in epicardial adipose tissue, less systemic and atrial inflammation, a more favorable autonomic balance, and indirect modulation of atrial substrate rather than classic ion channel effects. EP edge takeaway: GLP-one agonists start to look like adjunct rhythm stabilizing therapy, not just metabolic agents. This supports an uncomfortable but important truth: long term ablation success is tightly linked to systemic metabolic health. All right, Study three is a different kind of substrate question: can we detect AF earlier, before it declares itself with symptoms or a stroke? Enter the Watch trial: Apple Watch Screening with ECG Confirmation.
The background: a big fraction of AF episodes are asymptomatic, so diagnosis is delayed and strokes occur in people who never knew they had AF. Wearables can detect irregularity, but randomized evidence that pairs continuous photoplethysmography surveillance with rapid clinical grade ECG confirmation has been limited. WATCH was a prospective multicenter randomized trial in higher risk patients aged 65 and older with elevated stroke risk (CHADS VASc at least two in men or three in women). They randomized patients to six months of smartwatch monitoring versus standard care. Importantly, ECG adjudication was done by an independent e health team within twenty four hours.
The primary outcome was new onset AF lasting at least thirty seconds confirmed on ECG and the result is not subtle. AF detection was nine point six percent in the smartwatch group versus two point three percent with standard care. Hazard ratio four point four zero. Most detected episodes were asymptomatic and paroxysmal. So yes, this accelerates diagnosis, but it also creates new downstream work pathways for triage, confirmation, counseling, anticoagulation decisions, and capacity planning for EP and general cardiology.
The technology is moving faster than the clinic infrastructure. Next up, we are going to shift gears into VT ablation trials because if we can't even agree on what success means, comparing therapies becomes a semantic exercise. Study four is a systematic review on heterogeneity of outcome reporting in VT ablation trials and it's one of those papers that doesn't give you a new catheter but it absolutely changes how you read the literature. The premise is simple: comparing VT ablation studies is notoriously difficult and not just because the interventions differ. The definitions of success and failure are all over the map.
This review tried to quantify how much of reported efficacy is really driven by definitions. 59 prospective VT ablation studies spanning 2,000 through 2024, including randomized trials, feasibility studies, and registries. They categorized outcomes and used meta regression. Here's the heart of the problem: Acute success can mean non inducibility, or it can mean elimination of the clinical VT. And those are not equivalent.
Then recurrence definitions range from any VT recurrence at all, to VT that requires device therapy, to VT that requires shock only. And when you apply those different recurrence definitions to the same conceptual endpoint, failure, the rates diverge dramatically. Any VT recurrence about fifty one percent, VT that causes therapy about thirty seven percent, VT that causes shock about twenty three percent. So if you are reading two VT ablation trials and one looks better, you have to ask are they truly better or are they just counting events differently. This is exactly why meta analyses can become unstable and why guideline synthesis is harder than it should be.
EP outcome heterogeneity can artificially inflate perceived efficacy and it undermines comparisons across trials and across technologies. The paper's practical implication is a push toward a standardized core outcome set for VT ablation so that when we say success, we mean the same thing. Okay, next we are going to move from ventricles to autonomics and from lesion sets to precision neuromodulation. The fifth study is ELEGANCE, tailored cardio neuro ablation for reflex syncope and functional bradycardia. Study five is the ELEGANCE multicenter study on cardio neuro ablation, tailored, phenotype driven neuromodulation for reflex syncope and functional bradycardia.
Let me start with why this matters. Cardio neuro ablation has lived in a gray zone for years, promising physiology but heterogeneous technique, inconsistent endpoints, and a lot of skepticism, especially concerns about overablation, poor reproducibility, and autonomic overshoot like inappropriate sinus tachycardia. Elegance is important because it reframes CNA as precision autonomic therapy, not empirical denervation. One hundred and twenty three patients across multiple European centers, median age around 50, which is what you would expect for functional, not degenerative, bradycardia. They deliberately excluded structural conduction disease, anchoring CNA strictly to autonomic dysfunction phenotypes.
The phenotypes were roughly: Isolated functional sinus node dysfunction (forty three percent ), Isolated functional AV block (ten percent ), and a combined phenotype (forty seven percent ). Prospective multicenter clinical study comparing two strategies: standard CNA, meaning empirical ablation of all major atrial ganglionated plexi, often biatrial and extensive, versus tailored CNA, where the GP target is chosen based on the patient's dominant phenotype. It is not randomized, but is designed to compare procedural burden, efficiency, and outcomes. Now the intervention detail is the main value. They explicitly map phenotype to dominant vagal input to a specific ganglionated plexus target.
The goal is selective parasympathetic attenuation enough to prevent events without carpet bombing the atria. Here's how tailored CNA was performed. For functional sinus node dysfunction, the dominant issue is vagal input to the sinus node. The primary target is the superior paraseptal ganglionated plexus and the tailored strategy is to target that, only that, avoiding routine inferior or lateral GP ablation to reduce the risk of inappropriate sinus tachycardia. For functional AV block, the dominant issue is vagally mediated AV nodal suppression.
The primary target is the inferior paraseptal ganglionated plexus and again the tailored strategy is to target IPSGP only, avoiding unnecessary sinus node denervation. For the combined phenotype, they sequentially target both superior and inferior paraseptal GP but still keep it limited compared to standard CNA. Workflow wise, they emphasize pre procedural phenotyping documentation, tilt testing when applicable, and exclusion of intrinsic conduction disease. Ablation was predominantly left atrial first, with right atrial ablation reserved only if the response was inadequate after LA targeting. Energy was RF, with focused lesions at predefined GP anatomical locations.
Endpoints are also worth calling out: Elegance emphasized physiologic confirmation of vagal attenuation, an increase in intrinsic heart rate, reduction or abolition of vagally mediated pauses, loss of inducible cardio inhibitory response where tested, and reduced susceptibility to reflex bradycardia. Importantly, complete denervation was not the goal, clinical control was. Tailored CNA used fewer targets (about 1.6 plus or minus 0.7 GP targets per patient). Procedures were shorter, around sixty three minutes versus about eighty five minutes in the standard group. RF delivery time was about five point four minutes versus ten point four minutes, both differences statistically significant.
Acute procedural success was high and similar, about ninety three percent in tailored versus ninety percent in standard, with no significant difference. Follow-up was around sixteen months and syncope recurrence didn't differ between strategies. Inappropriate sinus tachycardia occurred in roughly eight percent overall without an excess signal in the tailored group. So the practical conclusion? Elegance argues that more ablation is not better.
With phenotype guided targeting, you can get equivalent outcomes with less RF, shorter procedures, and potentially lower risk of autonomic overshoot, plus a blueprint that's actually teachable. Alright, next study shifts from physiology to life experience, incident psychiatric disorders after ICD implantation, and why that is not soft but prognostically hard. Study six tackles something EP has historically treated as secondary, even though the outcomes are anything but: incident, psychiatric disorders after ICD implantation, and the prognostic impact paired with an editorial calling for a redesign of ICD aftercare. Why this matters? ICD follow-up usually focuses on shocks, lead performance, and heart failure trajectory.
But for many patients the ICD experience also carries a parallel burden, new onset depression, anxiety, insomnia and sometimes severe psychiatric disease. The key point here is that this is not just quality of life, it is linked to hard outcomes. The original study used the Korean National Health Insurance Service database, near population coverage, about ninety seven percent of South Korea, so you get large numbers and long follow-up. The cohort was six thousand three hundred and fifty six patients receiving de novo ICD implantation between twenty ten and twenty twenty compared with seventeen thousand six hundred and sixty four propensity match controls without ICDs. A critical design choice, they excluded patients with pre existing mental disorder diagnoses and they also excluded certain advanced cardiac disease signals aiming to start everyone at a mental disorder naive baseline at time zero.
Key results: First, incidence. At ten years, the cumulative incidence of newly diagnosed mental disorders was thirty seven point three percent in ICD recipients versus thirty four point five percent in matched controls. Second, what diagnoses drove the signal? Depression was most common, about eighteen point four percent. Insomnia was close behind, about sixteen point eight percent.
Anxiety was around five point eight percent ), severe disorders like schizophrenia spectrum were rare (about zero point seven percent ), but potentially high impact. Third, and this is the part that forces a practice rethink: prognostic impact. Among ICD recipients, developing a new mental disorder was associated with materially worse outcomes: all cause mortality (Hazard ratio two point zero zero), cardiac mortality hazard ratio 1.83, severe heart failure events, hazard ratio 2.12, and readmissions hazard ratio 1.65. That's a doubling of mortality signal. Nuance points: Not all mental disorders carry equal prognostic weight.
Timing matters, with worse association when mental disorders occur earlier after implantation, around the first few years, and there is an interaction signal where the adverse effect on mortality is more pronounced in patients with atrial fibrillation. Mechanistically, this is observational it doesn't prove causality. But the pathways are plausible. Depression and insomnia can impair adherence, amplify autonomic and inflammatory stress, and worsen outcomes after shocks or recurrent arrhythmia. The core limitation is operational.
Mental health is not ancillary. It should be a core component of EP aftercare. So the EP EDGE translation is practical, routine screening, shock triggered escalation, and an integrated referral pathway should be standard, not optional. Alright, final study moves from patient level outcomes to system level reality, catheter reprocessing, what it actually involves and why Europe's regulatory structure makes this more than a sterilization conversation. Study seven is a systematic review on reprocessing of electrophysiology catheters, methods, safety signals, and the Europe specific regulatory context.
Let's start by defining reprocessing because in EU framing it is explicitly more than re sterilization. It is a bundle: cleaning, disinfection, sterilization, testing, and restoration to ensure functional and technical safety. What do the actual workflows look like? First, cleaning and decontamination. The backbone is often manual brushing plus detergent or enzymatic solutions.
Some protocols add ultrasonication. Some include hydrogen peroxide as part of validated reuse protocols, and a few reports use chlorine plus enzymatic cleaning and manual brushing, which matters because cleaning chemistry can degrade materials or leave residues. A key process control point is endotoxin and pyrogen risk. Several studies emphasize avoiding potable water in cleaning and instead using filtered, non pyrogenic water. There is also mention that hydrogen peroxide gas plasma can reduce pyrogenic load introduced during handling and cleaning.
Second, terminal sterilization. Across the studies, the most common modalities were ethylene oxide and hydrogen peroxide gas plasma. Autoclaving was uncommon. Reuse counts varied widely by device and protocol. Third, cycle limits and validation.
Reported acceptable reuse counts range roughly from three to 20 cycles and that variability is repeatedly flagged as an evidence gap. Beyond sterilization, validated programs emphasize inspection, mechanical and electrical integrity checks, and microbiological verification. Now Europe specific regulation is where this becomes more than a methods paper. Under the EU Medical Device Regulation, reprocessing of CE marked single use devices is permissible under Article 17 only if national law allows it. That creates heterogeneity across member states.
So scalability is limited by policy, not just science. And here is the liability pivot. Under MDR, the reprocessor becomes the new legal manufacturer. The review describes three operational models: hospital based reprocessing, closed loop third party reprocessing where devices return to the originating hospital and open loop models where a third party redistributes devices across hospitals. Germany is described as a European leader, with national legislation allowing reprocessing for more than two decades before MDR and robust third party infrastructure.
One more practical constraint: ethylene oxide is regulated as carcinogenic and toxic, so it is often infeasible for most hospitals, pushing capacity towards centralized third party models. EPH take away: Reprocessing can look feasible and safe in limited clinical data sets when protocols are stringent. But can be safe is not the same as is safely scalable. If adopted, EP labs need governance, standardized processes, traceability, and surveillance robust enough to catch rare but catastrophic failures. Let's bring the whole issue together.
PULSAR suggests PFA durability may be driven by architecture and contact geometry as much as waveform. GLP-1RAS hint that metabolic therapy can act as a rhythm stabilizing adjunct after ablation. WATCH shows wearable screening can accelerate diagnosis, but will stress care pathways. VT outcome heterogeneity reminds us definitions can inflate efficacy. Elegance argues for phenotype guided, limited cardio neuroablation as a reproducible blueprint.
And the ICD mental health data tells us psychiatric morbidity is common and prognostically consequential. And with that, thanks for spending time with me on EP Edge Journal Watch. An abridged edition of this newsletter, with all references and graphics is available on LinkedIn. If you want the full newsletter, you can find it at epedge.substack.com. If you have comments, questions or concerns, email me at epedgecastgmail dot com.
Till next time bye for now