The Most Significant Updates in Electrophysiology in 2024

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EP LAB DIGEST. 2024;24(12):6,22.

Bradley P Knight, MD, FACC, FHRS

Dear Readers,
What were the most significant guideline updates and clinical trials in clinical cardiac electrophysiology (EP) in 2024? Here is a somewhat arbitrary list of 8 high-impact guidelines and studies published this year. 

1. Atrial Fibrillation (AF) Societal Guidelines 

•  Updated European Society of Cardiology (ESC) Guidelines for managing AF were unveiled at the annual ESC Congress in 2024 and simultaneously published in the European Heart Journal.¹ The new guidelines have a theme of patient-centered integrated care and introduced “AF-CARE”: [C]omorbidity and risk factor management, [A]voidance of stroke and thromboembolism, [R]ate and rhythm control, and [E]valuation and dynamic reassessment.1 Patient-specific pathways were proposed for patients with first-diagnosed, paroxysmal, persistent, and permanent AF. Because the risk of stroke in women appears to no longer be much higher than in men, the ESC guidelines modified the CHA2DS2-VASc score to simply CHA2DS2-VA. A CHA2DS2-VA score of 2 or more is now associated with a class I recommendation for oral anticoagulation (OAC), and a score of 1 has a class IIa recommendation.

• The European Cardiac Arrhythmia Society (ECAS) published a methods paper2 in anticipation of their guidelines on catheter ablation for AF, which are expected to be published soon, perhaps before the end of 2024. The methods paper was published in advance to accomplish 2 tasks: “(1) respond to the need for increased rigor and transparency in guidelines production; (2) reduce the size of the guideline document, and thus make it of greater practical value for the clinician.”²

2. Pulsed Field Ablation (PFA)

•  MANIFEST-17K Study. Three pivotal trials have been published that have led to United States Food and Drug Administration (FDA) approval of new PFA systems for patients with AF: (1) The ADVENT Trial, which randomized patients to the FARAPULSE (Boston Scientific) pentaspline PFA system versus thermal ablation with either cryoballoon (CB) ablation or radiofrequency (RF) ablation,³ the single-arm PULSED AF trial of the circular, over-the-wire PulseSelect (Medtronic) PFA system,⁴ and the single-arm InspIRE trial of the lasso-type variable-loop VARIPULSE (Johnson & Johnson MedTech) PFA system.⁵ Success rates ranged from 55%-73%. Of note, the MANIFEST-17K study was a European registry of 17,000 patients with AF who underwent ablation using the FARAPULSE catheter.⁶ The risk of major complications was impressively low, with zero cases of esophageal events or pulmonary vein stenosis. There was a case of persistent phrenic nerve paralysis early in the experience, but none with cases done at the expanded 82 sites. Although coronary spasm and hemolysis-related renal failure were rare, the cases highlighted the importance of monitoring for different mechanisms of patient injury with new ablation technologies. The AVANT GUARD Trial, which is evaluating the FARAPULSE PFA system as first-line therapy for persistent AF was briefly paused in October 2024 due to unanticipated observations in the trial, but has since resumed.
 
•  AdmIRE Trial. The AdmIRE trial investigated the use of the VARIPULSE PFA system in patients with symptomatic drug-resistant paroxysmal AF.⁷ After 1-year follow-up, 75% of patients achieved freedom from AF, atrial tachycardia, or atrial flutter after an initial blanking period. Outcomes were similar whether an ultra-high-density mapping catheter or VARIPULSE catheter was used for post-ablation mapping. A PFA catheter that is integrated into the 3D mapping system and can be used for high-resolution mapping and ablation offers several advantages, including efficiency and one fewer left atrial catheter exchange. These positive outcomes underscore the effectiveness of PFA for AF management, reinforcing its potential as a powerful alternative to traditional catheter ablation.

3. AF Stroke Prevention 

•  Meta-analysis of NOAH-AFNET 6 and ARTESiA. It remains to be seen exactly what threshold should be used to trigger prescription of OAC in individual patients with device-detected asymptomatic AF. A study-level meta-analysis of the NOAH-AFNET 6 and ARTESiA Trials on stroke prevention was published in 2024.⁸ These trials focused on stroke prevention using direct oral anticoagulants (DOACs) such as edoxaban and apixaban in patients with episodes of subclinical AF detected by cardiac devices, specifically looking at AF episodes between 6 minutes and 24 hours. The trials were similar, and the use of OAC was associated with an increase in bleeding in both studies. However, unlike NOAH, there was a statistically significant reduction in stroke in ARTESiA. The analysis found that OAC reduces the relative risk of stroke by approximately 32% and increases the relative risk of major bleeding by approximately 62%. These trials highlight the importance of balancing stroke prevention with bleeding risks, providing a nuanced view on anticoagulant use in patients with device-detected AF.

•  AF burden for stroke risk stratification. Most experts recommend the use of anticoagulation to prevent stroke in patients with AF based on the presence of other clinical risk factors for stroke rather than AF burden. However, as risk scores are being refined, there is mounting evidence that patients with more AF are at a higher risk for stroke. A 2024 study by Piccini et al found that for patients with implantable cardiac devices, device patterns and device-detected AF was additive to the CHA2DS2-VASc score in predicting strokes.⁹ These findings reinforce the use of AF burden as an essential metric for stroke risk assessment and treatment decisions, potentially guiding more tailored approaches for anticoagulation therapy, and point to the importance of smartwatch-guided “pill-in-pocket” anticoagulation for AF.¹⁰ 

4. Cardiac Implantable Electrical Devices (CIEDs)
 
•  LEADR. The continuous drive to develop progressively smaller-caliber implantable cardioverter-defibrillator (ICD) leads came to a halt after the Sprint Fidelis lead (Medtronic) was recalled in 2007 and Riata 7 French (F) leads (Abbott) were recalled in 2011. Since then, the FDA has had stricter guidance for the development of new pacing and defibrillator leads. However, widespread adoption of the lumenless, sheath-delivered model 3830 SelectSecure pacing lead (Medtronic) for conduction system pacing has led to the development of the new 4.7F OmniaSecure defibrillation lead (Medtronic), which is substantially smaller than the 8.6F Sprint Quattro Secure 6947M defibrillation lead (Medtronic). The LEADR study evaluated this new lead.¹¹ Of 643 patients who successfully underwent implantation of the lead, 505 patients completed 12-month follow-up and 119 patients completed defibrillation threshold testing at implant. Defibrillation success was 97.5%, and freedom from lead-related major complications at 6 and 12 months was 97.1%. According to Crossley et al, this lead has the potential to offer significant clinical benefits for patients and physicians.

•  MODULAR ATP Trial. While safe and effective, a limitation of the subcutaneous ICD (S-ICD) is its inability to provide bradycardia or anti-tachycardia pacing (ATP). Medtronic’s extravascular ICD addressed this through placement of a substernal lead that can pace and defibrillate. Boston Scientific developed a 2-device modular pacing system with an S-ICD that communicates with a leadless pacemaker (LP) in the right ventricle. The MODULAR ATP Trial evaluated the safety and effectiveness of this modular, communicative LP-ICD system in 293 patients.¹² Communication success between the S-ICD and LP was 98.8%, with a low LP implant complication rate of 2.5%. Almost all (97.4%) patients had a low and stable capture threshold. Appropriate therapy was successfully delivered in 61.3% of ATP episodes without any reported discomfort. It is important to keep in mind that the study was designed to test the safety and efficacy of the LP for the purposes of delivering ATP, not bradycardia. Patients were excluded if they required pacing for pacemaker dependency, chronotropic incompetence, or required rate responsive pacing. Defibrillation testing was performed during asynchronous LP pacing at high output to ensure absence of interaction between pacing stimuli and S-ICD arrhythmia detection,12 and there were no inappropriate shocks for oversensing of pacing, but during resting heart rate testing, there was intermittent oversensing of the paced QRS complex in about 10% of patients. How many patients were receiving pacing during follow-up and what was their burden? Also, screening for T-wave oversensing is still recommended preoperatively for the S-ICD, but screening of the paced QRS complex in these patients cannot occur before implantation of the LP. Future studies must address the persistent concerns about “device-device” interaction during ventricular arrhythmias that occur while the LP is pacing in patients with a high burden of pacing. 

Disclosures: Dr Knight has served as a paid consultant to Medtronic and was an investigator in the PULSED AF trial. In addition, he has served as a consultant, speaker, investigator, and/or has received EP fellowship grant support from Abbott, AltaThera, AtriCure, Baylis Medical, Biosense Webster, Biotronik, Boston Scientific, CVRx, Philips, and Sanofi; he has no equity or ownership in any of these companies.

References

1. Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): developed by the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC), with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2024;45(36):3314-3414. doi:10.1093/eurheartj/ehae176

2. Cappato R, Levy S, Providencia R, et al. Concise guidelines of the European Cardiac Arrhythmias Society (ECAS) on “catheter ablation of atrial fibrillation”: a prepublication of the methods in preparation of the final guidelines document. J Cardiovasc Electrophysiol. 2024;35(7):1490-1494. doi:10.1111/jce.16254

3. Pulsed field ablation for paroxysmal atrial fibrillation. N Engl J Med. 2024;390(11):1054-1056. doi:10.1056/NEJMc2313783

4. Verma A, Haines DE, Boersma LV, et al. Pulsed field ablation for the treatment of atrial fibrillation: PULSED AF pivotal trial. Circulation. 2023;147(19):1422-1432. doi:10.1161/CIRCULATIONAHA.123.063988

5. De Potter T, Grimaldi M, Duytschaever M, et al. Predictors of success for pulmonary vein isolation with pulsed field ablation using a variable loop catheter with 3D mapping integration: complete 12-month outcomes from inspIRE. Circ Arrhythm Electrophysiol. 2024;17(5):e012667. doi:10.1161/CIRCEP.123.012667

6. Ekanem E, Neuzil P, Reichlin T, et al. Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study. Nat Med. 2024;30(7):2020-2029. doi:10.1038/s41591-024-03114-3

7. Reddy VY, Calkins H, Mansou M, et al. Pulsed field ablation to treat paroxysmal atrial fibrillation: safety and effectiveness in the AdmIRE pivotal trial. Circulation. 2024;150(15):1174-1186. doi:10.1161/CIRCULATIONAHA.124.070333

8. McIntyre WF, Benz AP, Becher N, et al. Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: a study-level meta-analysis of the NOAH-AFNET 6 and ARTESIA Trials. Circulation. 2024;149(13):981-988. doi:10.1161/CIRCULATIONAHA.123.067512

9. Piccini JP, Stanelle EJ, Johnson CC, et al. Circ Arrhythm Electrophysiol. Oct 24:e012394. Online ahead of print. doi:10.1161/CIRCEP.123.012394

10. Peigh G, Passman RS. “Pill-in-Pocket” anticoagulation for stroke prevention in atrial fibrillation. J Cardiovasc Electrophysiol. 2023;34(10):2152-2157. doi:10.1111/jce.15866

11. Crossley GH 3rd, Sanders P, Hansky B, for the Lead EvaluAtion for Defibrillation and Reliability Trial Investigators. Safety, efficacy, and reliability evaluation of a novel small-diameter defibrillation lead: Global LEADR pivotal trial results. Heart Rhythm. 2024;21(10):1914-1922. doi:10.1016/j.hrthm.2024.04.067

12. Knops RD, Reddy VY, Roberts PR, et al, for the MODULAR ATP Investigators. A modular communicative leadless pacing-defibrillator system. N Engl J Med. 2024;391(15):1402-1412. doi:10.1056/NEJMoa2401807