Recurrent or Persistent Device Related Thrombus After Left Atrial Appendage Occlusion: The RE-DRT Study

Overview

This study is a prospective, multicenter international trial aimed at assessing the actual incidence, identifying associated factors, and evaluating the clinical consequences of both persistent and recurrent device-related thrombus (DRT) following percutaneous left atrial appendage occlusion (LAAO). While LAAO has shown efficacy in reducing the risk of stroke, device-related thrombus (DRT) remains a significant concern. The reported incidence of DRT varies, and it is associated with an elevated risk of ischemic stroke and death. The study highlights that persistent and recurrent DRT pose higher risks of thromboembolic events, and current data come from retrospective studies with non-standardized imaging follow-up protocols. The timing of imaging follow-up is crucial, and the study notes discrepancies in recommendations from expert statements. The EHRA/EAPCI suggests imaging at specific intervals post-procedure, while the SCAI/HRS recommends repeat imaging at shorter intervals to assess DRT resolution. The study underscores the need for dedicated prospective data to accurately determine the incidence, factors, and clinical impact of persistent and recurrent DRT after LAAO.

Detailed description

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a nonpharmacological alternative for stroke prevention in patients with non-valvular atrial fibrillation ineligible for chronic anticoagulation therapy. Large real-world observational studies have consistently reported the efficacy of LAAO in reducing the risk of ischemic stroke and systemic embolism, compared to predicted rates, without the need for anticoagulants. Despite ongoing refinement in LAAO procedural technique, significant challenges persist. Notably, device-related thrombus (DRT) remains the main concern after LAAO. The reported incidence rate varies, ranging from 3% to 7%, and has been associated with an elevated risk of ischemic stroke and all-cause death following LAAO. Several risk factors have been identified with DRT occurrence, most of which are non-modifiable. The diagnosis of DRT is followed by an intensification of the antithrombotic treatment. However, not all DRT are resolved, with a significant number persisting or recurring upon withdrawal of anticoagulation therapy. In these situations, the antithrombotic treatment must be maintained, increasing the risk of bleeding, and mitigating the potential benefits of LAAO.

Both persistent and recurrent DRT have been linked to an increased risk of thromboembolic events when compared to resolved DRT. In the pooled analysis of data from the PROTECT-AF and PREVAIL trials, around 12% of embolic events in patients with DRT occurred in the presence of multiple DRT episodes. The incidence of persistent DRT has been reported in one out of three patients diagnosed with DRT, with DRT recurrence occurring in one out of five patients. However, the real incidence of persistent and recurrent DRT is uncertain, as current data come from retrospective studies with non-standardized imaging follow-up protocols. This situation leads to a significant number of missed cases, increases the risk of bias, and likely underestimates the rate of persistent and recurrent DRT. The timing of the imaging follow-up can significantly affect the incidence of DRT. In consecutive patients examined through a pre-specified protocol, the incidence of specific findings would be much more accurate compared to imaging examinations based exclusively on a single adverse clinical event, where the real incidence and clinical associations cannot be accurately determined.

The EHRA/EAPCI expert LAAO statement recommends imaging within 6-24 weeks and then 12 months post-procedure, with no mention of imaging follow-up in case of persistent or recurrent DRT. In contrast, the recent SCAI/HRS expert consensus statement on transcatheter LAAO suggests that repeat imaging at 45- to 90-day intervals can be conducted to assess for DRT resolution and consider the eventual cessation of anticoagulation, although there is no evidence that support this recommendation. Finally, considering the substantial rate of recurrent DRT and its clinical implications, a long-term and sequential imaging follow-up strategy may be warranted. Therefore, there is an unmet need for dedicated prospective data to determine the real incidence, related factors, and clinical impact of persistent and recurrent DRT after LAAO.

Primary outcome measures

• Thromboembolic events (ischemic stroke, systemic embolism) [Time frame: 1-month, 6-month, 1-year, 2-year]

Eligibility criteria

Inclusion criteria

• Patients with diagnosis of probable/definite DRT after LAAO detected by transesophageal echocardiography (TEE) or cardiac computed tomography (CT).
• Age≥18 years old.

Exclusion criteria

• Unable to provide informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

Canada · 1 center

• IUCPQ-UL — Québec

Publications

• Mesnier J, Simard T, Jung RG, Lehenbauer KR, Piayda K, Pracon R, Jackson GG, Flores-Umanzor E, Faroux L, Korsholm K, Chun JKR, Chen S, Maarse M, Montrella K, Chaker Z, Spoon JN, Pastormerlo LE, Meincke F, Sawant AC, Moldovan CM, Qintar M, Aktas MK, Branca L, Radinovic A, Ram P, El-Zein RS, Flautt T, Ding WY, Sayegh B, Benito-Gonzalez T, Lee OH, Badejoko SO, Paitazoglou C, Karim N, Zaghloul AM, Aga PMID 38030358
• Saw J, Holmes DR, Cavalcante JL, Freeman JV, Goldsweig AM, Kavinsky CJ, Moussa ID, Munger TM, Price MJ, Reisman M, Sherwood MW, Turi ZG, Wang DD, Whisenant BK. SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure. Heart Rhythm. 2023 May;20(5):e1-e16. doi: 10.1016/j.hrthm.2023.01.007. Epub 2023 Mar 27. PMID 36990925
• Tzikas A, Holmes DR Jr, Gafoor S, Ruiz CE, Blomstrom-Lundqvist C, Diener HC, Cappato R, Kar S, Lee RJ, Byrne RA, Ibrahim R, Lakkireddy D, Soliman OI, Nabauer M, Schneider S, Brachmann J, Saver JL, Tiemann K, Sievert H, Camm AJ, Lewalter T. Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies. Eu PMID 27540038
• Holmes DR Jr, Korsholm K, Rodes-Cabau J, Saw J, Berti S, Alkhouli MA. Left atrial appendage occlusion. EuroIntervention. 2023 Feb 6;18(13):e1038-e1065. doi: 10.4244/EIJ-D-22-00627. PMID 36760206
• Holmes DR Jr, Reddy VY, Gordon NT, Delurgio D, Doshi SK, Desai AJ, Stone JE Jr, Kar S. Long-Term Safety and Efficacy in Continued Access Left Atrial Appendage Closure Registries. J Am Coll Cardiol. 2019 Dec 10;74(23):2878-2889. doi: 10.1016/j.jacc.2019.09.064. PMID 31806131
• Simard TJ, Hibbert B, Alkhouli MA, Abraham NS, Holmes DR Jr. Device-related thrombus following left atrial appendage occlusion. EuroIntervention. 2022 Jun 24;18(3):224-232. doi: 10.4244/EIJ-D-21-01010. PMID 35440430
• Alkhouli M, Alarouri H, Kramer A, Korsholm K, Collins J, De Backer O, Hatoum H, Nielsen-Kudsk JE. Device-Related Thrombus After Left Atrial Appendage Occlusion: Clinical Impact, Predictors, Classification, and Management. JACC Cardiovasc Interv. 2023 Nov 27;16(22):2695-2707. doi: 10.1016/j.jcin.2023.10.046. PMID 38030357
• Alkhouli M, Busu T, Shah K, Osman M, Alqahtani F, Raybuck B. Incidence and Clinical Impact of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion: A Meta-Analysis. JACC Clin Electrophysiol. 2018 Dec;4(12):1629-1637. doi: 10.1016/j.jacep.2018.09.007. Epub 2018 Nov 1. PMID 30573129

Identifiers

NCT: NCT06177704 · RE-DRT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗