Five key risk factors for device-related thrombus (DRT) following left atrial appendage occlusion (LAAO) were identified in a new multicenter registry study: hypercoagulability disorder, pericardial effusion, renal insufficiency, implantation depth >10 mm from the pulmonary vein limbus and non-paroxysmal atrial fibrillation.
After giving each factor a relative risk score in points, the researchers found that patients with 2 or more risk points for DRT had a 2.1-fold higher chance of developing such thrombus compared to those without the 5 risk factors.
The findings were published online on Monday, ahead of the July 27 issue of the Journal of the American College of Cardiology, by co-lead authors Trevor Simard, MD, from the Mayo Clinic School of Medicine, and Richard G. Jung, BSc, of the University of Ottawa Heart Institute, together with colleagues.
As an alternative to anticoagulation in stroke prevention for atrial fibrillation patients considered poor candidates for long-term oral anticoagulation (OAC), LAAO use has continued to grow, particularly given growing operator experience and technical improvements, the researchers added.
Still, DRT remains a challenge that “may affect the success of the LAAO field at large,” the researchers said, with estimates of occurrence in 3% to 4% of patients post-procedurally.
Despite significantly elevated ischemic risk associated with DRT, data on DRT prediction have been limited, the researchers said, lamenting that reproducible diagnostic criteria, optimal detection protocols and management strategies are all missing.
The ability to determine risk factors for DRT formation has been “elusive” in any case because of discrepant patient, anatomic, technical and pharmacological factors described across a handful of small studies, the authors noted.
The current international study was, therefore, established to determine independent predictors of DRT in a registry of 711 patients, both with (237 patients) and without DRT (474), after treatment with LAAO across 37 centers.
The DRT group were followed for a median of 1.8 years (interquartile range [IQR]: 0.9 to 3 years) and the no-DRT group were followed for a median of 1.6 years (IQR: 1 to 2.9 years) – similar timeframes (p = 0.76). Medical therapy regimens on discharge following LAAO did not differ between the control and DRT cohorts, with most patients being managed with either single antiplatelet therapy (SAPT, 36.3%) or dual antiplatelet therapy (DAPT, 26.2%) at time of DRT diagnosis.
DRTs were detected between 45 to 180 days in a plurality (38.8%) of cases. However, overall, the timing of DRT diagnosis varied “considerably,” the authors said, with early detection (between 0 to 45 days) for 24.9%, while 16% of cases were detected between 180 to 365 days and 20.3% of cases took more than 365 days to be detected.
Diagnosis by transesophageal echocardiography (TEE) happened in 200 cases (84.4%), and computed tomography (CT) scan in 33 cases (13.9%), although TEE plus CT diagnosis was relatively low at just four cases (1.7%), the researchers said.
Of the 237 DRT cases, the majority (131, 55.3%) were on the disk, 30 (12.7%) were on the screw, 20 (8.4%) were adjacent to the LAAO device, 11 (4.6%) were found elsewhere, two (0.8%) were on both the screw and the disk, two (0.8%) were on the disk and adjacent to LAAO, and 41 (17.3%) were not specified.
The five DRT risk factors identified by multivariable logistic regression analysis were: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% confidence interval [CI]: 3.39-90.45; p = 0.0006), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52; p = 0.02), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25; p = 0.02), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57- 3.69; p = <0.0001), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97; p = 0.005).
DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (hazard ratio [HR]: 2.37; 95% CI: 1.58-3.56; p < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; p = 0.01).
To generate a DRT risk score, the five risk factors were normalized to integer values of 4 points for hypercoagulability disorder, 4 points for pericardial effusion, and 1 point for renal insufficiency, LAAO depth of implantation >10 mm from the pulmonary vein limbus, or nonparoxysmal AF.
Elements with 4 points were considered “major risk factors,” while those with 1 point were minor risk factors. Patients with one of the major risk factors, or at least two minor risk factors, were considered to have a 2.1-fold increased risk of DRT compared with those without any risk factors, the researchers found.
Patients with DRT underwent more imaging assessments and experienced greater major adverse cardiac event (MACE) rates in their respective follow-up intervals, particularly those diagnosed later (>180 days).
Those diagnosed with DRT remained on antithrombotic agents more often than the no-DRT group, with 19% on OAC versus 4.2%, and 15.6% on SAPT plus OAC versus 2.7%.
Can DRT resolution work?
At last known follow-up, 25.3% of patients still had DRT, while the remaining DRTs were resolved with OAC. Yet notably, resolving DRT was “not portending improved rates of MACE, albeit with limited events,” the researchers said.
In an accompanying editorial, Oussama Wazni, MD, and colleagues from the Cleveland Clinic, noted that it therefore “remains unclear whether resolution of DRT truly mitigates the risks of embolic of cardiovascular events.”
Wazni et al. added that potential cofounders in such assessment “include, but are not limited to, the possibility of non-LAA sources of cerebral emboli, pre-existing risk factors, DRT recurrence, changes in therapy over time, and in this particular study, the small number of events thus limiting statistical power for definitive conclusions”.
They stressed that further studies would be needed “to clarify the natural history of DRTs and their management, resolution, and impact on cardiovascular events.”
The main clinical question is, thus, whether DRTs can be predicted and their occurrence prevented, the editorialists said.
“The only procedural risk factors that are modifiable from the current study are pericardial effusion and the device’s implantation depth. Albeit limited by lack of a core lab and standard protocols for assessment of implantation depth, it is reasonable based on these findings to suggest avoiding deeper implants whenever possible,” the editorialists added.
The study authors, meanwhile, concluded that – despite study limitations such as the fact that DRT diagnosis, patient risk factors and subsequent events were self-reported, as well as a lack of systematic standardized imaging and device assessment – the data show that patient and procedural risk factors can be used to predict DRT.
This should help in risk stratification and optimization of procedural techniques and postprocedural management, the authors concluded, calling for further refinement of risk stratification and the impact of periprocedural management on clinical outcomes.
Simard T, Jung RG, Lehenbauer K, et al. Predictors of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion. J Am Coll Cardiol 2021;78:297–313.
Wazni O, Saliba W, Hussein AA. Device-Related Thrombus After Left Atrial Appendage Occlusion. J Am Coll Cardiol 2021; 78: 314–6.
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