Comparison of the Efficacy of Successful Leak Closure Between Available Leak Closure Methods for Clinically Relevant and Persisting Leaks Arising After Incomplete LAAC: Insights From the LAA-Leak Registry
Conditions: Left Atrail Appendage Closure: Peri-device Leaks
Sponsor: Kansas City Heart Rhythm Research Foundation

 
 
 
Multimodality evaluation of LAA Leaks arising after 
incomplete LAAC: Insights from the LAA-Leak Registry 
 
 
 
 
NCT05131308 
 
 
 
05th October, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 

Multimodality evaluation of LAA Leaks arising after incomplete LAAC: Insights from the LAA-
Leak Registry 
 
Sponsor: Kansas City Heart Rhythm Research Foundation 
                6709 W 119th St Suite 121 
                Overland Park 
                KS 66209 
 
 
Principal Investigator:  
Dhanunjaya Lakkireddy, MD FACC 
                                                 Kansas City Heart Rhythm Institute 
                                                 5100 W 110th St  Suite 200 
                                                 Overland Park 
                                                 KS 66211 
 
Co-investigators:  
 
Rishi Charate, MD : Kansas City Heart Rhythm Institute 
Adnan Ahmed, MD : Kansas City Heart Rhythm Institute 
 
 
1. Background 
Left Atrial Appendage (LAA) Closure (LAAC) is a potent technique of LAA isolation and 
exclusion for stroke prevention in patients with atrial fibrillation, with evidence from the 
PROTECT-AF and PREVAIL-AF trials, including their 5-year follow-up assessments, 
solidifying LAAC as a viable option in these patients with comparable stroke reduction in 
comparison to oral anticoagulation (OAC) as well as a reduction in bleeding risk, hemorrhagic 
CVA, and mortality [1-3].  However, the surge in the multiple methods of LAA exclusion has 
also brought to attention postprocedural complications specific to LAAC, namely, peri-device 
leaks (PDL) [4]. The stroke implication and classification of PDL itself still lacks consensus, 
with an increased thromboembolic (TE) potential due to PDL seen in patients with LARIAT and 
surgical ligation procedures, yet no statistically significant relationship seen in percutaneous and 
endocardial LAA closure approaches [5-9]. PDL > 5mm has been widely accepted as clinically 
significant, although there remains limited data with no current established guidelines. [5, 6, 10].  
Placement of a septal occluder device such as Amplatzer Vascular Plug, Detachable 
embolization coils, Gore Cardioform Septal Occluder (CSO; W.L. Gore and Associates, Newark 
DE), and radiofrequency ablation (RFA) have all emerged as options to resolve residual PDL 
and post-surgical/ligation leaks [5, 10-12].  However, there exists no head-to-head comparison 
between these modalities.  Given their emergence, we proposed a multi-center observational 
study to further assess and evaluate these three treatment modalities for their efficacy for leak 
closure, assessment of pre-, peri- and post-procedural characteristics after leak closure, TE 
events, and bleeding risk, and complication rates.  

2. Objectives: 
Primary Objective:   
Our main objective is to collect data from multiple different centers that use different modalities 
to currently treat either central or peri-device leaks that occur after incomplete LAA closure, and 
compare each modality in their efficacy and safety outcomes.  
Primary Outcome: To compare the efficacy of the three current methods of PDL closure 
modalities in patients with prior incomplete LAAC.  
Secondary Outcome: To compare the rates or reduction of rates of thromboembolic events and 
procedure-related complications in patients after successful PDL closure with any of the three 
closure modalities. 
 
3. Research Methods and Statistical Considerations:  
Research Methods:  
This will be a multi- center retrospective observational comparison study.  
Study Population:  
All patients at risk for stroke or thromboembolism that demonstrated any degree of the 
significant leak on follow up TEE imaging at least 4-6 weeks following either epicardial, 
endocardial, or surgical LAAC were included in this study population. All patients were 
evaluated and followed with imaging, and per investigators' respective clinical judgement, then 
proceeded to have an intervention for leak closure with either detachable embolization coils, 
vascular plugs/CSO, or RFA. 
Inclusion Criteria:  
- 
patients at risk for stroke or thromboembolism that demonstrated any degree of the 
significant leak on follow up TEE imaging at least 4-6 weeks following either epicardial, 
endocardial, or surgical LAAC 
- 
Patients undergoing any form of eccentric or centric/central leak closure with available 
modalities (detachable embolization coils, vascular plug/septal/ASD occluders, or RF 
Ablation). Criteria for this was made based on the judgement of the operator, with no 
specific cutoffs for leak size, follow-up time from LAAC to leak closure, etc) 
- 
Age greater than 18 years 
Exclusion Criteria:  
- 
Patients not undergoing leak closure after incomplete LAAC 
- 
Patients unable to complete 45-day follow-up imaging for reevaluation of LAA leak 
- 
Patients unable to consent 
Primary Endpoints:  
1. To compare the efficacy of the three PDL closure modalities in patients with prior LAAC 

Secondary Endpoints:  
1. To compare the reduction/rates of TE events and procedure-related complications (DRT, 
pericardial effusion/cardiac tamponade, or CVA/TIA) in patients after successful PDL 
closure with any of the three closure modalities 
a. Periprocedural complications occurring from Postoperative day #0 – day 7 
b. Delayed procedure-related complications and adverse events within 90 days of 
procedure 
Informed Consent:  
Given that this study was observational and retrospective in design, no informed consent was 
obtained or required. Patients who met inclusion/exclusion criteria were de-identified and added 
to word documents/excel spreadsheets.  
Data storage/Confidentiality:  
Data will be collected in word documents, PDFs, and excel sheets. Data recorded on the 
worksheets will be entered into a secure password protected computer database by the research 
staff at corresponding heart institutes/cardiac centers. Only investigators involved in the study 
will have access to the data. All data will be reported in aggregate form and no names will be 
used for any publications resulting from the research. De identification of data will be done at the 
earliest. 
Sample Size:  
We will plan to aim for a total size of 160 patients in total among all three modalities.   
Statistical Analysis:  
Continuous variables will be summarized using mean and standard deviation, while categorical 
variables will be summarized as counts and percent of the total. Comparison analysis between 
groups will be made using Kruskal-Wallis tests for nonparametric data sets as appropriate. Leak 
sizes were measured initially and then via postprocedural follow-up, with overall rates of 
closure, minimal-mild leaks, and clinically significant leaks listed with associated p-values.  All 
tests were two-tailed, and a P value less than 0.05 was considered statistically significant.  All 
analyses were performed using SPSS Statistics version 28.0.0.0 (IBM). 
Data/Variable Points for Collection:  
- 
Age 
- 
Sex 
- 
Height 
- 
Weight 
- 
BMI 
- 
Diabetes (y/n) 
- 
Smoking (y/n) 
- 
Dyslipidemia (y/n) 
- 
Prior stroke/TIA (y/n) 

- 
Prior deep venous thrombosis/pulmonary embolism (y/n) 
- 
Ejection Fraction 
- 
History of CAD (y/n) 
- 
Congestive heart failure (y/n) 
- 
Chronic Kidney Disease (y/n) 
- 
Type of Atrial Fibrillation (paroxysmal, persistent, permanent) 
- 
Baseline antithrombotic regimen (aspirin, clopidogrel/prasugrel/ticagrelor, warfarin, 
direct oral anticoagulant, heparin) 
- 
TIA/stroke after Watchman 
- 
History of major bleeding 
- 
High Fall risk (y/n) 
- 
Previous major bleeding (y/n) 
- 
Previous minor bleeding (y/n) 
- 
Thromboembolism while on oral anticoagulant 
- 
CHA2DS2-VASc Score 
- 
HAS-BLED Score 
- 
Time passed since LAA closure (months) 
- 
Type of LAA Closure (watchman/watchman FLX, amulet, lariat, surgical ligation, 
atriclip) 
- 
Device Size (if applicable) 
- 
Thrombus on device (y/n) 
- 
Peri-device/central leak size in mm 
- 
Acute success (end of procedure closure) (y/n) 
- 
Procedure duration (minutes) 
- 
Flouroscopy time (minutes)  
- 
Contrast usage (mL) 
- 
Hospital length of stay 
- 
Type of procedural anesthesia (general vs light sedation vs local) 
- 
Procedural imaging (TEE, ICE, or both) 
- 
Devices attempted 
- 
Devices deployed 
- 
Combination procedures (combined AF ablation, or LAA occlusion + AF ablation) 
- 
Size/number of devices (plugs/coils) 
- 
Major procedural complications from postoperative day 0-7: stroke, TIA, air embolism, 
myocardial infarction, cardiac tamponade, device embolization, ventricular tachycardia 
- 
Minor procedural complications from postoperative day 0-7: pericardial effusion 
- 
Complications seen within 90 days of the procedure: cardiovascular death, non-
cardiovascular death, stroke/TIA, pericarditis 
- 
Follow-up transesophageal echocardiogram time (months)  
- 
Size of leak at follow up (in mm) 
- 
Follow-up time  
- 
Follow up antithrombotic regimen 
 

References 
1. 
Holmes, D.R., et al., Percutaneous closure of the left atrial appendage versus warfarin 
therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-
inferiority trial. Lancet, 2009. 374(9689): p. 534-42. PMID: 19683639 
2. 
Holmes, D.R., et al., Prospective Randomized Evaluation of the Watchman Left Atrial 
Appendage Closure Device in Patients With Atrial Fibrillation Versus Long-Term 
Warfarin Therapy. Journal of the American College of Cardiology, 2014. 64(1): p. 1-12. 
PMID: 27343417 
3. 
Reddy, V.Y., et al., 5-Year Outcomes After Left Atrial Appendage Closure. Journal of the 
American College of Cardiology, 2017. 70(24): p. 2964-2975. PMID: 29103847 
4. 
Nguyen, A., et al., Peridevice Leak After Left Atrial Appendage Closure: Incidence, Risk 
Factors, and Clinical Impact. Can J Cardiol, 2019. 35(4): p. 405-412. PMID: 30935631 
5. 
Sahore, A., et al., Clinical Implications and Management Strategies for Left Atrial 
Appendage Leaks. Card Electrophysiol Clin, 2020. 12(1): p. 89-96. PMID: 32067651 
6. 
Albaghdadi, M., et al., Peri-Device Leaks after Percutaneous Left Atrial Appendage 
Closure: Clinical Significance and Unmet Diagnostic Needs. Structural Heart, 2020. 
4(6): p. 475-481. https://doi.org/10.1080/24748706.2020.1817642 
7. 
Mohanty, S., et al., Risk of thromboembolic events after percutaneous left atrial 
appendage ligation in patients with atrial fibrillation: Long-term results of a multicenter 
study. Heart Rhythm, 2020. 17(2): p. 175-181. PMID: 31400519 
8. 
Aryana, A., et al., Association between incomplete surgical ligation of left atrial 
appendage and stroke and systemic embolization. Heart Rhythm, 2015. 12(7): p. 1431-7. 
PMID: 25998141 
9. 
Turagam, M.K., et al., Cardiovascular Therapies Targeting Left Atrial Appendage. 
Journal of the American College of Cardiology, 2018. 72(4): p. 448-463. PMID: 
29954658 
10. 
Jang, S.J., S.C. Wong, and B. Mosadegh, Leaks after Left Atrial Appendage Closure: 
Ignored or Neglected? Cardiology, 2021. 146(3): p. 384-391. PMID: 33735867 
11. 
Della Rocca, D.G., et al., First Experience of Transcatheter Leak Occlusion With 
Detachable Coils Following Left Atrial Appendage Closure. JACC: Cardiovascular 
Interventions, 2020. 13(3): p. 306-319. PMID: 31954677 
12. 
Rocca, D.G.D., et al., Use of a Novel Septal Occluder Device for Left Atrial Appendage 
Closure in Patients With Postsurgical and Postlariat Leaks or Anatomies Unsuitable for 
Conventional Percutaneous Occlusion. Circulation: Cardiovascular Interventions, 2020. 
13(10): p. e009227. PMID: 32942913