Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. LAAC Procedure
2.3. Post-Procedural Antithrombotic Treatment and Follow-Up Assessment
2.4. Study Endpoints and Definition
2.5. Statistical Methods
3. Results
3.1. Study Population
3.2. Bleeding History before LAAC
3.3. Procedural Outcomes
3.4. Nonprocedural Bleeding
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Hindricks, G.; Potpara, T.; Dagres, N.; Arbelo, E.; Bax, J.J.; Blomström-Lundqvist, C.; Boriani, G.; Castella, M.; Dan, G.A.; Dilaveris, P.E.; et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 2021, 42, 373–498. [Google Scholar] [CrossRef]
- Landmesser, U.; Tondo, C.; Camm, J.; Diener, H.C.; Paul, V.; Schmidt, B.; Settergren, M.; Teiger, E.; Nielsen-Kudsk, J.E.; Hildick-Smith, D. Left atrial appendage occlusion with the AMPLATZER Amulet device: One-year follow-up from the prospective global Amulet observational registry. EuroIntervention 2018, 14, e590–e597. [Google Scholar] [CrossRef]
- Phillips, K.P.; Santoso, T.; Sanders, P.; Alison, J.; Chan, J.L.K.; Pak, H.N.; Chandavimol, M.; Stein, K.M.; Gordon, N.; Razali, O.B. Left atrial appendage closure with WATCHMAN in Asian patients: 2 year outcomes from the WASP registry. Int. J. Cardiol. Heart Vasc. 2019, 23, 100358. [Google Scholar] [CrossRef] [PubMed]
- Freixa, X.; Gafoor, S.; Regueiro, A.; Cruz-Gonzalez, I.; Shakir, S.; Omran, H.; Berti, S.; Santoro, G.; Kefer, J.; Landmesser, U.; et al. Comparison of Efficacy and Safety of Left Atrial Appendage Occlusion in Patients Aged <75 to ≥75 Years. Am. J. Cardiol. 2016, 117, 84–90. [Google Scholar] [CrossRef] [PubMed]
- López-Mínguez, J.R.; Nogales-Asensio, J.M.; Infante De Oliveira, E.; Santos, L.; Ruiz-Salmerón, R.; Arzamendi-Aizpurua, D.; Costa, M.; Gutiérrez-García, H.; Fernández-Díaz, J.A.; Freixa, X.; et al. Major Bleeding Predictors in Patients with Left Atrial Appendage Closure: The Iberian Registry II. J. Clin. Med. 2020, 9, 2295. [Google Scholar] [CrossRef] [PubMed]
- Boersma, L.V.; Ince, H.; Kische, S.; Pokushalov, E.; Schmitz, T.; Schmidt, B.; Gori, T.; Meincke, F.; Protopopov, A.V.; Betts, T.; et al. Evaluating Real-World Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology: Final 2-Year Outcome Data of the EWOLUTION Trial Focusing on History of Stroke and Hemorrhage. Circ. Arrhythm. Electrophysiol. 2019, 12, e006841. [Google Scholar] [CrossRef]
- Osmancik, P.; Herman, D.; Neuzil, P.; Hala, P.; Taborsky, M.; Kala, P.; Poloczek, M.; Stasek, J.; Haman, L.; Branny, M.; et al. 4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation. J. Am. Coll. Cardiol. 2022, 79, 1–14. [Google Scholar] [CrossRef]
- Kaatz, S.; Ahmad, D.; Spyropoulos, A.C.; Schulman, S. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: Communication from the SSC of the ISTH. J. Thromb. Haemost. 2015, 13, 2119–2126. [Google Scholar] [CrossRef]
- Lip, G.Y.; Frison, L.; Halperin, J.L.; Lane, D.A. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: The HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J. Am. Coll. Cardiol. 2011, 57, 173–180. [Google Scholar]
- WHO. Nutritional Anaemias: Report of a WHO Scientific Group; World Health Organization: Geneva, Switzerland, 1968; pp. 5–37. [Google Scholar]
- Faroux, L.; Cruz-González, I.; Arzamendi, D.; Freixa, X.; Nombela-Franco, L.; Peral, V.; Caneiro-Queija, B.; Mangieri, A.; Trejo-Velasco, B.; Asmarats, L.; et al. Incidence, predictors, and clinical impact of bleeding recurrence in patients with prior gastrointestinal bleeding undergoing LAAC. Pacing. Clin. Electrophysiol. 2021, 44, 1216–1223. [Google Scholar] [CrossRef]
- Lai, K.C.; Lam, S.K.; Chu, K.M.; Hui, W.M.; Kwok, K.F.; Wong, B.C.; Hu, H.C.; Wong, W.M.; Chan, O.O.; Chan, C.K. Lansoprazole reduces ulcer relapse after eradication of Helicobacter pylori in nonsteroidal anti-inflammatory drug users—A randomized trial. Aliment. Pharmacol. Ther. 2003, 18, 829–836. [Google Scholar] [CrossRef] [PubMed]
- Raposeiras Roubín, S.; Abu Assi, E.; Barreiro Pardal, C.; Cespón Fernandez, M.; Muñoz Pousa, I.; Cobas Paz, R.; Parada, J.A.; Represa Montenegro, M.; Melendo Miu, M.; Blanco Prieto, S.; et al. New Cancer Diagnosis After Bleeding in Anticoagulated Patients with Atrial Fibrillation. J. Am. Heart Assoc. 2020, 9, e016836. [Google Scholar] [CrossRef] [PubMed]
- Kalman, R.S.; Pedrosa, M.C. Evidence-based review of gastrointestinal bleeding in the chronic kidney disease patient. Semin. Dial. 2015, 28, 68–74. [Google Scholar] [CrossRef]
- Gerson, L.B. Causes of gastrointestinal hemorrhage in patients with chronic renal failure. Gastroenterology 2013, 145, 895–897; discussion 897. [Google Scholar] [CrossRef] [PubMed]
- Chalasani, N.; Cotsonis, G.; Wilcox, C.M. Upper gastrointestinal bleeding in patients with chronic renal failure: Role of vascular ectasia. Am. J. Gastroenterol. 1996, 91, 2329–2332. [Google Scholar]
- Shovlin, C.L.; Awan, I.; Cahilog, Z.; Abdulla, F.N.; Guttmacher, A.E. Reported cardiac phenotypes in hereditary hemorrhagic telangiectasia emphasize burdens from arrhythmias, anemia and its treatments, but suggest reduced rates of myocardial infarction. Int. J. Cardiol. 2016, 215, 179–185. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Plauchu, H.; de Chadarévian, J.P.; Bideau, A.; Robert, J.M. Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am. J. Med. Genet. 1989, 32, 291–297. [Google Scholar] [CrossRef] [PubMed]
- Chaaban, M.R.; Zhang, D.; Resto, V.; Goodwin, J.S. Factors influencing recurrent emergency department visits for epistaxis in the elderly. Auris Nasus Larynx. 2018, 45, 760–764. [Google Scholar] [CrossRef]
- Abrich, V.; Brozek, A.; Boyle, T.R.; Chyou, P.H.; Yale, S.H. Risk factors for recurrent spontaneous epistaxis. Mayo Clin. Proc. 2014, 89, 1636–1643. [Google Scholar] [CrossRef]
- Nabauer, M.; Gerth, A.; Limbourg, T.; Schneider, S.; Oeff, M.; Kirchhof, P.; Goette, A.; Lewalter, T.; Ravens, U.; Meinertz, T.; et al. The Registry of the German Competence NETwork on Atrial Fibrillation: Patient characteristics and initial management. Europace 2009, 11, 423–434. [Google Scholar] [CrossRef]
- Ishii, M.; Ogawa, H.; Unoki, T.; An, Y.; Iguchi, M.; Masunaga, N.; Esato, M.; Chun, Y.H.; Tsuji, H.; Wada, H.; et al. Relationship of Hypertension and Systolic Blood Pressure with the Risk of Stroke or Bleeding in Patients with Atrial Fibrillation: The Fushimi AF Registry. Am. J. Hypertens. 2017, 30, 1073–1082. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Toyoda, K.; Yasaka, M.; Uchiyama, S.; Nagao, T.; Gotoh, J.; Nagata, K.; Koretsune, Y.; Sakamoto, T.; Iwade, K.; Yamamoto, M.; et al. Blood pressure levels and bleeding events during antithrombotic therapy: The Bleeding with Antithrombotic Therapy (BAT) Study. Stroke 2010, 41, 1440–1444. [Google Scholar] [CrossRef]
- Pracon, R.; Trochimiuk, P.; Debski, M.; Kepka, C.; Demkow, M. Do We Have Good Reasons to Pay Bleeding Penalty with Lifelong Aspirin After LAAO. JACC Cardiovasc. Interv. 2019, 12, 1741. [Google Scholar] [CrossRef] [PubMed]
- Flores-Umanzor, E.J.; Cepas-Guillen, P.L.; Arzamendi, D.; Cruz-González, I.; Regueiro, A.; Freixa, X. Rationale and design of a randomized clinical trial to compare two antithrombotic strategies after left atrial appendage occlusion: Double antiplatelet therapy vs. apixaban (ADALA study). J. Interv. Card. Electrophysiol. 2020, 59, 471–477. [Google Scholar] [CrossRef] [PubMed]
- Bouget, J.; Oger, E.; Nicolas, N. Emergency admissions for major haemorrhage associated with antithrombotics: A cohort study. Thromb. Res. 2015, 135, 84–89. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Glikson, E.; Chavkin, U.; Madgar, O.; Sagiv, D.; Nakache, G.; Yakirevitch, A.; Wolf, M.; Alon, E.E. Epistaxis in the setting of antithrombotic therapy: A comparison between factor Xa inhibitors, warfarin, and antiplatelet agents. Laryngoscope 2019, 129, 119–123. [Google Scholar] [CrossRef]
- Yaniv, D.; Zavdy, O.; Sapir, E.; Levi, L.; Soudry, E. The Impact of Traditional Anticoagulants, Novel Anticoagulants, and Antiplatelets on Epistaxis. Laryngoscope 2021, 131, 1946–1951. [Google Scholar] [CrossRef]
- Nazir, S.; Ahuja, K.R.; Khan Minhas, A.M.; Ariss, R.W.; Goel, S.S.; Gupta, R. Association of Peri-Procedural Major Bleeding with Outcomes in Patients Undergoing Percutaneous Left Atrial Appendage Closure. Am. J. Cardiol. 2021, 151, 122–123. [Google Scholar] [CrossRef]
- Demkow, M.; Konka, M.; Witkowski, A.; Pracoń, R.; Ścisło, P.; Huczek, Z.; Burysz, M.; Ogorzeja, W.; Suwalski, G.; Kurowski, A.; et al. How to Prevent Pulmonary Artery Wall Perforation Following Transcatheter Occlusion of Left Atrial Appendage. J. Am. Soc. Echocardiogr. 2021, 34, 195–197.e2. [Google Scholar] [CrossRef]
- Simard, T.; Jung, R.G.; Lehenbauer, K.; Piayda, K.; Pracoń, R.; Jackson, G.G.; Flores-Umanzor, E.; Faroux, L.; Korsholm, K.; Chun, J.K.R.; et al. Predictors of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion. J. Am. Coll. Cardiol. 2021, 78, 297–313. [Google Scholar] [CrossRef]
- Pracon, R.; Bangalore, S.; Dzielinska, Z.; Konka, M.; Kepka, C.; Kruk, M.; Kaczmarska-Dyrda, E.; Petryka-Mazurkiewicz, J.; Bujak, S.; Solecki, M.; et al. Device Thrombosis After Percutaneous Left Atrial Appendage Occlusion Is Related to Patient and Procedural Characteristics but Not to Duration of Postimplantation Dual Antiplatelet Therapy. Circ. Cardiovasc. Interv. 2018, 11, e005997. [Google Scholar] [CrossRef] [PubMed]
- Pracoń, R.; Zieliński, K.; Bangalore, S.; Konka, M.; Kruk, M.; Kępka, C.; Trochimiuk, P.; Dębski, M.; Przyłuski, J.; Kaczmarska, E.; et al. Residual stroke risk after left atrial appendage closure in patients with prior oral anticoagulation failure. Int. J. Cardiol. 2022, 354, 17–21. [Google Scholar] [CrossRef] [PubMed]
- Baharoglu, M.I.; Coutinho, J.M.; Marquering, H.A.; Majoie, C.B.; Roos, Y.B. Clinical Outcome in Patients with Intracerebral Hemorrhage Stratified by Type of Antithrombotic Therapy. Front. Neurol. 2021, 12, 684476. [Google Scholar] [CrossRef] [PubMed]
No. | Post-LAAC CSB Site | Type | Time (Days) | APT | HAS-BLED | Pre-LAAC Bleeding Site | History of Comorbidities Associated with the Pre-LAAC Bleeding Site |
---|---|---|---|---|---|---|---|
1 | GI | mCRB | 233 | single | 2 | intracranial | - |
2 | GI | mCRB | 10 | dual | 1 | GI | Crohn’s disease, S/P colon resection |
3 | GI | mCRB | 18 | dual | 3 | GI | diverticulosis and polyps in the colon, hemorrhoid disease, S/P chronic gastritis |
4 | epistaxis | nmCRB | 140 | none | 3 | epistaxis | - |
5 | epistaxis | mCRB | 76 | dual | 1 | epistaxis | HHT |
6 | GI | mCRB | 76 | dual | 2 | GI | diverticulosis, S/P polypectomy |
7 | GI | nmCRB | 107 | single | 1 | GI | S/P endoscopic resection of colorectal adenocarcinoma |
8 | GI | nmCRB | 48 | dual | 1 | GI | ulcerative colitis, chronic gastritis |
9 | epistaxis | mCRB | 4 | dual | 1 | epistaxis | HHT |
10 | GI | nmCRB | 10 | single | 5 | GI | gastric ulcer |
11 | GI | mCRB | 46 | dual | 4 | GI | gastric angiodysplasia, S/P argon plasma coagulation |
12 | genitourinary | nmCRB | 16 | dual | 2 | genitourinary | - |
13/ 14 | genitourinary | nmCRB | 60/72 | dual/ single | 3 | genitourinary | - |
15 | GI | mCRB (fatal) | 323 | none | 2 | GI | portal hypertension, alcoholic liver cirrhosis, peptic ulcer disease |
Variable | CSB after LAAC (n = 14) | No CSB after LAAC (n = 181) | p-Value |
---|---|---|---|
Female gender, n (%) | 5 (35.7) | 79 (43.6) | 0.780 |
Age (years); median (IQR) | 69 (56–81) | 74 (68–80) | 0.240 |
Age ≥ 75 years | 6 (42.9) | 88 (48.6) | 0.785 |
HAS-BLED score; median (IQR) | 2.0 (1.0–3.0) | 3.0 (2.0–3.0) | 0.201 |
Predicted annual bleeding risk; median (IQR) | 4.1 (3.4–5.8) | 5.8 (4.1–5.8) | 0.203 |
Comorbidities | |||
Hypertension, n (%) | 12 (85.7) | 154 (85.1) | 1.000 |
Diabetes mellitus, n (%) | 4 (28.6) | 55 (30.4) | 1.000 |
Smoking history, n (%) | 5 (35.7) | 47 (26.0) | 0.530 |
Prior ischemic stroke/TIA/PE, n (%) | 3 (21.4) | 57 (31.5) | 0.556 |
Coronary artery disease, n (%) | 5 (35.7) | 85 (47.8) | 0.420 |
PCI/CABG history, n (%) | 3 (21.4) | 69 (38.1) | 0.261 |
MI history, n (%) | 2 (14.3) | 53 (29.3) | 0.357 |
Carotid/peripheral artery disease, n (%) | 1 (7.1) | 31 (17.1) | 0.473 |
Pacemaker/ICD implanted, n (%) | 3 (21.4) | 42 (23.2) | 1.000 |
Permanent atrial fibrillation, n (%) | 11 (78.6) | 85 (47.0) | 0.027 |
Cancer history, n (%) | 1 (7.1) | 29 (16.0) | 0.700 |
Venous thromboembolism history, n (%) | 0 (0.0) | 12 (6.6) | 1.000 |
Bleeding history | |||
Bleedings history, n (%) | 14 (100) | 136 (75.1) | 0.043 |
Skin/oral/ocular bleeding, n (%) | 0 (0.0) | 27 (14.9) | 0.224 |
Intracranial bleeding, n (%) | 1 (7.1) | 36 (19.9) | 0.476 |
Genitourinary bleeding, n (%) | 2 (14.3) | 22 (12.2) | 0.684 |
Gastrointestinal bleeding, n (%) | 8 (57.1) | 52 (28.7) | 0.036 |
Epistaxis, n (%) | 3 (21.4) | 17 (9.4) | 0.161 |
Bleedings history while on anticoagulation, n (%) | 11 (78.6) | 113 (62.4) | 0.265 |
Transthoracic ECHO parameters | |||
LVEF < 40%, n (%) | 1 (7.1) | 14 (7.7) | 1.000 |
Moderate-to-severe mitral regurgitation, n (%) | 1 (7.1) | 29 (16.0) | 0.700 |
Laboratory results | |||
Hemoglobin (g/dL); median (IQR) | 12.2 (11.0–13.2) | 13.1 (11.8–14.6) | 0.071 |
Anemia, n (%) | 9 (64.3) | 65 (35.9) | 0.046 |
Platelets (103/mL); median (IQR) | 192 (172–226) | 183 (139–231) | 0.419 |
eGFR < 60 mL/min/1.73 m2, n (%) | 4 (28.6) | 89 (49.2) | 0.170 |
Admission SBP (mmHg); median (IQR) | 140 (131–161) | 130 (114–148) | 0.026 |
Admission DBP (mmHg); median (IQR) | 80 (77–82) | 76 (67–85) | 0.131 |
Admission heart rate (beats/min); median (IQR) | 75 (70–83) | 73 (64–83) | 0.283 |
Univariate | Multivariable | ||||
---|---|---|---|---|---|
HR (95%CI) | p-Value | HR (95%CI) | p-Value | ||
Admission SBP > 127 mmHg | 10.38 (1.36–79.37) | 0.024 | 10.73 (1.37–84.26) | 0.024 | |
Epistaxis history | 2.45 (0.68–8.76) | 0.170 | 5.84 (1.32–25.89) | 0.020 | |
Permanent AF | 3.90 (1.09–13.97) | 0.037 | 4.55 (1.20–17.20) | 0.025 | |
Gastrointestinal bleeding history | 3.23 (1.12–9.31) | 0.030 | 3.35 (1.01–11.08) | 0.048 | |
Anemia | 3.15 (1.06–9.40) | 0.040 | |||
eGFR <60 mL/min/1.73 m2 | 0.45 (0.14–1.42) | 0.172 |
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Zieliński, K.; Pracoń, R.; Konka, M.; Kruk, M.; Kępka, C.; Trochimiuk, P.; Dębski, M.; Kaczmarska, E.; Przyłuski, J.; Kowalik, I.; et al. Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure. Int. J. Environ. Res. Public Health 2022, 19, 13802. https://doi.org/10.3390/ijerph192113802
Zieliński K, Pracoń R, Konka M, Kruk M, Kępka C, Trochimiuk P, Dębski M, Kaczmarska E, Przyłuski J, Kowalik I, et al. Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure. International Journal of Environmental Research and Public Health. 2022; 19(21):13802. https://doi.org/10.3390/ijerph192113802
Chicago/Turabian StyleZieliński, Kamil, Radosław Pracoń, Marek Konka, Mariusz Kruk, Cezary Kępka, Piotr Trochimiuk, Mariusz Dębski, Edyta Kaczmarska, Jakub Przyłuski, Ilona Kowalik, and et al. 2022. "Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure" International Journal of Environmental Research and Public Health 19, no. 21: 13802. https://doi.org/10.3390/ijerph192113802