Thrombogenicity and Antithrombotic Strategies in Structural Heart Interventions and Nonaortic Cardiac Device Therapy—Current Evidence and Practice

Abstract As the number of, and the indications for, structural heart interventions are increasing worldwide, the optimal secondary prevention to reduce device thrombosis is becoming more important. To date, most of the recommendations are empiric. The current review discusses mechanisms behind device-related thrombosis, the available evidence with regard to antithrombotic regimen after cardiac device implantation, as well as providing an algorithm for identification of risk factors for device thrombogenicity and for management of device thrombosis after implantation of patent foramen ovale and left atrial appendage occluders, MitraClips/transcatheter mitral valve replacement, pacemaker leads, and left ventricular assist devices. Of note, the topic of antithrombotic therapy and thrombogenicity of prostheses in aortic position (transcatheter aortic valve replacement, surgical, mechanical, and bioprostheses) is not part of the present article and is discussed in detail in other contemporary focused articles.

[1]  H. Katus,et al.  Temporary oral anticoagulation after MitraClip – a strategy to lower the incidence of post-procedural stroke? , 2020, Acta cardiologica.

[2]  M. Hannan,et al.  2019 EACTS Expert Consensus on long-term mechanical circulatory support , 2019, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[3]  J. Tobis,et al.  New-onset atrial fibrillation following percutaneous patent foramen ovale closure: a systematic review and meta-analysis of randomised trials. , 2019, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[4]  A. Garan,et al.  Use of Cangrelor during Venoarterial Extracorporeal Membrane Oxygenation Following Percutaneous Coronary Intervention , 2019, The Journal of Heart and Lung Transplantation.

[5]  Deepak L. Bhatt,et al.  Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial. , 2019, Resuscitation.

[6]  T. Hohlfeld,et al.  Antiplatelet effects of aspirin and clopidogrel after left atrial appendage (LAA) occluder implantation. , 2019, International journal of cardiology.

[7]  W. Rottbauer,et al.  Apixaban After Percutaneous Edge-to-Edge Mitral Valve Repair in Patients With Maintained Sinus Rhythm. , 2019, JACC. Cardiovascular interventions.

[8]  B. Meier,et al.  European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. , 2019, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[9]  J. T. ten Berg,et al.  Percutaneous patent foramen ovale closure using the Occlutech Figulla device: More than 1,300 patient‐years of follow up , 2018, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[10]  P. Garot,et al.  Device-Related Thrombus After Left Atrial Appendage Closure , 2018, Interventional cardiology.

[11]  P. Voisine,et al.  Transcatheter Mitral-Valve Repair in Patients with Heart Failure. , 2019, The New England journal of medicine.

[12]  F. Laurent,et al.  Left atrial appendage patency and device-related thrombus after percutaneous left atrial appendage occlusion: a computed tomography study , 2018, European heart journal cardiovascular Imaging.

[13]  B. Meier,et al.  European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. , 2018, European heart journal.

[14]  P. Risteski,et al.  Repeat left ventricular assist device exchange with inflow or outflow correction for recurrent pump thrombosis and cerebral haemorrhage through limited incisions. , 2018, European Journal of Cardio-Thoracic Surgery.

[15]  L. Prahl Wittberg,et al.  Flow-induced platelet activation in components of the extracorporeal membrane oxygenation circuit , 2018, Scientific Reports.

[16]  V. Reddy,et al.  Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes , 2018, Circulation.

[17]  D. Maucort-Boulch,et al.  Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation , 2018, The New England journal of medicine.

[18]  J. Healey,et al.  Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2) , 2018, European heart journal.

[19]  G. Guyatt,et al.  Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline , 2018, British Medical Journal.

[20]  B. Kiaii,et al.  Thrombus in a Hypercoagulable Patient Following Patent Foramen Ovale Closure With the Gore Septal Occluder. , 2018, JACC. Cardiovascular interventions.

[21]  A. Camm,et al.  The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. , 2018, European heart journal.

[22]  Pascal Defaye,et al.  Device-Related Thrombosis After Percutaneous Left Atrial Appendage Occlusion for Atrial Fibrillation. , 2018, Journal of the American College of Cardiology.

[23]  R. Patten,et al.  High Thromboembolic Event Rate in Patients Supported With an Impella CP Device With an Anti-Xa Level of Less Than 0.1 u/mL , 2018 .

[24]  James W Long,et al.  Two‐Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure , 2018, The New England journal of medicine.

[25]  S. Bangalore,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 , 2018, Circulation. Cardiovascular interventions.

[26]  M. Gawaz,et al.  Formation of a left atrial thrombus during percutaneous mitral valve edge-to-edge repair induced by acute reduction of mitral regurgitation. , 2018, Journal of cardiology cases.

[27]  R. Formigari,et al.  Recurrent Stroke after Transcatheter PFO Closure in Cryptogenic Stroke or Tia: Long-Term Follow-Up , 2017, Cardiology research and practice.

[28]  Xavier Freixa,et al.  Device‐associated thrombus formation after left atrial appendage occlusion: A systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amulet , 2017, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[29]  T. Potpara,et al.  Left atrial appendage occluder implantation in Europe: indications and anticoagulation post-implantation. Results of the European Heart Rhythm Association Survey , 2017, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[30]  Jeroen J. Bax,et al.  2017 ESC/EACTS Guidelines for the management of valvular heart disease. , 2017, European heart journal.

[31]  Helle K. Iversen,et al.  Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke , 2017, The New England journal of medicine.

[32]  David E. Thaler,et al.  Long‐Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke , 2017, The New England journal of medicine.

[33]  Jean-Marc Schleich,et al.  Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke , 2017, The New England journal of medicine.

[34]  S. Kubo,et al.  Incidence, Characteristics, and Clinical Course of Device-Related Thrombus After Watchman Left Atrial Appendage Occlusion Device Implantation in Atrial Fibrillation Patients. , 2017, JACC. Clinical electrophysiology.

[35]  Dnp,et al.  Thrombotic valvular dysfunction with transcatheter mitral interventions for postsurgical failures , 2017, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[36]  L. Fleisher,et al.  2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. , 2017, Journal of the American College of Cardiology.

[37]  B. Meier,et al.  Patients with intracranial bleeding and atrial fibrillation treated with left atrial appendage occlusion: Results from the Amplatzer Cardiac Plug registry. , 2017, International journal of cardiology.

[38]  J. Granada,et al.  Transcatheter Mitral Valve Replacement: Insights From Early Clinical Experience and Future Challenges. , 2017, Journal of the American College of Cardiology.

[39]  J. Bauersachs,et al.  First series of left ventricular assist device exchanges to HeartMate 3 , 2017, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[40]  E. Horváth-Puhó,et al.  Risk of Stroke in Patients With Heart Failure: A Population-Based 30-Year Cohort Study , 2017, Stroke.

[41]  J. Deharo,et al.  An Oscillating Mass Attached to a Pacemaker Lead: Thrombus or Vegetation? A Fishing Story. , 2017, JACC Clinical Electrophysiology.

[42]  U. Ziemann,et al.  Thromboembolic Risk Reduction Via Transseptal Thrombus Aspiration in a Patient With Spontaneous Left Atrial Thrombus and Stroke. , 2017, JACC. Cardiovascular interventions.

[43]  J. Saw,et al.  Incidence and Clinical Impact of Device-Associated Thrombus and Peri-Device Leak Following Left Atrial Appendage Closure With the Amplatzer Cardiac Plug. , 2017, JACC. Cardiovascular interventions.

[44]  J. Weitz,et al.  Factors XI and XII as Targets for New Anticoagulants , 2017, Front. Med..

[45]  V. Rao,et al.  Ventricular Thrombosis Post-Venoarterial Extracorporeal Membrane Oxygenation. , 2017, Circulation. Heart failure.

[46]  Valluvan Jeevanandam,et al.  Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure , 2017, The New England journal of medicine.

[47]  M. Ozaki,et al.  Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT , 2017, Perfusion.

[48]  J. Leipsic,et al.  Transcatheter Mitral Valve Replacement for Patients With Symptomatic Mitral Regurgitation: A Global Feasibility Trial. , 2017, Journal of the American College of Cardiology.

[49]  G. Nickenig,et al.  Thrombus Formation After Left Atrial Appendage Occlusion With the Amplatzer Amulet Device. , 2017, JACC. Clinical electrophysiology.

[50]  Roxana Mehran,et al.  Prosthetic Heart Valve Thrombosis. , 2016, Journal of the American College of Cardiology.

[51]  C. Kemaloğlu,et al.  Thrombosis in Continuous Flow Left Ventricular Assist Devices: Our Clinical Experience With Medical and Surgical Management. , 2016, Transplantation proceedings.

[52]  B. Meier,et al.  Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. , 2016, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[53]  S. Kische,et al.  Percutaneous left atrial appendage occlusion: Device thrombosis in clopidogrel non-responders. , 2016, International journal of cardiology.

[54]  R. Virmani,et al.  Cerebral Protection During MitraClip Implantation: Initial Experience at 2 Centers. , 2016, JACC. Cardiovascular interventions.

[55]  V. Kocka,et al.  Periprocedural antithrombotic therapy during various types of percutaneous cardiovascular interventions , 2015, European heart journal. Cardiovascular pharmacotherapy.

[56]  P. Boekstegers,et al.  One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry , 2015, European heart journal.

[57]  P. Boekstegers,et al.  Risk and outcomes of complications during and after MitraClip implantation: Experience in 828 patients from the German TRAnscatheter mitral valve interventions (TRAMI) registry , 2015, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[58]  Leway Chen,et al.  Factors Related to Pump Thrombosis With the Heartmate II Left Ventricular Assist Device , 2015, Journal of cardiac surgery.

[59]  G. Wieselthaler,et al.  Antithrombotic therapy for left ventricular assist devices in adults: a systematic review , 2015, Journal of thrombosis and haemostasis : JTH.

[60]  J. Hirsh,et al.  Medical device‐induced thrombosis: what causes it and how can we prevent it? , 2015, Journal of thrombosis and haemostasis : JTH.

[61]  T. Potpara,et al.  Left atrial appendage closure-indications, techniques, and outcomes: results of the European Heart Rhythm Association Survey. , 2015, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[62]  S. Bertog,et al.  Incomplete left atrial appendage occlusion and thrombus formation after Watchman implantation treated with anticoagulation followed by further transcatheter closure with a second‐generation Amplatzer Cardiac Plug (Amulet device) , 2015, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[63]  H. Ghanbari,et al.  Antithrombotic Therapy and Outcomes After ICD Implantation in Patients With Atrial Fibrillation and Coronary Artery Disease: An Analysis From the National Cardiovascular Data Registry (NCDR)® , 2015, Journal of the American Heart Association.

[64]  L. Sylvia,et al.  Bivalirudin for Treatment of LVAD Thrombosis: A Case Series , 2014, ASAIO journal.

[65]  B. Meier,et al.  EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion. , 2014, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[66]  M. Huntgeburth,et al.  Thrombus formation at the MitraClip system during percutaneous mitral valve repair. , 2014, JACC. Cardiovascular interventions.

[67]  J. Mehilli,et al.  Dangerous liaison: successful percutaneous edge-to-edge mitral valve repair in patients with end-stage systolic heart failure can cause left ventricular thrombus formation. , 2014, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[68]  T. Meinertz,et al.  Predictors of recurrent stroke after percutaneous closure of patent foramen ovale. , 2014, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[69]  Michael J. Wilson,et al.  A Factor XIIa Inhibitory Antibody Provides Thromboprotection in Extracorporeal Circulation Without Increasing Bleeding Risk , 2014, Science Translational Medicine.

[70]  G. Felker,et al.  Thrombolytic therapy for thrombosis of continuous flow ventricular assist devices. , 2014, Journal of cardiac failure.

[71]  G. Ailawadi,et al.  Diagnosis, Nonsurgical Management, and Prevention of LVAD Thrombosis , 2014, Journal of cardiac surgery.

[72]  S. Chaparro,et al.  Argatroban as novel therapy for suspected thrombosis in patients with continuous-flow left ventricle assist device and hemolysis. , 2014, ASAIO journal.

[73]  S. Prasad,et al.  The use of eptifibatide for suspected pump thrombus or thrombosis in patients with left ventricular assist devices. , 2014, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[74]  Sean Pinney,et al.  Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device. , 2014, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[75]  G. Ewald,et al.  Unexpected abrupt increase in left ventricular assist device thrombosis. , 2014, The New England journal of medicine.

[76]  Y. Alsancak,et al.  PEDIATRIC AND CONGENITAL HEART DISEASE Original Studies Short and Long Term Complications of Device Closure of Atrial Septal Defect and Patent Foramen Ovale: Meta-Analysis of 28,142 Patients From 203 Studies , 2013 .

[77]  P. Azadani,et al.  Risk Factors and Prognosis for Clot Formation on Cardiac Device Leads , 2013, Pacing and clinical electrophysiology : PACE.

[78]  A. Diegeler,et al.  Stroke and thrombus formation appending to the MitraClip: what is the appropriate anticoagulation regimen? , 2013, The Journal of heart valve disease.

[79]  A. Curnis,et al.  Right giant atrial thrombosis and pulmonary embolism complicating pacemaker leads , 2013, BMJ Case Reports.

[80]  S. Russell,et al.  Algorithm for the diagnosis and management of suspected pump thrombus. , 2013, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[81]  Petr Neuzil,et al.  Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). , 2013, Journal of the American College of Cardiology.

[82]  Atul Verma,et al.  Pacemaker or defibrillator surgery without interruption of anticoagulation. , 2013, The New England journal of medicine.

[83]  K. Muthiah,et al.  Thrombolysis for suspected intrapump thrombosis in patients with continuous flow centrifugal left ventricular assist device. , 2013, Artificial organs.

[84]  F. Mohr,et al.  Fluoroscopy-Guided Resolution of Ingested Thrombus Leading to Functional Disturbance of a Continuous-Flow Left Ventricular Assist Device , 2012, Case reports in surgery.

[85]  D. Kahali,et al.  Permanent Pacemaker‐Related Upper Extremity Deep Vein Thrombosis: A Series of 20 Cases , 2012, Pacing and clinical electrophysiology : PACE.

[86]  Jennifer Taylor,et al.  ESC/EACTS Guidelines on the management of valvular heart disease. , 2012, European heart journal.

[87]  Marissa Miller,et al.  Long-term mechanical circulatory support (destination therapy): on track to compete with heart transplantation? , 2012, The Journal of thoracic and cardiovascular surgery.

[88]  B. Balkau,et al.  Short-acting P2Y12 blockade to reduce platelet dysfunction and coagulopathy during experimental extracorporeal circulation and hypothermia. , 2012, British journal of anaesthesia.

[89]  J. Wöhrle,et al.  PFO closuRE and CryptogenIc StrokE (PRECISE) registry: a multi-center, international registry , 2012, Clinical Research in Cardiology.

[90]  S. Klotz,et al.  Late left atrial thrombosis of an Amplatzer patent foramen ovale occluder. , 2011, Journal of Thoracic and Cardiovascular Surgery.

[91]  F. Marchlinski,et al.  Mobile Thrombus on Device Leads in Patients Undergoing Ablation: Identification, Incidence, Location, and Association With Increased Pulmonary Artery Systolic Pressure , 2011, Circulation.

[92]  W. Rottbauer,et al.  Large atrial thrombus formation after MitraClip implantation: is anticoagulation mandatory? , 2011, The Journal of heart valve disease.

[93]  Saibal Kar,et al.  Safety of Percutaneous Left Atrial Appendage Closure: Results From the Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) Clinical Trial and the Continued Access Registry , 2011, Circulation.

[94]  P. Karjalainen,et al.  Clinical and laboratory risk factors of thrombotic complications after pacemaker implantation: a prospective study. , 2010, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[95]  S. Russell,et al.  Advanced heart failure treated with continuous-flow left ventricular assist device. , 2009, The New England journal of medicine.

[96]  Nader Moazami,et al.  Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device. , 2009, Journal of the American College of Cardiology.

[97]  M. Schwerzmann,et al.  Late results after percutaneous closure of patent foramen ovale for secondary prevention of paradoxical embolism using the amplatzer PFO occluder without intraprocedural echocardiography: effect of device size. , 2009, JACC. Cardiovascular interventions.

[98]  O H Frazier,et al.  Use of a continuous-flow device in patients awaiting heart transplantation. , 2007, The New England journal of medicine.

[99]  E. Foster,et al.  Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial. , 2005, Journal of the American College of Cardiology.

[100]  J. Steinberg,et al.  Intracardiac Ultrasound Detection of Thrombus on Transseptal Sheath: Incidence, Treatment, and Prevention , 2005, Journal of cardiovascular electrophysiology.

[101]  G. Lazaros,et al.  Early Pacemaker Lead Thrombosis Leading to Massive Pulmonary Embolism , 2004, Echocardiography.

[102]  M. Vanderheyden,et al.  Thrombosis of a patent foramen ovale closure device: Thrombolytic management , 2002, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[103]  C. J. Cooper,et al.  Treatment of pacemaker-associated right atrial thrombus with 2-hour rTPA infusion. , 1993, American heart journal.

[104]  J. Loike,et al.  Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[105]  K. J. May,et al.  Streptokinase dissolution of a right atrial thrombus associated with a temporary pacemaker. , 1988, Archives of internal medicine.

[106]  S. Goldhaber,et al.  Treatment of right atrial thrombus with urokinase. , 1988, American Heart Journal.