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Advanced HF 2014: 09 patel

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Advanced HF 2014: 09 patel

  1. 1. Chetan B. Patel, MD Assistant Professor of Medicine Duke Cardiac Transplantation and Mechanical Circulatory Support Program LVAD Complications: Bleeding and Clotting Duke Advanced Heart Failure Symposium October 5th 2013
  2. 2. Disclosures • Consultant for Thoratec Corp and Heartware Inc. * Off label use of eptifibitide, tissue-plasminogen activator
  3. 3. LVAD therapy • Improving survival • 15,000 Heartmate II devices have now been implanted worldwide • Impact of mechanical circulatory support on the natural history of heart failure and vice versa • Effect of continuous flow on the human circulation Kirklin JK, et al JHLT 2012; 31:117-26.
  4. 4. LVAD therapy: Challenges Ahead Right Heart Failure Tricuspid Regurgitation Aortic Insufficiency “Walking” Ventricular Tachycardia
  5. 5. Bleeding Thrombosis LVAD therapy: Challenges Ahead • Predictable: • Artificial (metal) surface in contact with human circulation • Moving Parts • Systemic Anticoagulation • Unpredicted: • Impact of non-pulsatile flow on bleeding • Interaction between LVAD and the coagulation system independent of anticoagulation
  6. 6. Anticoagulation Strategies for Continuous Flow LVADs Historical Perspective – Initial experience with early version of the HMII demonstrated high pump thrombosis rate (40%) – Pump re-design and call for higher levels of anticoagulation (INR 2.5- 3.5) – Practice guidelines suggested INR 2.0-3.0 – Dual antiplatelet therapy – Perioperative heparin J Heart Lung Transplant 2010; 29:S1-S39
  7. 7. Early Bleeding/Thrombus HeartMate II Destination Therapy Trial CF LVAD (n=133) [211 pt-years] PF LVAD (n=59) [41 pt-years] Events/pt yr Events/pt yr Risk Ratio [95% Confidence Interval] p-value Pump Replacements 0.06 0.51 <0.001 Stroke 0.13 0.22 0.21 Ischemic 0.06 0.10 0.38 Hemorrhagic 0.07 0.12 0.33 Device-related infection 0.48 0.90 0.01 Local non-device infection 0.76 1.33 0.02 Sepsis 0.39 1.11 <0.001 Bleeding Bleeding requiring PRBC 1.66 2.45 0.06 Bleeding requiring surgery 0.24 0.29 0.57 Other Neurological 0.17 0.29 0.14 Right Heart Failure Extended Inotropes 0.14 0.46 <0.001 RVAD 0.02 0.07 0.12 Cardiac Arrhythmias 0.69 1.31 0.006 Respiratory Failure 0.31 0.80 <0.001 Renal Failure 0.10 0.34 <0.001 Hepatic Dysfunction 0.01 0.00 Device Thrombosis 0.02 0.00 Re-hospitalizations 2.64 4.25 0.02 0.0 0.5 1.0 1.5 2.0 Favors CF LVAD Favors PF LVAD N Engl J Med 2009; 361: 2241-51
  8. 8. Early Bleeding/Thrombus Heartware HVAD Bridge to Transplant Study Suarez J et al. Circ HF, 2011 Aaronson et al. Circulation, 2012
  9. 9. VAD Therapy goes Beyond The Surgery • To date > 60 HMII devices in 2013 • >75 durable LVADs implanted • Over 170 patients currently on device support • Patient-pump exposure Calendar 2011 Data from Annual Heart Report
  10. 10. Suarez J et al. Circ HF, 2011 Non-Surgical Bleeding after Continuous Flow Pump Support • 33 pts Montefiore • 20 pts HMII • 13 other (9 VentrAssist) • 8 GIB HMII J Card Surg, 2010
  11. 11. Non-Surgical Bleeding Texas Heart Institute • 172 HMII patients THI • 19% bleeding episode • Majority from AVMs Demirozu et al. J Heart Lung Transplant 2011 • Association made between AVM formation and severe aortic stenosis- Heyde’s Syndrome • Associated with low pulse pressure
  12. 12. Aorta Left ventricle CF LVAD Speed mmHgLVAD Physiology Ao valve Increasing LVAD speed leads to decreased contribution of left heart and a narrow pulse pressure
  13. 13. Acquired Von Willebrand Disease
  14. 14. Bleeding after Continuous Flow Pump Support  37 CF VAD patients at Duke and University of Minnesota  Plasma collected and stained for HMW vWF  100% of patients demonstrated loss of HMW vWF  10/37 patients had bleeding complications  Corrects after cardiac transplantation Crow et al. Ann Thoracic Surg, 2010 Uriel et al. JACC, 2010
  15. 15. Increased intraluminal pressure Lower pulse pressure;hypoperfusion Angiodysplasia (Heyde’s Syndrome) GI Bleeding Decrease in HMW multimers leading to impaired anticoagulation Acquired vWD vWF fragments Impaired platelet aggregation Continuous Flow Device Non-Surgical Bleeding after Continuous Flow Pump Support
  16. 16. N= 71 with 156 readmissions (4year) , 19% of all readmissions related to bleeding N=83 with 224 readmissions ( 3 year) , 66 readmissions in 34 patients (30% overall) related to bleeding Ann Thorac Surg 2013;95:1276–81) J Am Coll Cardiol 2013;61:153–63
  17. 17.  331 patients from a CF VAD BTT trial  10 patients with thrombotic events and 58 hemorrhagic events  Some centers reduced INR goal to 1.5-2.0 based on bleeding events  ASA 81 mg daily  No postoperative heparin J Heart Lung Transplant 2009; 28:881-7
  18. 18. Suarez J et al. Circ HF 2011 Management of Gastrointestinal Bleeding in Axial Flow VADs
  19. 19. To do list: Fix bleeding issues with LVAD therapy
  20. 20. The Other Side of the Bleeding-Clotting Quagmire
  21. 21. Romano et al. ISHLT 2011 • Event-free survival decreased with evidence of hemolysis • Pump thrombus = Hemolysis? What defines thrombosis? Hemolysis Definitions INTERMACS: Plasma free Hgb > 40 mg/dl occurring > 72 hours post-implant HeartMate II DT Trial: 2 plasma free Hgb >40 mg/dl within 24 hours of each other and an LDH > 1000 mg/dl within the same 24-hour period ADVANCE: plasma free Hgb > 40 mg/dl
  22. 22. • Will add cine image of aortic outflow with possible thrombus at CT Thrombosis is “invisible”
  23. 23. Managing Thrombotic Events • Pump thrombosis may present with: – Thromboembolism – Hemolysis (LDH, haptoglobin, plasma free Hgb) – Increasing power consumption with high flow rates – Abrupt pump dysfunction (stoppage) • Treatment will depend upon acuity, impact on patient, and pump performance • Anticoagulation and antiplatelet therapy is device-specific
  24. 24. • Adopted a stepped approach to treatment of pump thrombosis • Enhanced anticoagulation • Targeting different components of the coagulation cascade Circ Heart Fail. 2012;5:e68-e70
  25. 25. Duke Experience with Lytic Therapy Under Review, J Card Fail TPA
  26. 26. Duke Experience with Lytic Therapy Under Review, J Card Fail
  27. 27. Bleeding Thrombosis LVAD therapy: Challenges Ahead Stulak et al. J Heart Lung Transplant 2013, epub
  28. 28. Increased intraluminal pressure Lower pulse pressure; hypoperfusion Angiodysplasia (Heyde’s Syndrome) GI Bleeding Decrease in HMW multimers leading to impaired anticoagulation Acquired vWD vWF fragments Impaired platelet aggregation Continuous Flow Device Bleeding after Continuous Flow Pump Support
  29. 29. Challenges = Opportunities • Novel anticoagulants • Balance between antiplatelet therapy and anticoagulant • Intermittent pulsatility • Medical therapies to counteract acquired von- Willebrand’s disease • Pump Redesign • Novel biomarkers Characteristic Total (N=49) Ischemic (N=33) Non-Ischemic (N=16) Age, years 69.6 (54.0-73.6) 70.0 (64.3-74.1) 54.7 (41.7-72.5) Male, % 71.4 78.8 56.3 BMI 31.1 (26.5-35.5) 28.7 (26.5-34.2) 34.4 (24.7-39.2) Caucasian, % 71.4 84.9 43.8 Heartware Use, % 34.7 36.4 31.3 Ve-VO2 Slope 42 (35-47) 42 (36-47) 44 (31-47) NT-proBNP, pg/mL 3287 (2007-4810) 3067 (2037-3927) 4758 (1977-5869) Galectin-3, ng/mL 24.3 (16.3-35.0) 24.0 (20.1-32.3) 24.7 (14.8-38.0) Copeptin, pmol/L 419 (374-550) 425 (374-550) 389 (378-514) MR-proADM, nmol/L 210 (183-303) 206 (183-244) 231 (190-361) Soluble ST2, ng/mL 61.2 (42.8-112.8) 56.5 (41.7-102.0) 67.5 (52.3-226.3) Ahmad et al. AHA 2013
  30. 30. Summary • LVAD therapy improves survival and quality of life in patients with advanced heart failure • Continuous flow has provided a new set of challenges and unique physiology • The bleeding-clotting paradigm problem has been an area of intense interest-associated with high readmission rates and morbidity • Future work will focus on altering the impact of continuous flow on human circulation

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