Emma J Birks1,2, Stavros G Drakos3, Snehal R Patel4, Brian D Lowes5, Craig H Selzman6, Randall C Starling7, Jaimin Trivedi8, Mark S Slaughter8, Pavin Alturi9, Daniel Goldstein10, Simon Maybaum11, John Y Um12, Kenneth B Margulies13, Josef Stehlik3, Christopher Cunningham14, David J Farrar15, Jesus E Rame13,16. 1. Division of Cardiovascular Medicine (E.J.B.), University of Louisville, KY. 2. Division of Cardiovascular Medicine, University of Kentucky, Lexington (E.J.B.). 3. Division of Cardiovascular Medicine (S.G.D., J.S.), University of Utah, Salt Lake City. 4. Department of Cardiovascular Medicine (S.R.P.), Montefiore Medical Center, New York. 5. Division of Cardiovascular Medicine (B.D.L.), University of Nebraska, Omaha. 6. Division of Cardiothoracic Surgery (C.H.S.), University of Utah, Salt Lake City. 7. Kaufman Center for Heart Failure, Cleveland Clinic, OH (R.C.S.). 8. Department of Cardiovascular Surgery (J.T., M.S.S.), University of Louisville, KY. 9. Department of Surgery, University of Pennsylvania, Philadelphia (P.A.). 10. Department of Cardiovascular Surgery (D.G.), Montefiore Medical Center, New York. 11. Department of Cardiology, Hofstra Northwell School of Medicine, Hempstead, NY (S.M.). 12. Department of Cardiovascular Surgery (J.Y.U.), University of Nebraska, Omaha. 13. Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia (K.B.M., J.E.R.). 14. Clinical Trials Unit (C.C.), University of Louisville, KY. 15. Medical Affairs, Abbott, Pleasanton, CA (D.J.F.). 16. Department of Medicine, Jefferson University Hospital, Philadelphia, PA (J.E.R.).
Abstract
BACKGROUND: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. METHODS: Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months. RESULTS: Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant left ventricular ejection fraction, 57±8%; end-diastolic diameter, 4.81±0.58 cm; end-systolic diameter, 3.53±0.51 cm; pulmonary capillary wedge pressure, 8.1±3.1 mm Hg; pulmonary artery saturations 63.6±6.8% at 6000 rpm). Overall, 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The 15 ongoing explanted patients are now 2.26±0.97 years after explant. After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. CONCLUSIONS: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01774656.
BACKGROUND: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. METHODS: Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months. RESULTS: Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant left ventricular ejection fraction, 57±8%; end-diastolic diameter, 4.81±0.58 cm; end-systolic diameter, 3.53±0.51 cm; pulmonary capillary wedge pressure, 8.1±3.1 mm Hg; pulmonary artery saturations 63.6±6.8% at 6000 rpm). Overall, 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The 15 ongoing explanted patients are now 2.26±0.97 years after explant. After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. CONCLUSIONS: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01774656.
Authors: Veli K Topkara; Gabriel T Sayer; Kevin J Clerkin; Omar Wever-Pinzon; Koji Takeda; Hiroo Takayama; Craig H Selzman; Yoshifumi Naka; Daniel Burkhoff; Josef Stehlik; Maryjane A Farr; James C Fang; Nir Uriel; Stavros G Drakos Journal: J Am Coll Cardiol Date: 2022-03-08 Impact factor: 24.094
Authors: Palak Shah; Mitchell Psotka; Iosif Taleb; Rami Alharethi; Mortada A Shams; Omar Wever-Pinzon; Michael Yin; Federica Latta; Josef Stehlik; James C Fang; Guoqing Diao; Ramesh Singh; Naila Ijaz; Christos P Kyriakopoulos; Wei Zhu; Christopher W May; Lauren B Cooper; Shashank S Desai; Craig H Selzman; Abdallah G Kfoury; Stavros G Drakos Journal: Circ Heart Fail Date: 2021-05-05 Impact factor: 8.790
Authors: Veli K Topkara; Pierre Elias; Rashmi Jain; Gabriel Sayer; Daniel Burkhoff; Nir Uriel Journal: Circ Heart Fail Date: 2021-12-24 Impact factor: 8.790
Authors: Eleanor F Gerhard; Lu Wang; Ramesh Singh; Stephan Schueler; Leonard D Genovese; Andrew Woods; Daniel Tang; Nicola Robinson Smith; Mitchell A Psotka; Sian Tovey; Shashank S Desai; Djordje G Jakovljevic; Guy A MacGowan; Palak Shah Journal: J Heart Lung Transplant Date: 2021-08-11 Impact factor: 10.247