Mission of A-CURE®

The A-CURE Working Group at the A-CURE Faculty winter meeting in Orlando, FL, March, 2018. (L to R) Kenji Sunagawa, Hermann Reichenspurner, Nir Uriel, George Vetrovec, Eric Peterson, Shiv Annamalai, Bill O'Neill, Jeff Moses, Navin Kapur, Thorsten Siess, Patrick Hunziker, Ryan Tedford, Mohamad Alkhouli, Bart Meyns, Kiyo Ishikawa, Ralf Westenfeld, Jacob Moller, Andreas Schaefer, Bob Kloner

“Advancing the science and mechanistic understanding of acute cardiac unloading, supporting the translation of basic and clinical research into therapies aimed at heart muscle recovery.”

The mission of the A-CURE Working Group is to advance the science and mechanistic understanding of acute cardiac unloading and support the translation of basic and clinical research into therapies aimed at heart muscle recovery. Cardiac traumas such as myocardial infarction (commonly called a heart attack), myocarditis, peripartum cardiomyopathy, cardiogenic shock, and takotsubo cardiomyopathy amongst others each result in an impaired ability of the heart to pump blood. Without proper blood flow (also called cardiac output), all organ systems will eventually be starved of nutrients and oxygen, leading to their ultimate death—and death of the patient. As such, maintaining cardiac output is the primary objective of therapeutic approaches treating these traumas. However, fundamental difficulties arise when applying currently indicated therapies. With the exception of cardiopulmonary bypass, therapies intended to increase cardiac output each put further stress on the heart. This begins a vicious cycle in which increased cardiac output is required due to damage to the heart, but to achieve this the damaged heart must work harder. This exacerbates the stress placed on the already damaged heart, and leads to poorer outcomes in patients.1-9 Using current therapeutic approaches, the heart is never allowed to rest and recover from injury. The workload of the heart (pumping blood) is never uncoupled from heart function. New approaches are needed.

The A-CURE Working Group was established in order to focus clinical, preclinical, and basic research efforts on how best to exploit emerging technologies and position them as therapies that maximize the ability of the heart to rest and recover after damage. The research of this group largely focuses on capitalizing on the hemodynamic and energetic benefits of acute cardiac unloading of the ventricle during and after a cardiac trauma. 

References Cited

  1. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, Long JW, Ascheim DD, Tierney AR, Levitan RG, Watson JT, Meier P, Ronan NS, Shapiro PA, Lazar RM, Miller LW, Gupta L, Frazier OH, Desvigne-Nickens P, Oz MC, Poirier VL and Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure Study G. Long-term use of a left ventricular assist device for end-stage heart failure. The New England journal of medicine. 2001;345:1435-43.
  2. Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, Cheng ML, Wynne J, Committee ASA, Investigators and Group AS. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). Journal of the American College of Cardiology. 2005;46:57-64.
  3. Bayram M, De Luca L, Massie MB and Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. The American journal of cardiology. 2005;96:47G-58G.
  4. Cuffe MS, Califf RM, Adams KF, Jr., Benza R, Bourge R, Colucci WS, Massie BM, O’Connor CM, Pina I, Quigg R, Silver MA, Gheorghiade M and Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure I. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. Jama. 2002;287:1541-7.
  5. Elkayam U, Tasissa G, Binanay C, Stevenson LW, Gheorghiade M, Warnica JW, Young JB, Rayburn BK, Rogers JG, DeMarco T and Leier CV. Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure. American heart journal. 2007;153:98-104.
  6. Felker GM, Benza RL, Chandler AB, Leimberger JD, Cuffe MS, Califf RM, Gheorghiade M, O’Connor CM and Investigators O-C. Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. Journal of the American College of Cardiology. 2003;41:997-1003.
  7. Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K, Harjola VP, Mitrovic V, Abdalla M, Sandell EP, Lehtonen L, Steering C and Investigators of the Levosimendan Infusion versus Dobutamine S. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet. 2002;360:196-202.
  8. Investigators AA, Armstrong PW, Granger CB, Adams PX, Hamm C, Holmes D, Jr., O’Neill WW, Todaro TG, Vahanian A and Van de Werf F. Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial. Jama. 2007;297:43-51.
  9. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M and Investigators S. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. Jama. 2007;297:1883-91.
  10. Levine HJ, McIntyre KM and Glovsky MM. Relief of angina pectoris by Valsalva maneuver. The New England journal of medicine. 1966;275:487-9.
  11. Laschinger JC, Grossi EA, Cunningham JN, Jr., Krieger KH, Baumann FG, Colvin SB and Spencer FC. Adjunctive left ventricular unloading during myocardial reperfusion plays a major role in minimizing myocardial infarct size. The Journal of thoracic and cardiovascular surgery. 1985;90:80-5.
  12. Van Winkle DM, Matsuki T, Gad NM, Jordan MC and Downey JM. Left ventricular unloading during reperfusion does not limit myocardial infarct size. Circulation. 1990;81:1374-9.
  13. Smalling RW, Cassidy DB, Barrett R, Lachterman B, Felli P and Amirian J. Improved regional myocardial blood flow, left ventricular unloading, and infarct salvage using an axial-flow, transvalvular left ventricular assist device. A comparison with intra-aortic balloon counterpulsation and reperfusion alone in a canine infarction model. Circulation. 1992;85:1152-9.
  14. Laks H, Ott RA, Standeven JW, Hahn JW, Blair OM and Willman VL. The effect of left atrial-to-aortic assistance on infarct size. Circulation. 1977;56:II38-43.
  15. Meyns B, Stolinski J, Leunens V, Verbeken E and Flameng W. Left ventricular support by catheter-mounted axial flow pump reduces infarct size. Journal of the American College of Cardiology. 2003;41:1087-95.
  16. Braunwald E, Mann, D.L., Bonow, R.O., Zipes, D.P., Libby, P. . Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine – 10th Edition. Philadelphia, PA: Elsevier Sauders; 2015.