“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 A-Cure Mission
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.
The A-CURE Faculty and Speakers at the 2018 A-CURE Symposium. (L to R) Michel Ovize, Bob Kloner, Carsten Tschope, Ralf Westenfeld, Andreas Schaefer, Jacob Moller, Ryan Tedford, Nir Uriel, George Vetrovec, Haroon Faraz, Kiyotake Ishikawa, Patrick Hunziker, Bart Meyns, Kenji Sunagawa, Dan Burkhoff, Jim Udelson, Navin Kapur, Jeff Moses, Mark Anderson, Hermann Reichenspurner
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.
- Investigations dating back to the 1960s have suggested that ventricular unloading (see “What is acute cardiac unloading”) before, during, or after the index ischemic event (heart attack) may positively affect cardiac function post-infarction (10-14). However, unloading the ventricle through either mechanical or medical means was clinically impractical. Therefore, interest in unloading was limited.
- With the development of percutaneous left ventricular support devices (pLVAD) in the early 2000’s, interest in the therapeutic utility of acute ventricular unloading was invigorated. In 2003, Meyns et al. published the first preclinical report demonstrating the effectiveness of unloading on myocardial infarct scar formation in the Journal of the American College of Cardiology (15).
- Over the proceeding decade, several laboratories from around the world began independent investigations into the utility of and molecular mechanisms underlying acute cardiac unloading. The developing collaborations and communication amongst these laboratories were brought together by Abiomed Inc. to form the A-CURE Working Group. Since 2015 the group has convened on an annual basis in private meetings to discuss the current efforts of the individual labs and gain insight and feedback from the member groups.
- The inaugural Annual A-CURE Symposium was held in Rome, Italy, on August 26, 2016 prior to the European Society of Cardiology Congress. The aim of the A-CURE Symposium is to bring together clinical and basic researchers from around the world to share their research and ideas that investigate this emerging therapeutic field.
- The meeting agenda featured keynote addresses by Dr. Eugene Braunwald (Founder of the TIMI Study Group, founding editor of Braunwald’s Heart Disease) (16) and Dr. Joseph Hill (Editor-in-Chief of Circulation). The symposium was attended by 100+ clinicians, scientists, and research professionals from 21 different countries.
- The 2nd Annual A-CURE Symposium took place on August 25, 2017, in Barcelona, Spain prior to the European Society of Cardiology Congress. The welcome dinner was established and hosted on August 24 to promote networking between researchers.
- The symposium featured a keynote lecture by Dr. Valentin Fuster (Editor-in-Chief of JACC), 16 selected talks, 3 panel discussions and an interactive poster session.
- The 3rd Annual A-CURE Symposium took place on November 9, 2018, in Chicago, IL. The 2018 Symposium was the first held in the United States.
- The keynote address was given by Dr. James Udelson, Chief of Cardiology at Tufts Medical Center. A special panel discussion on STEMI-DTU Pivotal Trial Design and Execution was given by the DTU study committee.
- The 4th A-CURE Symposium took place in Paris, France on Aug 30, 2019 prior to the 2019 European Society of Cardiology Congress. The 4th Annual A-CURE Symposium presented cutting-edge research focused on acute cardiac unloading and myocardial recovery.
- The 4th A-CURE featured a keynote lecture by Dr. Douglas Mann at Washington University in St. Louis, and a special panel discussion on strategies to recover a failing heart by renowned cardiologists from the US and EU.
- The A-CURE Symposia continued to be held throughout the time of pandemic with the 5th A-CURE Virtual Symposium held on Dec 15, 2020 using an online platform.
- The 5th A-CURE Symposium featured 3 themed sessions with 17 top-notch talks, including 2 exciting panel discussions on the topics of Unloading in Pediatric Population with top pediatric cardiologists/surgeons and Successful Industry and Academic Collaboration with MIT/Harvard investigators.
- The 6th Annual A-CURE Symposium was a live virtual meeting on January 28, 2022. Over 150 physicians, scientists, and researchers joined the one-day virtual conference featuring 22 talks from global experts in the field of cardiac unloading and heart recovery. Drs. Dan Burkhoff, Mark Anderson, Kiyotake Ishikawa, and Navin Kapur served as the hosts of the meeting, along with the A-CURE faculty leading the 4 themed sessions.
- The Keynote Address was given by Dr. Clyde Yancy, Chief of Cardiology at Northwestern University; the Distinguished Lecture in Heart Recovery given by Dr. Emma Birks at University of Kentucky; and the Innovation Lecture was given by Dr. Navin Kapur at Tufts Medical Center.
- This year, the A-CURE Working group is proud to bring the 7th Annual A-CURE Symposium back in-person on Nov 4, 2022, in Chicago, IL. Start the week in Chicago with our complimentary Welcome and Networking Dinner on November 3, 2022.
- Join the only academic symposium dedicated to the science and clinical application of cardiac unloading and myocardial recovery. Registration is open now!
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Levine HJ, McIntyre KM and Glovsky MM. Relief of angina pectoris by Valsalva maneuver. The New England journal of medicine. 1966;275:487-9.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
What is Acute Cardiac Unloading?
Acute cardiac unloading is any maneuver, therapy, or intervention that decreases the power expenditure of the ventricle and limits the hemodynamic forces that lead to ventricular remodeling after insult or injury to the heart.See Details
2022 A-CURE® Faculty
Have a question about acute cardiac unloading? Email the A-CURE Working Group faculty to inquire about the science of unloading, experimental protocols, potential collaborations, or other questions on acute unloading.Meet all members