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| AATS/NHLBI: Cardiothoracic Surgery Exploring Collaborative Clinical Research Opportunities |
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Title and Author Therapies for Advanced Heart Failure; "Cardiologists Perspective on the Future"Clyde W. Yancy, MD Abstract Mechanical circulatory support [MCS] is now accepted as appropriate evidence-based therapy for advanced heart failure, also known as destination therapy. It is known that MCS facilitates ventricular recovery typified by a reversal of profibrotic signals, an upregulation of adrenergic receptors, restoration of the integrity of SERCA2A, and near reversal of the upregulation of the calcium exporter protein: Epac2. Exciting new data now demonstrate that certain microRNA signals are similarly and favorably influenced by MCS. These and several other favorable signals suggest that MCS affords an opportunity to modify the natural history of advanced heart failure without the requirement for either transplantation or permanent mechanical support. These signals are at times sufficiently robust to allow for explantation of the left ventricular assist device and a return to reasonably intact ventricular function yet this experience has been the exception, not the norm.Early experience with concomitant aggressive medical therapy appeared to facilitate more recovery but to-date that experience has not been replicated by other investigators. An opportunity now exists to augment the potential cellular benefits of MCS using cell-based regeneration strategies. Whether using autologous stem cells or gene transfer techniques, an opportunity exists to amplify the recovery potential initiated by MCS. The investigatory needs here are several: anticipating the likely myocardial phenotype response to MCS; identifying best candidate progenitor cells from among the many currently being investigated including inducible progenitor cells derived from somatic cell lines; and most importantly, exercising careful surveillance for any off-target or unintended consequences of concomitant mechanical and cellular circulatory support. Key Research Gap Requiring NHLBI Leadership
Key Citations 1: Hall, JL, Fermin DR, Birks EJ. Clinical, molecular and genomic changes in response to a left ventricular assist device. JACC 2011; 57: 641-52.2: Baba HA and Wohlschlaeger J. Morphological and molecular changes of the myocardium after left ventricular mechanical support. Current Cardiology Reviews, 2008, 4, 157-169 3: Mokashi SA, Guan J, Wang D, Tchantchaleishvili V et al. Preventing cardiac remodeling: the combination of cell-based therapy and cardiac support therapy preserves left ventricular function in rodent model of myocardial ischemia. The Journal of Thoracic and Cardiovascular Surgery 2010; 140: 1374-80. |
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Copyright © 2012 American Association for Thoracic Surgery
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
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It is very important that you consult a doctor about any specific medical problem or question.
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
general guidance and not as a definitive basis for diagnosis or treatment in any particular case.
It is very important that you consult a doctor about any specific medical problem or question.