(Circulation. 2004;110:e333-e336.)
© 2004 American Heart Association, Inc.
Special Report |
From the University of California, Los Angeles (G.D.B.); The Johns Hopkins University, Baltimore, Md (M.L.W., E.P.S.); University of Lleida, Lleida, Spain (M.B.); Technion-Israel Institute of Technology, Technion City, Israel (R.B.); Columbia University, New York, NY (D.B., H.M.S.); University of Alabama at Birmingham (H.C.C., R.E.I.); Allegheny-Singer Research Institute, Pittsburgh, Pa (M.D.); National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md (N.D.E., L.J.R., G.S.); California Institute of Technology, Pasadena, Calif (M.G.); Palo Alto Medical Foundation, Palo Alto, Calif (N.B.I.); The University of Vermont, Burlington, Vt (M.M.L.); University of California, San Diego (A.D.M.); University of Southern California, Los Angeles, Calif (G.M.P.); Oregon Health Sciences University, Portland, Ore (D.J.S.); The Medical University of South Carolina, Charleston, SC (F.G.S.); and Denia, Spain (F.T.-G.).
Correspondence and reprint requests to Edward P. Shapiro, MD, Division of Cardiology, Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Ave, Baltimore, MD 21224. E-mail eshapiro{at}jhmi.edu
| Introduction |
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There has been a remarkable growth in the understanding of cellular myocardial function at the genetic/molecular level with development of the ability to perform genetic manipulation of cardiac and other cells within the heart. It is critically important to recognize that the complex molecular machinery that enables the heart to fulfill its role in the circulatory system can only function effectively within an architectural design that allows the contractile apparatus to perform with optimal mechanical efficiency, determined by appropriate integration of the vectors of force generated by cardiac sarcomeres. Integration of new genetic techniques and advances in imaging technology must be matched with a new understanding of the importance of shape and fiber architecture to provide insights into disease that can lead to new therapies.
A shift in emphasis from concepts of ventricular function that consider only contractile state and load to those that also incorporate interaction and dynamic rearrangement of myocardial layers2 is needed. A starting point for discussion at the workshop was the anatomic concept that has been proposed by Torrent-Guasp,3 in which both ventricles are considered to consist of a single myofiber band extending from the right ventricular muscle just below the pulmonary artery to the left ventricular muscle where it attaches to the aorta, twisted and wrapped into a double helical coil during evolutionary and embryological development. In this construct, sequential activation and contraction beginning in fibers near the pulmonary artery and spreading toward the aortic end of the band might explain the pattern of ejection and suction needed for ventricular output and filling. This model is an example of an emphasis that relates fiber architecture to chamber shape and mechanics and has implications for improved understanding of electrical, electromechanical, and mechanical determinants of cardiac function. Disease resulting from ischemic, non-ischemic, and valvular mechanisms may produce architectural distortion and create a more spherical ventricular shape. The conceptual underpinning of management may therefore involve restoration of the normal structural scaffold, so that successful interventions can be designed to achieve normalization of fiber orientation.
To advance the understanding of the relationship between form and function of the intact heart and to integrate these findings into therapy, we recommend intensive study along the following pathways.
| Understanding Normal and Abnormal Shape and Fiber Mechanics |
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| Advancing Imaging |
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| Advancing Therapeutics Through Surgery and Devices |
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The working group developed these recommendations, which highlight a number of important and new areas for future research, to address these critical issues. Development of new ideas and directions within all 3 of the above areas will feed into and support each of the other 2. Accomplishing these goals will require a multidisciplinary collaboration of physiologists, biomedical engineers, clinicians, radiologists, and surgeons. In addition, these lines of research are sufficiently complicated to require the cooperation of both theorists and experimentalists; that is, we should encourage the development and validation of new and improved integrative computational models, which provide testable hypotheses concerning myocardial mechanics. Experiments involving genetic and molecular perturbations, or therapeutic interventions including surgery, would then provide tests of model predictions and also develop new parameters to insert into models so that realistic testing can evolve. New funding opportunities should encourage projects with a wide range of scopes, varying from individual grants to multidisciplinary collaborative programs. The highest priority in this endeavor should be to attain a more sophisticated understanding of the contributions of fiber and intracellular architecture to chamber function through the development of improved imaging methods and their creative application, and to investigate the application of these principles to human disease through surgery or other modalities.
| Acknowledgments |
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| References |
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