Keynote speaker one
Professor Natalia Trayanova, Johns Hopkins University, Baltimore
MRI-Based Modeling of Cardiac Electrophysiology and Electromechanics
Simulating cardiac electromechanical function is one of the most striking examples of a successful integrative multi-scale modeling approach applied to a living system directly relevant to human disease. Today, after nearly fifty years of research in the field and the rapid progress of high-performance computing, we stand at the threshold of a new era: anatomically-detailed tomographically-reconstructed models that integrate from the ion channel or sarcomere to the electromechanical interactions in the intact heart are being developed. Such models hold high promise for interpretation of clinical and physiological measurements in terms of cellular mechanisms; for improving the basic understanding of the mechanisms of dysfunction in disease conditions, such as reentrant arrhythmias, myocardial ischemia, and heart failure; and for the development and performance optimization of medical devices. Attempt is made to extend these models beyond electromechanics and include regulatory processes such as energy metabolism. Here we provides specific examples of the state-of-the-art in cardiac integrative modeling, including 1) improving ventricular ablation procedure by using MRI reconstructed heart geometry and structure to investigate the reentrant circuits formed in the presence of an infarct scar; 2) employing an electromechanical model of the heart to determine the mechanisms for electromechanical delay in heart failure; and 3) understanding the origin of alternans in heart failure.
Keynote speaker two
Professor Igor R. Efimov, Washington University in St. Louis, USA
Molecular and functional remodeling of the failing human heart
The existing paradigm of electromechanical remodeling during heart failure is based upon numerous animal models, which have been studied over the years to ascertain the pattern and molecular basis of electrical activation under normal and pathological conditions. However, clinical relevance of these findings is yet to be determined due to significant interspecies difference. In collaboration with cardiac transplantation and cardiology programs at Washington University School of Medicine, we have developed an experimental program, which has acquired and studied in vitro 131 live human hearts as of today, 41% of which are donor hearts rejected from transplantation and 59% are explanted failing hearts. Using optical imaging we have investigated excitation in the normal and failing human hearts in specific anatomical structures: sinus node, atria-ventricular node, atria and ventricles. Using low- and high-density arrays we have investigated mRNA expression and remodeling in these structures during ischemic and non-ischemic cardiomyopathy. We further evaluated differences in gene expression between atria and ventricles, left ventricular endocardium and epicardium, males and females, and two age categories: 30 vs 60 year olds. Conclusions: Our data provide for the first time the quantitative basis for molecular and functional modeling of the human heart at the tissue and organ levels. Our data indicate that caution must be exercised during the translation of findings in the animal models to clinic.