Working Group on Cellular and Molecular Mechanisms of Right Heart Failure
Executive Summary

October 6 - 7, 2005

The National Heart, Lung, and Blood Institute convened a meeting of investigators on October 6-7, 2005 , in Bethesda , Maryland , to define specific areas of both basic and clinical research to be supported, in order to further our understanding of the mechanisms and the development of new treatments for right heart failure. Experts presented their work in heart failure and pulmonary disease research, and clinical practice. Discussions focused on whether information known about the left ventricle and cardiac failure in general, could be directly applied to the right ventricle and associated pulmonary vascular diseases.

This work group was a rare meeting, in which experts in both heart failure and lung disease were brought together. Each discipline acknowledged that they needed to understand more about the “other” organ, which they had for the most part ignored. The general consensus was that fundamental issues regarding regulation of the right heart are as yet unexplored. These discussions should serve as a catalyst, to encourage new collaborations and research on the right heart, that will greatly benefit patients with heart and lung diseases.

Several recommendations on priorities for future research directions were generated.

• Promote awareness in the pulmonary and cardiology research communities about the lack of knowledge of the right ventricle. Encourage new and established investigators to jump into this open area of research.
• We need to understand how to define normal parameters of right ventricular function; there are no gold standards by which to assess this. This definition of function should include geometry, ejection volume, hypertrophy, dilation, contraction, and oxygen supply to the ventricular wall. Ideally, a combination of approaches, including imaging techniques (CT, MRI, PET), implanted monitoring devices, echocardiograms, and electrocardiograms would be used.
• Promote translational research on the right heart, particularly studies of human tissue, to determine what are the important markers of right ventricular function and dysfunction. Studies to identify markers in plasma as well as those in the tissue might help provide a means of diagnosing or predicting right ventricular dysfunction, and preventing failure. Robust parameters that predict outcome for patients with right heart failure are needed.
• Develop animal models of right ventricular failure. Animal models would be particularly useful in determining factors that initiate right ventricular dysfunction. Models would also help to identify biomarkers and changes in gene expression and protein synthesis associated with right ventricular failure.
• Determine whether right ventricular hypertrophy is good or bad. Research is needed to compare hypertrophy seen in athletes with that seen in patients with diseases such as pulmonary hypertension. Mechanisms of right ventricular hypertrophy and remodeling need to be determined.
• We need to understand the differences, similarities and interplay of the left and right heart. This issue can be addressed with chamber specific studies in animal models, that examine changes in gene expression, protein synthesis, histology and geometry during development, injury, and stress (exercise and disease).
• Few studies address the interaction of right ventricular and pulmonary function. Research is needed to study the complex interaction of the heart and lungs, and how changes in one affect the other. Examples of changes include: inflammation, stress due to hypoxia or exercise, autoimmune reactions, infarction, and hypertension.
• The developmental aspects of right heart formation need to be studied to identify mechanisms involved in congenital heart disease and related pulmonary vascular disease.
• Encourage collaborations with the National Institute of Biomedical Imaging and Bioengineering to promote the development of imaging methods to study right ventricular function and dysfunction.
• Promote the development of new therapeutic strategies for right heart failure. These new strategies might include cell based or gene therapy, new drugs, or new combinations of existing drugs.

Work group chair:

• Norbert Voelkel, M.D., University of Colorado Health Sciences Center

NHLBI Staff:

• Elizabeth M. Denholm, Ph.D., Division of Lung Diseases
• Dorothy Gail, Ph.D., Division of Lung Diseases
• Mark Gladwin, M.D., Division of Intramural Research

Participants:

• Robyn Barst, M.D., Columbia University
• Jocelyn Dupuis , M.D., Ph.D., Institut de Cardiologie de Montreal
• Leslie Leinwand, Ph.D., University of Colorado at Boulder
• Carlin Long, M.D., University of Colorado Health Sciences Center
• Michael McGoon, M.D., Mayo Clinic
• Daniel Meldrum, M.D., Indiana University / Purdue University
• Robert Quaife, M.D., University of Colorado Health Sciences Center
• Lewis Rubin, M.D., University of California , San Diego
• Frank Smart, M.D., Texas Heart Institute
• Yuichiro Suzuki, Ph.D., Georgetown University

October 2005