Associate Professor of Medicine
Dr. Champion received his B.S. in Biological Science from Emory University in Atlanta, Georgia. He received his MD/PhD in Cardiovascular Pharmacology from Tulane University in New Orleans, Louisiana. After his medical school training, Dr. Champion joined the Olser Housestaff Service of the Johns Hopkins University School of Medicine where he completed his internship and residency. He subsequently completed his training in Cardiovascular Disease and Heart Failure and Transplant Cardiology at Johns Hopkins where he stayed on as an Assistant Professor of Medicine. He Directed the Bernard Laboratory for the Study of Cardiovascular Disease from 2005-2009. In July of 2009, Dr. Champion joined the faculty of the Division of Pulmonary, Allergy and Critical Care Medicine, the Vascular Medicine Institute and the Cardiovascular Institute at the University of Pittsburgh as an Associate Professor of Medicine. He directs Translational Research for the University of Pittsburgh Vascular Medicine Institute and the Pulmonary Vascular Disease Center. In addition, he directs the Clinical and Translational Vascular Unit of the University of Pittsburgh.
Dr. Champion’s research has spanned basic and clinical science work on mechanisms of pulmonary hypertension, cardiac hypertrophy and heart failure, and erectile dysfunction. He has authored and co-authored more than 215 publications in peer-reviewed journals and his laboratory has been funded by NIH grants including as well as grants from the American Heart Association, WW Smith Charitable Trust, and the Bernard Foundation. He is the recipient of the American Physiological Society Shin Chun Wang Young Investigator Award, the Giles F. Filley Young Investigator Award as well as the Cornand and Comroe Young Investigator Award from the Cardiopulmonary Council of the AHA, and The Zipes Distinguished Young Investigator Award by the American College of Cardiology. He has served on the Executive Council for the Cardiopulmonary Council of the American Heart Association since 1997. More recently, he is a founding member of the Pulmonary Vascular Research Institute (PVRI), an independent, international organization whose mission is to promote knowledge and stimulate new ideas in the field of cardiopulmonary medicine by fostering multidiscipline approaches, collaboration and communication across the science spectrum. Dr. Champion serves as an At Large Member of the Executive Council and Senior Fellow.
Dr. Champion subspecializes in Pulmonary Vascular Disease and Heart Failure and Transplant Cardiology. He has extensive experience in the evaluation and management of patients with pulmonary hypertension (pulmonary vascular disease) and right heart failure that is caused by a number of different diseases (heart failure, pulmonary arterial hypertension, COPD/emphysema, interstitial lung disease (ILD), connective tissue disease (such as scleroderma, lupus, and CREST syndrome), valvular disease, and sickle cell disease.
Dr. Champion's clinical research is dedicated to the study of pulmonary vascular disease and heart failure. We have focused on the use of advanced non-invasive and invasive catheterization-based methods to assess pulmonary vascular and cardiac mechanics in patients in an effort to better diagnose early cardiovascular disease as well better assess response to drug and mechanical therapy. In addition, we are very interested as to the mechanisms and genetic predeterminants of acute stress cardiomyopathy, a condition in which emotional or physical stress results in transient heart failure.
Dr. Champion's basic science investigations span an array of inquiries, such as understanding the basic mechanisms underlying the physiology and pathophysiology of the pulmonary vascualture and the heart. Recent studies have investigated the beneficial influences of nitric oxide/cGMP/protein kinase G and cGMP-targeted phosphdiesterase signaling cascades on cardiac maladaptive stress remodeling. Recently, his lab has particularly focused on the role of phosphodiesterase type 5 and its pharmacologic inhibitors (e.g. sildenafi, tadalafil), on vascular and myocyte signaling cascades modulated by protein kinase G. Moreover, he has been particularly interested in the role of nitric oxide synthase dysregulation coupled with oxidant stress in the heart and lung.
Phosphodiesterase type 5A (PDE5A) selectively hydrolyzes cyclic GMP. Inhibitors of PDE5A such as sildenafil are widely used to treat erectile dysfunction, but growing evidence from our lab and others supports important roles for the enzyme in both the vasculature and heart. In disorders such as cardiac failure, PDE5A upregulation may contribute to a decline in cGMP and protein kinase G signaling, exacerbating dysfunction. PDE5A plays an important role in the pulmonary vasculature where its inhibition benefits patients with pulmonary hypertension. In the heart, PDE5A signaling appears compartmentalized, and its inhibition is cardioprotective against ischemia-reperfusion and antracycline toxicity, blunts acute adrenergic contractile stimulation, and can suppress chronic hypertrophy and dysfunction attributable to pressure-overload. Figure 1 (below) shows that inhibition of PDE5A with sildenafil prevents load-induced cardiac hypertrophy. The left panel is an example of heart sections (top) and M-mode echocardiogram (bottom). The right panel shows PAS-methanamine-stained myocardium from the ventricle of vehicle- and sildenafil-treated mice. The black color reflect fibrosis and, in control mice, aortic constriction is associated with a marked increase in cell size and fibrosis. In contrast, mice treated with sildenafil showed a significantly lower amount of fibrosis in response to increased load. Our laboratory is studying the mechanism(s) by which PDE5A inhibitors improve cardiac function in models of disease and patients.
Figure 1: Sildenafil inhibitshypertrophy/dilation induced by transaortic constriction in mice. From Takimoto, Champion et al. Nature Medicine 2005; 11:214-222
Takimoto E, Champion HC (Co-first author), Belardi D, Moslehi J, Mongillo M, Mergia E, Montrose DC, Isoda T, Aufiero K, Zaccolo M, Dostmann WR, Smith CJ, Kass DA. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res. 96:100-9, 2005. PMID: 15576651
Takimoto E, Champion HC (Co-first author), Li M, Belardi D, Moslehi J, Mongillo M, Mergia E, Montrose DC, Isoda T, Wang Y, Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 11: 214-222, 2005. PMID: 15665834
Takimoto E, Champion HC (Co-first author), Li M, Tavazzi B, Lazzarino G, Paolocci N, Wang Y, Kass DA. Oxidant Stress from nitric oxide synthase-3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load. J. Clin. Invest. 115:1221-1231, 2005. PMID: 15841206
Hsu LL, Champion HC (Co-First Author), Campbell-Lee SA, Bivalacqua TJ, Manci EA, Diwan BA, Schimel DM, Cochard AE, Wang X, Schechter AN, Noguchi CT, Gladwin MT. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood. 2007 Apr 1;109(7):3088-98. PMID: 17158223
Hemnes AR, Zaiman A, Champion HC. PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS Generation and RhoA/Rho kinase Activation. Am J Physiol Lung Cell Mol Physiol. 2007
Wittstein IS, Thiemann DR, Lima JAC, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emotional stress. New Engl J Med, 352: 539-548, 2005
Tedford RJ, Hemnes AR, Russell SD, Wittstein IS, Mahmud M, Zaiman AL, Mathai SC, Thiemann DR, Hassoun PM, Girgis RE, Orens JB, Shah AS, Yuh D, Conte JV, Champion HC. PDE5A inhibitor treatment of persistent pulmonary hypertension after mechanical circulatory support. Circ Heart Fail. 2008 Nov;1(4):213-9.
Hemnes AR, Zaiman A, Champion HC. PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation. Am J Physiol Lung Cell Mol Physiol. 2008 Jan;294(1):L24-33. PMID: 17965319
Hemnes AR and Champion HC. Right heart function and haemodynamics in pulmonary hypertension. Int. J. Clin. Practice. 62: 11-20, 2008.
Champion HC, Michelakis ED, Hassoun PM. A Comprehensive Invasive and Non-Invasive Approach to the Right Ventricle-Pulmonary Circulation Unit: State of the Art, Clinical and Research Implications. Circulation 2009 Sep 15;120(11):992-1007. PMID: 19752350