For 15 years, the Kawut Lab has focused on the clinical epidemiology of pulmonary vascular disease and right ventricular function. In this role, the Lab has performed multicenter studies of clinical and genetic risk factors for a variety of pulmonary vascular diseases. Dr. Kawut was the first to show that female sex was a risk factor for Porto pulmonary hypertension, one of the only forms of pulmonary arterial hypertension with a sex predilection.
Moreover, one of the first high-throughput gene analyses in pulmonary hypertension was performed at the Kawut Lab, an effort that demonstrated that variants in aromatase and estrogen receptor genes were risk factors for Porto pulmonary hypertension. These studies have led to further investigation into the sexual dimorphism of pulmonary arterial hypertension.
Dr. Kawut 's group performed one of the first NIH-funded randomized clinical trials in pulmonary arterial hypertension. The Kawut Lab has also used clinical trial data from prior Phase III studies to examine the usefulness of end points in pulmonary arterial hypertension research and to demonstrate differential responsiveness to treatment among patients with different demographics. Such an approach could one day lead to a "personalized medicine" approach to treating pulmonary vascular disease.
The Kawut Lab has had a longstanding interest in right ventricular morphology and response to disease. The group has studied the determinants (and impact) of right ventricular structure and function in healthy individuals and in those with advanced pulmonary vascular disease, showing that sex and race have important effects. Recent work has demonstrated that right ventricular hypertrophy in individuals without clinical cardiovascular disease at baseline increase the risk of heart failure or cardiovascular death. This group has also studied the impact of obstructive lung disease (e.g. COPD) on right ventricular morphology and function.
The Kawut Lab is the site of federally-funded and industry-funded clinical studies in pulmonary arterial hypertension and other forms of pulmonary vascular disease. Current research projects include:
- Sorafenib for Hepatopulmonary Syndrome (SHPS) (NIH UM1 HL116886) — This is a multicenter Phase II randomized clinical trial of sorafenib (tyrosine kinase inhibitor) for hepatopulmonary syndrome in patients with liver disease. This study is based on prior studies showing the importance of angiogenesis in this disease.
Pulmonary Vascular Complications of Liver Disease (PVCLD2) (NIH R01 HL113988) - This is a multicenter cohort study of patients undergoing liver transplantation evaluation to understand the role of estrogen in determining the risk of Porto pulmonary hypertension. The PVCLD study group performed the first multicenter epidemiologic study of the clinical risk factors for Porto pulmonary hypertension (PPHTN) in patients with severe liver disease and portal hypertension.
Anastrozole in Pulmonary Hypertension (AIPH) (NIH K24-HL103844) - This is a double-blind, placebo-controlled Phase II clinical trial of the efficacy of inhibition of aromatase in patients with pulmonary arterial hypertension. The study will evaluate how well the drug is tolerated and whether anastrozole reduces estradiol levels and improves the function of the right ventricle.
The Kawut Lab of the Penn Cardiovascular Institute publishes the findings of its clinical research in the nation's leading clinical journals.
- Kawut SM, Vogel-Claussen J, Austin JHM, Hoffman EA, Prince MR, Lima JA, Bluemke DA, Smith BM, Hueper K, Parikh MA, Poor HD, Barr RG. Cor pulmonale parvus in chronic obstructive pulmonary disease and emphysema: The MESA COPD Study. J Am Coll Cardiol 2014; 64:2000-9.
- Ventetuolo CE, Gabler NB, Fritz JS, Smith KA, Palevsky HI, Klinger JR, Halpern SD, Kawut SM. Are hemodynamics surrogate end points in pulmonary arterial hypertension? Circulation 2014; 130: 768-75. PMID: 24951771.
- Leary PJ, Kaufman JD, Barr RG, Bluemke DA, Curl CL, Hough CL, Lima JA, Szpiro AA, Van Hee VC, Kawut SM. Traffic related air pollution and the right ventricle: The Multi-Ethnic Study of Atherosclerosis. Am J Resp Crit Care Med 2014; 1: 1093-100. PMID: 24593877.
- Goldberg DS, Krok K, Batra S, Trotter JF, *Kawut SM, *Fallon MB. Impact of the hepatopulmonary syndrome MELD exception policy on outcomes of patients after liver transplantation: an analysis of the UNOS database. Gastroenterology, 2014; 146: 1256-65. PMID: 24412528.
- Ventetuolo CE, Praestgaard A, Palevsky HI, Klinger JR, Halpern SD, Kawut SM. Sex and hemodynamics in pulmonary arterial hypertension. Eur Respir J 2014; 43: 523-530. PMID: 23949961
- Whitman I, Patel VV, Soliman EZ, Bluemke DA, Praestgaard A, Jain A, Herrington D, Lima JAC, Kawut SM. Validity of the surface electrocardiogram criteria for right ventricular hypertrophy: The MESA - Right Ventricle Study. JACC 2014; 63: 672-681.
- Kawut SM, Barr RG, Praestgaard A, Johnson C, Chahal H, Ogunyankin K, Bristow M, Kizer JR, Tandri H, Bluemke D. Right ventricle structure is associated with the risk of heart failure and cardiovascular death: The MESA-Right Ventricle Study. Circulation. 2012;126(14):1681-8
- Gabler NB, Fench B, Strom BL, Palevsky HI, Taichman DB, Kawut SM, Halpern SD. Validation of the six-minute-walk distance as a surrogate endpoint in pulmonary arterial hypertension trials. Circulation. 2012;126:349-356.
- Kawut SM, Lima JA, Barr RG, Chahal H, Jain A, Tandri H, Praestgaard A, Bagiella E, Kizer JR, Johnson WC, Kronmal RA, Bluemke DA. Sex and race differences in right ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis-Right Ventricle Study. Circulation. 2011;7:2542- 2551. PMID: 21646505, PMCID: PMC311939
- Kawut SM, Bagiella E, Lederer D, Shimbo D, Horn EM, Roberts KE, Barr RG, Rosenzweig E, Post W, Palevsky HI, Tracy R, Hassoun PM, Girgis RE on behalf of the ASA-STAT Study Group. A randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Circulation. 2011;123:2985-2993. PMID: 21593252.
- Roberts KE, Fallon MB, Krowka MJ, Brown RS, Trotter JF, Peter I, Tighiouart H, Knowles JA, Rabinowitz D, Benza RL, Badesch DB, Taichman DB, Horn EM, Zacks S, Kaplowitz N, Kawut SM for the PVCLD Study Group. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med. 2009;179:835-842. PMID: 19218192, PMCID: PMC2975568
- Kawut SM, Al-Naamani N, Agerstrand C, Berman-Rosenzweig ES, Rowan C, Barst RJ, Bergmann S, Horn EM. Determinants of right ventricular ejection fraction in pulmonary arterial hypertension. Chest. 2009;135:752-759. PMID: 18849396, PMCID: PMC2834785