Traditionally, evaluation of patients with suspected coronary artery disease has focused on the epicardial coronary system. More recently, investigators have come to appreciate better that the status of the coronary microcirculation can influence significantly long-term morbidity and mortality. Although cardiac transplant recipients commonly develop microcirculatory dysfunction, its timing and its effect on outcomes is unclear. Patients with acute myocardial infarction, despite successful recanalization of an occluded epicardial artery, suffer from microcirculatory dysfunction, both in the infarcted region, as well as in myocardium remote from the infarction. However, the incidence and implications of micro-circulatory dysfunction in areas remote from an acutely infarcted territory are poorly understood. To date, evaluation of the coronary microcirculation has been limited by techniques which incorporate the epicardial system into their assessment. Additionally, most methods require specialized equipment and/or analyses. Others are limited by their qualitative nature. Finally, the majority of methods are noninvasive, yet many patients first present for evaluation of their coronary arterial system in the cardiac catheterization laboratory. The first goal of this project is to demonstrate that an invasive, coronary wire-based method for evaluating the coronary microcirculation is easy to perform and interpret, quantitative, and correlates well with standard methods for assessing the microcirculation. The technique will be validated in a porcine model of epicardial artery and microcirculatory disease. It's correlation with PET imaging, the current gold standard noninvasive method of evaluating the microcirculation, will then be tested in patients with and without microcirculatory dysfunction. The second and third goals of this study will be to apply this technique to gain a better understanding of the role of the microcirculation in the outcomes of cardiac transplant patients and those suffering from acute myocardial infarction.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL072808-03
Application #
7012261
Study Section
Special Emphasis Panel (ZHL1-CSR-J (O1))
Program Officer
Scott, Jane
Project Start
2004-02-01
Project End
2009-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
3
Fiscal Year
2006
Total Cost
$125,962
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Fearon, William F; Low, Adrian F; Yong, Andy S et al. (2013) Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention. Circulation 127:2436-41
Haddad, Francois; Khazanie, Prateeti; Deuse, Tobias et al. (2012) Clinical and functional correlates of early microvascular dysfunction after heart transplantation. Circ Heart Fail 5:759-68
Yamasaki, Masao; Sakurai, Ryota; Hirohata, Atsushi et al. (2011) Impact of donor-transmitted atherosclerosis on early cardiac allograft vasculopathy: new findings by three-dimensional intravascular ultrasound analysis. Transplantation 91:1406-11
Sinha, Seema S; Pham, Michael X; Vagelos, Randall H et al. (2008) Effect of rapamycin therapy on coronary artery physiology early after cardiac transplantation. Am Heart J 155:889.e1-6
Fearon, William F; Shah, Maulik; Ng, Martin et al. (2008) Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 51:560-5
Sakurai, Ryota; Yamasaki, Masao; Nakamura, Mamoo et al. (2007) Determinants of lumen loss between years 1 and 2 after cardiac transplantation. Transplantation 84:1097-102
Hirohata, Atsushi; Nakamura, Mamoo; Waseda, Katsuhisa et al. (2007) Changes in coronary anatomy and physiology after heart transplantation. Am J Cardiol 99:1603-7
Fearon, William F; Potena, Luciano; Hirohata, Atsushi et al. (2007) Changes in coronary arterial dimensions early after cardiac transplantation. Transplantation 83:700-5
Fearon, William F; Hirohata, Atsushi; Nakamura, Mamoo et al. (2006) Discordant changes in epicardial and microvascular coronary physiology after cardiac transplantation: Physiologic Investigation for Transplant Arteriopathy II (PITA II) study. J Heart Lung Transplant 25:765-71

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