The overall objective of this application is to support the Principal Investigator's development in a career focused on patient-oriented research. To accomplish this objective, the proposed program has both training and scientific components. The training component will include specific coursework and instruction in biostatistics, clinical epidemiology, research methodology, and trial design, fulfilling the requirements for a Masters of Clinical Research (MCR) degree. The scientific component of the proposed award will be in the field of acute myocardial ischemia. Enhanced external counterpulsation (EECP) is a noninvasive technique that has been shown to benefit patients with chronic stable angina. This technique has not been tested in patients hospitalized with acute coronary syndromes. The intraaortic balloon pump (IABP) is used in high-risk patients with acute coronary syndromes, but is limited by its invasive approach. We have preliminary data showing that the hemodynamic effects of EECP are similar to those achieved with IABP. The scientific program will test the following hypotheses: 1) EECP results in increased left ventricular efficiency using pressure-volume catheters; 2a) EECP increases myocardial perfusion and decreases biomarkers of left ventricular dysfunction (B-type natriuretic peptide, or BNP) in patients with acute coronary syndrome; and 2b) EECP reduces the incidence of clinically apparent and silent myocardial ischemia in patients with acute coronary syndrome. A hemodynamic study will assess the effects of EECP on left ventricular energetics using high-fidelity micromanometer-tipped catheters during EECP in the Cardiac Catheterization Laboratory. A second study will be a phase II, blinded clinical trial randomizing 132 patients in the Coronary Care Unit with acute coronary syndrome to low-pressure """"""""sham"""""""" EECP or active EECP. All patients will have baseline and 48-hour measures of BNP, contrast-enhanced myocardial echocardiography for myocardial perfusion measurements, and continuous ST-segment monitoring. This research plan will be conducted in the Moffitt-Long Hospital of the UCSF. This institution has a Cardiac Care Unit (CCU) that serves as a treatment site for patients with acute coronary syndrome. The General Clinical Research Center (GCRC) is also in this institution, and assists with all aspects of investigator-initiated studies, including inpatient beds outpatient examination space, nursing care, as well as biostatistical and database consultation.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Mentored Patient-Oriented Research Career Development Award (K23)
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National Center for Research Resources Initial Review Group (RIRG)
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Wilde, David B
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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Shah, Sanjiv J; Michaels, Andrew D (2010) Acute effects of intravenous nesiritide on cardiac contractility in heart failure. J Card Fail 16:720-7
Efstratiadis, Stilianos; Michaels, Andrew D (2009) Acute hemodynamic effects of intravenous nesiritide on left ventricular diastolic function in heart failure patients. J Card Fail 15:673-80
Michaels, Andrew D; Tacy, Theresa; Teitel, David et al. (2009) Invasive left ventricular energetics during enhanced external counterpulsation. Am J Ther 16:239-46
Efstratiadis, Stilianos; Michaels, Andrew D (2008) Computerized acoustic cardiographic electromechanical activation time correlates with invasive and echocardiographic parameters of left ventricular contractility. J Card Fail 14:577-82
Gupta, Saurabh; Khan, Farman; Shapiro, Mia et al. (2008) The associations between tricuspid annular plane systolic excursion (TAPSE), ventricular dyssynchrony, and ventricular interaction in heart failure patients. Eur J Echocardiogr 9:766-71
Shah, Sanjiv J; Nakamura, Kenta; Marcus, Gregory M et al. (2008) Association of the fourth heart sound with increased left ventricular end-diastolic stiffness. J Card Fail 14:431-6
Weeks, Sarah G; Shapiro, Mia; Foster, Elyse et al. (2008) Echocardiographic predictors of change in left ventricular diastolic pressure in heart failure patients receiving nesiritide. Echocardiography 25:849-55
Michaels, Andrew D; McKeown, Barry; Kostal, Michael et al. (2005) Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake. Circulation 111:1504-9
Marcus, Gregory M; Gerber, Ivor L; McKeown, Barry H et al. (2005) Association between phonocardiographic third and fourth heart sounds and objective measures of left ventricular function. JAMA 293:2238-44
Michaels, Andrew D; Raisinghani, Ajit; Soran, Ozlem et al. (2005) The effects of enhanced external counterpulsation on myocardial perfusion in patients with stable angina: a multicenter radionuclide study. Am Heart J 150:1066-73

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