Abstract

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012–2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making.

Highlights

  • There is growing interest in coronary microvascular disease (CMVD) which has been associated with worsened cardiovascular outcomes [1] and may be involved in the pathogenesis of heart failure [2, 3]

  • Since CMVD often coexists with coronary artery disease (CAD), we included all patients with adequate Myocardial Blood Flow Reserve (MBFR) measurements, regardless of their CAD status or the presence of perfusion defects, in examining the risk factors and disease processes that are associated with decreased MBFR (S1 Table)

  • Cardiovascular diseases such as CAD, Congestive Heart Failure (CHF), stroke, and Peripheral Artery Disease (PAD) were associated with decreased MBFR

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Summary

Introduction

There is growing interest in coronary microvascular disease (CMVD) which has been associated with worsened cardiovascular outcomes [1] and may be involved in the pathogenesis of heart failure [2, 3]. PET (positron emission tomography) has been used extensively for myocardial perfusion imaging (MPI) given superior imaging characteristics compared to SPECT. Myocardial Blood Flow Reserve and Cardiovascular Outcomes. In addition to enhanced MPI, cardiac PET can provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values, defined as the ratio of hyperemic MBF to resting MBF [5]. Low MBFR has been shown to correlate with worsened outcomes in various populations, including patients with diabetes, renal disease, and obesity and patients without coronary artery disease (CAD) [6,7,8,9,10]. With the availability of several commercial software packages to quantify MBF and MBFR, PET has reproducibly shown value as a prognostic biomarker of adverse outcomes [11,12,13,14,15]

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