The OVERALL OBJECTIVE of this proposal is to integrate the anatomic and physiologic information derived from computed tomographic angiograms for the precise identification of coronary artery lesions that cause ischemia. This proposal is a companion study to ISCHEMIA Trial. For patients with stable ischemic heart disease, myocardial ischemia may arise as a consequence of obstructive coronary artery disease (CAD) and is useful for guiding decisions of revascularization. To date, non-invasive stress tests have served as a mainstay for identifying ischemia;these tests include echocardiography, magnetic resonance and myocardial perfusion scintigraphy (MPS). Among these, MPS is performed most commonly due to its ability to identify obstructive CAD, reclassify CAD likelihood, and predict adverse events. CT has emerged as a non-invasive method that permits direct visualization of CAD, demonstrates high performance for obstructive CAD compared to invasive coronary angiography (ICA), and predicts adverse prognosis. Beyond stenosis, CT enables evaluation of additional atherosclerotic plaque characteristics (APCs) that demonstrate high agreement to invasive methods and may augment determination of coronary lesions that cause ischemia. Recent developments in CT also permit physiologic assessment of CAD by applying computational fluid dynamics to typically- acquired CT scans for calculation of coronary artery pressure and flow, thus enabling the non-invasive calculation of fractional flow reserve (FFRCT), a measure of vessel-specific ischemia. The OVERALL HYPOTHESIS of this proposal is that integrating anatomic APCs with physiologic FFRCT will optimize identification of coronary lesions that are ischemia-causing. We propose 3 specific aims:
AIM 1 : To assess performance of anatomic APCs by CT for diagnosis of vessel-specific ischemia.
AIM 2 : To assess performance of physiologic FFRCT for diagnosis of vessel-specific ischemia.
AIM 3 : To directly compare an integrated anatomic-physiologic (APC-FFRCT) CT measure to MPS for diagnosis of lesion-specific ischemia. The work in this proposal will provide the rationale for a novel diagnostic paradigm that is more accurate than conventional stress imaging testing for identifying patients who manifest ischemia and pinpointing the coronary lesions that are the cause;thus, allowing for better selection of individuals for revascularization and eliminating unnecessary invasive procedures.

Public Health Relevance

For patients with ischemic heart disease, non-invasive stress tests are targeted towards identifying individuals with myocardial ischemia, or reduced blood flow to the heart muscle. Non-invasive computed tomography (CT) scans of the heart now allow for advanced characterization of heart artery blockages, as well as determination of whether blockages cause ischemia. This study will establish whether CT permits diagnosis of ischemia in a manner more accurate than stress testing for not only identifying patients who have ischemia but also pinpointing the blockages that are the cause.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Fleg, Jerome
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Weill Medical College of Cornell University
Schools of Medicine
New York
United States
Zip Code
Cho, Iksung; Al'Aref, Subhi J; Berger, Adam et al. (2018) Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study. Eur Heart J 39:934-941
Rizvi, Asim; Han, Donghee; Danad, Ibrahim et al. (2018) Diagnostic Performance of Hybrid Cardiac Imaging Methods for Assessment of Obstructive Coronary Artery Disease Compared With Stand-Alone Coronary Computed Tomography Angiography: A Meta-Analysis. JACC Cardiovasc Imaging 11:589-599
Baskaran, Lohendran; Ó Hartaigh, Bríain; Schulman-Marcus, Joshua et al. (2017) Dense calcium and lesion-specific ischemia: A comparison of CCTA with fractional flow reserve. Atherosclerosis 260:163-168
Xiong, Guanglei; Sun, Peng; Zhou, Haoyin et al. (2017) Comprehensive Modeling and Visualization of Cardiac Anatomy and Physiology from CT Imaging and Computer Simulations. IEEE Trans Vis Comput Graph 23:1014-1028
Min, James K; Gilmore, Amanda; Jones, Erica C et al. (2017) Cost-effectiveness of diagnostic evaluation strategies for individuals with stable chest pain syndrome and suspected coronary artery disease. Clin Imaging 43:97-105
Danad, Ibrahim; Szymonifka, Jackie; Twisk, Jos W R et al. (2017) Diagnostic performance of cardiac imaging methods to diagnose ischaemia-causing coronary artery disease when directly compared with fractional flow reserve as a reference standard: a meta-analysis. Eur Heart J 38:991-998
Rizvi, Asim; Hartaigh, Bríain Ó; Danad, Ibrahim et al. (2017) Diffuse coronary artery disease among other atherosclerotic plaque characteristics by coronary computed tomography angiography for predicting coronary vessel-specific ischemia by fractional flow reserve. Atherosclerosis 258:145-151
Shalev, Aryeh; Nakazato, Ryo; Arsanjani, Reza et al. (2016) SYNTAX Score Derived From Coronary CT Angiography for Prediction of Complex Percutaneous Coronary Interventions. Acad Radiol 23:1384-1392
Valenti, Valentina; Hartaigh, Bríain Ó; Cho, Iksung et al. (2016) Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality: A 15-Year Follow-Up Study of 9715 Patients. Circ Cardiovasc Imaging 9:e003528
Zhou, Haoyin; Sun, Peng; Ha, Seongmin et al. (2016) Watertight modeling and segmentation of bifurcated Coronary arteries for blood flow simulation using CT imaging. Comput Med Imaging Graph 53:43-53

Showing the most recent 10 out of 41 publications