Prognostic Relationship Between Coronary Artery Calcium Score, Perfusion Defects, and Myocardial Blood Flow Reserve in Patients With Suspected Coronary Artery Disease

Abstract

Background: Coronary artery calcium score (CACS) is an anatomic measure of calcified atherosclerosis. Myocardial perfusion defects and reduced myocardial blood flow reserve (MBFR) are physiological measures of ischemia and coronary circulatory health. We aimed to assess the relative prognostic importance of MBFR, perfusion defects, and CACS in patients with suspected coronary artery disease. Methods: A total of 5983 consecutive patients without known history of coronary artery disease or cardiomyopathy, who underwent a CACS and 82 Rb positron emission tomography myocardial perfusion imaging between 2010 and 2016, were followed for all-cause death (n=785) over median of 3 years. Prognostic value was assessed using multivariable Cox regression models, and incremental risk discrimination for imaging variables was evaluated by comparing model c-indices after adjusting for clinical risk factors (RF). Results: Mean age was 67.1 years, 60% were female, and 83% were symptomatic. CACS was 0 in 22%, abnormal perfusion in 19%, and MBFR <2 in 53.3%. When added to RF, the model with MBFR had the best fit (c=0.78, P <0.0001). Addition of CACS to model with RF and perfusion (c=0.77) offered modest improvement in discrimination over the model with RF and perfusion (c=0.76, P =0.02). Adding CACS to a model with RF, perfusion, and MBFR did not provide incremental prognostic value (c=0.785 for both, P =0.16). CACS and MBFR both had independent prognostic value in patients with normal and abnormal myocardial perfusion imaging. Even among patients with CACS of 0, MBFR <2 was present in 37.8%, being associated with higher risk of death (hazard ratio per 0.1↓, 1.10 [1.04–1.15]; P <0.001), but perfusion defects were not. Conclusions: Use of anatomic testing such as CACS of 0 to avoid myocardial perfusion imaging in symptomatic patients could lead to missing microvascular dysfunction in 4 out of 10 patients, a finding associated with a high mortality risk. Higher CACS was independently associated with the risk of death but did not provide incremental prognostic value over positron emission tomography with MBFR.

Post COVID‐19 syndrome with impairment of flow‐mediated epicardial vasodilation and flow reserve

“…Such possibility is supported by recent assessment of myocardial perfusion and MBF with 82 rubidum PET/CT in 1515 symptomatic patients with known or suspected CAD. 15 Impaired augmentation of left ventricular ejection fraction and myocardial blood flow were indeed independently associated with angina symptoms and dyspnea, respectively. 15 This may agree somehow with current observations that unraveled an impaired augmentation of left ventricular ejection fraction with pharmacologic stress in about 50%–60% of symptomatic patients.…”

“… 15 Impaired augmentation of left ventricular ejection fraction and myocardial blood flow were indeed independently associated with angina symptoms and dyspnea, respectively. 15 This may agree somehow with current observations that unraveled an impaired augmentation of left ventricular ejection fraction with pharmacologic stress in about 50%–60% of symptomatic patients. Conversely, we did not find a significant association between impaired increase in left ventricular ejection fraction and myocardial flow reserve in the whole study group, PASC‐CVS, and control patients, respectively.…”

“…LVEF reserve was studied in clinically relevant categories of (≤0% denoting no increase or decrease in LVEF with stress) versus >0% (increase in LVEF with stress). 15 A visual four‐point scoring system was used to indicate coronary artery calcifications (0 = normal, 1 = mild, 2 = moderate, and 3 = severe calcifications) of the LAD, LCx, and RCA on the nongated and low‐dose CT for attenuation correction. 16 From all three coronary vessels the mean coronary calcium score (CCS) was calculated.…”

Calcified Coronary Plaque and Flow Reserve: Nonredundant and Complimentary Markers of Cardiovascular Prognosis

“…As a tool that interrogates coronary physiology, it can provide diagnostic value in patients across the full spectrum of CAD, 10 have demonstrated that global MBFR averaged over the left ventricle can distinguish patients at low or high risk for adverse cardiovascular events, including cardiac death, 11,12 beyond comprehensive clinical assessment, 13 myocardial perfusion defects, 14 left ventricular ejection fraction, low-level troponin elevation, 15 diastolic dysfunction, 16 CAC, 17 or luminal plaque severity. 18 In this issue of Circulation: Cardiovascular Imaging, Patel et al 19 further show that absence of CAC does not exclude high-risk ischemia or coronary vasomotor dysfunction in patients being evaluated for suspected CAD. In this carefully conducted regional longitudinal analysis, 5983 patients without known CAD or cardiomyopathy who underwent clinical cardiac stress testing with 82 Rubidium positron emission tomography myocardial perfusion imaging with CAC scoring between 2010 and 2016 were followed over median 3 years for all-cause death.…”

“…In this issue of Circulation: Cardiovascular Imaging , Patel et al 19 further show that absence of CAC does not exclude high-risk ischemia or coronary vasomotor dysfunction in patients being evaluated for suspected CAD. In this carefully conducted regional longitudinal analysis, 5983 patients without known CAD or cardiomyopathy who underwent clinical cardiac stress testing with 82 Rubidium positron emission tomography myocardial perfusion imaging with CAC scoring between 2010 and 2016 were followed over median 3 years for all-cause death.…”