Incremental prognostic value of hybrid [15O]H2O positron emission tomography-computed tomography: combining myocardial blood flow, coronary stenosis severity, and high-risk plaque morphology.

AIMS: This study sought to determine the prognostic value of combined functional testing using positron emission tomography (PET) perfusion imaging and anatomical testing using coronary computed tomography angiography (CCTA)-derived stenosis severity and plaque morphology in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: In this retrospective study, 539 patients referred for hybrid [15O]H2O PET-CT imaging because of suspected CAD were investigated. PET was used to determine myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenoses and high-risk plaque (HRP) morphology. Patients were followed up for the occurrence of all-cause death and non-fatal myocardial infarction (MI). During a median follow-up of 6.8 (interquartile range 4.8-7.8) years, 42 (7.8%) patients experienced events, including 23 (4.3%) deaths, and 19 (3.5%) MIs. Annualized event rates for normal vs. abnormal results of PET MBF, CCTA-derived stenosis, and HRP morphology were 0.6 vs. 2.1%, 0.4 vs. 2.1%, and 0.8 vs. 2.8%, respectively (P < 0.001 for all). Cox regression analysis demonstrated prognostic values of PET perfusion imaging [hazard ratio (HR) 3.75 (1.84-7.63), P < 0.001], CCTA-derived stenosis [HR 5.61 (2.36-13.34), P < 0.001], and HRPs [HR 3.37 (1.83-6.18), P < 0.001] for the occurrence of death or MI. However, only stenosis severity [HR 3.01 (1.06-8.54), P = 0.039] and HRPs [HR 1.93 (1.00-3.71), P = 0.049] remained independently associated. CONCLUSION: PET-derived MBF, CCTA-derived stenosis severity, and HRP morphology were univariably associated with death and MI, whereas only stenosis severity and HRP morphology provided independent prognostic value.

Diagnostic Value of Transluminal Attenuation Gradient for the Presence of Ischemia as Defined by Fractional Flow Reserve and Quantitative Positron Emission Tomography.

OBJECTIVES: The aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)-derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BACKGROUND: In addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. METHODS: Patients with suspected coronary artery disease underwent coronary CTA and [15O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA-derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow ≤2.30 ml/min/g) and FFR (≤0.80) was determined. RESULTS: A total of 557 (91.9%) coronary arteries of 201 patients were included for analysis. TAG, TAG-CCO, and TDG did not discriminate between vessels with or without ischemia as defined by either PET or FFR. Furthermore, these parameters did not have incremental diagnostic accuracy over coronary CTA alone for the presence of ischemia as defined by PET and FFR. There was a significant correlation between TDG and TAG (r = 0.47; p < 0.001) and between TDG and TAG-CCO (r = 0.37; p < 0.001). CONCLUSIONS: TAG, TAG-CCO, and TDG do not provide incremental diagnostic value over coronary CTA alone for the presence of ischemia as defined by [15O]H2O PET and/or FFR. The lack of diagnostic value of contrast enhancement-based flow estimations appears related to coronary luminal dimension variability.

Predictive value of targeted proteomics for coronary plaque morphology in patients with suspected coronary artery disease.

BACKGROUND: Risk stratification is crucial to improve tailored therapy in patients with suspected coronary artery disease (CAD). This study investigated the ability of targeted proteomics to predict presence of high-risk plaque or absence of coronary atherosclerosis in patients with suspected CAD, defined by coronary computed tomography angiography (CCTA). METHODS: Patients with suspected CAD (n = 203) underwent CCTA. Plasma levels of 358 proteins were used to generate machine learning models for the presence of CCTA-defined high-risk plaques or complete absence of coronary atherosclerosis. Performance was tested against a clinical model containing generally available clinical characteristics and conventional biomarkers. FINDINGS: A total of 196 patients with analyzable protein levels (n = 332) was included for analysis. A subset of 35 proteins was identified predicting the presence of high-risk plaques. The developed machine learning model had fair diagnostic performance with an area under the curve (AUC) of 0·79 ±â€¯0·01, outperforming prediction with generally available clinical characteristics (AUC = 0·65 ±â€¯0·04, p < 0·05). Conversely, a different subset of 34 proteins was predictive for the absence of CAD (AUC = 0·85 ±â€¯0·05), again outperforming prediction with generally available characteristics (AUC = 0·70 ±â€¯0·04, p < 0·05). INTERPRETATION: Using machine learning models, trained on targeted proteomics, we defined two complementary protein signatures: one for identification of patients with high-risk plaques and one for identification of patients with absence of CAD. Both biomarker subsets were superior to generally available clinical characteristics and conventional biomarkers in predicting presence of high-risk plaque or absence of coronary atherosclerosis. These promising findings warrant external validation of the value of targeted proteomics to identify cardiovascular risk in outcome studies. FUND: This study was supported by an unrestricted research grant from HeartFlow Inc. and partly supported by a European Research Area Network on Cardiovascular Diseases (ERA-CVD) grant (ERA CVD JTC2017, OPERATION). Funders had no influence on trial design, data evaluation, and interpretation.

Additional value of transluminal attenuation gradient in CT angiography to predict hemodynamic significance of coronary artery stenosis.

OBJECTIVES: The current study evaluates the incremental value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (CCO), and TAG with exclusion of calcified coronary segments (ExC) over coronary computed tomography angiogram (CTA) alone using fractional flow reserve (FFR) as the gold standard. BACKGROUND: TAG is defined as the contrast opacification gradient along the length of a coronary artery on a coronary CTA. Preliminary data suggest that TAG provides additional functional information. Interpretation of TAG is hampered by multiple heartbeat acquisition algorithms and coronary calcifications. Two correction models have been proposed based on either dephasing of contrast delivery by relating coronary density to corresponding descending aortic opacification (TAG-CCO) or excluding calcified coronary segments (TAG-ExC). METHODS: Eighty-five patients with intermediate probability of coronary artery disease were prospectively included. All patients underwent step-and-shoot 256-slice coronary CTA. TAG, TAG-CCO, and TAG-ExC analyses were performed followed by invasive coronary angiography in conjunction with FFR measurements of all major coronary branches. RESULTS: Thirty-four patients (40%) were diagnosed with hemodynamically-significant coronary artery disease (i.e., FFR ≤0.80). On a per-vessel basis (n = 253), 59 lesions (23%) were graded as hemodynamically significant, and the diagnostic accuracy of coronary CTA (diameter stenosis ≥50%) was 95%, 75%, 98%, and 54% for sensitivity, specificity, negative predictive value, and positive predictive value, respectively. TAG and TAG-ExC did not discriminate between vessels with or without hemodynamically significant lesions (-13.5 ± 17.1 HU [Hounsfield units] × 10 mm(-1) vs. -11.6 ± 13.3 HU × 10 mm(-1), p = 0.36; and 13.1 ± 15.9 HU × 10 mm(-1) vs. -11.4 ± 11.7 HU × 10 mm(-1), p = 0.77, respectively). TAG-CCO was lower in vessels with a hemodynamically-significant lesion (-0.050 ± 0.051 10 mm(-1) vs. -0.036 ± 0.034 10 mm(-1), p = 0.03) and TAG-ExC resulted in a slight improvement of the net reclassification index (0.021, p < 0.05). CONCLUSIONS: TAG did not provide incremental diagnostic value over 256-slice coronary CTA alone in assessing the hemodynamic consequences of a coronary stenosis. Correction for temporal nonuniformity of contrast delivery or exclusion of calcified coronary segments slightly enhanced the results.