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Background Coronary artery disease (CAD) is a major contributor to cardiovascular events in individuals with diabetes. Quantification of coronary atherosclerotic burden is now feasible from coronary computed tomography angiography (CTA) whereas positron emission tomography (PET) enables quantitative assessment of myocardial perfusion. We studied the prognostic implications of quantitatively measured coronary plaque burden and myocardial perfusion in diabetic vs. non-diabetic patients with suspected CAD. Methods In this observational cohort study, 1311 symptomatic patients with suspected CAD underwent coronary CTA and [ 15 O]H 2 O PET perfusion imaging. Coronary plaque burden was quantified using artificial intelligence–based analysis and reported as percent atheroma volume (PAV). Myocardial perfusion was assessed as regional stress myocardial blood flow (sMBF), with abnormal perfusion defined as ≥ 2 adjacent segments with sMBF < 2.3 ml/g/min. The composite endpoint was all-cause death, myocardial infarction (MI), or unstable angina pectoris (UAP) over 7 years. Results Among the 1311 patients, 251 (19%) had diabetes and 134 (10%) experienced an adverse event during follow-up. The annual event rate was low (0.8% [95% CI 0.6–1.1%]) in non-diabetic patients with normal myocardial perfusion and increased significantly with the presence of either diabetes (2.3% [95% CI 1.4–3.8%]), abnormal perfusion (2.6% [95% CI 2.1–3.3%]), or both (3.2% [95% CI 2.1–4.8%]) ( p  < 0.001). Among patients with normal myocardial perfusion, those with diabetes had two-fold PAV as compared with non-diabetic individuals (median 8.2% vs. 4.1%, p  < 0.001). In multivariable Cox regression models, both PAV (HR 1.03 [95% CI 1.01–1.05] per 1% increase, p  < 0.001) and regional sMBF (HR 1.04 [95% CI 1.01–1.07] per 0.1 ml/g/min decrease, p  = 0.016) were independent predictors of adverse outcome in non-diabetic patients. In diabetic patients, only PAV (HR 1.04 [95% CI 1.01–1.07], p  = 0.014) was predictive, whereas sMBF was not. Conclusions Coronary atherosclerotic plaque burden appears as an important predictor of long-term cardiovascular outcomes both in diabetic and non-diabetic patients. In patients with diabetes, normal myocardial perfusion does not necessarily imply low event risk, partly attributable to higher coronary plaque burden. Quantitative imaging methods for detailed CAD phenotyping shed light on the complex relationship between diabetes and clinical outcomes. Graphical abstract

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [ 15 O]H 2 O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [ 15 O]H 2 O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min −1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Noninvasive assessment of coronary artery disease remains a challenging task, with a large armamentarium of diagnostic modalities. Myocardial perfusion imaging (MPI) is widely used for this purpose whereby cardiac positron emission tomography (PET) is considered the gold standard. Next to relative radiotracer distribution, PET allows for measurement of absolute myocardial blood flow. This quantification of perfusion improves diagnostic accuracy and prognostic value. Cardiac hybrid imaging relies on the fusion of anatomical and functional imaging using coronary computed tomography angiography and MPI, respectively, and provides incremental value as compared with either stand-alone modality.

PurposeWe sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue.MethodsSymptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement.ResultsAmong 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase.ConclusionsPost revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

It is unknown whether gender influences the atherosclerotic plaque characteristics (APCs) of lesions of varying angiographic stenosis severity. This study evaluated the imaging data of 303 symptomatic patients from the derivation arm of the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial, all of whom underwent coronary computed tomographic angiography and clinically indicated nonemergent invasive coronary angiography upon study enrollment. Index tests were interpreted by 2 blinded core laboratories, one of which performed quantitative coronary computed tomographic angiography using an artificial intelligence application to characterize and quantify APCs, including percent atheroma volume (PAV), low-density noncalcified plaque (LD-NCP), noncalcified plaque (NCP), calcified plaque (CP), lesion length, positive arterial remodeling, and high-risk plaque (a combination of LD-NCP and positive remodeling ≥1.10); the other classified lesions as obstructive (≥50% diameter stenosis) or nonobstructive (<50% diameter stenosis) based on quantitative invasive coronary angiography. The relation between APCs and angiographic stenosis was further examined by gender. The mean age of the study cohort was 64.4 ± 10.2 years (29.0% female). In patients with obstructive disease, men had more LD-NCP PAV (0.5 ± 0.4 vs 0.3 ± 0.8, p = 0.03) and women had more CP PAV (11.7 ± 1.6 vs 8.0 ± 0.8, p = 0.04). Obstructive lesions had more NCP PAV compared with their nonobstructive lesions in both genders, however, obstructive lesions in women also demonstrated greater LD-NCP PAV (0.4 ± 0.5 vs 1.0 ± 1.8, p = 0.03), and CP PAV (17.4 ± 16.5 vs 25.9 ± 18.7, p = 0.03) than nonobstructive lesions. Comparing the composition of obstructive lesions by gender, women had more CP PAV (26.3 ± 3.4 vs 15.8 ± 1.5, p = 0.005) whereas men had more NCP PAV (33.0 ± 1.6 vs 26.7 ± 2.5, p = 0.04). Men had more LD-NCP PAV in nonobstructive lesions compared with women (1.2 ± 0.2 vs 0.6 ± 0.2, p = 0.02). In conclusion, there are gender-specific differences in plaque composition based on stenosis severity.

PurposeTo compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD).MethodsFifty-nine patients with stable CAD underwent CMR and [15O]H2O PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress.ResultsCMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P < 0.001 for stress MBF and r = 0.36; P < 0.001 for MFR). Bland-Altman analysis revealed a significant bias of 0.2 ± 1.0 mL/min/g for stress MBF and − 0.5 ± 1.2 for MFR. CMR-derived stress MBF and MFR demonstrated area under the curves of respectively 0.72 (95% CI: 0.65 to 0.79) and 0.76 (95% CI: 0.69 to 0.83) and had optimal cutoff values of 2.35 mL/min/g and 2.25 for detecting abnormal myocardial perfusion, defined as [15O]H2O PET-derived stress MBF ≤ 2.3 mL/min/g and MFR ≤ 2.5. Using these cutoff values, CMR and PET were concordant in 137 (77%) vascular territories for stress MBF and 135 (80%) vascular territories for MFR.ConclusionCMR measurements of stress MBF and MFR showed modest agreement to those obtained with [15O]H2O PET. Nevertheless, stress MBF and MFR were concordant between CMR and [15O]H2O PET in 77% and 80% of vascular territories, respectively.

ObjectiveThe study evaluates the relationship of coronary stenosis, atherosclerotic plaque characteristics (APCs) and age using artificial intelligence enabled quantitative coronary computed tomographic angiography (AI-QCT).MethodsThis is a post-hoc analysis of data from 303 subjects enrolled in the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial who were referred for invasive coronary angiography and subsequently underwent coronary computed tomographic angiography (CCTA). In this study, a blinded core laboratory analysing quantitative coronary angiography images classified lesions as obstructive (≥50%) or non-obstructive (<50%) while AI software quantified APCs including plaque volume (PV), low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), calcified plaque (CP), lesion length on a per-patient and per-lesion basis based on CCTA imaging. Plaque measurements were normalised for vessel volume and reported as % percent atheroma volume (%PAV) for all relevant plaque components. Data were subsequently stratified by age <65 and ≥65 years.ResultsThe cohort was 64.4±10.2 years and 29% women. Overall, patients >65 had more PV and CP than patients <65. On a lesion level, patients >65 had more CP than younger patients in both obstructive (29.2 mm3 vs 48.2 mm3; p<0.04) and non-obstructive lesions (22.1 mm3 vs 49.4 mm3; p<0.004) while younger patients had more %PAV (LD-NCP) (1.5% vs 0.7%; p<0.038). Younger patients had more PV, LD-NCP, NCP and lesion lengths in obstructive compared with non-obstructive lesions. There were no differences observed between lesion types in older patients.ConclusionAI-QCT identifies a unique APC signature that differs by age and degree of stenosis and provides a foundation for AI-guided age-based approaches to atherosclerosis identification, prevention and treatment.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min-1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

The introduction of wire-free microcirculatory resistance index from functional angiography (angio-IMR) promises swift detection of coronary microvascular dysfunction, however it has not been properly validated. We sought to validate angio-IMR against invasive IMR and PET derived microvascular resistance (MVR). Moreover, we studied if angio-IMR could aid in the detection of ischemia with non-obstructive coronary arteries (INOCA). In this investigator-initiated study symptomatic patients underwent [ 15 O]H 2 O positron emission tomography (PET) and invasive angiography with 3-vessel fractional flow reserve (FFR). Invasive IMR was measured in 40 patients. Angio-IMR and QFR were computed retrospectively. MVR was defined as the ratio of mean distal coronary pressure to PET derived coronary flow. PET and QFR/angio-IMR analyses were performed by blinded core labs. The right coronary artery was excluded. A total of 211 patients (mean age 61 ± 9, 148 (70%) male) with 312 vessels with successful angio-IMR analyses were included. Angio-IMR correlated moderately with invasive IMR ( r  = 0.48, p  < 0.01), whereas no correlation was found between angio-IMR and MVR ( r =-0.07, p  = 0.25). Angio-IMR did not differ for vessels without obstructive coronary artery disease (CAD) (FFR-) but with reduced stress perfusion (PET+) compared to vessels without obstructive CAD (FFR-) with normal stress perfusion (PET-) (median 28.19 IQR 20.42–38.99 vs. 31.67 IQR 23.47–40.63, p  = 0.40). Angio-IMR correlated moderately with invasively measured IMR, whereas angio-IMR did not correlate with PET derived MVR. Moreover, angio-IMR did not reliably identify patients with INOCA. Graphical Abstract