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PurposeWe evaluated the value of reduced global and segmental absolute stress myocardial blood flow (sMBF) quantified by [15O] water positron emission tomography (PET) for predicting cardiac events in patients with suspected obstructive coronary artery disease (CAD).MethodsGlobal and segmental sMBF during adenosine stress were retrospectively quantified in 530 symptomatic patients who underwent [15O] water PET for evaluation of coronary stenosis detected by coronary computed tomography angiography.ResultsCardiovascular death, myocardial infarction, or unstable angina occurred in 28 (5.3%) patients at a 4-year follow-up. Reduced global sMBF was associated with events (area under the receiver operating characteristic curve 0.622, 95% confidence interval (95% CI) 0.538–0.707, p = 0.006). Reduced global sMBF (< 2.2 ml/g/min) was found in 22.8%, preserved global sMBF despite segmentally reduced sMBF in 35.3%, and normal sMBF in 41.9% of patients. Compared with normal sMBF, reduced global sMBF was associated with the highest risk of events (adjusted hazard ratio (HR) 6.970, 95% CI 2.271–21.396, p = 0.001), whereas segmentally reduced sMBF combined with preserved global MBF predicted an intermediate risk (adjusted HR 3.251, 95% CI 1.030–10.257, p = 0.044). The addition of global or segmental reduction of sMBF to clinical risk factors improved risk prediction (net reclassification index 0.498, 95% CI 0.118–0.879, p = 0.010, and 0.583, 95% CI 0.203–0.963, p = 0.002, respectively).ConclusionIn symptomatic patients evaluated for suspected obstructive CAD, reduced global sMBF by [15O] water PET identifies those at the highest risk of adverse cardiac events, whereas segmental reduction of sMBF with preserved global sMBF is associated with an intermediate event risk.

Background Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and adverse outcomes. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). The aim of the present study was to study whether diabetes changes the relationship of CAD and long-term outcome. Methods We retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was evaluated by 15 O-water PET myocardial perfusion imaging. The relationship of the phenotype of CAD and long-term outcome in patients with no diabetes, prediabetes, or type 2 diabetes was investigated. A composite endpoint included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP). Results A total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of median follow-up, 164 adverse events occurred (106 deaths, 41 MIs, 17 UAPs). The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and 27% in diabetic patients. The event rate was lowest in patients with normal coronary arteries and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 0.2% vs. 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings. Conclusions Coronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in non-diabetic and diabetic patients.

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

ObjectivesApplication of computational fluid dynamics (CFD) to three-dimensional CTCA datasets has been shown to provide accurate assessment of the hemodynamic significance of a coronary lesion. We aim to test the feasibility of calculating a novel CTCA-based virtual functional assessment index (vFAI) of coronary stenoses > 30% and ≤ 90% by using an automated in-house-developed software and to evaluate its efficacy as compared to the invasively measured fractional flow reserve (FFR).Methods and resultsIn 63 patients with chest pain symptoms and intermediate (20–90%) pre-test likelihood of coronary artery disease undergoing CTCA and invasive coronary angiography with FFR measurement, vFAI calculations were performed after 3D reconstruction of the coronary vessels and flow simulations using the finite element method. A total of 74 vessels were analyzed. Mean CTCA processing time was 25(± 10) min. There was a strong correlation between vFAI and FFR, (R = 0.93, p < 0.001) and a very good agreement between the two parameters by the Bland–Altman method of analysis. The mean difference of measurements from the two methods was 0.03 (SD = 0.033), indicating a small systematic overestimation of the FFR by vFAI. Using a receiver-operating characteristic curve analysis, the optimal vFAI cutoff value for identifying an FFR threshold of ≤ 0.8 was ≤ 0.82 (95% CI 0.81 to 0.88).ConclusionsvFAI can be effectively derived from the application of computational fluid dynamics to three-dimensional CTCA datasets. In patients with coronary stenosis severity > 30% and ≤ 90%, vFAI performs well against FFR and may efficiently distinguish between hemodynamically significant from non-significant lesions.Key PointsVirtual functional assessment index (vFAI) can be effectively derived from 3D CTCA datasets.In patients with coronary stenoses severity > 30% and ≤ 90%, vFAI performs well against FFR.vFAI may efficiently distinguish between functionally significant from non-significant lesions.

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

Endothelial wall shear stress (ESS) is a biomechanical force which plays a role in the formation and evolution of atherosclerotic lesions. The purpose of this study is to evaluate coronary computed tomography angiography (CCTA)-based ESS in coronary arteries without atherosclerosis, and to assess factors affecting ESS values. CCTA images from patients with suspected coronary artery disease were analyzed to identify coronary arteries without atherosclerosis. Minimal and maximal ESS values were calculated for 3-mm segments. Factors potentially affecting ESS values were examined, including sex, lumen diameter and distance from the ostium. Segments were categorized according to lumen diameter tertiles into small (< 2.6 mm), intermediate (2.6–3.2 mm) or large (≥ 3.2 mm) segments. A total of 349 normal vessels from 168 patients (mean age 59 ± 9 years, 39% men) were included. ESS was highest in the left anterior descending artery compared to the left circumflex artery and right coronary artery (minimal ESS 2.3 Pa vs. 1.9 Pa vs. 1.6 Pa, p < 0.001 and maximal ESS 3.7 Pa vs. 3.0 Pa vs. 2.5 Pa, p < 0.001). Men had lower ESS values than women, also after adjusting for lumen diameter (p < 0.001). ESS values were highest in small segments compared to intermediate or large segments (minimal ESS 3.8 Pa vs. 1.7 Pa vs. 1.2 Pa, p < 0.001 and maximal ESS 6.0 Pa vs. 2.6 Pa vs. 2.0 Pa, p < 0.001). A weak to strong correlation was found between ESS and distance from the ostium (ρ = 0.22–0.62, p < 0.001). CCTA-based ESS values increase rapidly and become widely scattered with decreasing lumen diameter. This needs to be taken into account when assessing the added value of ESS beyond lumen diameter in highly stenotic lesions.

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 [ O]H 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.

Contrast-induced nephropathy (CIN) is a potentially serious complication of contrast agents used in computed tomography angiography (CTA). The aim of this study was to evaluate whether persistent renal dysfunction occurs in patients undergoing coronary CTA for suspected stable coronary artery disease (CAD). From a cohort of 957 patients undergone coronary CTA, we identified 402 patients with plasma creatinine levels collected before and within 6 months after CTA. According to the definition of CIN, patients with a ≥25 % increase in plasma creatinine after CTA were evaluated. The post-CTA measurements in 402 patients (195 men, age 62.9 ± 9.3 years) were performed at a median of 99 days after CTA. On average, there was no change in plasma creatinine level between the pre- and post-CTA measurements (75.8 ± 16.0 and 75.7 ± 16.4 µmol/L, respectively; P = 0.63) but both increases and decreases were commonly detected. Fourteen (3.5 %) patients had a ≥25 % increase in plasma creatinine levels after CTA. A more detailed evaluation of these patients revealed that in 4 patients the increase was explained by other morbidities, whereas in 9 patients the creatinine level returned to the previous levels at later follow-up (median time to normalization: 311 days). Only in 1 (0.2 %) remaining patient, there was a persistent increase in plasma creatinine level, possibly related to the iodine contrast agent exposure. Alterations in plasma creatinine concentration occur frequently. Persistent renal dysfunction attributable to iodine contrast agent exposure is rare in patients referred to coronary CTA for suspected CAD.