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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., Competing Interests: Declarations. Competing interests: RK, JT and JH are employees of Medis Medical Imaging. Disclosures: RK, JT and JH are employees of Medis Medical Imaging. JK has received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer and Merck, outside of the submitted work. TvdH has received speaker fees and institutional research grants from Abbott and Philips. PK received research grants from HeartFlow Inc. The remaining authors have nothing to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Machine Learning (ML) allows integration of the numerous variables delivered by cardiac PET/CT, while traditional survival analysis can provide explainable prognostic estimates from a restricted number of input variables. We implemented a hybrid ML-and-survival analysis of multimodal PET/CT data to identify patients who developed myocardial infarction (MI) or death in long-term follow up., Methods: Data from 739 intermediate risk patients who underwent coronary CT and selectively stress 15 O-water-PET perfusion were analyzed for the occurrence of MI and all-cause mortality. Images were evaluated segmentally for atherosclerosis and absolute myocardial perfusion through 75 variables that were integrated through ML into an ML-CCTA and an ML-PET score. These scores were then modeled along with clinical variables through Cox regression. This hybridized model was compared against an expert interpretation-based and a calcium score-based model., Results: Compared with expert- and calcium score-based models, the hybridized ML-survival model showed the highest performance (CI .81 vs .71 and .64). The strongest predictor for outcomes was the ML-CCTA score., Conclusion: Prognostic modeling of PET/CT data for the long-term occurrence of adverse events may be improved through ML imaging score integration and subsequent traditional survival analysis with clinical variables. This hybridization of methods offers an alternative to traditional survival modeling of conventional expert image scoring and interpretation., (© 2023. The Author(s).)

Background: New Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myocardial blood flow (MBF). The aim of the study was to evaluate BSREM reconstruction for quantitation in patients with suspected coronary artery disease (CAD)., Methods and Results: We analyzed cardiac [ 15 O]H 2 O PET studies of 177 patients evaluated for CAD. Differences between BSREM and Ordered-Subset-Expectation-Maximization with Time-Of-Flight (TOF) and Point-Spread-Function (PSF) modeling (OSEM-TOF-PSF) in terms of MBF, perfusable tissue fraction, and vascular volume fraction were measured. Classification of ischemia was assessed between the algorithms. OSEM-TOF-PSF and BSREM provided similar global stress MBF in patients with ischemia (1.84 ± 0.21 g⋅ml -1 ⋅min -1 vs 1.86 ± 0.21 g⋅ml -1 ⋅min -1 ) and no ischemia (3.26 ± 0.34 g⋅ml -1 ⋅min -1 vs 3.28 ± 0.34 g⋅ml -1 ⋅min -1 ). Global resting MBF was also similar (0.97 ± 0.12 g⋅ml -1 ⋅min -1 and 1.12 ± 0.06 g⋅ml -1 ⋅min -1 ). The largest mean relative difference in MBF values was 7%. Presence of myocardial ischemia was classified concordantly in 99% of patients using OSEM-TOF-PSF and BSREM reconstructions CONCLUSION: OSEM-TOF-PSF and BSREM image reconstructions produce similar MBF values and diagnosis of myocardial ischemia in patients undergoing [ 15 O]H 2 O PET due to suspected obstructive coronary artery disease., (© 2023. The Author(s).)

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., (© 2022. The Author(s).)

Background: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD., Methods and Results: Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [ 15 O]H 2 O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001)., Conclusions: Adding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD., (© 2022. The Author(s).)

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.