Natural History of Myocardial αvß3 Integrin Expression After Acute Myocardial Infarction: Correlation with Changes in Myocardial Blood Flow.

Angiogenesis is an essential part of the cardiac repair process after myocardial infarction, but its spatiotemporal dynamics remain to be fully deciphered.68Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvß3 integrin expression, which is a marker of angiogenesis. Methods: In this prospective single-center trial, we aimed to monitor angiogenesis through myocardial integrin αvß3 expression in 20 patients with ST-segment elevation myocardial infarction (STEMI). In addition, the correlations between the expression levels of myocardial αvß3 integrin and the subsequent changes in 82Rb PET/CT parameters, including rest and stress myocardial blood flow (MBF), myocardial flow reserve (MFR), and wall motion abnormalities, were assessed. The patients underwent 68Ga-NODAGA-RGD PET/CT and rest and stress 82Rb-PET/CT at 1 wk, 1 mo, and 3 mo after STEMI. To assess 68Ga-NODAGA-RGD uptake, the summed rest 82Rb and 68Ga-NODAGA-RGD images were coregistered, and segmental SUVs were calculated (RGD SUV). Results: At 1 wk after STEMI, 19 participants (95%) presented increased 68Ga-NODAGA-RGD uptake in the infarcted myocardium. Seventeen participants completed the full imaging series. The values of the RGD SUV in the infarcted myocardium were stable 1 mo after STEMI (1 wk vs. 1 mo, 1.47 g/mL [interquartile range (IQR), 1.37-1.64 g/mL] vs. 1.47 g/mL [IQR, 1.30-1.66 g/mL]; P = 0.9), followed by a significant partial decrease at 3 mo (1.32 g/mL [IQR, 1.12-1.71 g/mL]; P = 0.011 vs. 1 wk and 0.018 vs. 1 mo). In segment-based analysis, positive correlations were found between RGD SUV at 1 wk and the subsequent changes in stress MBF (Spearman ρ: r = 0.17, P = 0.0033) and MFR (Spearman ρ: r = 0.31, P < 0.0001) at 1 mo. A negative correlation was found between RGD SUV at 1 wk and the subsequent changes in wall motion abnormalities at 3 mo (Spearman ρ: r = -0.12, P = 0.035). Conclusion: The present study found that αvß3 integrin expression is significantly increased in the infarcted myocardium 1 wk after STEMI. This expression remains stable after 1 mo and partially decreases after 3 mo. Initial αvß3 integrin expression at 1 wk is significantly weakly correlated with subsequent improvements in stress MBF, MFR, and wall motion analysis.

Comparing various AI approaches to traditional quantitative assessment of the myocardial perfusion in [82Rb] PET for MACE prediction.

Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [ 82 Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model ( p < 0.001 ), where the best AUC of 73.9% (CI 72.5-75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3-74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE.

Impact of thoracoabdominal imaging on diagnosis and management in patients with suspected infective endocarditis.

BACKGROUND: Embolic events (EEs) are a common complication of infective endocarditis (IE) and their presence can impact diagnosis and modify the therapeutic plan. The present study aimed to describe the role of thoracoabdominal imaging, either thoracoabdominal-pelvic Computed Tomography or 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography, on diagnosis and management of patients with suspected IE. METHODS: This study was conducted at a university hospital, from January 2014 to June 2022. EEs and IE were defined according to modified Duke criteria. RESULTS: Among 966 episodes with suspected IE and thoracoabdominal imaging, 528 (55%) patients were asymptomatic. At least one EE was found in 205 (21%) episodes. Based on thoracoabdominal imaging findings, the diagnosis was reclassified from rejected to possible or from possible to definite IE in 6 (1%) and 10 (1%) episodes, respectively. Among the 413 patients with IE, at least one EE was found on thoracoabdominal imaging in 143 (35%) episodes. Together with the presence of left-side valvular vegetation >10 mm, the results of thoracoabdominal imaging established a surgical indication (prevention of embolism) in 15 (4%) episodes, 7 of which were asymptomatic. CONCLUSIONS: Thoracoabdominal imaging performed in asymptomatic patients with suspected IE improved the diagnosis in only a small proportion of patients. Thoracoabdominal imaging led to a new surgical indication (in association with left-side valvular vegetation >10 mm) in only a small percentage of patients.

Comparison of the prognostic value of impaired stress myocardial blood flow, myocardial flow reserve, and myocardial flow capacity on low-dose Rubidium-82 SiPM PET/CT.

BACKGROUND: The most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE) has not been characterized with low-dose silicon photomultipliers (SiPM) technology, which allows halving injected activity and radiation dose delivering less than 1.0 mSv in a 70-kg individual. METHODS AND RESULTS: We prospectively enrolled 234 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT (5 MBq/kg) and were followed up for MACE over 652 days (interquartile range 559-751 days). For each participant, global stress myocardial blood flow (stress MBF), global myocardial flow reserve (MFR), and regional severely reduced myocardial flow capacity (MFCsevere) were measured. The Youden index was used to select optimal thresholds. In multivariate analysis after adjustments for clinical risk factors, reduced global stress MBF < 1.94 ml/min/g, reduced global MFR < 1.98, and regional MFCsevere > 3.2% of left ventricle emerged all as independent predictors of MACE (HR 4.5, 3.1, and 3.67, respectively, p < 0.001). However, only reduced global stress MBF remained an independent prognostic factor for MACE after adjusting for clinical risk factors and the combined use of global stress MBF, global MFR, and regional MFCsevere impairments (HR 2.81, p = 0.027). CONCLUSION: Using the latest SiPM PET technology with low-dose 82Rb halving the standard activity to deliver < 1 mSv for a 70-kg patient, impaired global stress MBF, global MFR, and regional MFC were powerful predictors of cardiovascular events, outperforming traditional cardiovascular risk factors. However, only reduced global stress MBF independently predicted MACE, being superior to global MFR and regional MFC impairments.

Overview of the RGD-Based PET Agents Use in Patients With Cardiovascular Diseases: A Systematic Review.

Studies using arginine-glycine-aspartate (RGD)-PET agents in cardiovascular diseases have been recently published. The aim of this systematic review was to perform an updated, evidence-based summary about the role of RGD-based PET agents in patients with cardiovascular diseases to better address future research in this setting. Original articles within the field of interest reporting the role of RGD-based PET agents in patients with cardiovascular diseases were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until October 26, 2021. Literature shows an increasing role of RGD-based PET agents in patients with cardiovascular diseases. Overall, two main topics emerged: the infarcted myocardium and atherosclerosis. The existing studies support that αvß3 integrin expression in the infarcted myocardium is well evident in RGD PET/CT scans. RGD-based PET radiotracers accumulate at the site of infarction as early as 3 days and seem to be peaking at 1-3 weeks post myocardial infarction before decreasing, but only 1 study assessed serial changes of myocardial RGD-based PET uptake after ischemic events. RGD-based PET uptake in large vessels showed correlation with CT plaque burden, and increased signal was found in patients with prior cardiovascular events. In human atherosclerotic carotid plaques, increased PET signal was observed in stenotic compared with non-stenotic areas based on MR or CT angiography data. Histopathological analysis found a co-localization between tracer accumulation and areas of αvß3 expression. Promising applications using RGD-based PET agents are emerging, such as prediction of remodeling processes in the infarcted myocardium or detection of active atherosclerosis, with potentially significant clinical impact.

Impact of Adaptive Statistical Iterative Reconstruction-V on Coronary Artery Calcium Scores Obtained From Low-Tube-Voltage Computed Tomography - A Patient Study.

OBJECTIVE: To evaluate the impact of adaptive statistical iterative reconstruction-V (ASIR-V) on the accuracy of ultra-low-dose coronary artery calcium (CAC) scoring. MATERIALS AND METHOD: One-hundred-and-three patients who underwent computed tomography (CT) for CAC scoring were prospectively included. All underwent standard scanning with 120-kilovolt-peak (kVp) and with 80- and 70-kVp tube voltage. ASiR-V was applied to the 80- and 70-kVp scans at different levels. The 120-kVp scans reconstructed with filtered back projection served as the standard of reference. Recently published novel kVp-adapted thresholds were used for calculation of CAC scores from 80- and 70-kVp scans and the resulting CAC scores were compared against the standard of reference. Patients were stratified into six CAC score risk categories: 0, 1-10, 11-100, 101-400, 401-1000, and >1000. RESULTS: Increasing levels of ASIR-V led to an increasing underestimation of CAC scores with bias ranging from -128 to -118 and from -205 to -198 for the 80- and 70-kVp scans, respectively, when compared with the standard of reference. Reconstruction with 20% and 40% ASIR-V for the 80- and 70-kVp scans, respectively, yielded noise levels comparable to the standard of reference. Nevertheless, a change in risk-class was observed in 29 (28.6%) and 46 (44.7%) patients, exclusively to a lower risk-class, when CAC scores were derived from these reconstructions. CONCLUSION: ASIR-V leads to noise reduction in CT scans acquired with low tube-voltages. However, ASIR-V introduces substantial inaccuracies and marked underestimation of ultra-low-dose CAC scoring as compared with standard-dose CAC scoring despite normalization of noise.

Imaging angiogenesis in atherosclerosis in large arteries with 68Ga-NODAGA-RGD PET/CT: relationship with clinical atherosclerotic cardiovascular disease.

BACKGROUND: Integrin alpha-V-beta-3 (αvß3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvß3 integrin ligand for PET. MATERIALS AND METHODS: The data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann-Whitney U test, Pearson correlation and Spearman correlation. RESULTS: 68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03-2.55] vs. 1.81 [1.56-1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). CONCLUSIONS: 68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.

Splenic switch-off as a predictor for coronary adenosine response: validation against 13N-ammonia during co-injection myocardial perfusion imaging on a hybrid PET/CMR scanner.

BACKGROUND: Inadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET). METHODS: We prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of  > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress (SMRstress) and rest. RESULTS: Sixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMRstress were significantly lower in patients with SSO (SIR: 0.56 ± 0.13 vs. 0.93 ± 0.23; p < 0.001 and SMRstress: 1.09 ± 0.47 vs. 1.68 ± 0.62; p < 0.001). Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO (3.07 ± 1.03 vs. 2.48 ± 0.96; p = 0.038), but there was only a weak inverse correlation between SMRstress and MFR (R = -0.378; p = 0.02) as well as between SIR and MFR (R = -0.356; p = 0.004). CONCLUSIONS: The presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation.

Diagnostic Performance of 18F-FDG PET/CT in Native Valve Endocarditis: Systematic Review and Bivariate Meta-Analysis.

BACKGROUND: Infectious endocarditis is a life-threatening disease, requiring prompt and accurate diagnosis. The aim of this article is to perform a systematic review and meta-analysis of the literature to estimate the performance of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the diagnosis of native valve endocarditis (NVE). METHODS: Selected articles evaluating the diagnostic accuracy of 18F-FDG PET/CT in patients with suspected NVE, resulting from a comprehensive literature search through the PubMed/MEDLINE and Cochrane library databases until April 2020, were included for the systematic review and meta-analysis. RESULTS: Seven studies (351 episodes of suspected NVE) were included. 18F-FDG PET/CT yielded a pooled sensitivity of 36.3% and a pooled specificity of 99.1% for the diagnosis of NVE. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 8.3, 0.6, and 15.3, respectively. The sensitivity increased using contemporary PET/CT device with state-of-the-art patient preparation as well as innovative image acquisitions or adding the results of 18F-FDG PET/CT in a multimodality strategy. CONCLUSIONS: In our systematic review and meta-analysis, 18F-FDG PET/CT yielded a poor pooled sensitivity with an otherwise excellent pooled specificity for the diagnosis of NVE; however, several factors may increase the sensitivity without affecting the specificity and these factors should be better evaluated in future studies.

Potential of Radiation Dose Reduction by Optimizing Z-Axis Coverage in Coronary Computed Tomography Angiography on a Latest-Generation 256-Slice Scanner.

OBJECTIVE: The purpose of this study was to quantify the reduction in radiation dose achievable by using the optimal z-axis coverage in coronary computed tomography (CT) angiography (CCTA) on a latest-generation 256-slice scanner. METHODS: A total of 408 scans were reviewed that were performed on a wide-range detector scanner allowing up to 16-cm z-axis coverage (adjustable in 2-cm increments). For each CCTA study, we assessed the radiation dose (ie, dose-length product and volume CT dose index) and measured the minimum z-axis coverage necessary to cover the complete cardiac anatomy. We calculated the potential radiation dose savings achievable through reduction of the z-axis coverage to the minimum necessary. RESULTS: The majority of the CCTA scans were performed with a z-axis coverage of 16 cm (n = 285, 69.9%), followed by 14 cm (n = 121, 29.7%) and 12 cm (n = 2, 0.5%). In the group that was scanned with a collimation of 16 cm, radiation dose could have been reduced by 12.5% in 55 patients, 25% in 195 patients, and 37.5% in 33 patients when using optimal z-axis coverage for CCTA. In the group that was scanned with a collimation of 14 cm, radiation dose could have been reduced by 14.3% in 90 patients, and 28.6% in 30 patients, whereas in the group that was scanned with a collimation of 12 cm, dose could have been reduced by 16.7% in 2 patients. CONCLUSIONS: Using correct z-axis coverage in CCTA on a latest-generation 256-slice scanner yields average dose reductions of 22.0% but may be as high as 37.5%.

[Cardiology]. / Cardiologie.

In 2019, the guidelines on the new entity « chronic coronary syndrome ¼ have been published. They influence importantly the work-up and treatment of patients with stable coronary artery disease. We will also report on publications showing the benefit of percutaneous aortic valve implantation (TAVI) in patients with aortic stenosis and low risk surgical risk. With regard to infectious endocarditis, we elucidate the importance of the vegetation's size for predicting mortality and the prognostic value of the positron emission tomography in predicting septic embolism. We highlight the spectacular results of the DAPA-HF study in patients with heart failure and review publications showing the important role of the detection of myocardial fibrosis and scar by cardiac MRI for risk stratification of sudden cardiac death.

L'année 2019 a été marquée par la publication de recommandations sur une nouvelle entité, appelée « syndrome coronarien chronique ¼, qui modifient de manière importante la prise en charge et le traitement des patients avec une maladie coronarienne stable. On relève plusieurs publications démontrant, chez les patients ayant une sténose aortique, et étant à bas risque chirurgical, le bénéfice d'un traitement percutané par rapport à un traitement chirurgical. La prise en charge de l'endocardite a été challengée par deux publications montrant que la taille de la végétation est un facteur de risque de mortalité et la valeur pronostique de la tomographie par émission de positons dans la survenue d'emboles septiques. Nous discutons les résultats spectaculaires de l'étude DAPA-HF dans le domaine d'insuffisance cardiaque et plusieurs études montrant l'intérêt de la recherche de cicatrice myocardique à l'IRM cardiaque dans la stratification du risque de mort subite.

Stairs instead of elevators at the workplace decreases PCSK9 levels in a healthy population.

BACKGOUND: Regular physical activity is recommended to lower low-density lipoprotein cholesterol (LDL-C) in a healthy population. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) was shown to reduce (LDL-C) levels; however, the impact of physical exercise on PCSK9 levels remains unclear. MATERIALS AND METHODS: We used data from 67 healthy hospital employees who participated in a 6-month intervention promoting active use of stairs instead of elevators during 3 months, followed by 3 months without recommendation. We confirmed the degree of physical activity with estimated aerobic capacity (VO2 max ) and measured serum PCSK9 levels at baseline, 3 and 6 month. Using a multilevel regression model, we analysed changes of PCSK9 levels over time adjusting for age, gender, aerobic capacity, baseline LDL-C, and LDL-C and body mass index (BMI) changes. RESULTS: At baseline, PCSK9 levels were associated with higher aerobic capacity (P-value = 0·024). At 3 months, we observed a significant decrease in mean PCSK9 levels from 403·6 to 324·3 ng/mL (P-value = 0·001), as well a significant decrease in mean LDL-C levels from 3·5 to 3·3 mM (P-value = 0·01). During this period, mean aerobic capacity (VO2 max ) increased from 37·0 to 40·4 mL/kg/min (P-value < 0·001). Physical activity was independently associated with a decrease in PCSK9 levels after adjustment for age, gender, baseline aerobic capacity, and LDL-C and BMI changes. CONCLUSION: Daily physical activity at the work place is independently associated with a decrease in PCSK9 levels over time.