The prognostic value of automated coronary calcium derived by a deep learning approach on non-ECG gated CT images from 82Rb-PET/CT myocardial perfusion imaging.

BACKGROUND: Assessment of both coronary artery calcium(CAC) scores and myocardial perfusion imaging(MPI) in patients suspected of coronary artery disease(CAD) provides incremental prognostic information. We used an automated method to determine CAC scores on low-dose attenuation correction CT(LDACT) images gathered during MPI in one single assessment. The prognostic value of this automated CAC score is unknown, we therefore investigated the association of this automated CAC scores and major adverse cardiovascular events(MACE) in a large chest-pain cohort. METHOD: We analyzed 747 symptomatic patients referred for 82RubidiumPET/CT, without a history of coronary revascularization. Ischemia was defined as a summed difference score≥2. We used a validated deep learning(DL) method to determine CAC scores. For survival analysis CAC scores were dichotomized as low(<400) and high(≥400). MACE was defined as all cause death, late revascularization (>90 days after scanning) or nonfatal myocardial infarction. Cox proportional hazard analysis were performed to identify predictors of MACE. RESULTS: During 4 years follow-up, 115 MACEs were observed. High CAC scores showed higher cumulative event rates, irrespective of ischemia (nonischemic: 25.8% vs 11.9% and ischemic: 57.6% vs 23.4%, P-values <0.001). Multivariable cox regression revealed both high CAC scores (HR 2.19 95%CI 1.43-3.35) and ischemia (HR 2.56 95%CI 1.71-3.35) as independent predictors of MACE. Addition of automated CAC scores showed a net reclassification improvement of 0.13(0.022-0.245). CONCLUSION: Automatically derived CAC scores determined during a single imaging session are independently associated with MACE. This validated DL method could improve risk stratification and subsequently lead to more personalized treatment in patients suspected of CAD.

Normal imaging findings after aortic valve implantation on 18F-Fluorodeoxyglucose positron emission tomography with computed tomography.

BACKGROUND: To determine the normal perivalvular 18F-Fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography (PET) with computed tomography (CT) within one year after aortic prosthetic heart valve (PHV) implantation. METHODS: Patients with uncomplicated aortic PHV implantation were prospectively included and underwent 18F-FDG PET/CT at either 5 (± 1) weeks (group 1), 12 (± 2) weeks (group 2) or 52 (± 8) weeks (group 3) after implantation. 18F-FDG uptake around the PHV was scored qualitatively (none/low/intermediate/high) and quantitatively by measuring the maximum Standardized Uptake Value (SUVmax) and target to background ratio (SUVratio). RESULTS: In total, 37 patients (group 1: n = 12, group 2: n = 12, group 3: n = 13) (mean age 66 ± 8 years) were prospectively included. Perivalvular 18F-FDG uptake was low (8/12 (67%)) and intermediate (4/12 (33%)) in group 1, low (7/12 (58%)) and intermediate (5/12 (42%)) in group 2, and low (8/13 (62%)) and intermediate (5/13 (38%)) in group 3 (P = 0.91). SUVmax was 4.1 ± 0.7, 4.6 ± 0.9 and 3.8 ± 0.7 (mean ± SD, P = 0.08), and SUVratio was 2.0 [1.9 to 2.2], 2.0 [1.8 to 2.6], and 1.9 [1.7 to 2.0] (median [IQR], P = 0.81) for groups 1, 2, and 3, respectively. CONCLUSION: Non-infected aortic PHV have similar low to intermediate perivalvular 18F-FDG uptake with similar SUVmax and SUVratio at 5, 12, and 52 weeks after implantation.

Sex differences in flow cytometry-based platelet reactivity in stable outpatients suspected of myocardial ischemia.

BACKGROUND: Antiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear. We therefore investigated the role of sex differences in platelet reactivity in a cohort of outpatients with chest pain, in response to treatment with antiplatelet agents. METHODS: Platelet reactivity was measured in 382 randomly selected patients participating in the Myocardial Ischemia Detection by Circulating Biomarkers (MYOMARKER) study, an observational cohort study of outpatients suspected of myocardial ischemia. In all patients, blood was collected during diagnostic workup, and platelet reactivity was assessed with a flow cytometry-based platelet activation test that quantifies both platelet degranulation (P-selectin expression) and platelet aggregation (fibrinogen binding to integrin αIIbß3) in whole blood. RESULTS: Platelet reactivity was higher in women compared with men when activated with protease activating receptor 1-activating peptide SFLLRN (PAR1-AP) and adenosine 5'-phosphate (ADP), independent of age, basal activation status, estimated glomerular filtration rate < 60, platelet count, statin use, the use of P2Y12 inhibitors, or the use of aspirin. P2Y12 inhibitor use strongly reduced fibrinogen binding after stimulation with PAR1-AP, but only slightly reduced platelet P-selectin expression. Calculation of the relative inhibition in P2Y12 users indicated 62% inhibition of the response toward ADP. Stratified analysis showed that women (n = 14) using P2Y12 inhibitors showed less inhibition of fibrinogen binding after PAR1-AP stimulation than men (n = 38) using P2Y12 inhibitors. CONCLUSIONS: These findings call for further study of differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia.

Automated calcium scores collected during myocardial perfusion imaging improve identification of obstructive coronary artery disease.

BACKGROUND: Myocardial perfusion imaging (MPI) is an accurate noninvasive test for patients with suspected obstructive coronary artery disease (CAD) and coronary artery calcium (CAC) score is known to be a powerful predictor of cardiovascular events. Collection of CAC scores simultaneously with MPI is unexplored. AIM: We aimed to investigate whether automatically derived CAC scores during myocardial perfusion imaging would further improve the diagnostic accuracy of MPI to detect obstructive CAD. METHODS: We analyzed 150 consecutive patients without a history of coronary revascularization with suspected obstructive CAD who were referred for 82Rb PET/CT and available coronary angiographic data. Myocardial perfusion was evaluated both semi quantitatively as well as quantitatively according to the European guidelines. CAC scores were automatically derived from the low-dose attenuation correction CT scans using previously developed software based on deep learning. Obstructive CAD was defined as stenosis >70% (or >50% in the left main coronary artery) and/or fractional flow reserve (FFR) ≤0.80. RESULTS: In total 58% of patients had obstructive CAD of which seventy-four percent were male. Addition of CAC scores to MPI and clinical predictors significantly improved the diagnostic accuracy of MPI to detect obstructive CAD. The area under the curve (AUC) increased from 0.87 to 0.91 (p: 0.025). Sensitivity and specificity analysis showed an incremental decrease in false negative tests with our MPI + CAC approach (n = 14 to n = 4), as a consequence an increase in false positive tests was seen (n = 11 to n = 28). CONCLUSION: CAC scores collected simultaneously with MPI improve the detection of obstructive coronary artery disease in patients without a history of coronary revascularization.

Improving the Diagnostic Performance of 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Prosthetic Heart Valve Endocarditis.

BACKGROUND: 18F-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments. METHODS: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded. RESULTS: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein <40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of ≥2.0 was a 100% sensitive and 91% specific predictor of PVE. CONCLUSIONS: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were.

18F-fluorodeoxyglucose positron emission/computed tomography and computed tomography angiography in prosthetic heart valve endocarditis: from guidelines to clinical practice.

The timely diagnosis of prosthetic heart valve endocarditis remains challenging yet of utmost importance. 18F-fluorodeoxyglucose (18 F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) were recently introduced as additional diagnostic tools in the most recent ESC guidelines on infective endocarditis. However, how to interpret PET/CT findings with regard to what is to be considered abnormal, what the potential confounders may be, as well as which patients benefit most from these additional imaging techniques and how to best perform them in these often-complex patients, remains unclear. This review focusses on factors regarding patient selection and image acquisition that need to be taken into account when employing 18F-FDG PET/CT and CTA in daily clinical practice, and the importance of a multidisciplinary Endocarditis Team herein. Furthermore, it emphasizes the need for standardized acquisition protocols and image interpretation, especially now that these techniques are starting to be widely embraced by the cardiovascular society.

Standardized uptake values in FDG PET/CT for prosthetic heart valve endocarditis: a call for standardization.

BACKGROUND: The significance of and threshold values for the standardized uptake value (SUV) in FDG PET/CT to diagnose prosthetic heart valve (PHV) endocarditis (PVE) are unclear at present. METHODS: A literature search was performed in the PubMed and EMBASE medical databases, comprising the following terms: (FDG OR *fluorode* OR *fluoro-de*) AND (endocarditis OR prosthetic heart valve OR valve replacement). Studies reporting SUVs correlated to the diagnosis of PVE were selected for analysis. RESULTS: 8 studies were included, with a total of 330 PHVs assessed. SUVs for PVE varied substantially across studies due to differences in acquisition, reconstruction, and measurement protocols, with median SUVmax values for rejected PVE ranging from 0.5 to 4.9 and for definite PVE ranging from 4.2 to 7.4. CONCLUSION: Reported SUV values for PVE are not interchangeable between sites, and further standardization of quantification is desirable. To this end, optimal protocols for patient preparation, image acquisition, and reconstruction and measurement methods need to be standardized across centers.

Primary cardiac lymphoma with central nervous system relapse.

Primary cardiac lymphoma (PCL), a rare disease, often presents with symptoms resembling other cardiac diseases. The correct diagnosis is crucial, as cardiac lymphoma can be cured with immuno-chemotherapy. PCL has a high risk of central nervous system recurrence (CNS); therefore, screening for CNS involvement and even prophylaxis may be necessary.

Additional Heparin Preadministration Improves Cardiac Glucose Metabolism Suppression over Low-Carbohydrate Diet Alone in ¹8F-FDG PET Imaging.

UNLABELLED: Adequate suppression of cardiac glucose metabolism increases the interpretability and diagnostic reliability of (18)F-FDG PET studies performed to detect cardiac inflammation and infection. There are no standardized guidelines, though prolonged fasting (>6 h), carbohydrate-restricted diets, fatty meals, and heparin loading all have been proposed. The aim of this study was to compare the 3 preparatory protocols used in our institution. METHODS: (18)F-FDG PET scans were selected and grouped according to 3 preparatory protocols (50 consecutive scans per group): 6-h fast (group 1), low-carbohydrate diet plus 12-h fast (group 2), and low-carbohydrate diet plus 12-h fast plus intravenous heparin preadministration (50 IU/kg) (group 3). Consecutive scans were retrospectively included from time frames during which the particular protocol was used. Group 1 included oncologic indications, and groups 2 and 3 infection or inflammation detection. Cardiac segments for which inflammation or infection foci had been confirmed on other imaging modalities were excluded from the analysis. (18)F-FDG uptake in normal myocardium was scored according to a scale ranging from 0 (uptake less than that in left ventricle blood pool) to 4 (diffuse uptake greater than that in liver). Adequate suppression was defined as uptake less than that in liver and without any focus (scores 0-2). RESULTS: Adequate suppression differed significantly between groups: 28% in group 1, 54% in group 2, and 88% in group 3 (P< 0.0001 for all comparisons). CONCLUSION: Single-dose heparin administration before (18)F-FDG PET in addition to a low-carbohydrate diet significantly outperforms a low-carbohydrate diet alone in adequately suppressing cardiac glucose metabolism.

Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial.

Aim Increasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF. Methods DIASTOLE is a multicentre, randomized controlled trial. Sixty patients, diagnosed with HFNEF and treated for hypertension, will be randomly allocated in a 1:1 ratio to undergo renal denervation on top of medical treatment (n = 30) or to maintain medical treatment alone (n = 30). The primary objective is to investigate the efficacy of pRDN by means of pulsed wave Doppler echocardiographic parameters. Secondary objectives include safety of pRDN and a comparison of changes in the following parameters after pRDN: LV mass, LV volume, LVEF, and left atrial volume as determined by magnetic resonance imaging. Also, MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure, heart rate variability, exercise capacity, and quality of life will be assessed. Perspective DIASTOLE is a randomized controlled trial evaluating renal denervation as a treatment option for HFNEF. The results of the current trial will provide important information regarding the treatment of HFNEF, and therefore may have major impact on future therapeutic strategies. Trail registration NCT01583881.

18F-FDG PET in squamous cell carcinoma of the oral cavity and oropharynx: a study on inter- and intraobserver agreement.

PURPOSE: Good observer agreement is mandatory for an effective imaging technique. However, little is known about the observer agreement of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in head and neck squamous cell carcinoma. The aim of the present study was to evaluate the inter- and intraobserver agreement of interpretations of (18)F-FDG PET in head and neck SCC and to assess the influence of observer experience, tumor localizing, and tumor size on the agreement. PATIENTS AND METHODS: (18)F-FDG PET scans of 80 patients with oral and oropharyngeal SCC were reassessed twice by 2 experienced nuclear medicine physicians and 2 residents in nuclear medicine. The absolute agreement and Cohen's kappa were calculated by comparing the results of the 4 observers for the primary tumor, cervical metastases, and distant metastases/second primary tumor. To analyze the sensitivity and specificity, the results were compared with the findings from the histologic specimens or the follow-up data. RESULTS: The interobserver agreement of the nuclear medicine physicians revealed an absolute agreement and kappa of 0.91 and 0.58 for detecting the primary tumor, 0.94 and 0.83 for detecting cervical metastases, and 0.85 and 0.53 for detecting distant metastases/second primary tumors, respectively. The intraobserver agreement was greater overall than the interobserver agreement. Compared with the nuclear medicine physicians, the residents scored lower in interobserver agreement. The interobserver agreement decreased when localizing the malignancy more precisely. The agreement and sensitivity increased with tumor size. However, for small metastases, a high observer agreement was found owing to the nondetection of these malignancies. CONCLUSIONS: Good inter- and intraobserver agreement in SCC in the oral cavity or oropharynx with (18)F-FDG PET was found. Observer experience had limited influence on observer agreement. However, the agreement level decreased when a more precise anatomic tumor localization was required.