Non-invasive Risk Stratification Tool Research Articles

FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study

Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using ⁶⁸Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT). In this prospective observational pilot study, consecutive patients with IIM and participants without rheumatic conditions or ILD serving as a control group were recruited at the Medical University of Vienna, Austria, and underwent FAPi PET/CT imaging. Standard-of-care procedures including clinical examination, assessment of severity of dyspnoea, high-resolution computed tomography (HR-CT), and pulmonary function testing (PFT) were performed on all patients with IIM at baseline and for patients with IIM-ILD at follow-up of 12 months. Baseline pulmonary FAPi-uptake was assessed by the maximum (SUVmax) and mean (SUVmean) standardized uptake values (SUV) over the whole lung (wl). SUV was corrected for blood pool background activity and target-to-background ratios (TBR) were calculated. We compared pulmonary FAPi-uptake between patients with IIM-ILD and those without ILD, as well as controls, and correlated baseline FAP-uptake with standard diagnostic tools such as HR-CT and PFT. For predictive implications, we investigated whether patients with IIM and progressive ILD exhibited higher baseline FAPi-uptake compared to those with stable ILD. Metrics are reported as mean with standard deviation (±SD). Between November 16, 2021 and October 10, 2022, a total of 32 patients were enrolled in the study. Three participants from the control group were excluded due to cardiopulmonary disease. In individuals with IIM-ILD (n=14), wlTBRmax and wlTBRmean were significantly increased as compared with both non-ILD-IIM patients (n=5) and the control group (n=16): wlTBRmax: 2.06±1.04 vs. 1.04±0.22 (p=0.019) and 1.08±0.19 (p=0.0012) and wlTBRmean: 0.45±0.19 vs. 0.26±0.06 (p=0.025) and 0.27±0.07 (p=0.0024). Similar values were observed in wlTBRmax or wlTBRmean between non-ILD IIM patients and the control group. Patients with progressive ILD displayed significantly enhanced wlTBRmax and wlTBRmean values at baseline compared to patients with stable ILD: wlTBRmax: 1.30±0.31 vs. 2.63±1.04 (p=0.0084) and wlTBRmean: 0.32±0.08 vs. 0.55±0.19 (p=0.021). Strong correlations were found between FAPi-uptake and disease extent on HR-CT (wlTBRmax: R=0.42, p=0.07; wlTBRmean: R=0.56, p=0.013) and severity of respiratory symptoms determined by the New York Heart Association (NYHA) classification tool (wlTBRmax: R=0.52, p=0.022; wlTBRmean: R=0.59, p=0.0073). Further, pulmonary FAPi-uptake showed inverse correlation with forced vital capacity (FVC) (wlTBRmax: R=-0.56, p=0.012; wlTBRmean: R=-0.64, p=0.0033) and diffusing capacity of the lungs for carbon monoxide (DLCO) (wlTBRmax: R=-0.52, p=0.028; wlTBRmean: R=-0.68, p=0.0017). Our study demonstrates higher fibroblast activation in patients with IIM-ILD compared to non-ILD patients and controls. Intensity of pulmonary FAPi accumulation was associated with progression of ILD. Considering that this study was carried out on a small population, FAPi PET/CT may serve as a useful non-invasive tool for risk stratification of lung disease in IIM. The Austrian Research Fund.

Non-Contrast and Contrast-Enhanced Cardiac Computed Tomography Imaging in the Diagnostic and Prognostic Evaluation of Coronary Artery Disease.

In recent decades, cardiac computed tomography (CT) has emerged as a powerful non-invasive tool for risk stratification, as well as the detection and characterization of coronary artery disease (CAD), which remains the main cause of morbidity and mortality in the world. Advances in technology have favored the increasing use of cardiac CT by allowing better performance with lower radiation doses. Coronary artery calcium, as assessed by non-contrast CT, is considered to be the best marker of subclinical atherosclerosis, and its use is recommended for the refinement of risk assessment in low-to-intermediate risk individuals. In addition, coronary CT angiography (CCTA) has become a gate-keeper to invasive coronary angiography (ICA) and revascularization in patients with acute chest pain by allowing the assessment not only of the extent of lumen stenosis, but also of its hemodynamic significance if combined with the measurement of fractional flow reserve or perfusion imaging. Moreover, CCTA provides a unique incremental value over functional testing and ICA by imaging the vessel wall, thus allowing the assessment of plaque burden, composition, and instability features, in addition to perivascular adipose tissue attenuation, which is a marker of vascular inflammation. There exists the potential to identify the non-obstructive lesions at high risk of progression to plaque rupture by combining all of these measures.

Pulmonary artery pulsatility index in patients with tricuspid valve regurgitation: a simple non-invasive tool for risk stratification.

Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle in patients with TR and to investigate their association with outcomes. The pulmonary artery pulsatility index (PAPi) has emerged as a haemodynamic risk predictor in left heart disease and pulmonary hypertension (PH). Whether PAPi discriminates risk in unselected patients with greater than or equal to moderate TR is unknown. In 5079 patients with greater than or equal to moderate TR (regardless of aetiology) and PA systolic and diastolic pressures measured on their first echocardiogram, we compared all-cause mortality at 5 years based on the presence or absence of PH and PAPi levels. A total of 2741 (54%) patients had PH. The median PAPi was 3.0 (IQR 1.9, 4.4). Both the presence of PH and decreasing levels of PAPi were associated with larger right ventricles, worse right ventricular systolic function, higher NT-pro BNP levels, greater degrees of right heart failure, and worse survival. In a subset of patients who had an echo and right heart catheterization within 24 h, the correlation of non-invasive to invasive PA pressures and PAPi levels was very good (r = 0.76). In patients with greater than or equal to moderate TR with and without PH, lower PAPi is associated with right ventricular dysfunction, right heart failure, and worse survival. Incorporating PA pressure and PAPi may help stratify disease severity in patients with greater than or equal to moderate TR regardless of aetiology.

Prognostic value of cardiovascular magnetic resonance T1 mapping and extracellular volume fraction in nonischemic dilated cardiomyopathy

BackgroundHeart failure- (HF) and arrhythmia-related complications are the main causes of morbidity and mortality in patients with nonischemic dilated cardiomyopathy (NIDCM). Cardiovascular magnetic resonance (CMR) imaging is a noninvasive tool for risk stratification based on fibrosis assessment. Diffuse interstitial fibrosis in NIDCM may be a limitation for fibrosis assessment through late gadolinium enhancement (LGE), which might be overcome through quantitative T1 and extracellular volume (ECV) assessment. T1 and ECV prognostic value for arrhythmia-related events remain poorly investigated. We asked whether T1 and ECV have a prognostic value in NIDCM patients. MethodsThis prospective multicenter study analyzed 225 patients with NIDCM confirmed by CMR who were followed up for 2 years. CMR evaluation included LGE, native T1 mapping and ECV values. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE) which was divided in two groups: HF-related events and arrhythmia-related events. Optimal cutoffs for prediction of MACE occurrence were calculated for all CMR quantitative values. ResultsFifty-eight patients (26%) developed a MACE during follow-up, 42 patients (19%) with HF-related events and 16 patients (7%) arrhythmia-related events. T1 Z-score (p = 0.008) and global ECV (p = 0.001) were associated with HF-related events occurrence, in addition to left ventricular ejection fraction (p < 0.001). ECV > 32.1% (optimal cutoff) remained the only CMR independent predictor of HF-related events occurrence (HR 2.15 [1.14–4.07], p = 0.018). In the arrhythmia-related events group, patients had increased native T1 Z-score and ECV values, with both T1 Z-score > 4.2 and ECV > 30.5% (optimal cutoffs) being independent predictors of arrhythmia-related events occurrence (respectively, HR 2.86 [1.06–7.68], p = 0.037 and HR 2.72 [1.01–7.36], p = 0.049). ConclusionsECV was the sole independent predictive factor for both HF- and arrhythmia-related events in NIDCM patients. Native T1 was also an independent predictor in arrhythmia-related events occurrence. The addition of ECV and more importantly native T1 in the decision-making algorithm may improve arrhythmia risk stratification in NIDCM patients.Trial registration NCT02352129. Registered 2nd February 2015—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02352129

Validation of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from UK Biobank

BackgroundCurrently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, in which 10% 10-year CVD risk indicates clinical intervention. However, this benchmark has limited efficacy in clinical practice and the need for a more simple, non-invasive risk stratification tool is necessary. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aims to further validate our biomarker, Reti-CVD, (1) to detect risk group of ≥ 10% in 10-year CVD risk and (2) enhance risk assessment in individuals with QRISK3 of 7.5–10% (termed as borderline-QRISK3 group) using the UK Biobank.MethodsReti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of Reti-CVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding Reti-CVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups.ResultsAmong 48,260 participants with no history of CVD, 6.3% had CVD events during the 11-year follow-up. Reti-CVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.41; 95% confidence interval [CI], 1.30–1.52) with a 13.1% (95% CI, 11.7–14.6%) 10-year CVD risk in Reti-CVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in Reti-CVD-high-risk group (11.5% in non-statin cohort [n = 45,473], 11.5% in stage 1 hypertension cohort [n = 11,966], and 14.2% in middle-aged cohort [n = 38,941]). C statistics increased by 0.014 (0.010–0.017) in non-statin cohort, 0.013 (0.007–0.019) in stage 1 hypertension cohort, and 0.023 (0.018–0.029) in middle-aged cohort for CVD event prediction after adding Reti-CVD to QRISK3.ConclusionsReti-CVD has the potential to identify individuals with ≥ 10% 10-year CVD risk who are likely to benefit from earlier preventative CVD interventions. For borderline-QRISK3 individuals with 10-year CVD risk between 7.5 and 10%, Reti-CVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in adult groups that may be pre-disposed to CVD.

Investigating and modeling positron emission tomography factors associated with large cell transformation from low-grade lymphomas.

Low-grade lymphomas have a 1%-3% annual risk of transformation to a high-grade histology, and prognostic factors remain undefined. We set to investigate the role of positron emission tomography (PET) metrics in identification of transformation in a retrospective case-control series of patients matched by histology and follow-up time. We measured PET parameters including maximum standard uptake value (SUV-max) and total lesion glycolysis (TLG), and developed a PET feature and lactate dehydrogenase (LDH)-based model to identify transformation status within discovery and validation cohorts. For our discovery cohort, we identified 53 patients with transformation and 53 controls with a similar distribution of follicular lymphoma (FL). Time to transformation and control follow-up time was similar. We observed a significant incremental increase in SUV-max and TLG between control, pretransformation and post-transformation groups (P<0.05). By multivariable analysis, we identified a significant interaction between SUV-max and TLG such that SUV-max had highest significance for low volume cases (P=0.04). We developed a scoring model incorporating SUV-max, TLG, and serum LDH with improved identification of transformation (area under the curve [AUC]=0.91). Our model performed similarly for our validation cohort of 23 patients (AUC=0.90). With external and prospective validation, our scoring model may provide a specific and noninvasive tool for risk stratification for patients with low-grade lymphoma.

Abstract 11739: Cardiac Magnetic Resonance Imaging Derived Inferior Vena Cava Cross-Sectional Area Correlates With Measures of Fontan Associated Liver Disease

Background: There is currently no clear consensus on appropriate screening techniques to evaluate the presence or severity of Fontan-associated liver disease (FALD). Cardiac MRI (CMR) is used routinely for post-Fontan surveillance, but CMR-derived measures that relate to the severity of FALD are yet to be defined. Methods: This was a cross-sectional single-center study of post-Fontan patients who underwent a CMR. CMR exams were re-analyzed by a single pediatric cardiologist. The inferior vena cava cross-sectional area (CSA) was measured on CMR and indexed to height (indexed IVC-CSA). Other CMR measurements included ventricular volumes and systolic function, ascending aorta flow, Fontan CSA, and pulmonary artery CSA. Surrogates of FALD included Gamma-Glutamyl Transferase (GGT), Fibrosis-4 laboratory score (FIB-4), and imaging findings. Findings consistent with cirrhosis on liver ultrasound included increased liver echogenicity and/or nodularity. Statistical analyses were performed to investigate potential relationships between CMR parameters and markers of FALD. Results: Sixty-one patients were included. The median age was 2.7 years at the time of Fontan surgery and 17.0 years at the time of CMR. A larger indexed IVC-CSA was significantly associated with a higher FIB-4 score (Spearman’s ρ = 0.28, P = 0.04), a higher GGT level (Spearman’s ρ = 0.40, P = 0.02), and findings consistent with cirrhosis on liver ultrasound (OR 1.17, 95% CI: (1.01, 1.35), P = 0.04). None of the other measured CMR parameters were associated with markers of FALD. A larger indexed IVC-CSA on CMR was associated with higher systemic ventricle end-diastolic pressure (EDP) on cardiac catheterization (Spearman’s ρ = 0.39, P = 0.018) as well as older age (Spearman’s ρ = 0.46, P = &lt;0.001). Conclusions: A larger indexed IVC-CSA was the only finding on CMR that was associated with markers of FALD. This measure has the potential to serve as an additional non-invasive tool for risk stratification of FALD.

Abstract 10113: Validation of a Deep-Learning-Based Retinal Biomarker in the Prediction of Cardiovascular Disease: Data From UK Biobank

Introduction: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, with a benchmark of 10% for 10-year CVD risk determining clinical intervention. Yet, effects on clinical practice are limited and the barriers call for a simple, non-invasive risk stratification tool. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aimed to further validate our biomarker, Reti-CVD, 1) to detect risk group of ≥10% in 10-year CVD risk and 2 ) enhance risk assessment in individuals with QRISK3 of 7.5%-10% (termed as borderline-QRISK3 group) using the UK Biobank. Methods: RetiCVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of RetiCVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding RetiCVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. Results: Among 45,233 participants with no history of CVD, 6.7% had CVD events during the 11-year follow-up. RetiCVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.34 (95% confidence interval [CI], 1.26-1.42) with a 14.7% (95% CI, 13.6-15.9%) 10-year CVD risk in RetiCVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in RetiCVD-high-risk group (12.8% in non-statin cohort [n=16240], 11.5% in stage 1 hypertension cohort [n=5102], and 14.9% in middle-aged cohort [n=11,474]). C statistics increased by 0.013 (0.010-0.017) in non-statin cohort, 0.017 (0.010-0.024) in stage 1 hypertension cohort, and 0.022 (0.017-0.027) in middle-aged cohort for CVD event prediction after adding RetiCVD to QRISK3. Conclusion: RetiCVD has the potential to identify individuals with ≥10% 10-year CVD risk who are likely to benefit from earlier, upstream preventative CVD interventions. For borderline-QRISK3 individuals, RetiCVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in early vulnerable adult groups.

The crucial role of tricuspid regurgitation in patients with pulmonary arterial hypertension

Abstract Introduction Pulmonary arterial hypertension (PAH) is a rare and progressive disease with high morbidity and mortality rate and its prognosis is critically affected by right ventricle (RV) dysfunction. Several studies have demonstrated that the presence of moderate-severe tricuspid regurgitation (TR) is associated with poor prognosis in PAH. However, the echocardiographic correlates and the impact on functional capacity of significant TR in PAH patients have not been thoroughly investigated. Purpose The aims of this study were to confirm the prognostic role of moderate-to-severe TR in PAH patients and to assess the effects of significant TR on remodelling of right cardiac chambers evaluated by echocardiography and on exercise capacity determined by six minute-walking-test (6MWT) and cardiopulmonary exercise testing (CPET). Methods This study is a retrospective longitudinal analysis of 103 patients with newly diagnosed PAH enrolled from 2010 to march 2021. Patients with portopulmonary PAH and with congenital heart disease PAH were excluded. Median follow up (FU) was 27 months and the primary endpoint was all-cause mortality. Results Our cohort was characterised by high BNP mean values (382 pg/mL), poor exercise capacity (260 mt at 6MWT, peak VO2 11 mL/kg/min at CPET), right ventricular dysfunction and severe PH at right heart catheterization (cardiac index 2.3 L/min/mq, mean pulmonary artery pressure 48 mmHg, pulmonary vascular resistance 12 WU). Sixty-nine percent (70/103) of the cohort had significant TR. Thirty percent of patients (30/103) died during follow-up. At Cox univariate regression, moderate to severe TR was significantly associated with higher risk of death (HR 4.48, p=0.004) (Figure 1). At bivariate analysis combining TR grade and TAPSE/sPAP, significant TR showed to be associated with higher risk of death (HR 3.59, p=0.05). In particular, the combination of normal TAPSE and mild TR identified a subgroup of patients who had no events during the follow-up period (Figure 2). At echocardiography patients with moderate-to-severe TR had more peripheral venous congestion, worse right ventricular function (TAPSE and TAPSE/sPAP), lower stroke volume index. The presence of moderate-to-severe TR promoted negative remodelling of the right atrium and of the right ventricle, which was more spherical, hypertrophic and stiff. Exercise capacity of patient with significant TR was significantly reduced both at CPET and at 6MWT. Conclusions Moderate-to-severe tricuspid regurgitation is associated with poor exercise capacity (both at CPET and at 6MWT) and poor survival in patients with PAH. Echocardiography can easily detect morphological and functional abnormalities associated with a worse prognosis in patients with PAH and represents an important non-invasive tool for risk stratification. Funding Acknowledgement Type of funding sources: None.

Late ventricular potential for risk prediction of sudden cardiac death risk: a valuable tool or an unnecessary step?

Abstract Background/Introduction Signal-averaged electrocardiography (SA-ECG) is a high-resolution electrocardiography that can detect late ventricular potential, which known to be a noninvasive tool for risk stratification of sudden cardiac death (SCD) by predicting reentrant ventricular tachyarrhythmia. There is a paucity of data with SA-ECG on SCD survivors without structural heart disease, whereas majority of previous studies had been focused on post myocardial infarction survivors. Purpose This study assessed the clinical utility of SA-ECG as a risk stratification modality for lethal arrhythmic event in patients at risk of SCD without definite structural heart disease. Methods Total 629 patients who experienced or had potential risk of SCD were studied with SA-ECG. Among them, 48 patients who were found to have significant structural heart disease were excluded, except arrhythmogenic right ventricular cardiomyopathy. Major arrhythmic event (MAE) was defined as composite of all-cause death, aborted SCD, and sustained VT during any time either before visit of clinic or during follow up period. Syncope and non-sustained VT was defined as non-major arrhythmic event. SA-ECG was defined positive when fulfilling three or more criterion: (1) unfiltered QRS duration ≥114ms, (2) filtered QRS duration ≥114ms, (3) duration of terminal QRS &amp;lt;40uV exceeding 40ms, and (4) root mean square voltage in the terminal 40ms of ≤20ms. Results Among total 581 patients, 145 patients with positive SA-ECG showed higher incidence of MAE compared to patients with negative SA-ECG (21.4% vs. 6.7%, OR 3.816 [95% CI 2.208–6.597], p&amp;lt;0.001, Table). As the number of positive SA-ECG criteria increases, incidence of MAE tended to increase sequentially, which was markedly noted from 2 positive to 3 positive criteria (10.7% to 20.8%, p&amp;lt;0.001, Figure). In particular, patient with inherited arrhythmia showed higher rate of positive late potential compared to those with non-inherited arrhythmia (51.0% vs. 19.3%, p&amp;lt;0.001). Conclusion This study showed that at least 3 out of 4 diagnostic criteria in SA-ECG can independently predict lethal arrhythmic events and the positive late potential was associated with lethal arrhythmic event that leads to SCD, suggesting risk prediction for SCD using SA-ECG in patients even without structural heart disease including inherited arrhythmias. Funding Acknowledgement Type of funding sources: None.

A Noninvasive Risk Stratification Tool Build Using an Artificial Intelligence Approach for Colorectal Polyps Based on Annual Checkup Data.

Colorectal cancer is the leading cause of cancer-related deaths worldwide, and early detection has proven to be an effective method for reducing mortality. The machine learning method can be implemented to build a noninvasive stratifying tool that helps identify patients with potential colorectal precancerous lesions (polyps). This study aimed to develop a noninvasive risk-stratified tool for colorectal polyps in asymptomatic, healthy participants. A total of 20,129 consecutive asymptomatic patients who underwent a health checkup between January 2005 and August 2007 were recruited. Positive relationships between noninvasive risk factors, such as age, Helicobacter pylori infection, hypertension, gallbladder polyps/stone, and BMI and colorectal polyps were observed (p < 0.0001), regardless of sex, whereas significant findings were noted in men with tooth disease (p = 0.0053). A risk stratification tool was developed, for colorectal polyps, that considers annual checkup results from noninvasive examinations. For the noninvasive stratified tool, the area under the receiver operating characteristic curve (AUC) of obese females (males) aged <50 years was 91% (83%). In elderly patients (>50 years old), the AUCs of the stratifying tools were >85%. Our results indicate that the risk stratification tool can be built by using random forest and serve as an efficient noninvasive tool to identify patients requiring colonoscopy.

Multi-Parametric Magnetic Resonance Imaging-Based Radiomics Analysis of Cervical Cancer for Preoperative Prediction of Lymphovascular Space Invasion.

BackgroundDetection of lymphovascular space invasion (LVSI) in early cervical cancer (CC) is challenging. To date, no standard clinical markers or screening tests have been used to detect LVSI preoperatively. Therefore, non-invasive risk stratification tools are highly desirable.ObjectiveTo train and validate a multi-parametric magnetic resonance imaging (mpMRI)-based radiomics model to detect LVSI in patients with CC and investigate its potential as a complementary tool to enhance the efficiency of risk assessment strategies.Materials and MethodsThe model was developed from the tumor volume of interest (VOI) of 125 patients with CC. A total of 1037 radiomics features obtained from conventional magnetic resonance imaging (MRI), including a small field-of-view (sFOV) high-resolution (HR)-T2-weighted MRI (T2WI), apparent diffusion coefficient (ADC), T2WI, fat-suppressed (FS)-T2WI, as well as axial and sagittal contrast-enhanced T1-weighted MRI (T1c). We conducted a radiomics-based characterization of each tumor region using pretreatment image data. Feature selection was performed using the least absolute shrinkage and selection operator method on the training set. The predictive performance was compared with single variates (clinical data and single-layer radiomics signatures) analyzed using a receiver operating characteristic (ROC) curve. Three-fold cross-validation performed 20 times was used to evaluate the accuracy of the trained classifiers and the stability of the selected features. The models were validated by using a validation set.ResultsFeature selection extracted the six most important features (3 from sFOV HR-T2WI, 1 T2WI, 1 FS-T2WI, and 1 T1c) for model construction. The mpMRI-combined radiomics model (area under the curve [AUC]: 0.940) reached a significantly higher performance (better than the clinical parameters [AUC: 0.730]), including any single-layer model using sFOV HR-T2WI (AUC: 0.840), T2WI (AUC: 0.770), FS-T2WI (AUC: 0.710), ADC maps (AUC: 0.650), sagittal, and axial T1c values (AUC: 0.710, 0.680) in the validation set.ConclusionBiomarkers using multi-parametric radiomics features derived from preoperative MR images could predict LVSI in patients with CC.

Case Report: Arrhythmic Mitral Valve Prolapse–The Importance of Risk Stratification

Mitral valve prolapse (MVP) is a common condition that is generally regarded as benign, however specific sub-types can lead to serious events. Arrhythmic mitral valve prolapse (AMVP) is an important sub-type for clinicians to screen as it is a significant cause of sudden cardiac death (SCD) in young adults. AMVP hallmark imaging features include fibrosis of papillary muscles and inferobasal LV free wall. Cardiac MRI and/or electrophysiological (EP) studies allow for identification of these features and provide a promising non-invasive tool for risk stratification.

Validation of the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a novel HRCT-based radiomic classifier for indeterminate pulmonary nodules.

Implementation of low-dose chest computed tomography (CT) lung cancer screening and the ever-increasing use of cross-sectional imaging are resulting in the identification of many screen- and incidentally detected indeterminate pulmonary nodules. While the management of nodules with low or high pre-test probability of malignancy is relatively straightforward, those with intermediate pre-test probability commonly require advanced imaging or biopsy. Noninvasive risk stratification tools are highly desirable. We previously developed the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a conventional predictive radiomic model based on eight imaging features capturing nodule location, shape, size, texture and surface characteristics. Herein we report its external validation using a dataset of incidentally identified lung nodules (Vanderbilt University Lung Nodule Registry) in comparison to the Brock model. Area under the curve (AUC), as well as sensitivity, specificity, negative and positive predictive values were calculated. For the entire Vanderbilt validation set (n=170, 54% malignant), the AUC was 0.87 (95% CI 0.81-0.92) for the Brock model and 0.90 (95% CI 0.85-0.94) for the BRODERS model. Using the optimal cut-off determined by Youden's index, the sensitivity was 92.3%, the specificity was 62.0%, the positive (PPV) and negative predictive values (NPV) were 73.7% and 87.5%, respectively. For nodules with intermediate pre-test probability of malignancy, Brock score of 5-65% (n=97), the sensitivity and specificity were 94% and 46%, respectively, the PPV was 78.4% and the NPV was 79.2%. The BRODERS radiomic predictive model performs well on an independent dataset and may facilitate the management of indeterminate pulmonary nodules.

On-site assessment of computed tomography-derived fractional flow reserve in comparison with myocardial perfusion imaging and invasive fractional flow reserve

Myocardial perfusion imaging (MPI) using Single Photon Emission Computed Tomography has been established as a standard noninvasive tool for risk stratification of coronary artery disease (CAD). We evaluated the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR) in comparison with MPI using invasive fractional flow reserve (invasive FFR) as a gold standard. We enrolled 97 patients with suspected CAD. Diagnostic performance of CT angiography (CTA), and CT-FFR was compared in 105 lesions of 97 patients. Invasive FFR ≤ 0.8 was detected in 38 (36%) lesions. Diagnostic performance of CT-FFR was improved compared with CTA (AUC 0.83 vs. 0.60, p < 0.0001). The lesions with both CTA and MPI findings (n = 47), invasive FFR ≤ 0.8 was detected in 19 (40.4) lesions. CT-FFR (AUC 0.81, 95% CI 0.72-0.94) significantly improved diagnostic performance compared with CTA-50% (AUC 0.59, p = 0.00019) and MPI (AUC 0.64, p = 0.0082). In lesions with ≥ 50% on CTA (n = 42), diagnostic accuracy of CT-FFR (AUC 0.81) was significantly superior to MPI (AUC 0.64, p = 0.0239). In conclusions, CT-FFR improved diagnostic accuracy to detect invasive FFR ≤ 0.8 compared with luminal stenosis on CTA and ischemia on MPI. Patients with ≥ 50% stenosis on CTA would be the candidates for CT-FFR.

Electrocardiograms for cardiomyopathy risk stratification in children with anthracycline exposure

BackgroundEarly recognition of anthracycline-induced cardiomyopathy may reduce morbidity and mortality in children, but risk stratification tools are lacking. This study evaluates whether electrocardiogram (ECG) changes precede echocardiographic abnormalities in children with anthracycline-induced cardiomyopathy.MethodsWe performed a retrospective analysis of 589 pediatric cancer patients who received anthracyclines at a tertiary referral center. ECG endpoints were sum of absolute QRS amplitudes in the 6 limb leads (ΣQRS(6 L)) and corrected QT interval (QTc). Cardiomyopathy was defined by echocardiogram as ejection fraction < 50%, shortening fraction < 26%, or left ventricular end-diastolic diameter z-score > 2.5.ResultsMedian age at start of therapy was 7.8 years (IQR 3.7–13.6); median follow-up time was 3.6 years (IQR 1.1–5.8). 19.5% of patients met criteria for cardiomyopathy. Male sex, race, older age at first dose, and larger body surface area were associated with development of cardiomyopathy. A 0.6 mV decrease in ΣQRS(6 L) and 10 ms increase in QTc were associated with an increased risk of developing cardiomyopathy with hazard ratios of 1.174 (95% CI = 1.057–1.304, p = 0.003) and 1.098 (95%CI = 1.027–1.173, p = 0.006) respectively. Kaplan-Meier estimates showed a lower chance of cardiomyopathy-free survival for QTc ≥ 440 ms and ΣQRS(6 L) ≤ 3.2 mV over time. After controlling for confounders, total anthracycline dose predicted a decrease in ΣQRS(6 L) and an increase in QTc independent of cardiomyopathy status (p = 0.01 and p < 0.001 respectively). Cardiotoxic radiation did not predict changes in ECG parameters. Cardiomyopathy was associated with increased mortality (34% versus 12%, p < 0.001).ConclusionIn children receiving anthracyclines, decrease in ΣQRS(6 L) and QTc prolongation are associated with increased risk of developing cardiomyopathy. ECG is a potential non-invasive risk stratification tool for prediction of anthracycline-induced cardiomyopathy and requires prospective validation.

LBP-26-Magnetically controlled capsule endoscopy as a non-invasive tool for risk stratification of gastroesophageal varices in compensated cirrhosis (CHESS1801): A prospective multicenter study

LBP-26-Magnetically controlled capsule endoscopy as a non-invasive tool for risk stratification of gastroesophageal varices in compensated cirrhosis (CHESS1801): A prospective multicenter study

Automatic detection of T wave alternans using tensor decompositions in multilead ECG signals

Objective: T wave alternans (TWA) is a promising non-invasive risk stratification tool for sudden cardiac death which can be detected from surface ECG. This paper proposes a novel method to automatically detect TWA based on tensor decomposition methods. Approach: Two different tensor decomposition approaches are examined and compared, namely canonical polyadic decomposition and the more generalized variation PARAFAC2 which allows the T waves to shift in time. Results and Significance: Results on different artificial and clinical signals show that the presented methods are a robust and reliable way for TWA detection, and show the potential benefit of tensors in ECG signal processing.

216-73: QT/RR regression correlation coefficient as non-invasive risk stratification tool

216-73: QT/RR regression correlation coefficient as non-invasive risk stratification tool

Circulating Exosomes in Pancreatic Cancer: Will They Succeed on the Long, Littered Road to Early Detection Marker?

Pancreatic cancer is the fourth leading cause of cancer death in the US and is projected to be the second leading cause of cancer death by 2020. The high mortality of pancreatic ductal adenocarcinoma (PDAC),3 the most common form of pancreatic cancer, is largely a consequence of diagnosis at an advanced stage, when the tumor can no longer be surgically resected for cure. Nevertheless, symptoms rarely develop with early disease, and established risk factors for PDAC—tobacco smoking, obesity, personal history of chronic pancreatitis or diabetes, and family history of pancreatic cancer—are insufficient to risk-stratify the population to facilitate disease screening. Despite extensive research efforts and many potential candidates, no noninvasive biomarker has reached the clinic with utility for early detection of PDAC. Experimental studies indicate that more than a decade elapses from formation of the founder malignant clone to a patient's diagnosis, suggesting a window of opportunity for early detection. With this issue in mind, 2 recent studies have exposed new and interesting biology related to the release of exosomes from pancreatic tumors into peripheral blood (1, 2), raising the possibility of a noninvasive tool for risk stratification and earlier PDAC diagnosis. Exosomes are small, extracellular membrane–enclosed vesicles released from most cell types. Because they initially form from intracellular compartments, they contain nucleic acids and proteins, which can be transferred to other cells upon fusion with their extracellular membrane. Although the full spectrum of exosome biology remains to be defined, it is increasingly clear that exosomes are secreted from cancer cells at higher rates than from healthy cells and are important in facilitating cancer progression and spread (3). By use of proteomics, Melo et al. (1) compared exosomes secreted from cancer cell lines and nontumorigenic cells and identified glypican 1 (GPC1) as a membrane-bound protein preferentially present …