Thresholds For Risk Stratification Research Articles

A generalized health index: automated thoracic CT-derived biomarkers predict life expectancy.

To identify image biomarkers associated with overall life expectancy from low-dose computed tomography and integrate them as an index for assessing an individual's health. Two categories of CT image features, body composition tissues and cardiopulmonary vasculature characteristics, were quantified from LDCT scans in the Pittsburgh Lung Screening Study cohort(n = 3,635). Cox proportional-hazards models identified significant image features which were integrated with subject demographics to predict the subject's overall hazard. Subjects were stratified using composite model predictions and feature-specific risk stratification thresholds. The model's performance was validated extensively, including 5-fold cross-validation on PLuSS baseline, PLuSS follow-up examinations, and the National Lung Screening Trial (NLST). The composite model had significantly improved prognostic ability compared to the baseline model (p < 0.01) with AUCs of 0.774 (95% CI: 0.757-0.792) on PLuSS, 0.723 (95% CI: 0.703-0.744) on PLuSS follow-up, and 0.681 (95% CI: 0.651-0.710) on the NLST cohort. The identified high-risk stratum were several times more likely to die, with mortality rates of 79.34% on PLuSS, 76.47% on PLuSS follow-up, and 46.74% on NLST. Two cardiopulmonary structures (intrapulmonary artery vein ratio, intrapulmonary vein density) and two body composition tissues (SM density, bone density) identified high-risk patients. Body composition and pulmonary vasculatures are predictive of an individual's health risk; their integrations with subject demographics facilitate the assessment of an individual's overall health status or susceptibility to disease. CT-computed body composition and vasculature biomarkers provide improved prognostic value. The integration of CT biomarkers and patient demographic information improves subject risk stratification.

Age and sex specific thresholds for risk stratification of cardiovascular disease and clinical decision making: prospective open cohort study

ObjectiveTo quantify the potential advantages of using 10 year risk prediction models for cardiovascular disease, in combination with risk thresholds specific to both age and sex, to identify individuals at...

Diagnostic Accuracy of American College of Radiology Thyroid Imaging Reporting Data System: A Single-center Cross-sectional Study.

This study aims to evaluate the diagnostic accuracy of the American College of Radiology Thyroid Imaging Reporting Data System (ACR TI-RADS) in identifying nodules that need to undergo fine-needle aspiration biopsy (FNAB) and identify specific thyroid ultrasound characteristics of nodules associated with thyroid malignancy in Filipinos in a single tertiary center. One hundred seventy-six thyroid nodules from 130 patients who underwent FNAB from January 2018 to December 2018 were included. The sonographic features were described and scored using the ACR TI-RADS risk classification system, and the score was correlated to their final cytopathology results. The calculated malignancy rates for TI-RADS 2 to TI-RADS 5 were 0%, 3.13%, 7.14%, and 38.23%, respectively, which were within the TI-RADS risk stratification thresholds. The ACR TI-RADS had a sensitivity of 89.5% and specificity of 54%, LR + of 1.95 and LR - of 0.194, NPV of 97.7%, PPV of 19.1%, and accuracy of 58%. The ACR TI-RADS may provide an effective malignancy risk stratification for thyroid nodules and may help guide the decision for FNAB among Filipino patients. The classification system may decrease the number of unnecessary FNABs for nodules with low-risk scores.

Identifying consistent echocardiographic thresholds for risk stratification in pulmonary arterial hypertension.

Several indices of right heart remodeling and function have been associated with survival in pulmonary arterial hypertension (PAH). Outcome analysis and physiological relationships between variables may help develop a consistent grading system. Patients with Group 1 PAH followed at Stanford Hospital who underwent right heart catheterization and echocardiography within 2 weeks were considered for inclusion. Echocardiographic variables included tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) fractional area change (RVFAC), free wall strain (RVFWS), RV dimensions, and right atrial volumes. The main outcome consisted of death or lung transplantation at 5 years. Mathematical relationships between variables were determined using weighted linear regression and severity thresholds for were calibrated to a 20% 1-year mortality risk. PAH patients (n = 223) had mean (SD) age of 48.1 (14.1) years, most were female (78%), with a mean pulmonary arterial pressure of 51.6 (13.8) mmHg and pulmonary vascular resistance index of 22.5(6.3) WU/m2. Measures of right heart size and function were strongly related to each other particularly RVFWS and RVFAC (R 2 = 0.82, p < 0.001), whereas the relationship between TAPSE and RVFWS was weaker (R 2 = 0.28, p < 0.001). Death or lung transplantation at 5 years occurred in 78 patients (35%). Guided by outcome analysis, we ascertained a uniform set of parameter thresholds for grading the severity of right heart adaptation in PAH. Using these quantitative thresholds, we, then, validated the recently reported REVEAL-echo score (AUC 0.68, p < 0.001). This study proposes a consistent echocardiographic grading system for right heart adaptation in PAH guided by outcome analysis.

BNP and NT-proBNP Thresholds for the Assessment of Prognosis in Patients Without Heart Failure

BackgroundBrain natriuretic peptide (BNP)/N-terminal-pro hormone brain natriuretic peptides (NT-proBNP) enable risk stratification, diagnosing, and monitoring of heart failure patients. An additional prognostic value for BNP/NT-proBNP in nonheart failure patients and general population cohorts is described in the literature, but specific cut-off levels are only described for heart failure patients. ObjectivesThis study aimed to determine thresholds for risk stratification in nonheart failure patients. MethodsBased on the Essen Coronary Artery Disease registry we excluded patients with known heart failure or elevated BNP/NT-pro BNP levels. The resulting cohort was divided into a derivation and validation cohort using random sampling. The prognostic value of BNP/NT-proBNP of incident mortality was evaluated in the derivation cohort using univariate and multivariable cox regression analysis. In receiver operating characteristic analysis and corresponding area under the curve the optimal threshold was determined using Youdens J index. The findings were verified in the validation cohort. ResultsA total of 3,690 patients (age 62.9 ± 12.5 years, 71% male, 68% patients with coronary artery disease) were included. During a mean follow-up of 2.6 ± 3.4 years (median 1.2 [IQR: 0.4-2.88]), 169 deaths of any cause occurred. Based on Youden’s J index, BNP-thresholds of 9.6 and 29pg/ml and NT-proBNP thresholds of 65 and 77pg/ml for men and women, respectively, were determined. BNP/NT-proBNP levels above these thresholds were associated with increased mortality in the derivation cohort (HR: 2.44 [95% CI: 1.32-4.53], P = 0.005). The predictive value was confirmed in the validation cohort (HR: 2.78 [95% CI: 1.26-6.14], P = 0.01). ConclusionsWe here describe sex-specific BNP/NT-proBNP thresholds that allow prediction of impaired survival in patients without heart failure, independent of traditional cardiovascular risk factors.

Digital PCR to Measure SARS-CoV-2 RNA, Variants, and Outcomes in Youth.

The role of SARS-CoV-2 viral load in predicting contagiousness, disease severity, transmissibility, and clinical decision-making continues to be an area of great interest. However, most studies have been in adults and have evaluated SARS-CoV-2 loads using cycle thresholds (Ct) values, which are not standardized preventing consistent interpretation critical to understanding clinical impact and utility. Here, a quantitative SARS-CoV-2 reverse-transcription digital PCR (RT-dPCR) assay normalized to WHO International Units was applied to children at risk of severe disease diagnosed with COVID-19 at St Jude Children's Research Hospital between March 28, 2020, and January 31, 2022. Demographic and clinical information from children, adolescents and young adults treated at St Jude Children's Research Hospital were abstracted from medical records. Respiratory samples underwent SARS-CoV-2 RNA quantitation by RT-dPCR targeting N1 and N2 genes, with sequencing to determine the genetic lineage of infecting virus. Four hundred and sixty-two patients aged 0-24 years (median 11 years old) were included during the study period. Most patients were infected by the omicron variant (43.72%), followed by ancestral strain (22.29%), delta (13.20%) and alpha (2.16%). Viral load at presentation ranged from 2.49 to 9.14 log10 IU/ml, and higher viral RNA loads were associated with symptoms (OR 1.32: CI95% 1.16-1.49) and respiratory disease (OR 1.23: CI95% 1.07-1.41). Viral load did not differ by SARS-CoV-2 variant, vaccination status, age, or baseline diagnosis. SARS-CoV-2 RNA loads predict the presence of symptomatic and respiratory diseases. The use of standardized, quantitative methods is feasible, allows for replication, comparisons across institutions, and has the potential to facilitate consensus quantitative thresholds for risk stratification and treatment.

Risk assessment and stratification of mild cognitive impairment among the Chinese elderly: attention to modifiable risk factors

BackgroundThe early identification of individuals at risk of mild cognitive impairment (MCI) has major public health implications for Alzheimer’s disease prevention.ObjectiveThis study aims to develop and validate a risk assessment...

Abstract 9320: Biological Sex as a Modifier of the Natural History of Dilated Cardiomyopathy

Introduction: Dilated cardiomyopathy (DCM) has a ~20% 5-year mortality rate. Understanding the impact of biological sex offers scope to improve outcomes. Objective: Investigate potential sex specific differences in the outcome of DCM. Methods: Prospective longitudinal observational cohort study of 604 patients (n=206 women, 398 men) with DCM confirmed by cardiac MRI. The median follow up for cardiovascular death, major heart failure and arrhythmic events was 3.9 years. Results: At baseline women had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less myocardial fibrosis and lower serum troponin concentrations (all p&lt;0.05, Table 1), with no difference in age at study enrolment or medication. Despite this favourable profile, within 2 years women had more primary outcome events than men (Figure) with Kaplan Meier estimates of 10.7% vs 5.1%; adjusted* hazard ratio 3.47, 95% CI 1.81 to 6.65, [*age, LVEF, troponin, LMNA , left atrial volume and myocardial fibrosis]. Between 2-5 years, men and women had similar outcomes (adjusted* HR 0.55; 0.17,1.78). An LVEF &lt;35% in men (HR 3.21, 1.67 to 6.18, C-statistic 0.647) but &lt;40% in women (HR 2.37, 1.05 to 5.36, C statistic 0.602) had the greatest discrimination for predicting outcome. Conclusions: Female sex is an adverse modifier of the early natural history of DCM. There is evidence for sex specific risk stratification thresholds. Sex should be considered a determining variable in DCM care.

COMPARISON OF PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE GUIDELINES BETWEEN AUSTRALIA, ENGLAND AND THE UNITED STATES

Objective: Background: Cardiovascular disease (CVD) primary prevention guidelines recommend absolute CVD risk estimation to guide lipid and blood pressure lowering therapy recommendations but these are inconsistent despite relying on similar evidence. This study aimed to understand the effect of such inconsistencies on the populations recommended for treatment according to CVD primary prevention guidelines in Australia, England and the United States. Design and method: Methods: Data were drawn from Australian(n = 3,942), English(n = 1,899) and United States(n = 2,949) national health surveys in adults aged 40 years or older. Participants were classified as recommended for therapy based on absolute CVD risk stratification and clinical characteristics denoting high risk according to each country's guidelines. Agreement was assessed by Kappa statistic. Results: Results: Agreement in therapy recommendation according to CVD primary prevention guidelines was minimal to weak (Kappa = 0.30–0.51). This reflected different populations being targeted due to different risk thresholds (risk calculation agreement Kappa = 0.07–0.45) and different clinical risk criteria (high risk characteristic agreement Kappa = 0.22–0.73). Conclusions: Conclusion: Despite a similar evidence base apparently underpinning guidance, there is very little agreement between populations targeted for CVD primary prevention in Australia, England and the United States. This disparity is driven by differences in both absolute CVD risk stratification thresholds and the clinical characteristics considered to denote high risk. Whilst different countries may adopt different policies on the appropriate level of risk to target, given a largely common evidence base, international consensus on how to define population CVD risk would allow optimum targeting of primary prevention.

New indicators for systematic assessment of aortic morphology: a narrative review.

In order to prevent the occurrence of aortic adverse events in ascending thoracic aortic aneurysm patients, preventive surgery is the sole option in case of large aneurysm. Identifying high-risk patients timely and accurately requires effective predictive indicators of aortic adverse events and accurate risk stratification thresholds. Absolute diameter measured after a single imaging examination, which has been used as the predictive indicator for decades, has been proved to be ineffective for risk stratification in moderately dilated aorta. Previously, new indicators combining absolute diameters with personalized parameters have been reported to show better predictive power of aortic adverse events than absolute diameters by correcting the effect of these parameters on the diameters. Meanwhile, combining three-dimensional parameters to formulate risk stratification thresholds not only may characterize the aortic risk morphology more precisely, but also predict aortic adverse events more accurately. These new indicators may provide more systematic assessment methods of patients’ risk, formulate more personalized intervention strategies for ascending thoracic aortic aneurysm patients, and also provide a basis for researchers to develop more accurate and effective risk thresholds. We also highlight that the algorithm obtained by combining multiple indicators may be a better choice compared with single indicator, but this still requires the support of more evidence. Due to the particularity of syndromic aortic disease, whether these new indicators can be used for its risk stratification is still uncertain. Therefore, the scope of this manuscript does not include this kind of disease.

Patient-Specific Metabolism Assessed By Visceral Fat and Diabetes May Alter Prognosis in Relapsed/Refractory Hodgkin Lymphoma

Background: Hodgkin lymphoma (HL) is a rare lymphoma that often affects young people, with a median age of diagnosis of 39. While the 5-year PFS rate for patients after front-line chemotherapy is 94.6%, those who relapse have a 50% to 60% rate of cure (Alinari and Blum, Blood 2016). We recently discovered that increased abdominal visceral fat normalized to subcutaneous fat (rVFA) is associated with poorer outcomes in females, but not males, with diffuse large B-cell lymphoma (DLBCL). (Teja e tal ASH 2018) Interestingly, increased body mass index overall has been found to be associated with favorable prognosis in DLBCL (Carson et al., Journal of Clinical Oncology 2012). The correlation between these findings and elevated fasting blood glucose further supports a relationship between metabolism and prognosis in lymphoma. Since HL patients are generally younger and healthier than DLBCL patients at diagnosis, we sought to determine if rVFA and other metabolic markers had similar prognostic value in relapsed/refractory HL patients. Methods: We conducted a retrospective study of 95 consecutively treated relapsed/refractory HL patients treated at Washington University in St. Louis, who presented with first relapse between 2004 and 2018. We recorded baseline clinical risk factors such as sex, age, BMI, IPI, diabetes status, extranodal sites at relapse, and duration of response to initial therapy. Treatment and response to therapy by PET/CT were also recorded. In 80 patients, pre-treatment CT images were available to determine areas of subcutaneous and visceral fat at the level of the umbilicus. These values were normalized to total fat to calculate rVFA (Nguyen Radiology, 2018). Thresholds for risk stratification and sex differences were obtained using Cutoff Finder (Budczies PLOS One 2012). Data was analyzed with SPSS. Results: Ninety-five patients were eligible for analysis (54M, 41F) and 50 (53%) had refractory disease to initial therapy. (Table 1) The overall response rate to salvage therapy was 77%. There was no significant difference in overall survival (OS) (p = 0.55) or progression-free survival (PFS) (p = 0.49) between males and females in our study. Patients with higher BMI at diagnosis had a trend towards inferior OS and PFS after relapse. Those with BMI&amp;lt;25 had a 5-year PFS and OS of 71% and 90% compared to the BMI ≥25 group with PFS and OS of 58% and 84% respectively (p=0.09). The five patients with type II diabetes had a significantly lower 5-year OS rate of 40% compared to 90% for non-diabetic patients (p&amp;lt;0.001). (Figure 1) Eighty patients had CT images available for rVFA analysis (45M, 35F). Both males and females had a median rVFA of 28%. Patients with rVFA greater than 34% had inferior OS after relapse (HR= 8.85, 95% CI: 2.38-32.93, p&amp;lt;0.001). When controlled for sex, rVFA threshold values above 36% and 27% predicted worse outcomes for males and females respectively (HR=2x109, 95% CI: 0- Inf, p=0.0048 for 0.36 threshold; HR= 8.86, 95% CI: 1.7- 46.16, p=0.0018 for 0.27 threshold). (Figure 1) Conclusion: In this cohort, elevated rVFA was associated with inferior OS in all patients with relapsed/refractory HL, which is consistent with our findings in DLBCL as well as other solid tumors. Our results also suggest an association between diabetes and HL prognosis. Given the association of increased BMI, rVFA, diabetes and poorer outcomes in our cohort, there may be an association between a patient's metabolism and prognosis in Hodgkin lymphoma. Further studies should be conducted to examine the relationship between metabolism and cancer prognosis in a larger cohort. Disclosures Bartlett: Seattle Genetics: Consultancy, Research Funding; Immune Design: Research Funding; Forty Seven: Research Funding; Millennium: Research Funding; Merck: Research Funding; BTG: Consultancy; Roche/Genentech: Consultancy, Research Funding; BMS/Celgene: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Acerta: Consultancy; Kite, a Gilead Company: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Autolus: Research Funding; ADC Therapeutics: Consultancy; Affimed Therapeutics: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ippolito:Vital Images, Inc: Research Funding. Mehta-Shah:Karyopharm Therapeutics: Consultancy; C4 Therapeutics: Consultancy; Verastem: Research Funding; Celgene: Research Funding; Genetech/Roche: Research Funding; Corvus: Research Funding; Bristol Myers-Squibb: Research Funding; Kyowa Hakko Kirin: Consultancy; Innate Pharmaceuticals: Research Funding.

EmPHasis-10 health-related quality of life score predicts outcomes in patients with idiopathic and connective tissue disease-associated pulmonary arterial hypertension: results from a UK multicentre study

Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure.1745 patients with idiopathic PAH (IPAH), drug-induced PAH (DPAH), heritable PAH (HPAH) (collectively “(I/D/H)PAH”), or connective tissue disease-associated PAH (CTD-PAH), who had completed emPHasis-10 questionnaires at one of six UK referral centres between 2014 and 2017, were identified. Correlations with exercise capacity and World Health Organization (WHO) functional class were assessed, and exploratory risk stratification thresholds were tested.Moderate correlations were seen between emPHasis-10 scores and 6-min walk distance (r=−0.546), incremental shuttle walk distance (r=−0.504) and WHO functional class (r=0.497) (all p<0.0001). Distribution of emPHasis-10 score differed significantly between each WHO functional class (all p<0.0001). On multivariate analysis, emPHasis-10 score, but not WHO functional class, was an independent predictor of mortality. In a risk stratification approach, scores of 0–16, 17–33 and 34–50 identified incident patients with 1-year mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO functional class III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis-10 scores had improved exercise capacity (p<0.0001) and patients who transitioned between risk groups demonstrated similar survival to patients originally in those risk groups.The emPHasis-10 score is an independent prognostic marker in patients with (I/D/H)PAH or CTD-PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity.

Intermountain chronic disease risk score (ICHRON) validation for prediction of incident chronic disease diagnoses in an australian primary prevention population

BackgroundThe Intermountain Chronic Disease Risk Score (ICHRON) is a primary prevention risk prediction tool that uses commonly ordered blood tests and is designed to be calculated by the electronic health record. ICHRON was highly predictive of 3-year chronic disease (ChrD) diagnosis in an internal validation; however, external validation is needed. MethodsICHRON was calculated among patients from a region of Australia using sex-specific weightings of age and components of the comprehensive metabolic panel and the complete blood count. Original ICHRON weightings and risk stratification thresholds from the US-based derivation at Intermountain Healthcare were used. ICHRON was evaluated as a predictor of an incident 3-year ChrD diagnosis (coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, stroke, dementia, diabetes, renal failure, chronic obstructive pulmonary disease, and peripheral vascular disease). ResultsA total 5,512 females (49.6 ± 19.2) and 3,461 males (53.0 ± 18.6) were studied. Among females, 50.3%, 33.7% and 16.0% were low, moderate, and high-risk, respectively; and for males, 39.6%, 35.0%, and 25.4%. Frequency of a 3-year ChrD diagnosis among females was 2.2%, 8.5%, and 15.9% for low, moderate, and high-risk groups, respectively, and 4.7%, 9.7%, and 20.0% among males. C-statistics were 0.726 (0.700, 0.752) for females and 0.694 (0.665, 0.724) for males. ConclusionICHRON predicted ChrD diagnosis at 3-years among an external, geographically distant validation cohort. These findings show the value of ICHRON for primary care patients in distinct locales. Additionally, electronic calculation of ICHRON empowers the clinical use of this tool to identify and differentially manage and treat high-risk patients.

Correlation Between Oncotype DX, PREDICT and the Nottingham Prognostic Index: Implications for the Management of Early Breast Cancer.

IntroductionBreast cancer remains the most common cancer diagnosis in the UK. The current clinical practice utilises two different types of modalities to estimate the prognosis, risk of recurrence and benefit from adjuvant chemotherapy treatment in patients with early breast cancer. The first set of modalities includes risk calculators based on clinicopathological features, e.g. PREDICT or the Nottingham Prognostic Index (NPI); the second includes genetic profiling of tumour tissue using Oncotype DX (ODX; Genomic Health, Redwood City, CA) testing. PREDICT, NPI and ODX stratify breast cancers into high-, intermediate- and low-risk categories to help guide adjuvant chemotherapy treatment decisions. This study compares PREDICT, NPI and ODX Recurrence Scores (RS), with the aim of assessing 1) the correlation between the RS for PREDICT, NPI and ODX and 2) whether early breast cancer patients are stratified into similar risk categories by all three modalities.MethodsThis retrospective study included early breast cancer patients treated at a National Health Service (NHS) hospital over a 12-month period (October 1, 2017 to September 30, 2018). Inclusion criteria: consecutive patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. All patients were discussed at the local multidisciplinary team (MDT) meeting and underwent ODX testing. Exclusion criteria: patients without ODX test scores; patients with an in-breast recurrence; patients who did not undergo a sentinel lymph node biopsy (SLNB); and patients with ductal carcinoma in situ (DCIS) only. NPI and PREDICT scores were calculated for each patient using online tools, and ODX data was obtained through Genomic Health and MDT records. Patients were risk-stratified into high, intermediate and low risk of recurrence groups based on their PREDICT, NPI and ODX scores. The thresholds for risk stratification were based on current practice, which is evidence-based. Correlations between PREDICT, NPI and ODX scores were analysed using Spearman's correlation coefficient.ResultsForty-six patients (mean age: 56 years), with a total of 57 early breast cancers, underwent ODX testing. Risk categories generated by PREDICT very strongly correlated with NPI for all patients (r=0.92; P<0.0001). However, the RS generated by ODX testing only strongly correlated for patients with low-risk PREDICT scores (r=0.51; P=0.0134), while no correlation between RS and PREDICT was observed for patients with intermediate- or high-risk PREDICT scores (r=-0.0064; P=0.9767). Similar results were seen between NPI and RS. Overall, only 19/46 (41.3%) patients had an RS which corresponded to PREDICT risk category, while 18/46 (39.1%) patients had an RS that indicated a higher risk of recurrence than PREDICT, and 9/46 (19.6%) patients had an RS indicating a lower risk of recurrence than PREDICT. Similar results were found when comparing RS and NPI.ConclusionThe risk of recurrence estimated by ODX in patients deemed low risk by PREDICT or NPI highly correlated, while no such correlation existed in patients with an estimated intermediate- or high-risk breast cancer. In PREDICT- or NPI-estimated intermediate- and high-risk patients, ODX provided valuable additional prognostic information to guide adjuvant treatment, while the potential avoidance of ODX testing in low-risk patients presents significant cost-savings.

Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality.Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making.Methods: Consecutive patients with PAH (n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort.Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m2 identified patients at low (<5%) and high (>10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37–54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality.Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH.

Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer

In cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple “high-risk” demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.

High-Sensitivity Troponin and the Application of Risk Stratification Thresholds in Patients With Suspected Acute Coronary Syndrome.

Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTnl) for risk stratification and the early rule-out of myocardial infarction, but multiple thresholds have been described. We evaluate the safety and effectiveness of risk stratification thresholds in patients with suspected acute coronary syndrome. Consecutive patients with suspected acute coronary syndrome (n=48 282) were enrolled in a multicenter trial across 10 hospitals in Scotland. In a prespecified secondary and observational analysis, we compared the performance of the limit of detection (<2 ng/L) and an optimized risk stratification threshold (<5 ng/L) using the Abbott high-sensitivity troponin I assay. Patients with myocardial injury at presentation, with ≤2 hours of symptoms or with ST-segment elevation myocardial infarction were excluded. The negative predictive value was determined in all patients and in subgroups for a primary outcome of myocardial infarction or cardiac death within 30 days. The secondary outcome was myocardial infarction or cardiac death at 12 months, with risk modeled using logistic regression adjusted for age and sex. In total, 32 837 consecutive patients (61±17 years, 47% female) were included, of whom 23 260 (71%) and 12,716 (39%) had hs-cTnl concentrations of <5 ng/L and <2 ng/L at presentation. The negative predictive value for the primary outcome was 99.8% (95% CI, 99.7%-99.8%) and 99.9% (95% CI, 99.8%-99.9%) in those with hs-cTnl concentrations of <5 ng/L and <2 ng/L, respectively. At both thresholds, the negative predictive value was consistent in men and women and across all age groups, although the proportion of patients identified as low risk fell with increasing age. Compared with patients with hs-cTnl concentrations of ≥5 ng/L but <99th centile, the risk of myocardial infarction or cardiac death at 12 months was 77% lower in those <5 ng/L (5.3% vs 0.7%; adjusted odds ratio, 0.23 [95% CI, 0.19-0.28]) and 80% lower in those <2 ng/L (5.3% vs 0.3%; adjusted odds ratio, 0.20 [95% CI, 0.14-0.29]). Use of risk stratification thresholds for hs-cTnl identify patients with suspected acute coronary syndrome and at least 2 hours of symptoms as low risk at presentation irrespective of age and sex. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer.

To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC). We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs). The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3months; 3-8.9months; 9-14. months; and ≥15months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15months were 9, 19, 40 and 50months, respectively. Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.

Multiinstitutional Analysis of Thyroid Nodule Risk Stratification Using the American College of Radiology Thyroid Imaging Reporting and Data System.

Guidelines for managing thyroid nodules are highly dependent on risk stratification based on sonographic findings. The purpose of this study is to evaluate the risk stratification system used by the American College of Radiology Thyroid Imaging Reporting and Data System (TIRADS). Patients with thyroid nodules who underwent sonography and fine-needle aspiration were enrolled in a multiinstitutional study. The sonographic nodule features evaluated in the study were composition, echogenicity, margins, and echogenic foci. Images were reviewed by two radiologists who were blinded to the results of cytologic analysis. Nodules were assigned points for each feature, and the points were totaled to determine the final TIRADS level (TR1-TR5). The risk of cancer associated with each point total and final TIRADS level was determined. A total of 3422 nodules, 352 of which were malignant, were studied. The risk of malignancy was closely associated with the composition, echogenicity, margins, and echogenic foci of the nodules (p < 0.0001, in all cases). An increased aggregate risk of nodule malignancy was noted as the TIRADS point level increased from 0 to 10 (p < 0.0001) and as the final TIRADS level increased from TR1 to TR5 (p < 0.0001). Of the 3422 nodules, 2948 (86.1%) had risk levels that were within 1% of the TIRADS risk thresholds. Of the 474 nodules that were more than 1% outside these thresholds, 88.0% (417/474) had a risk level that was below the TIRADS threshold. The aggregate risk of malignancy for nodules associated with each individual TIRADS point level (0-10) and each final TIRADS level (TR1-TR5) falls within the TIRADS risk stratification thresholds. A total of 85% of all nodules were within 1% of the specified TIRADS risk thresholds.

Abstract 16395: Comparing Cardiopulmonary Exercise Measures of Men and Women With HFrEF and Their Relationship to Prognosis: The Henry Ford HospITal CardioPulmonary Exercise Testing (FIT-CPET) Project

Introduction: Several cardiopulmonary exercise test (CPET) variables (e.g., peak oxygen consumption (VO2), ventilatory efficiency (VE-VCO2) slope, and % predicted peak VO2 (%pVO2)) are regularly used to estimate prognosis in patients with systolic heart failure (HFrEF). Although known sex differences in physiology (i.e., muscle mass, lung volume) result in lower peak VO2 values in healthy women vs. men, this influence on CPET variables and subsequent prognosis in patients with HFrEF is not well described. Purpose: Compare the peak VO2, VE-VCO2 slope and %pVO2 values in men and women that correspond to prognosis using the International Society of Heart Transplant (ISHT) reported North American 1 and 3-y cardiac transplant survival rates (i.e., 86% and 79%, respectively). Methods: Patients with a CPET between 1997 and 2010 were identified. HFrEF was confirmed through a manual query of the medical record. Deaths through December 2011 were identified from the National Death Index. Receiver operator characteristic (ROC) curves were developed for each CPET measure and the threshold values and area under the curve (AUC) values associated with 86% and 79% specificity for each sex were determined. Results: A total of 1,201 patients (33% female; 55% Black; 33% ischemic; age = 55 + 13 y; BMI = 31 +7 kg.m-2; EF = 22 + 9%) were included in this analysis. Specificity threshold values and the corresponding AUC, for each CPX variable, are shown in the Table. At 1-y there were 167 (14%) deaths with a 10% event rate for women and 16% for men. At 3-y there were 335 (31%) deaths with a 25% event rate for women and 35% for men. Conclusions: In this large, racially diverse population both peak VO2 and %pVO2 had clinically meaningful differences for risk stratification thresholds depending on sex. This was not true for VE-VCO2 slope. Clinical decisions regarding the need for advanced therapies such as transplant or ventricular assist devices, when based on peak VO2 or %pVO2, might consider the patient’s sex.