Predicting Significant Coronary Obstruction in a Population with Suspected Coronary Disease and Absence of Coronary Calcium: CORE-64 / CORE320 Studies. / Predição de Obstrução Coronariana Significativa em População com Suspeita de Doença Coronariana e Ausência de Cálcio Coronariano: CORE-64 e CORE320.

BACKGROUND: Coronary artery calcium (CAC) scanning can be performed using non-contrast computed tomography to predict cardiovascular events, but has less value for risk stratification in symptomatic patients. OBJECTIVE: To identify and validate predictors of significant coronary obstruction (SCO) in symptomatic patients without coronary artery calcification. METHODS: A total of 4,258 participants were screened from the CORE64 and CORE320 studies that enrolled patients referred for invasive angiography, and from the Quanta Registry that included patients referred for coronary computed tomography angiography (CTA). Logistic regression models evaluated associations between cardiovascular risk factors, CAC, and SCO. An algorithm to assess the risk of SCO was proposed for patients without CAC. Significance level of 5% was used in the analyses. RESULTS: Of the 509 participants of the CORE study, 117 (23%) had zero coronary calcium score; 13 (11%) patients without CAC had SCO. Zero calcium score was related to younger age, female gender, lower body mass index, no diabetes, and no dyslipidemia. Being a current smoker increased ~3.5 fold the probability of SCO and other CV risk factors were not significantly associated. Considering the clinical findings, an algorithm to further stratify zero calcium score patients was proposed and had a limited performance in the validation cohort (AUC 58; 95%CI 43, 72). CONCLUSION: A lower cardiovascular risk profile is associated with zero calcium score in a setting of high-risk patients. Smoking is the strongest predictor of SCO in patients without CAC.

FUNDAMENTO: A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. OBJETIVO: Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. MÉTODOS: Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. RESULTADOS: Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). CONCLUSÃO: Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

Predição de Obstrução Coronariana Significativa em População com Suspeita de Doença Coronariana e Ausência de Cálcio Coronariano: CORE-64 e CORE320 / Predicting Significant Coronary Obstruction in a Population with Suspected Coronary Disease and Absence of Coronary Calcium: CORE-64 / CORE320 Studies

Resumo Fundamento A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. Objetivo Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. Métodos Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. Resultados Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). Conclusão Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

Abstract Background Coronary artery calcium (CAC) scanning can be performed using non-contrast computed tomography to predict cardiovascular events, but has less value for risk stratification in symptomatic patients. Objective To identify and validate predictors of significant coronary obstruction (SCO) in symptomatic patients without coronary artery calcification. Methods A total of 4,258 participants were screened from the CORE64 and CORE320 studies that enrolled patients referred for invasive angiography, and from the Quanta Registry that included patients referred for coronary computed tomography angiography (CTA). Logistic regression models evaluated associations between cardiovascular risk factors, CAC, and SCO. An algorithm to assess the risk of SCO was proposed for patients without CAC. Significance level of 5% was used in the analyses. Results Of the 509 participants of the CORE study, 117 (23%) had zero coronary calcium score; 13 (11%) patients without CAC had SCO. Zero calcium score was related to younger age, female gender, lower body mass index, no diabetes, and no dyslipidemia. Being a current smoker increased ~3.5 fold the probability of SCO and other CV risk factors were not significantly associated. Considering the clinical findings, an algorithm to further stratify zero calcium score patients was proposed and had a limited performance in the validation cohort (AUC 58; 95%CI 43, 72). Conclusion A lower cardiovascular risk profile is associated with zero calcium score in a setting of high-risk patients. Smoking is the strongest predictor of SCO in patients without CAC.

Incidence and risk factors of contrast-induced nephropathy after transcatheter arterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate incidence and risk factors of contrast-induced nephropathy (CIN) after TACE in patients with HCC. METHODS: In this single-center retrospective study, we examined 461 consecutive TACE sessions in 260 patients between January 2003 and October 2015. CIN was defined as an increase in serum creatinine levels by ≥ 0.5 mg/dl or ≥ 25% from baseline within 72 h after TACE. We calculated incidence rate of CIN and tried to identify its risk factors by logistic regression analysis. RESULTS: Twenty-one cases of CIN (5%) were observed in 461 TACE sessions. One patient required subsequent hemodialysis transiently. In univariate analysis, tumor size > 5 cm [odds ratio (OR) 5.76, 95% confidence interval (CI) 2.34-14.14, p < 0.001], chronic kidney disease (OR 2.54, 95% CI 1.05-6.14, p = 0.04), serum hemoglobin level [OR 0.79 (per 1 g/dl increase), 95% CI 0.64-0.98, p = 0.03] and serum albumin level [OR 0.44 (per 1 g/dl increase), 95% CI 0.19-1.02, p = 0.05] were associated with the development of CIN. Stepwise logistic regression methods showed that tumor size > 5 cm (OR 7.81, 95% CI 2.99-20.46, p < 0.001) and serum albumin [OR 0.29 (per 1 g/dl increase), 95% CI 0.11-0.75, p = 0.01] were risk factors of CIN. CONCLUSIONS: In this study, HCC tumor size and lower serum albumin level were independent predictors of CIN after TACE.

Comparative Effectiveness of CT-Derived Atherosclerotic Plaque Metrics for Predicting Myocardial Ischemia.

OBJECTIVES: This study sought to investigate the performance of various cardiac computed tomography (CT)-derived atherosclerotic plaque metrics for predicting provocable myocardial ischemia. BACKGROUND: The association of coronary arterial diameter stenosis with myocardial ischemia is only modest, but cardiac CT provides several other, readily available atherosclerosis metrics, which may have incremental value. METHODS: The study analyzed 873 nonstented coronary arteries and their myocardial perfusion territories in 356 patients (mean 62 years of age) enrolled in the CORE320 (Coronary Artery Evaluation using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) study. Myocardial perfusion defects in static CT perfusion imaging were graded at rest and after adenosine in 13 myocardial segments using a 4-point scale. The summed difference score was calculated by subtracting the summed rest score from the summed stress score. Reversible ischemia was defined as summed difference score ≥1. In a sensitivity analysis, results were also provided using single-photon emission computed tomography (SPECT) as the reference standard. Vessel based predictor variables included maximum percent diameter stenosis, lesion length, coronary calcium score, maximum cross-sectional calcium arc, percent atheroma volume (PAV), low-attenuation atheroma volume, positive (external) vascular remodeling, and subjective impression of "vulnerable plaque." The study used logistic regression models to assess the association of plaque metrics with myocardial ischemia. RESULTS: In univariate analysis, all plaque metrics were associated with reversible ischemia. In the adjusted logistic model, only maximum percent diameter stenosis (1.26; 95% confidence interval: 1.15 to 1.38) remained an independent predictor. With SPECT as outcome variable, PAV and "vulnerable" plaque remained predictive after adjustment. In vessels with intermediate stenosis (40% to 70%), no single metric had clinically meaningful incremental value. CONCLUSIONS: Various plaque metrics obtained by cardiac CT predict provocable myocardial ischemia by CT perfusion imaging through their association with maximum percent stenosis, while none had significant incremental value. With SPECT as reference standard, PAV and "vulnerable plaque" remained predictors of ischemia after adjustment but the predictive value added to stenosis assessment alone was small.

Association of early left ventricular dysfunction with advanced magnetic resonance white matter and gray matter brain measures: The CARDIA study.

INTRODUCTION: Relations between heart failure and clinically manifested stroke are well known, but the associations between heart and brain early abnormalities are not totally clear. AIMS: We explore relations of subclinical brain abnormalities with early cardiac dysfunction in a large healthy middle-aged biracial cohort. METHODS: The CARDIA study enrolled 5115 young adults aged 18-30 years at baseline (1985-1986). We assessed 719 Caucasian and African American participants of the CARDIA study, with echocardiograms and brain MRI at follow-up year 25 (2010-2011). Echocardiography assessed aortic root diameter; LVEF; circumferential, longitudinal, and radial deformation. Cerebral MRI DTI, and, on a subset, ASL perfusion sequences were used to assess white matter fractional anisotropy and gray matter cerebral blood flow (CBF). Linear regression explored relations between cardiac parameters and cerebral measures, adjusting for anthropometrics, risk factors, and brain constitutional variation. RESULTS: Mean age 50 ± 4 years, SBP 118 ± 15 mm Hg; 60% white, and 48% men. Mean CBF was 46 ± 9 mL/100 g/min, and white matter fractional anisotropy was 0.31 ± 0.02. Worse circumferential deformation and larger aortic root were related to worse white matter fractional anisotropy. Worse radial systolic deformation was related to worse CBF in multivariable models. LVEF did not relate to early brain abnormalities. CONCLUSIONS: In spite of no apparent effect of LV ejection fraction, early subclinical cardiac dysfunction and brain abnormalities are present and associated in middle-aged generally healthy individuals.

Association of serum leptin with future left ventricular structure and function: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND/OBJECTIVES: Earlier studies differ on whether serum leptin is associated with adverse or beneficial cardiac structure. We determined the association between serum leptin with subsequent cardiac structure and function. METHODS: MESA is a multicenter longitudinal study of Black, White, Hispanic and Asian-American men and women. Cardiac MRI (CMR) was completed 6 to 8 years after leptin was measured. Left ventricular (LV) mass and volumes were indexed to body surface area. Multivariable linear regression models were constructed to assess the associations between leptin and risk factor adjusted (age, race, gender, systolic blood pressure, anti-hypertensive usage, LDL, HDL, hyperlipidemia medication usage, diabetes, diabetic medication usage, chronic kidney disease, alcohol and tobacco use, adiponectin and BMI) CMR variables. RESULTS: Relative to participants in the lowest quintile of leptin concentration, participants in the highest quintile had a lower risk factor adjusted LV mass (-14 g), LV mass index (-9 g/m(2)), LV end diastolic volume index (LVEDVi) (-7 ml/m(2)), LV end systolic volume index (LVESVi) (-3 ml/m(2)) and stroke volume (-5 ml) (all p≤0.05). On regression analysis, a doubling of leptin concentration was associated with lower LV mass (-2.5 g ± 0.7 g), LV mass index (-1.7 ± 0.3g/m(2)), LVEDVi (-1.5 ± 0.4 ml/m(2)), LVESVi (-0.7 ± 0.2 ml/m(2)) and stroke volume (-1.0 ± 0.5 ml) (all p ≤ 0.05). CONCLUSIONS: Higher leptin was associated with more favorable subsequent cardiac structure. Further study is needed to assess the prognostic and therapeutic implications of these observations.

Association of obesity in early adulthood and middle age with incipient left ventricular dysfunction and structural remodeling: the CARDIA study (Coronary Artery Risk Development in Young Adults).

OBJECTIVES: The goal of this study was to investigate the relationship of body mass index (BMI) and its 25-year change to left ventricular (LV) structure and function. BACKGROUND: Longstanding obesity may be associated with clinical cardiac dysfunction and heart failure. Whether obesity relates to cardiac dysfunction during young adulthood and middle age has not been investigated. METHODS: The CARDIA (Coronary Artery Risk Development in Young Adult) study enrolled white and black adults ages 18 to 30 years in 1985 to 1986 (Year-0). At Year-25, cardiac function was assessed by conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). Twenty-five-year change in BMI (classified as low: <27 kg/m(2) and high: ≥27 kg/m(2)) was categorized into 4 groups (Low-Low, High-Low, Low-High, and High-High). Multiple linear regression was used to quantify the association between categorical changes in BMI (Low-Low as reference) with LV structural and functional parameters obtained in middle age, adjusting for baseline and 25-year change in risk factors. RESULTS: The mean BMI was 24.4 kg/m(2) in 3,265 participants included at Year-0. Change in BMI adjusted for risk factors was directly associated with incipient myocardial systolic dysfunction assessed by STE (High-High: ß-coefficient = 0.67; Low-High: ß-coefficient = 0.35 for longitudinal peak systolic strain) and diastolic dysfunction assessed by TDI (High-High: ß-coefficient = -074; Low-High: ß-coefficient = -0.45 for e') and STE (High-High: ß-coefficient = -0.06 for circumferential early diastolic strain rate). Greater BMI was also significantly associated with increased LV mass/height (High-High: ß-coefficient = 26.11; Low-High: ß-coefficient = 11.87). CONCLUSIONS: Longstanding obesity from young adulthood to middle age is associated with impaired LV systolic and diastolic function assessed by conventional echocardiography, TDI, and STE in a large biracial cohort of adults age 43 to 55 years.

Association of early adult modifiable cardiovascular risk factors with left atrial size over a 20-year follow-up period: the CARDIA study.

OBJECTIVES: We investigate how early adult and 20-year changes in modifiable cardiovascular risk factors (MRF) predict left atrial dimension (LAD) at age 43-55 years. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled black and white adults (1985-1986). We included 2903 participants with echocardiography and MRF assessment in follow-up years 5 and 25. At years 5 and 25, LAD was assessed by M-mode echocardiography, then indexed to body surface area (BSA) or height. Blood pressure (BP), body mass index (BMI), heart rate (HR), smoking, alcohol use, diabetes and physical activity were defined as MRF. Associations of MRF with LAD were assessed using multivariable regression adjusted for age, ethnicity, gender and year-5 left atrial (LA) size. RESULTS: The participants were 30±4 years; 55% white; 44% men. LAD and LAD/height were modest but significantly higher over the follow-up period, but LAD/BSA decreased slightly. Increased baseline and 20-year changes in BP were related to enlargement of LAD and indices. Higher baseline and changes in BMI were also related to higher LAD and LAD/height, but the opposite direction was found for LAD/BSA. Increase in baseline HR was related to lower LAD but not LAD indices, when only baseline covariates were included in the model. However, baseline and 20-year changes in HR were significantly associated to LA size. CONCLUSIONS: In a biracial cohort of young adults, the most robust predictors for LA enlargement over a 20-year follow-up period were higher BP and BMI. However, an inverse direction was found for the relationship between BMI and LAD/BSA. HR showed an inverse relation to LA size.

Asymptomatic insulinoma: a case report and autopsy series.

AIMS: We investigated the prevalence and characterization of asymptomatic pancreatic tumors in response to our experience of asymptomatic insulinoma. METHODS: A patient with a moderately low glucose level and pancreatic incidentaloma detected by CT was examined. Pancreas specimens from 423 autopsy cases were also pathologically examined systematically by hematoxylin-eosin staining. RESULTS: The examined patient showed no profile characteristic of insulinoma by fasting or loading tests, however, ASVS led to diagnosis of insulin-producing tumor. The tumor was resected with the pancreatic body and tail and revealed to be 10 mm in diameter, with 98.5% of the cells positive for insulin. Pathological evaluation confirmed a well-differentiated endocrine pancreatic tumor, which was suggestive of an incidentally detected asymptomatic insulinoma. Microscopic evaluations of pancreatic specimens from 423 autopsy cases revealed pancreatic monotonous lesions in 6 cases (1.42%). In 4 autopsy specimens large enough for immuno-histochemical evaluation, the lesions were positive for glucagon but negative for insulin. CONCLUSIONS: As concerns the present study, retrospective immunohistochemical investigation in autopsy cases revealed the presence of asymptomatic glucagonoma but no asymptomatic insulinoma. Advances in diagnostic imaging, however, might raise the probability of detecting early asymptomatic stages of insulinoma incidentally. ASVS appears to be sensitive even for asymptomatic incidental insulinomas.

Impact of coronary calcium on outcome following sirolimus-eluting stent implantation.

There remain a small but sizable number of patients who develop restenosis after sirolimus-eluting stent (SES) implantation. However, the cause of SES restenosis has not been fully elucidated. The study population consisted of 52 patients with 69 lesions who underwent noninvasive coronary imaging by 64-slice multidetector computed tomography before SES deployment. Agatston calcium scores in target lesions were measured. All patients underwent follow-up coronary angiography at 8 months. Three coronary segments (in stent, proximal edge, and distal edge) were analyzed by quantitative coronary angiography. Agatston calcium score in target lesions averaged 214.7. Late lumen losses in the proximal edge, stent, and distal edge were 0.16 ± 0.45, 0.47 ± 0.58, and 0.07 ± 0.29 mm, respectively. Lesions with restenosis at follow-up showed a trend to produce higher preprocedural calcium scores (629) compared to those without restenosis (153, p = 0.08). There was a significant positive correlation between lesion calcium score and in-stent late lumen loss (r = 0.47, p <0.01). In conclusion, assessment of coronary calcium by multidetector computed tomography might be useful to predict outcomes after SES implantation.