Thomas Mayrhofer

High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial.

BACKGROUND It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain. OBJECTIVES The primary aim of this study was to determine whether high-risk plaque features, as detected by CTA in the emergency department (ED), may improve diagnostic certainty of ACS independently and incrementally to the presence of significant CAD and clinical risk assessment in patients with acute chest pain but without objective evidence of myocardial ischemia or myocardial infarction (MI). METHODS We included patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial. Readers assessed coronary CTA qualitatively for the presence of nonobstructive CAD (1% to 49% stenosis), significant CAD (≥50% or ≥70% stenosis), and the presence of at least 1 of the high-risk plaque features (positive remodeling, low <30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic regression analysis, we determined the association of high-risk plaque with ACS (MI or unstable angina pectoris) during the index hospitalization and whether this was independent of significant CAD and clinical risk assessment. RESULTS Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image quality (mean age 53.9 ± 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5; unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%; nonobstructive CAD in 217 patients [46.0%] and significant CAD with ≥50% stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95% CI: 1.8 to 43.3; p = 0.006) after adjustment for ≥50% stenosis (OR: 38.6; 95% CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of cardiovascular risk factors). Similar results were observed after adjustment for ≥70% stenosis. CONCLUSIONS In patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin, presence of high-risk plaques on coronary CTA increased the likelihood of ACS independent of significant CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).

High-Risk Coronary Plaque at Coronary CT Angiography Is Associated with Nonalcoholic Fatty Liver Disease, Independent of Coronary Plaque and Stenosis Burden: Results from the ROMICAT II Trial

PURPOSE To determine the association between nonalcoholic fatty liver disease (NAFLD) and the presence of high-risk coronary atherosclerotic plaque as assessed with coronary computed tomographic (CT) angiography. MATERIALS AND METHODS This study was approved by the local ethics committees; informed consent was obtained. Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial Infarction using Computer Assisted Tomography, or ROMICAT, II trial who underwent both nonenhanced CT to assess calcium score and contrast material-enhanced coronary CT angiography were included. Readers assessed coronary CT angiography images for the presence of coronary plaque, significant stenosis (≥50%), and high-risk plaque features (positive remodeling, CT attenuation < 30 HU, napkin-ring sign, spotty calcium). NAFLD was defined as hepatic steatosis at nonenhanced CT (liver minus spleen CT attenuation < 1 HU) without evidence of clinical liver disease, liver cirrhosis, or alcohol abuse. To determine the association between high-risk plaque and NAFLD, univariable and multivariable logistic regression analyses were performed, with high-risk plaque as a dependent variable and NAFLD, traditional risk factors, and extent of coronary atherosclerosis as independent variables. RESULTS Overall, 182 (40.9%) of 445 patients had CT evidence of NAFLD. High-risk plaque was more frequent in patients with NAFLD than in patients without NAFLD (59.3% vs 19.0%, respectively; P < .001). The association between NAFLD and high-risk plaque (odds ratio, 2.13; 95% confidence interval: 1.18, 3.85) persisted after adjusting for the extent and severity of coronary atherosclerosis and traditional risk factors. CONCLUSION NAFLD is associated with advanced high-risk coronary plaque, independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease.

Bronchobiliary fistula after hemihepatectomy : cholangiopancreaticography, computed tomography and magnetic resonance cholangiography findings

A bronchobiliary fistula (BBF), which is defined by an abnormal communication between the biliary system and the bronchial tree, is an uncommon complication after hemihepatectomy, trauma, hydatid disease, choledocholithiasis and other causes of biliary obstruction. We report the case of a 56-year-old man with colon cancer, who developed a BBF 2 months after right hemihepatectomy for liver metastases. The findings at endoscopic retrograde cholangiopancreaticography (ERCP), computed tomography (CT) and magnetic resonance cholangiography (MRC) included a stricture of the common bile duct and biliary leakage from the liver resection plane with biliary infiltration of the right lower lobe of the lung. The patient was treated successfully by endoscopic insertion of a biliary plastic stent which bridged the stricture and lead to closure of the fistula.

Computed tomography-based high-risk coronary plaque score to predict acute coronary syndrome among patients with acute chest pain--Results from the ROMICAT II trial.

BACKGROUND Coronary computed tomography angiography (CTA) can be used to detect and quantitatively assess high-risk plaque features. OBJECTIVE To validate the ROMICAT score, which was derived using semi-automated quantitative measurements of high-risk plaque features, for the prediction of ACS. MATERIAL AND METHODS We performed quantitative plaque analysis in 260 patients who presented to the emergency department with suspected ACS in the ROMICAT II trial. The readers used a semi-automated software (QAngio, Medis medical imaging systems BV) to measure high-risk plaque features (volume of <60HU plaque, remodeling index, spotty calcium, plaque length) and diameter stenosis in all plaques. We calculated a ROMICAT score, which was derived from the ROMICAT I study and applied to the ROMICAT II trial. The primary outcome of the study was diagnosis of an ACS during the index hospitalization. RESULTS Patient characteristics (age 57 ± 8 vs. 56 ± 8 years, cardiovascular risk factors) were not different between those with and without ACS (prevalence of ACS 7.8%). There were more men in the ACS group (84% vs. 59%, p = 0.005). When applying the ROMICAT score derived from the ROMICAT I trial to the patient population of the ROMICAT II trial, the ROMICAT score (OR 2.9, 95% CI 1.4-6.0, p = 0.003) was a predictor of ACS after adjusting for gender and ≥ 50% stenosis. The AUC of the model containing ROMICAT score, gender, and ≥ 50% stenosis was 0.91 (95% CI 0.86-0.96) and was better than with a model that included only gender and ≥ 50% stenosis (AUC 0.85, 95%CI 0.77-0.92; p = 0.002). CONCLUSIONS The ROMICAT score derived from semi-automated quantitative measurements of high-risk plaque features was an independent predictor of ACS during the index hospitalization and was incremental to gender and presence of ≥ 50% stenosis.

hs-Troponin I Followed by CT Angiography Improves Acute Coronary Syndrome Risk Stratification Accuracy and Work-Up in Acute Chest Pain Patients: Results From ROMICAT II Trial

OBJECTIVES This study compared diagnostic accuracy of conventional troponin/traditional coronary artery disease (CAD) assessment and highly sensitive troponin (hsTn) I/advanced CAD assessment for acute coronary syndrome (ACS) during the index hospitalization. BACKGROUND hsTnI and advanced assessment of CAD using coronary computed tomography angiography (CTA) are promising candidates to improve the accuracy of emergency department evaluation of patients with suspected ACS. METHODS We performed an observational cohort study in patients with suspected ACS enrolled in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia using Computer Assisted Tomography) trial and randomized to coronary CTA who also had hsTnI measurement at the time of the emergency department presentation. We assessed coronary CTA for traditional (no CAD, nonobstructive CAD, ≥50% stenosis) and advanced features of CAD (≥50% stenosis, high-risk plaque features: positive remodeling, low <30-Hounsfield units plaque, napkin-ring sign, spotty calcium). RESULTS Of 160 patients (mean age: 53 ± 8 years, 40% women) 10.6% were diagnosed with ACS. The ACS rate in patients with hsTnI below the limit of detection (n = 9, 5.6%), intermediate (n = 139, 86.9%), and above the 99th percentile (n = 12, 7.5%) was 0%, 8.6%, and 58.3%, respectively. Absence of ≥50% stenosis and high-risk plaque ruled out ACS in patients with intermediate hsTnI (n = 87, 54.4%; ACS rate 0%), whereas patients with both ≥50% stenosis and high-risk plaque were at high risk (n = 13, 8.1%; ACS rate 69.2%) and patients with either ≥50% stenosis or high-risk plaque were at intermediate risk for ACS (n = 39, 24.4%; ACS rate 7.7%). hsTnI/advanced coronary CTA assessment significantly improved the diagnostic accuracy for ACS as compared to conventional troponin/traditional coronary CTA (area under the curve 0.84, 95% confidence interval [CI]: 0.80 to .88 vs. 0.74, 95% CI: 0.70 to 0.78; p < 0.001). CONCLUSIONS hsTnI at the time of presentation followed by early advanced coronary CTA assessment improves the risk stratification and diagnostic accuracy for ACS as compared to conventional troponin and traditional coronary CTA assessment. (Multicenter Study to Rule Out Myocardial Infarction/Ischemia by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).

Sensitive troponin assays in patients with suspected acute coronary syndrome: Results from the multicenter rule out myocardial infarction using computer assisted tomography II trial

BACKGROUND Sensitive troponin (Tn) assays have been developed for the evaluation of patients with suspected acute coronary syndrome (ACS). We sought to compare the performance of a commercially available sensitive Tn I (sTnI) and precommercial highly sTnI (hsTnI) method to conventional Tn (cTn) assays. METHODS Among patients with acute chest pain but normal cTn in the emergency department of 6 centers, sTnI and hsTnI were measured at baseline, 2 and 4 hours after presentation. Diagnostic accuracy of sTnI and hsTnI relative to cTn for diagnosis during index hospitalization as well as their associations with coronary artery disease in patients randomized to coronary computed tomographic angiography (CTA) was assessed. RESULTS Overall, 322 patients were enrolled, of whom 161 had a CTA; 28 had ACS (8.7%), including 21 with unstable angina pectoris (UAP). Both sTnI and hsTnI values at baseline and second draw had significantly higher sensitivity for ACS and UAP than cTn and had significantly greater area under the receiver operator characteristic curve than cTn at first and second draws. Compared with cTn, 29% of ACS cases previously categorized as UAP were reclassified to acute myocardial infarction with sTnI or hsTnI. An hsTnI below limit of detection had 100% negative predictive value for ACS or significant coronary artery stenosis in those randomized to CTA. CONCLUSIONS In patients with acute chest discomfort, use of sTnI and hsTnI methods led to significant improvement in the early diagnostic accuracy for ACS, reclassifying one-third of UAP to myocardial infarction. Very low values for hsTnI excluded underlying coronary artery disease.

Risk preferences: consequences for test and treatment thresholds and optimal cutoffs.

Risk attitudes include risk aversion as well as higher-order risk preferences such as prudence and temperance. This article analyzes the effects of such preferences on medical test and treatment decisions, represented either by test and treatment thresholds or—when the test result is not given—by optimal cutoff values for diagnostic tests. For a risk-averse decision maker, effective treatment is a risk-reducing strategy since it prevents the low health outcome of forgoing treatment in the sick state. Compared with risk neutrality, risk aversion thus lowers both the test and the treatment threshold and decreases the optimal test cutoff value. Risk vulnerability, which combines risk aversion, prudence, and temperance, is relevant if there is a comorbidity risk: thresholds and optimal cutoff values decrease even more. Since common utility functions imply risk vulnerability, our findings suggest that diagnostics in low prevalence settings (e.g., screening) may be considered more beneficial when risk preferences are taken into account.

Early Resting Myocardial Computed Tomography Perfusion for the Detection of Acute Coronary Syndrome in Patients With Coronary Artery Disease

Background—Acute rest single-photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) has high predictive value for acute coronary syndrome (ACS) in emergency department patients. Prior studies have shown excellent agreement between rest/stress computed tomography perfusion (CTP) and SPECT-MPI, but the value of resting CTP (rCTP) in acute chest pain triage remains unclear. We sought to determine the diagnostic accuracy of early rCTP, incremental value beyond obstructive coronary artery disease (CAD; ≥50% stenosis), and compared early rCTP to late stress SPECT-MPI in patients with CAD presenting with suspicion of ACS to the emergency department. Methods and Results—In this prespecified subanalysis of 183 patients (58.1±10.2 years; 33% women), we included patients with any CAD by coronary computed tomography angiography (CCTA) from Rule Out Myocardial Infarction Using Computer-Assisted Tomography I. rCTP was assessed semiquantitatively, blinded to CAD interpretation. Overall, 31 had ACS and 48 had abnormal rCTP. Sensitivity and specificity of rCTP for ACS were 48% (95% confidence interval [CI], 30%–67%) and 78% (95% CI, 71%–85%), respectively. rCTP predicted ACS (adjusted odds ratio, 3.40 [95% CI, 1.37–8.42]; P=0.008) independently of obstructive CAD, and sensitivity for ACS increased from 77% (95% CI, 59%–90%) for obstructive CAD to 90% (95% CI, 74%–98%) with addition of rCTP (P=0.05). In a subgroup undergoing late rest/stress SPECT-MPI (n=81), CCTA/rCTP had noninferior discriminatory value to CCTA/SPECT-MPI (area under the curve, 0.88 versus 0.90; P=0.64) using a noninferiority margin of 10%. Conclusions—Early rCTP provides incremental value beyond obstructive CAD to detect ACS. CCTA/rCTP is noninferior to CCTA/SPECT-MPI to discriminate ACS and presents an attractive alternative to triage patients presenting with acute chest pain. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00990262.

The 2013 ACC/AHA cardiovascular prevention guidelines improve alignment of statin therapy with coronary atherosclerosis as detected by coronary computed tomography angiography

The recently released 2013 ACC/AHA guidelines for management of blood cholesterol have substantially increased the number of adults who are eligible for preventive statin therapy. We sought to determine whether eligibility for statin therapy as determined by the 2013 ACC/AHA guideline recommendation is better aligned with the actual presence of coronary artery disease (CAD) as detected by coronary CT angiography (CCTA) when compared to prior guidelines including the 2004 NCEP ATP III and 2011 ESC/EAS guidelines. In this secondary analysis of the prospective observational ROMICAT I (Rule Out Myocardial Infarction with Computer Assisted Tomography) cohort study, we included all men and women aged 40-79 years presenting with acute chest pain but not diagnosed with acute coronary syndrome nor on admission statin. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy by the 2013 ACC/AHA, the 2004 NCEP ATP III, and the 2011 ESC/EAS guidelines. We determined the presence and severity of CAD as detected by CCTA. The 2013 ACC/AHA algorithm identified nearly twice as many individuals as eligible for statins (n = 77/189; 41%) as compared to the 2004 ATP III criteria: (n = 41/189; 22%), (p < .0001) In addition, the 2013 ACC/AHA guidelines were more sensitive for treatment of CCTA-detected CAD than the 2004 ATP III guidelines [53.4% (42.5-64.1) vs 27.3% (18.3-37.8), p < .001] and the 2011 ESC/EAE guidelines [53.4% (42.5-64.1) vs 34.1% (24.3-45.0), p < .001]. However, the specificity of these guidelines was modestly reduced compared to the 2004 ATP III guidelines [70.3 (60.4-79.0) vs 83.2 (74.4-89.9), p < .001] and the 2011 ESC/EAE guidelines [70.3 (60.4-79.0) vs 86.1 (77.8-92.2), p < .001], suggesting increased treatment of subjects without CCTA-detected CAD. Overall, the 2013 ACC/AHA guidelines are more sensitive to identify patients who have CAD detected by CCTA eligible for statin therapy as compared with prior guidelines, with an acceptable trade-off in specificity for recommending statin therapy in those without CAD.

The Prognostic Value of Coronary Artery Calcium in the PROMISE Study

Background —Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However limited data exist as to how CAC compares to functional testing (FT) in estimating prognosis in symptomatic patients. Methods —In the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, patients with stable chest pain (or dyspnea) and intermediate pre-test probability for obstructive coronary artery disease (CAD) were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4,209) and compared to results of FT (n=4,602). We stratified CAC and FT results as normal or mildly, moderately or severely abnormal (for CAC: 0, 1-99 Agatston Score [AS], 100-400 AS and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia and severe=large ischemic region abnormality). The primary endpoint was all-cause death, myocardial infarction or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios and C-statistic to determine predictive and discriminatory value. Results — Overall, the distribution of normal or mildly, moderately or severely abnormal test results was significantly different between FT and CAC (FT = normal 3588 [78.0%], mild 432 [9.4%], moderate 217 [4.7%], severe 365 [7.9%]; CAC = normal 1,457 [34.6%], mild 1340 [31.8%], moderate 772 [18.3%], severe 640 [15.2%], p 0) whereas less than half of events occurred in patients with mild, moderate or severely abnormal FT (n=57/132; 43%) (p Conclusion —Among stable outpatients presenting with suspected CAD, most patients experiencing clinical events have measurable CAC at baseline while less than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests. Clinical Trial Registration —URL: https://clinicaltrials.gov; Unique Identifier: NCT01174550Background: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients. Methods: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1–99 Agatston score [AS], 100–400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values. Results: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81–5.44; and FT: HR, 2.65; 95% confidence interval, 1.46–4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99–6.36; and FT: HR, 3.88; 95% confidence interval, 2.58–5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72). Conclusions: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.