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Stephen W Smith,
Deborah B Diercks, John T Nagurney,
Judd E Hollander,
Chadwick D Miller,
Jon W Schrock,
Adam J Singer,
Fred S Apple,
Peter A McCullough,
Christian T Ruff,
Arturo Sesma,
W Frank Peacock
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ABSTRACT: The impact of regulatory requirements, which require central adjudication for the diagnosis of acute myocardial infarction (AMI) in cardiac biomarker studies, is unclear. We determined the impact of local (at the site of subject enrollment) versus central adjudication of AMI on final diagnosis.
This is a retrospective analysis of data from the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study, an 18-center prospective study of patients with suspected acute coronary syndromes, with enrollment from December 19, 2006, to September 20, 2007. Local adjudication of AMI was performed by a single site investigator at each center following the protocol-specified definition and according to the year 2000 definition of AMI, which based cardiac troponin (cTn) elevation on local cut points for each of the 13 different assays. After completion of the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study primary analysis and to evaluate a new troponin assay, a Food and Drug Administration-mandated central adjudication was performed by 3 investigators at different institutions. This adjudication used the 2007 Universal Definition of AMI, which differs by use of the manufacturer's 99th percentile cTn cut point. We describe the outcome of this process and compare it with the local adjudication. Central adjudicators were not blinded to local adjudications. For central adjudication, discrepant diagnoses were resolved by consensus. Local versus central cTn cut points differed for 6 assays. Both definitions required a rise and/or fall of cTn. Discrepant cases were reviewed by the lead author. Difficult cases were defined as having a difference between local and central adjudication, an elevated cTn with a temporal rise and fall, and a negative or absent risk stratification test. Statistics were by χ, κ, and logistic regression.
Of 1,107 patients enrolled, 11 had indeterminate central adjudication, leaving 1,096 for analysis. In spite of high agreement across central versus local adjudicators, κ = 0.79 (95% CI [0.73, 0.85]), AMI was diagnosed more often by central adjudication, 134 (12.2%) versus 104 (9.5%), with 44 local diagnoses (4%) changed from non-AMI to AMI (n = 37) or AMI to non-AMI (n = 7) (P < .001). These 44 represented 34% (95% CI 26%-42%) of 141 cases in which either central or local adjudication was AMI. Of diagnoses changed to AMI, 3 reasons contributed approximately one-third each: the local use of a non-99th percentile cTn cutoff (32%), the possibility of human error (34%), and difficult cases (34%).
Despite an acceptable κ, over a third of patients with a diagnosis of AMI were not assigned that diagnosis by both sets of adjudicators. This supports the importance of 1 standard method for diagnosis of AMI.
American heart journal 03/2013; 165(3):273-279.e1. · 4.65 Impact Factor
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Deborah B Diercks,
Bryn E Mumma,
W Frank Peacock,
Judd E Hollander,
Basmah Safdar,
Simon A Mahler,
Chadwick D Miller,
Francis L Counselman,
Robert Birkhahn,
Jon Schrock,
Adam J Singer, John T Nagurney
[show abstract]
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ABSTRACT: Guidelines recommend that patients presenting to the emergency department (ED) with chest pain who are at low risk for acute coronary syndrome (ACS) receive an objective cardiac evaluation with a stress test or coronary imaging. It is uncertain whether all women derive benefit from this process. The study aim was to determine the incremental value of objective cardiac testing after serial cardiac markers and physician risk assessment.
Women enrolled in the 18-site Myeloperoxidase in the Diagnosis of Acute Coronary Syndrome (MIDAS) study had serial troponin I measured at time 0 and 90 minutes and physician risk assessment for the presence of ACS. Risk estimates obtained at the time of ED evaluation were dichotomized as high or non-high risk. The primary outcome was the composite of acute myocardial infarction (AMI) or revascularization at 30 days. Logistic regression with receiver operator characteristic (ROC) curves and net reclassification index were used to determine the diagnostic accuracy for the composite outcome of 30-day MI or revascularization for two models: 1) troponin I results and physician risk assessment alone and 2) troponin I results, physician risk assessment, and objective cardiac testing.
A total of 460 women with a median age 58 years (interquartile range [IQR] = 48.5 to 68 years) were included, and 32 (6.9%) experienced AMI or revascularization by 30 days. Comparison of the area under the ROC curves (AUC) showed that the addition of objective cardiac testing to the combination of troponin I results and physician risk assessment did not significantly improve prediction of 30-day AMI or revascularization (AUC = 0.85 vs. 0.89; p = 0.053). Using a threshold of 1%, net reclassification index showed that the addition of objective cardiac testing to troponin I results and physician risk assessment worsened the prediction for 30-day AMI and revascularization. All of the reclassified patients were false positives, with nine (2.1%) patients incorrectly reclassified from <1% risk to ≥1% risk of 30-day AMI or revascularization.
In the era of contemporary troponin assays, objective cardiac testing after an ED clinician risk assessment of non-high risk and negative troponin I results at 0 and 90 minutes does not improve the prediction of 30-day AMI or revascularization in women presenting with chest pain or other symptoms of cardiac ischemia.
Academic Emergency Medicine 03/2013; 20(3):265-70. · 1.86 Impact Factor
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Waleed Ahmed,
Christopher L Schlett,
Shanmugam Uthamalingam,
Quynh A Truong,
Wolfgang Koenig,
Ian S Rogers,
Ron Blankstein, John T Nagurney,
Ahmed Tawakol,
James L Januzzi,
Udo Hoffmann
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ABSTRACT: OBJECTIVES: The goal of this study was to determine the ability of a single, resting high-sensitivity troponin T (hsTnT) measurement to predict abnormal myocardial perfusion imaging (MPI) in patients presenting with acute chest pain to the emergency department (ED). BACKGROUND: HsTnT assays precisely detect very low levels of troponin T, which may be a surrogate for the presence and extent of myocardial ischemia. METHODS: We included all patients from the ROMICAT I (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial, an observational cohort study, who underwent both single-photon emission computed tomography (SPECT)-MPI stress testing and 64-slice computed tomography angiography (CTA) and in whom hsTnT measurements were available. We assessed the discriminatory value of hsTnT for abnormal SPECT-MPI and the association of reversible myocardial ischemia by SPECT-MPI and the extent of coronary atherosclerosis by CTA to hsTnT levels. RESULTS: Of the 138 patients (mean age 54 ± 11 years, 46% male), 19 (13.7%) had abnormal SPECT-MPI. Median hsTnT levels were significantly different between patients with normal and abnormal SPECT-MPI (9.41 pg/ml [interquartile range (IQR): 5.73 to 19.20 pg/ml] vs. 4.89 pg/ml [IQR: 2.34 to 7.68 pg/ml], p = 0.001). Sensitivity of 80% and 90% to detect abnormal SPECT-MPI was reached at hsTnT levels as low as 5.73 and 4.26 pg/ml, respectively. Corresponding specificity was 62% and 46%, and negative predictive value was 96% and 96%, respectively. HsTnT levels had good discriminatory ability for prediction of abnormal SPECT-MPI (area under the curve: 0.739, 95% confidence interval: 0.609 to 0.868). Both reversible myocardial ischemia and the extent of coronary atherosclerosis (combined model r(2) = 0.19 with partial of r(2) = 0.12 and r(2) = 0.05, respectively) independently and incrementally predicted the measured hsTnT levels. CONCLUSIONS: In patients with acute chest pain, myocardial perfusion abnormalities and coronary artery disease are predicted by resting hsTnT levels. Prospective evaluations are warranted to confirm whether resting hsTnT could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and improve the effectiveness of patient management.
JACC. Cardiovascular imaging 01/2013; 6(1):72-82. · 14.29 Impact Factor
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Simon A Mahler,
Chadwick D Miller,
Judd E Hollander, John T Nagurney,
Robert Birkhahn,
Adam J Singer,
Nathan I Shapiro,
Ted Glynn,
Richard Nowak,
Basmah Safdar,
Mary Peberdy,
Francis L Counselman,
Abhinav Chandra,
Joshua Kosowsky,
James Neuenschwander,
Jon W Schrock,
Stephen Plantholt,
Deborah B Diercks,
W Frank Peacock
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ABSTRACT: BACKGROUND: The HEART score and North American Chest Pain Rule (NACPR) are decision rules designed to identify acute chest pain patients for early discharge without stress testing or cardiac imaging. This study compares the clinical utility of these decision rules combined with serial troponin determinations. METHODS AND RESULTS: A secondary analysis was conducted of 1005 participants in the Myeloperoxidase In the Diagnosis of Acute coronary syndromes Study (MIDAS). MIDAS is a prospective observational cohort of Emergency Department (ED) patients enrolled from 18 US sites with symptoms suggestive of acute coronary syndrome (ACS). The ability to identify participants for early discharge and the sensitivity for ACS at 30days were compared among an unstructured assessment, NACPR, and HEART score, each combined with troponin measures at 0 and 3h. ACS, defined as cardiac death, acute myocardial infarction, or unstable angina, occurred in 22% of the cohort. The unstructured assessment identified 13.5% (95% CI 11.5-16%) of participants for early discharge with 98% (95% CI 95-99%) sensitivity for ACS. The NACPR identified 4.4% (95% CI 3-6%) for early discharge with 100% (95% CI 98-100%) sensitivity for ACS. The HEART score identified 20% (95% CI 18-23%) for early discharge with 99% (95% CI 97-100%) sensitivity for ACS. The HEART score had a net reclassification improvement of 10% (95% CI 8-12%) versus unstructured assessment and 19% (95% CI 17-21%) versus NACPR. CONCLUSIONS: The HEART score with 0 and 3hour serial troponin measures identifies a substantial number of patients for early discharge while maintaining high sensitivity for ACS.
International journal of cardiology 10/2012; · 7.08 Impact Factor
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Maros Ferencik,
Christopher L Schlett,
Fabian Bamberg,
Quynh A Truong,
John H Nichols,
Antonio J Pena,
Michael D Shapiro,
Ian S Rogers,
Sujith Seneviratne,
Blair Alden Parry,
Ricardo C Cury,
Thomas J Brady,
David F Brown, John T Nagurney,
Udo Hoffmann
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ABSTRACT: The objective was to determine the association of four clinical risk scores and coronary plaque burden as detected by computed tomography (CT) with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain. The hypothesis was that the combination of risk scores and plaque burden improved the discriminatory capacity for the diagnosis of ACS.
The study was a subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial-a prospective observational cohort study. The authors enrolled patients presenting to the emergency department (ED) with a chief complaint of acute chest pain, inconclusive initial evaluation (negative biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers, and subsequent diagnostic testing, such as exercise treadmill testing, nuclear stress perfusion imaging, and/or invasive coronary angiography), as deemed clinically appropriate. The clinical providers were blinded to CT results. The chest pain score was calculated and the results were dichotomized to ≥10 (high-risk) and <10 (low-risk). Three risk scores were calculated, Goldman, Sanchis, and Thrombolysis in Myocardial Infarction (TIMI), and each patient was assigned to a low-, intermediate-, or high-risk category. Because of the low number of subjects in the high-risk group, the intermediate- and high-risk groups were combined into one. CT images were evaluated for the presence of plaque in 17 coronary segments. Plaque burden was stratified into none, intermediate, and high (zero, one to four, and more than four segments with plaque). An outcome panel of two physicians (blinded to CT findings) established the primary outcome of ACS (defined as either an acute myocardial infarction or unstable angina) during the index hospitalization (from the presentation to the ED to the discharge from the hospital). Logistic regression modeling was performed to examine the association of risk scores and coronary plaque burden to the outcome of ACS. Unadjusted models were individually fitted for the coronary plaque burden and for Goldman, Sanchis, TIMI, and chest pain scores. In adjusted analyses, the authors tested whether the association between risk scores and ACS persisted after controlling for the coronary plaque burden. The prognostic discriminatory capacity of the risk scores and plaque burden for ACS was assessed using c-statistics. The differences in area under the receiver-operating characteristic curve (AUC) and c-statistics were tested by performing the -2 log likelihood ratio test of nested models. A p value <0.05 was considered statistically significant.
Among 368 subjects, 31 (8%) subjects were diagnosed with ACS. Goldman (AUC = 0.61), Sanchis (AUC = 0.71), and TIMI (AUC = 0.63) had modest discriminatory capacity for the diagnosis of ACS. Plaque burden was the strongest predictor of ACS (AUC = 0.86; p < 0.05 for all comparisons with individual risk scores). The combination of plaque burden and risk scores improved prediction of ACS (plaque + Goldman AUC = 0.88, plaque + Sanchis AUC = 0.90, plaque + TIMI AUC = 0.88; p < 0.01 for all comparisons with coronary plaque burden alone).
Risk scores (Goldman, Sanchis, TIMI) have modest discriminatory capacity and coronary plaque burden has good discriminatory capacity for the diagnosis of ACS in patients with acute chest pain. The combined information of risk scores and plaque burden significantly improves the discriminatory capacity for the diagnosis of ACS.
Academic Emergency Medicine 07/2012; 19(8):934-42. · 1.86 Impact Factor
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Udo Hoffmann,
Quynh A Truong,
David A Schoenfeld,
Eric T Chou,
Pamela K Woodard, John T Nagurney,
J Hector Pope,
Thomas H Hauser,
Charles S White,
Scott G Weiner, [......],
Issam Mikati,
W Frank Peacock,
Pearl Zakroysky,
Douglas Hayden,
Alexander Goehler,
Hang Lee,
G Scott Gazelle,
Stephen D Wiviott,
Jerome L Fleg,
James E Udelson
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ABSTRACT: It is unclear whether an evaluation incorporating coronary computed tomographic angiography (CCTA) is more effective than standard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes.
In this multicenter trial, we randomly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to standard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012. The primary end point was length of stay in the hospital. Secondary end points included rates of discharge from the emergency department, major adverse cardiovascular events at 28 days, and cumulative costs. Safety end points were undetected acute coronary syndromes.
The rate of acute coronary syndromes among 1000 patients with a mean (±SD) age of 54±8 years (47% women) was 8%. After early CCTA, as compared with standard evaluation, the mean length of stay in the hospital was reduced by 7.6 hours (P<0.001) and more patients were discharged directly from the emergency department (47% vs. 12%, P<0.001). There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days. After CCTA, there was more downstream testing and higher radiation exposure. The cumulative mean cost of care was similar in the CCTA group and the standard-evaluation group ($4,289 and $4,060, respectively; P=0.65).
In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating CCTA into a triage strategy improved the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department, but it resulted in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care. (Funded by the National Heart, Lung, and Blood Institute; ROMICAT-II ClinicalTrials.gov number, NCT01084239.).
New England Journal of Medicine 07/2012; 367(4):299-308. · 53.30 Impact Factor
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ABSTRACT: Compared to troponin alone, a dual-marker strategy with natriuretic peptides may improve acute coronary syndrome (ACS) diagnosis with a single blood draw and provide physiologic information regarding underlying heart disease. We evaluate the value of adding natriuretic peptides (myocyte stress markers) to troponins (myocardial injury markers) for diagnosing ACS in emergency department patients with chest pain.
In 328 patients (53 ± 12 years, 63% men) with an initially negative conventional troponin and nonischemic electrocardiogram who underwent 64-slice cardiac computed tomography (CT), we measured conventional troponin-T (cTnT), high-sensitivity troponin-T (hsTnT), N-terminal pro-B type natriuretic peptide, and mid-regional pro-atrial natriuretic peptide. ACS was defined as myocardial infarction or unstable angina. CT was evaluated for coronary plaque, stenosis, and regional wall motion abnormality.
Patients with ACS (n = 29, 9%) had higher concentrations of each biomarker compared to those without (all P < .01). Adding natriuretic peptides, especially N-terminal pro-B type natriuretic peptide, to both cTnT or hsTnT improved the C-statistics and net reclassification index for ACS, largely driven by correctly reclassifying events. Dual-negative marker results improved sensitivity (cTnT 38% to 83%-86%, hsTnT 59% to 86%-90%; all P < .01) and negative predictive value (cTnT 94% to 97%-98%, hsTnT 96% to 97%-98%) for ACS. Patients with dual-negative markers had the lowest percentage of CT coronary plaque, stenosis, and regional wall motion abnormality (all P-trend <.001).
Among emergency department patients with low-intermediate likelihood of ACS, combining natriuretic peptides with either conventional or highly-sensitive troponin improved discriminatory capacity and allowed for better reclassification of ACS, findings supported by structural and functional CT results.
American heart journal 06/2012; 163(6):972-979.e1. · 4.65 Impact Factor
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ABSTRACT: BACKGROUND: Multi-detector cardiac computed tomography (CT) allows for simultaneous assessment of aortic distensibility (AD), coronary atherosclerosis, and thoracic aortic atherosclerosis. OBJECTIVES: We sought to determine the relationship of AD to the presence and morphological features in coronary and thoracic atherosclerosis. METHODS: In 293 patients (53±12years, 63% male), retrospectively-gated MDCT were performed. We measured intraluminal aortic areas across 10 phases of the cardiac cycle (multiphase reformation 10% increments) at pre-defined locations to calculate the ascending, descending, and local AD (at locations of thoracic plaque). AD was calculated as maximum change in area/(minimum area×pulse pressure). Coronary and thoracic plaques were categorized as calcified, mixed, or non-calcified. RESULTS: Ascending and descending AD were lower in patients with any coronary plaque, calcified or mixed plaque than those without (all p<0.0001) but not with non-calcified coronary plaque (p≥0.46). Per 1mm Hg(-1) 10(-3) increase in ascending and descending AD, there was an 18-29% adjusted risk reduction for having any coronary, calcified plaque, or mixed coronary plaque (ascending AD only) (all p≤0.04). AD was not associated with non-calcified coronary plaque or when age was added to the models (all p>0.39). Local AD was lower at locations of calcified and mixed thoracic plaque when compared to non-calcified thoracic atherosclerosis (p<0.04). CONCLUSIONS: A stiffer, less distensible aorta is associated with coronary and thoracic atherosclerosis, particularly in the presence of calcified and mixed plaques, suggesting that the mechanism of atherosclerosis in small and large vessels is similar and influenced by advancing age.
International journal of cardiology 05/2012; · 7.08 Impact Factor
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ABSTRACT: Little information exists regarding how accurately emergency physicians (EPs) predict the probability of acute coronary syndrome (ACS). Our objective was to determine if EPs can accurately predict ACS in a prospectively identified cohort of emergency department (ED) patients who met enrolment criteria for a study of coronary computed tomographic angiography (CCTA) and were admitted for a "rule out ACS" protocol.
A prospective observational pilot study in an academic medical centre was carried out. EPs caring for patients with chest pain provided whole-number estimates of the probability of ACS after clinical review. This substudy was part of the now published Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) study, a study of CCTA and admission of patients for a rule out ACS protocol after a nondiagnostic evaluation. Predictions were grouped into probability groups based on the validated Goldman criteria. ACS was determined by an adjudication committee using American Heart Association/American College of Cardiology/European Society of Cardiology guidelines.
A total of 334 predictions were obtained for a study population with a mean age of 54 (SD 12) years, 63% of whom were male. There were 35 ACS events. EPs predicted ACS better than by chance, and increasingly higher estimates were associated with a higher incidence of ACS (p = 0.0004). The percentage of patients with ACS was 0%, 6%, 7%, and 17%, respectively, for very low, low, intermediate, and high probability groups. EPs' estimates had a sensitivity of 63% using a > 20% probability of ACS to define a positive test. Lowering this threshold to > 7% to define a test as positive increased the sensitivity of physician estimates to 89% but lowered specificity from 65% to 24%.
Our data suggest that for a selected ED cohort meeting eligibility criteria for a study of CCTA, EPs predict ACS better than by chance, with an increasing proportion of patients proving to have ACS with increasing probability estimates. Lowering the estimate threshold does not result in an overall sensitivity level that is sufficient to send patients home from the ED and is associated with a poor specificity.
CJEM: Canadian journal of emergency medical care = JCMU: journal canadien de soins medicaux d'urgence 05/2012; 14(3):147-56. · 1.18 Impact Factor
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Maros Ferencik,
Christopher L Schlett,
Brian B Ghoshhajra,
Mathias F Kriegel,
Subodh B Joshi,
Pal Maurovich-Horvat,
Ian S Rogers,
Dahlia Banerji,
Fabian Bamberg,
Quynh A Truong,
Thomas J Brady, John T Nagurney,
Udo Hoffmann
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ABSTRACT: We tested the hypothesis that morphologic lesion assessment helps detect acute coronary syndrome (ACS) during index hospitalization in patients with acute chest pain and significant stenosis on coronary computed tomographic angiogram (CTA). Patients who presented to an emergency department with chest pain but no objective signs of myocardial ischemia (nondiagnostic electrocardiogram and negative initial biomarkers) underwent CT angiography. CTA was analyzed for degree and length of stenosis, plaque area and volume, remodeling index, CT attenuation of plaque, and spotty calcium in all patients with significant stenosis (>50% in diameter) on CTA. ACS during index hospitalization was determined by a panel of 2 physicians blinded to results of CT angiography. For lesion characteristics associated with ACS, we determined cutpoints optimized for diagnostic accuracy and created lesion scores. For each score, we determined the odds ratio (OR) and discriminatory capacity for the prediction of ACS. Of the overall population of 368 patients, 34 had significant stenosis and 21 of those had ACS. Scores A (remodeling index plus spotty calcium: OR 3.5, 95% confidence interval [CI] 1.2 to 10.1, area under curve [AUC] 0.734), B (remodeling index plus spotty calcium plus stenosis length: OR 4.6, 95% CI 1.6 to 13.7, AUC 0.824), and C (remodeling index plus spotty calcium plus stenosis length plus plaque volume <90 HU: OR 3.4, 95% CI 1.5 to 7.9, AUC 0.833) were significantly associated with ACS. In conclusion, in patients presenting with acute chest pain and stenosis on coronary CTA, a CT-based score incorporating morphologic characteristics of coronary lesions had a good discriminatory value for detection of ACS during index hospitalization.
The American journal of cardiology 04/2012; 110(2):183-9. · 3.58 Impact Factor
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ABSTRACT: Pericardial adipose tissue (PAT) is a pathogenic fat depot associated with coronary atherosclerosis and cardiovascular events. We hypothesized that higher PAT is associated with coronary high-risk lesions as determined by cardiac CT.
We included 358 patients (38% female; median age 51 years) who were admitted to the ED with acute chest pain and underwent 64-slice CT angiography. The cardiac CT data sets were assessed for presence and morphology of CAD and PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at least two of the following characteristics: positive remodeling, low-density plaque, and spotty calcification. PAT was defined as any pixel with CT attenuation of -190 to -30 HU within the pericardial sac.
Based on cardiac CT, 50% of the patients (n=180) had no CAD, 46% (n=165) had CAD without high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT in patients with high-risk lesions was significantly higher compared to patients without high-risk lesions and without any CAD (151.9 [109.0-179.4]cm(3) vs. 110.0 [81.5-137.4]cm(3), vs. 74.8 [58.2-111.7]cm(3), respectively p=0.04 and p<0.0001). These differences remained significant after adjusting for traditional risk factors including BMI (all p<0.05). The area under the ROC curve for the identification of high-risk lesions was 0.756 in a logistic regression model with PAT as a continuous predictor.
PAT volume is nearly twice as high in patients with high-risk coronary lesions as compared to those without CAD. PAT volume is significantly associated with high risk coronary lesion morphology independent of clinical characteristics and general obesity.
Atherosclerosis 02/2012; 222(1):129-34. · 3.79 Impact Factor
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Ron Blankstein,
Waleed Ahmed,
Fabian Bamberg,
Ian S Rogers,
Christopher Lothar Schlett,
Khurram Nasir,
Joao Fontes,
Ahmed Tawakol,
Thomas J Brady, John T Nagurney,
Udo Hoffmann,
Quynh A Truong
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ABSTRACT: The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA.
The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect >50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a >70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis >50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men <40 years old or women <50 years old or individuals who achieved at least 13 metabolic equivalents on ETT.
Among low- to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of >50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA.
Circulation Cardiovascular Imaging 02/2012; 5(2):233-42. · 5.94 Impact Factor
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Deborah B Diercks,
W Frank Peacock,
Judd E Hollander,
Adam J Singer,
Robert Birkhahn,
Nathan Shapiro,
Ted Glynn,
Richard Nowack,
Basmah Safdar,
Chadwick D Miller,
Elizabeth Lewandrowski, John T Nagurney
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ABSTRACT: Guidelines recommend that serial cardiac marker testing to rule out acute myocardial infarction (AMI) be performed for 8 to 12 hours after symptom onset. We aim to determine the diagnostic accuracy of a contemporary point-of-care (POC) troponin I (TnI) assay within 3 hours for patients presenting within 8 hours of symptom onset.
The MIDAS study collected blood from patients presenting with suspected acute coronary syndrome at presentation and at 90 minutes, 3 hours, and 6 hours in whom the emergency physician planned an objective cardiac ischemia evaluation. Criterion standard diagnoses were adjudicated by experienced clinicians using all available medical records per American Heart Association/American College of Cardiology criteria. Reviewers were blinded to the investigational marker, Cardio3 TnI POC. The Cardio3 TnI reference value was defined as >0.05 ng/mL. Measures of diagnostic accuracy are presented with 95% CI.
A total of 858 of 1107 patients met the inclusion criteria. The study cohort had 476 men (55.5%) with median age of 57.0 years (interquartile range 48.0-67.0 years). Median time from symptom onset to initial blood draw was 3.9 hours (interquartile range 2.7-5.2 hours). Acute myocardial infarction was diagnosed in 82 patients (9.6%). The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio over 3 hours were 84.1, 93.4, 12.8, and 0.17, respectively. There was no significant improvement in diagnostic accuracy associated with adding 6-hour serial testing to the 3-hour sample.
In suspected patients with acute coronary syndrome presenting to the emergency department within 8 hours of symptom onset, 3 hours of serial testing with the Cardio3 TnI POC platform provides similar diagnostic accuracy for AMI as longer periods.
American heart journal 01/2012; 163(1):74-80.e4. · 4.65 Impact Factor
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ABSTRACT: The aim of this study was to determine the 2-year prognostic value of cardiac computed tomography (CT) for predicting major adverse cardiac events (MACE) in patients presenting to the emergency department (ED) with acute chest pain.
CT has high potential for early triage of acute chest pain patients. However, there is a paucity of data regarding the prognostic value of CT in this ED cohort.
We followed 368 patients from the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial (age 53 ± 12 years; 61% male) who presented to the ED with acute chest pain, negative initial troponin, and a nonischemic electrocardiogram for 2 years. Contrast-enhanced 64-slice CT was obtained during index hospitalization, and caregivers and patients remained blinded to the results. CT was assessed for the presence of plaque, stenosis (>50% luminal narrowing), and left ventricular regional wall motion abnormalities (RWMA). The primary endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization.
Follow-up was completed in 333 patients (90.5%) with a median follow-up period of 23 months. At the end of the follow-up period, 25 patients (6.8%) experienced 35 MACE (no cardiac deaths, 12 myocardial infarctions, and 23 revascularizations). Cumulative probability of 2-year MACE increased across CT strata for coronary artery disease (CAD) (no CAD 0%; nonobstructive CAD 4.6%; obstructive CAD 30.3%; log-rank p < 0.0001) and across combined CT strata for CAD and RWMA (no stenosis or RWMA 0.9%; 1 feature-either RWMA [15.0%] or stenosis [10.1%], both stenosis and RWMA 62.4%; log-rank p < 0.0001). The c statistic for predicting MACE was 0.61 for clinical Thrombolysis In Myocardial Infarction risk score and improved to 0.84 by adding CT CAD data and improved further to 0.91 by adding RWMA (both p < 0.0001).
CT coronary and functional features predict MACE and have incremental prognostic value beyond clinical risk score in ED patients with acute chest pain. The absence of CAD on CT provides a 2-year MACE-free warranty period, whereas coronary stenosis with RWMA is associated with the highest risk of MACE.
JACC. Cardiovascular imaging 05/2011; 4(5):481-91. · 14.29 Impact Factor
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Ian S Rogers,
Dahlia Banerji,
Emily L Siegel,
Quynh A Truong,
Brian B Ghoshhajra,
Thomas Irlbeck,
Suhny Abbara,
Rajiv Gupta,
Ricardo J Benenstein,
Garry Choy,
Laura L Avery,
Robert A Novelline,
Fabian Bamberg,
Thomas J Brady, John T Nagurney,
Udo Hoffmann
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ABSTRACT: Newer cardiac computed tomographic (CT) technology has permitted comprehensive cardiothoracic evaluations for coronary artery disease, pulmonary embolism, and aortic dissection within a single breath hold, independent of the heart rate. We conducted a randomized diagnostic trial to compare the efficiency of a comprehensive cardiothoracic CT examination in the evaluation of patients presenting to the emergency department with undifferentiated acute chest discomfort or dyspnea. We randomized the emergency department patients clinically scheduled to undergo a dedicated CT protocol to assess coronary artery disease, pulmonary embolism, or aortic dissection to either the planned dedicated CT protocol or a comprehensive cardiothoracic CT protocol. All CT examinations were performed using a 64-slice dual source CT scanner. The CT results were immediately communicated to the emergency department providers, who directed further management at their discretion. The subjects were then followed for the remainder of their hospitalization and for 30 days after hospitalization. Overall, 59 patients (mean age 51.2 ± 11.4 years, 72.9% men) were randomized to either dedicated (n = 30) or comprehensive (n = 29) CT scanning. No significant difference was found in the median length of stay (7.6 vs 8.2 hours, p = 0.79), rate of hospital discharge without additional imaging (70% vs 69%, p = 0.99), median interval to exclusion of an acute event (5.2 vs 6.5 hours, p = 0.64), costs of care (p = 0.16), or the number of revisits (p = 0.13) between the dedicated and comprehensive arms, respectively. In addition, radiation exposure (11.3 mSv vs 12.8 mSv, p = 0.16) and the frequency of incidental findings requiring follow-up (24.1% vs 33.3%, p = 0.57) were similar between the 2 arms. Comprehensive cardiothoracic CT scanning was feasible, with a similar diagnostic yield to dedicated protocols. However, it did not reduce the length of stay, rate of subsequent testing, or costs. In conclusion, although this "triple rule out" protocol might be helpful in the evaluation of select patients, these findings suggest that it should not be used routinely with the expectation that it will improve efficiency or reduce resource use.
The American journal of cardiology 03/2011; 107(5):643-50. · 3.58 Impact Factor
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ABSTRACT: Twelve-lead surface electrocardiography (ECG) and computed tomography (CT) are used to evaluate for myocardial ischemia and coronary artery disease (CAD), respectively. We aimed to determine features on resting ECG that predict coronary artery stenosis by cardiac CT. In 309 acute chest pain patients, we compared the initial triage resting ECG to contrast-enhanced 64-slice cardiac CT angiography. We assessed for 6 quantitative (QT interval, QTc interval, QTc > 440 ms, gender-specific QTc, QT dispersion and QRS duration) and 4 qualitative ECG parameters (ST depression >0.05 to ≤0.1 mV, T wave inversion ≥0.1 mV, T wave flattening, and any T wave abnormalities) and for the presence of coronary stenosis by CT (>50% luminal narrowing). Specificities of these ECG parameters were excellent (83.6-97.0%) while sensitivities were poor (12.2-29.3%). For coronary stenosis detection, the ECG features with the greatest performance were the presence of ST depression (positive likelihood ratio [LR+] 4.09) and T wave inversion (LR+ 4.58). In multivariable analyses, the risk for coronary stenosis increased by 33-41% for every 20 ms prolongation of the QTc interval after adjusting for age, gender, and cardiac risk factors or adjustment for Framingham risk score. Similarly, there was an increase of fourfold with the presence of ST depression >0.05 to ≤0.1 mV or T wave inversion ≥0.1 mV. In acute chest pain patients, resting ECG features of QTc interval prolongation, mild ST depression, and T wave inversion are independently associated with the presence of CT coronary stenosis and their presence suggests an increase risk of CAD.
The international journal of cardiovascular imaging 02/2011; 28(2):365-74. · 2.15 Impact Factor
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Elizabeth A Hoge,
John J Worthington, John T Nagurney,
Yuchiao Chang,
Elaine B Kay,
Christine M Feterowski,
Anna R Katzman,
Jared M Goetz,
Maria L Rosasco,
Natasha B Lasko,
Randall M Zusman,
Mark H Pollack,
Scott P Orr,
Roger K Pitman
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ABSTRACT: Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the β-adrenergic blocker propranolol, to reduce this overconsolidation.
In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post-trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured.
Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects.
The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event.
CNS Neuroscience & Therapeutics 01/2011; 18(1):21-7. · 4.44 Impact Factor
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Sujith K Seneviratne,
Quynh A Truong,
Fabian Bamberg,
Ian S Rogers,
Michael D Shapiro,
Christopher L Schlett,
Claudia U Chae,
Ricardo Cury,
Suhny Abbara,
Thomas J Brady, John T Nagurney,
Udo Hoffmann
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ABSTRACT: The incremental value of regional left ventricular function (LVF) over coronary assessment to detect acute coronary syndrome (ACS) is uncertain.
We analyzed 356 patients (mean age, 53+/-12 years; 62% men) with acute chest pain and inconclusive initial emergency department evaluation. Patients underwent 64-slice contrast-enhanced cardiac computed tomography before hospital admission. Caregivers and patients remained blinded to the results. Regional LVF and presence of coronary atherosclerotic plaque and significant stenosis (>50%) were separately assessed by 2 independent readers. Incremental value of regional LVF to predict ACS was determined in the entire cohort and in subgroups of patients with nonobstructive coronary artery disease, inconclusive assessment for stenosis (defined as inability to exclude significant stenosis due to calcium or motion), and significant stenosis. During their index hospitalization, 31 patients were ultimately diagnosed with ACS (8 myocardial infarction, 22 unstable angina), of which 74% (23 patients) had regional LV dysfunction. Adding regional LVF resulted in a 10% increase in sensitivity to detect ACS by cardiac computed tomography (87%; 95% confidence interval, 70% to 96%) and significantly improved the overall accuracy (c-statistic: 0.88 versus 0.94 and 0.79 versus 0.88, for extent of plaque and presence of stenosis, respectively; both P<0.03). The diagnostic accuracy of regional LVF for detection of ACS has 89% sensitivity and 86% specificity in patients with significant stenosis (n=33) and 60% sensitivity and 86% specificity in patients with inconclusive coronary computed tomographic angiography (n=33).
Regional LVF assessment at rest improves diagnostic accuracy for ACS in patients with acute chest pain, especially in those with coronary artery disease and thus may be helpful to guide further management in patients at intermediate risk for ACS.
Circulation Cardiovascular Imaging 07/2010; 3(4):375-83. · 5.94 Impact Factor
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Quynh A Truong,
Leon M Ptaszek,
Elizabeth M Charipar,
Carolyn Taylor,
Joao D Fontes,
Matthias Kriegel,
Thomas Irlbeck,
Michael Toepker,
Christopher L Schlett,
Fabian Bamberg,
Ron Blankstein,
Thomas J Brady, John T Nagurney,
Udo Hoffmann
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ABSTRACT: Cardiac computed tomography (CT) is a state-of-the-art technology that provides an accurate noninvasive method to quantify left ventricular mass for analysis of left ventricular hypertrophy (LVH). We aimed to examine seven ECG-based LVH criteria against two CT indexation criteria for LVH: a CT-specific body surface area cutoff and the obesity-independent height criteria.
In 333 patients (mean age 53 +/- 12 years, 61% men), 64-slice contrast-enhanced CT was performed and 12-lead surface ECG within 24 h. Left ventricular mass was measured at end-diastole. Using both CT indexation criteria, the cohort was subdivided into patients with LVH and without LVH. The seven ECG criteria for LVH were the Cornell voltage index, Cornell voltage duration product, Cornell/strain index, Sokolow-Lyon index, Romhilt-Estes scores at least 4 and at least 5, and Gubner-Ungerleider.
The ECG parameters had high specificities (85-97%) and variable low sensitivities (4-43%) when compared to either CT criteria of LVH. The three Cornell-based methods performed the best (test-positive likelihood ratio: 4.5-6.7), followed by the Sokolow-Lyon and Romhilt-Estes scores (test-positive likelihood ratio: 2.3-4.0). With the exception of the Gubner-Ungerleider criterion, the other six ECG criteria were associated with at least one of the CT-based LVH (adjusted odds ratio 2.4-9.5) and had incremental predictive value beyond that of hypertension history.
Using cardiac CT as a gold standard for LVH assessment, ECG criteria for LVH have high specificities with the three Cornell-based criteria providing the best test performance for identifying patients with LVH.
Journal of hypertension 05/2010; 28(9):1959-67. · 4.02 Impact Factor
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James L Januzzi,
Fabian Bamberg,
Hang Lee,
Quynh A Truong,
John H Nichols,
Mahir Karakas,
Asim A Mohammed,
Christopher L Schlett, John T Nagurney,
Udo Hoffmann,
Wolfgang Koenig
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ABSTRACT: For evaluation of patients with chest pain and suspected acute coronary syndrome (ACS), consensus guidelines recommend use of a cardiac troponin cut point that corresponds to the 99 th percentile of a healthy population. Most conventional troponin methods lack sufficient precision at this low level.
In a cross-sectional study, 377 patients (mean age 53.7 years, 64.2% male) with chest pain and low to intermediate likelihood for ACS were enrolled in the emergency department. Blood was tested with a precommercial high-sensitivity troponin T assay (hsTnT) and compared with a conventional cardiac troponin T method. Patients underwent a 64-slice coronary computed tomography coronary angiogram at the time of phlebotomy, on average 4 hours from initial presentation. Among patients with acute chest pain, 37 (9.8%) had an ACS. Using the 99th percentile cut point for a healthy population (13 pg/mL), hsTnT had 62% sensitivity, 89% specificity, 38% positive predictive value, and 96% negative predictive value for ACS. Compared with the cardiac troponin T method, hsTnT detected 27% more ACS cases (P=.001), and an hsTnT above the 99 th percentile strongly predicted ACS (odds ratio 9.0, 95% confidence interval 3.9 to 20.9, P<0.001). Independent of ACS diagnosis, computed tomography angiography demonstrated that concentrations of hsTnT were determined by numerous factors, including the presence and severity of coronary artery disease, left ventricular mass, left ventricular ejection fraction, and regional left ventricular dysfunction.
Among low- to intermediate-risk patients with chest pain, hsTnT provides good sensitivity and specificity for ACS. Elevation of hsTnT identifies patients with myocardial injury and significant structural heart disease, irrespective of the diagnosis of ACS.
Circulation 03/2010; 121(10):1227-34. · 14.74 Impact Factor
