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.
Contrast-enhanced computed tomographic (CT) angiography has become a standard procedure in the evaluation of pulmonary embolus (PE) and aortic dissection (AD). Cardiac computed tomography has proved to be an effective tool to rule out coronary artery disease (CAD), with a sensitivity of 93% to 99% and negative predictive value of 95% to 99%. Recent data have suggested the potential to improve the efficiency of the treatment of patients with acute chest pain and a low-to-intermediate probability of acute coronary syndrome. These data have suggested that the noninvasive detection of CAD and left ventricular function using computed tomography might significantly improve the diagnosis and treatment of patients with suspicion of acute coronary syndrome. About 20% of patients with acute chest pain present to the emergency department (ED) with undifferentiated acute chest pain and often require multiple examinations to exclude PE and/or AD, in addition to excluding obstructive CAD. The results of several recent studies have suggested that high temporal resolution, dual-source CT technology permits simultaneous assessment of CAD, PE, and AD, independent of the heart rate, in a single scan. However, it is unknown whether providing such a comprehensive assessment would lead to improved efficiency in the treatment of these patients. Thus, our goal was to determine whether providing a comprehensive cardiothoracic CT examination would result in significant improvement in the efficiency of treating patients presenting to the ED with undifferentiated acute chest discomfort or dyspnea in the setting of a tertiary academic hospital.
Methods
Our subject population consisted of patients who presented to the ED of a tertiary academic center with undifferentiated acute chest discomfort and/or shortness of breath with a component of chest discomfort of ≥5 minutes’ duration within the previous 24 hours. Specifically, we included subjects if the assessing ED attending physician had independently decided that the patient’s care plan should include a cardiac, PE, or AD CT examination after the standard initial clinical evaluation to rule out acute coronary syndrome, PE, or AD. The potential subjects were ≥30 years old and in sinus rhythm. The women were required to be of nonchildbearing potential or to have had negative findings from a pregnancy test.
The exclusion criteria included positive cardiac biomarkers, changes on the electrocardiogram diagnostic of myocardial ischemia, a known history of CAD (e.g., previous myocardial infarction, previous coronary stent placement, and/or coronary artery bypass graft surgery), a known history of thoracic aortic disease (i.e., thoracic aortic aneurysm >5 cm in diameter, history of AD, and/or a history of thoracic aortic aneurysm repair), a known history of PE within the previous 6 months, and cardiopulmonary instability (e.g., heart rate >100 beats/min, systolic blood pressure <105 mm Hg, or oxygen saturation <90%). The potential subjects were not eligible if they had a serum creatinine clearance of <60 ml/min by Cockcroft-Gault, had a known allergy to iodinated contrast agents, were receiving metformin therapy, or were unable or unwilling to discontinue therapy for 48 hours after the CT evaluation. Nitroglycerin was not administered if the subject had used a PDE-5 inhibitor (i.e., sildenafil, tadalafil, or vardenafil) within the previous 72 hours.
Our trial was designed as a prospective, randomized, controlled diagnostic trial to assess the relative efficiency of the comprehensive cardiothoracic CT protocol. We screened all patients who had presented with a chief complaint of chest discomfort and/or shortness of breath to the ED on weekdays from 8 a.m. to 6 p.m . The eligible patients willing to participate in the present trial were randomized to receive either the dedicated cardiac, pulmonary, or aortic CT scan initially scheduled as a part of their clinical care to exclude CAD, PE, or AD or to receive a comprehensive cardiothoracic CT scan—a single CT scan designed to exclude CAD, PE, and AD.
Before recruitment, the randomized study group allocations were placed into sealed and numbered opaque envelopes. Accordingly, the treating ED physicians, study physicians, and subjects had no knowledge of the study arm into which the subject would be assigned before randomization. After consent, each subject opened the appropriate, sealed envelope in the presence of the study physicians to reveal the study arm into which the subject was assigned. After randomization, the treating ED physicians, study physicians, and subjects had full knowledge of the group assignment. The CT scans were completed immediately after patient consent and randomization.
We prospectively collected data on the demographics, risk factor profile, and clinical course for all patients. The presence of risk factors was established from patient interview and a review of the available medical records. The subjects were then followed for the remainder of their hospitalization to determine the length of stay, costs incurred, and any additional diagnostic testing thought necessary to achieve a diagnosis for the presenting symptoms. The medical records were reviewed to obtain the results of all diagnostic tests performed during the index hospitalization and for a period of 30 days after discharge. The institutional review board of Massachusetts General Hospital approved the study protocol, and all patients provided written informed consent.
Electrocardiographic-gated comprehensive computed tomography was performed using dual-source computed tomography (Definition, Siemens Medical Solutions, Forchheim, Germany). To determine the contrast volume and scan trigger time, a 20-mL intravenous bolus of contrast agent (iopamidol 370 mg iodine/ml, Isovue 370, Bracco Diagnostics, Princeton, New Jersey) was injected intravenously at a rate of 5 ml/s for opacification of the coronary artery lumen followed by saline injected intravenously at the same rate. Sequential scans were obtained at the level of the right pulmonary artery and aortic root at 2-second intervals beginning 4 seconds after contrast administration. The peak opacification time for the right pulmonary artery and aortic root was recorded. The interval to peak opacification in the aortic root served as the trigger time for initiating scan acquisition. To determine the total contrast volume to be infused for CT angiography, the difference between the interval to peak opacification in the right pulmonary artery and the interval to peak opacification in the aorta was added to the time required to cover the scan length, and this value was multiplied by the infusion rate. Retrospective image acquisition was performed during a single breath hold in inspiration in a caudal–cranial direction from the diaphragm to the lung apices. The imaging parameters included a slice collimation of 2 × 64 × 0.6 mm, a gantry rotation time of 330 ms, a temporal resolution of 83 ms, a tube voltage of 100 to 120 kVp, and a maximal tube current of 400 mA. To lower the radiation exposure, we used a 100 kVp for subjects with a body mass index <30 kg/m 2 and a 120 kVp for subjects with a body mass index ≥30 kg/m 2 . Aggressive tube current modulation, attenuation adaptation, and adaptive pitch selection were used in all patients.
Imaging in the dedicated arm was also performed using dual-source computed tomography (Definition, Siemens Medical Solutions). Cardiac CT scans were performed according to the standard protocol using retrospective electrocardiographic gating, field of view from the carina to the diaphragm, test contrast bolus followed by sufficient contrast with cover of the scan length as triggered by the aortic root, and a maximal tube current of 400 mA and 100 kVp for body mass index <30 kg/m 2 and 120 kVp for a body mass index ≥30 kg/m 2 , tube current modulation, attenuation adaptation, and adaptive pitch selection. Dedicated helical CT evaluation of the pulmonary arteries and dedicated CT evaluation of the aorta were performed according to the department protocol without electrocardiographic gating. Dedicated CT examination of the pulmonary arteries (240 mA, 120 kVp) covered a field of view from the lung apices to the diaphragm and used bolus tracking software in the right ventricle to trigger delivery of a fixed bolus of contrast according to weight (≤100 lb, 110 ml; 101 to 160 lb, 120 ml, and >160 lb, 130 ml). Lower extremity venography was acquired from the tibial plateaus to the top of the iliac crests approximately 180 seconds after the start of the initial infusion. Dedicated CT examination of the aorta (250 mA, 120 kVp) covered a field of view from the lung apices to the iliac bifurcation. A noncontrast-enhanced scan to evaluate for intramural hematoma was followed by a contrast-enhanced scan that used bolus tracking software in the descending thoracic aorta to trigger delivery of a fixed bolus (90 ml) of contrast.
The CT data sets were postprocessed and interpreted in real-time by cardiac imaging and emergency radiology physicians using a dedicated workstation immediately after the examination. Dedicated cardiac CT examinations and comprehensive CT examinations were qualitatively evaluated by Core Cardiology Training Symposium (COCATS) level III-trained physicians from the cardiac imaging service for the presence of coronary atherosclerotic plaque, luminal narrowing, and global and regional left ventricular function. All CT data sets were assessed for the presence of extracardiac findings, such as pneumonia, pneumothorax, and rib fracture and other cardiac pathologic features. The results were relayed to the emergency medicine attending physician caring for the patient immediately after the final interpretation. Although the subsequent patient treatment was at the full discretion of the ED attending physician caring for the patient, the ED physicians were offered nonbinding recommendations for the management of CAD as determined from the previous findings at the reporting of the CT findings by the cardiac imaging attending physicians: (1) no CAD and normal left ventricular function, discharge without additional cardiopulmonary diagnostic testing; (2) CAD with <25% luminal narrowing and normal left ventricular function, discharge without additional cardiopulmonary diagnostic testing if the findings from repeated electrocardiography and cardiac enzyme testing were negative at 6 hours; (3) CAD with <25% narrowing and global or regional left ventricular dysfunction or CAD with 25% to 75% narrowing, myocardial perfusion imaging if the findings from repeated electrocardiography and cardiac enzyme testing were negative at 6 hours; and (4) CAD with >75% narrowing, cardiology consultation for consideration of myocardial perfusion imaging or invasive angiography.
The primary end point of the present study was the length of hospital stay, defined as the interval from presentation to the ED to discharge from the ED or inpatient hospital unit, whichever occurred later. The present study was powered to detect a difference of 11.6 hours, which was previously reported for computed tomography versus nuclear imaging, with 90% power at a significance level of 0.05. Although no previous studies we are aware of have compared the length of stay between these CT strategies, we chose this length of stay difference as a surrogate, given the similarities in the diagnostic strategies.
The secondary end points included the interval to exclusion of an acute event, the rate of hospital discharge without additional imaging, the index hospitalization cost, radiation exposure, rate of incidental findings requiring follow-up, and the occurrence of major cardiovascular adverse events or follow-up visits within 30 days of follow-up.
The interval to the exclusion of an acute event was defined as the interval from presentation to the ED to the performance of the last diagnostic test clinically necessary to exclude acute coronary syndrome, PE, and/or thoracic AD. The rate of hospital discharge without additional imaging was defined as discharge that occurred when no additional diagnostic imaging test (e.g., single photon emission computed tomography, transthoracic echocardiography, or magnetic resonance imaging) was performed after the CT scan. The cost of the index hospitalization was determined from the ED and inpatient care costs, including laboratory and imaging tests.
Acute coronary syndrome was defined as either an acute myocardial infarction (ST-segment elevation myocardial infarction or non–ST-segment elevation myocardial infarction) or unstable angina according to the clinical discharge diagnosis. The presence of PE and AD was established or excluded according to the CT findings. A follow-up telephone interview using a standardized questionnaire was conducted 1 month after enrollment to determine the occurrence of events (i.e., death from all causes, myocardial infarction, and coronary revascularization). Any potential major cardiovascular adverse events, such as a report of recurrent symptoms resulting in medical consultation, diagnostic testing, or hospital admission, were subsequently validated by a review of the medical records by the outcome panel, whenever available.
The descriptive statistics were expressed as the mean ± SD or median with the interquartile range for continuous variables, depending on normality, and as the frequency and proportions for nominal variables. An analysis of the baseline characteristics of the groups was conducted using t tests for normal continuous variables, the Wilcoxon rank sum test for the non-normal continuous variables, and Fisher’s exact tests for binary variables. The length of stay, cost of hospitalization, and scan data are presented as the median and interquartile range, and the differences between the groups were assessed using Wilcoxon rank sum tests. All analyses were performed using SAS, version 9.1 (SAS Institute, Cary, North Carolina). A 2-tailed p value of <0.05 was considered statistically significant.
Results
A total of 59 patients agreed to participate and were enrolled during a cumulative 9-month enrollment period, 30 of whom were randomized to undergo a dedicated CT evaluation and 29 to undergo a comprehensive CT evaluation. The baseline characteristics of the enrolled subjects are listed in Table 1 . The most common exclusion criteria were a known history of CAD (45%) and serum creatinine clearance of <60 ml/min (22%). Sample images from a comprehensive scan are displayed in Figure 1 . The mean age of all subjects was 51 years; no difference was found in the age between subjects undergoing a dedicated CT scan (52.6 ± 10.6 years) and those undergoing a comprehensive CT scan (49.7 ± 12.2 years; p = 0.34). The subjects were primarily white (88%) and men (73%); however, no significant difference was found in gender composition (67% vs 79%, p = 0.38) or race (93% vs 83%, p = 0.42) between the 2 groups.
| Variable | Overall (n = 59) | Comprehensive (n = 29) | Dedicated (n = 30) | p Value |
|---|---|---|---|---|
| Age (years) | 51.2 ± 11.4 | 49.7 ± 12.2 | 52.6 ± 10.6 | 0.34 |
| Men | 43 (73%) | 23 (79%) | 20 (67%) | 0.38 |
| Body mass index (kg/m 2 ) | 28.7 ± 5.3 | 28.7 ± 6.0 | 28.7 ± 4.7 | 0.99 |
| White | 52 (88%) | 27 (93%) | 25 (83%) | 0.42 |
| Primary suspicion | 0.93 | |||
| Acute coronary syndrome | 30 (51%) | 14 (48%) | 16 (53%) | |
| Pulmonary embolus | 24 (41%) | 12 (41%) | 12 (40%) | |
| Aortic dissection | 5 (9%) | 3 (10%) | 2 (7%) | |
| Average Thrombolysis In Myocardial Infarction score | 0.9 ± 0.9 | 1.1 ± 1.1 | 0.7 ± 0.8 | 0.10 |
| Hypertension | 16 (27%) | 13 (45%) | 3 (10%) | 0.003 |
| Hyperlipidemia | 13 (22%) | 8 (28%) | 5 (17%) | 0.36 |
| Diabetes mellitus | 6 (10%) | 3 (10%) | 3 (10%) | 1.00 |
| Current or past smoker | 12 (20%) | 6 (21%) | 6 (20%) | 1.00 |
| Family history of coronary artery disease | 26 (44%) | 13 (45%) | 13 (4%) | 1.00 |
Overall, the primary clinical suspicion for which a CT scan had been considered before recruitment was 50.8% acute coronary syndrome, 40.7% PE, and 8.5% AD. No difference was found between the dedicated and comprehensive groups (acute coronary syndrome 53.3% vs 48.3%; PE 40.0% vs 41.4%; AD 6.7% vs 10.3%, p = 0.93). acute coronary syndrome, PE, and AD were ruled out in all but 1 patient in the dedicated CT arm, who was diagnosed with PE according to the CT findings. As listed in Table 2 , no significant difference was found in the primary end point, the median length of stay (7.6 vs 8.2 hours, p = 0.79), or in the secondary end points, the rate of hospital discharge without additional imaging (70% vs 69%, p = 0.99), interval to the exclusion of the acute event (5.2 vs 6.5 hours, p = 0.64), or hospitalization costs (p = 0.16), between the dedicated and comprehensive CT arms, respectively. Additional testing was ordered by the treating physicians for 47% of all subjects in the dedicated CT arm to exclude an acute event versus 52% of subjects in the comprehensive CT arm, a difference that was not statistically significant (p = 0.61). A summary of additional testing is shown in Figure 2 .
