“Triple rule-out” (TRO) computed tomography is an electrocardiographically synchronized study of the chest intended to allow the evaluation of three important causes of acute chest pain with one test: acute coronary syndrome (ACS), dissection or other acute aortic syndrome, and acute pulmonary embolism (PE) . In the study reported in this issue, Halpern et al compared image quality and arterial enhancement in a TRO protocol to that obtained with a dedicated coronary computed tomographic angiographic (cCTA) protocol. In the largest study on this topic yet published, the authors demonstrate similar subjective coronary image quality and objective aortic, coronary, and pulmonary arterial enhancement for the two approaches. It is worth noting that there are some differences between the two patient groups studied—an acute chest pain emergency department (ED) cohort for the TRO protocol and an outpatient cohort with a mix of presentations for the dedicated cCTA protocol—that may affect perceived image quality. Although patient size, the use of β-blockers, and heart rate were well matched, the TRO group was younger and had more women than the cCTA group. The authors’ definition of coronary image quality evaluated only image blurring, which is primarily influenced by heart rate, heart rate variability, and patient size. However, other factors can affect coronary visualization on computed tomography, including the presence of coronary calcium, which was likely greater in the outpatient cCTA group given the higher pretest probability of coronary artery disease (CAD) generally seen in outpatients undergoing cCTA imaging than ED patients. An ideal study would randomize ED patients to a cCTA or a TRO protocol prospectively, but this may not be practically possible, and it is reasonable to expect that the results of such a study would be similar.
Although this and other studies demonstrate the feasibility of such an approach to imaging patients with acute chest pain, questions remain concerning the use of an all-in-one study compared to protocols dedicated to evaluating each entity, with regard to both patient safety (contrast and radiation dose) and clinical necessity.
In two previous publications, this group attempted to address these concerns by evaluating radiation dose and diagnostic outcomes in the same cohort of patients . The authors showed that by using electrocardiographically gated tube-current modulation, the average dose for a TRO study could be decreased from 18.0 to 8.8 mSv, and studies could be performed with <100 mL of intravenous contrast. These findings are somewhat at odds with a smaller study performed using the same scanner model that reported a mean dose of 32.2 mSv for a TRO protocol performed without tube-current modulation, using 130 mL of contrast. Another study, performed using a dual-source scanner , demonstrated an average dose of 16.6 mSv using stricter tube-current modulation (the low-dose tube current was only 4% of the reference value) with 110 mL of contrast. This difference can be explained by the greater amount of the chest scanned covered in the higher dose protocols, about 30 versus 21 cm, which would translate into both more radiation and the need for more contrast to maintain adequate pulmonary artery opacification during a longer scan. This raises the issue of what defines a TRO study: Is scanning from the aortic arch to base of the heart sufficient, as in the current study, or must one cover the entire chest to exclude PE confidently, as in the previous two studies, although only 30% of PEs are identified in the upper lobes , so that few would be missed by not scanning above the aortic arch. However, one could ask whether many more would be missed by following a dedicated cCTA protocol, as long as full field of view images were reconstructed. This is a relevant point given recent concerns about radiation dose received during computed tomography. Halpern et al estimated a 25% to 30% increase in dose for the TRO protocol, whereas Rahmani et al measured a 50% increase using the same scanner, and Schertler et al estimated a 137% increase for dual-source computed tomography. The incremental dose received in a TRO study over dedicated cCTA imaging will of course depend on the length chosen for each scan, which partially explains the differences between these studies. These numbers can also be compared to an average dose of 5 to 7 mSv for standard nongated PE studies , which generally cover the entire chest. Although the increased contrast dose should be of some concern, centers performing cCTA or TRO studies on patients with acute chest pain generally limit them to those with normal renal function.
The clinical necessity of a TRO protocol may be assessed by examining the incidence of each of the three entities being evaluated. In the outcomes study of the same patient cohort , 22 of 197 patients (11%) had >50% coronary stenosis, whereas only three (1.5%) and one (0.5%) had PE or aortic dissection, respectively, and it is not known whether these would have been detected anyway using a dedicated cCTA protocol. At my institution, we perform dedicated cCTA imaging on low to intermediate-risk ED patients with chest pain of concern for ACS using a weight-based three-phase contrast injection protocol to maintain some right ventricular and pulmonary arterial opacification, for a total contrast dose of 80 to 120 mL. In our initial published series of 568 patients, we diagnosed coronary stenosis >50% in 11% of patients, but none of the studies demonstrated PE or acute aortic syndrome, and no patients had a discharge diagnosis of either of these entities , though we have since found one PE in >1500 studies (unpublished results). Although, as noted by Dodd et al , pulmonary artery opacification on cCTA studies may not be adequate to exclude PE), the results at both our centers suggest that these diagnosis are very uncommon in ED patients with chest pain with suspicion of ACS. Interestingly, Schertler et al , performed TRO studies on 125 patients with high clinical suspicion of PE as determined by Wells score and positive d -dimer; acute aortic syndrome was also considered a possibility in 11%. They diagnosed PE in 21% of patients, acute aortic syndrome in 4%, and significant CAD in 3%, including only patients later shown also to have evidence of ACS. An additional 6% of patients had significant CAD, but they were without clinical suspicion, signs, or laboratory findings of ACS, and the CAD was felt to be incidental, for a total of 13% of patients diagnosed with the non-PE elements of the TRO protocol.
In summary, Halpern et al and others have demonstrated that it is possible to perform a TRO study with good coronary, pulmonary, and aortic image quality, but no one has yet demonstrated its necessity in patients presenting with acute chest pain of concern for ACS. The incidence of PE and aortic dissection in low to intermediate-risk patients with ACS seems to be quite low and may not justify the considerably increased radiation dose required using current computed tomographic techniques, although one study suggests that TRO scans may have a role in patients with high clinical suspicion of PE. Newer techniques such as prospective electrocardiographic triggering, large-volume detectors, and high-pitch helical electrocardiographically gated scanning may allow TRO studies to be performed at a much lower radiation dose, perhaps reducing the threshold of clinical necessity required for their acceptance.
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