Sinai EM Journal Club

For the final journal club of the year, Ravi picked an article from Goldstein (and others)  entitled, “A Randomized Controlled Trial of Multi-Sliced Coronary Computed Tomography for Evaluation of Acute Chest Pain” (available from the Journal of the American College of Cardiology, 2007 Vol 49, No. 8, pp863-871).

It’s not the definitive, practice-changing study we’re waiting for, but it draws upon previous work (such as JAMA 2005; 293:2471-8) estabilishing multi-slice CT coronary angiography as effective in diagnosing occlusion, and attempts to compare the safety, efficacy and efficiency of MSCT against established protocols.

Specifically, the authors looked at safety (in terms of major adverse cardiac events — MACE — at 6 months), diagnostic efficacy (difined as correctly diagnosing, or excluding, CAD as the cause of chest pain, without repeat testing or MACE within 6 months), and efficiency (a combination of time-to-diagnosis and cost during first ED visit).  We must note that the trial received funding from Minestrelli Advanced Cardiac Research Imaging (sometimes spelled Ministrelli).

They enrolled 203 “low risk” patients with acute chest pain (older than 25 years, symptoms of angina or equivalent within 12 hours, and low risk of infarction according to criteria from Goldman and others). Patients were excluded if they had known CAD, EKG changes, elevated enzymes, or cardiomyopathy with low EF, arrhythmia, history of contrast reactions or beta-blocker allergy, morbid obesity, renal insufficiency, or recent contrast CT.

If the patients’ 0-hr and 4-hr EKG and serum biomarkers were normal, they were randomized into the MSCT or the standard-of-care group. Enrollment was 24 hrs a day, but MSCT and SPECT was only available 7a-6p, so the cost of waiting was also figured into their results.

The 99 patients in the MSCT arm got beta-blockade (if they weren’t already on it) of atenonol 50-100mg +/- metoprolol 5-30mg to get their HR below 65 (though greater HR was not a contraindication to the study). Everyone also got a sublingual nitrogen a minute before the CT. The coronary lesions seen on CT were clasified on a 5 point scale, with 0 = no stenosis and 5 = total occlusion.

These patients in the MSCT arm would go home if their coronary scores were 1 or lower (or if their calcium score was under 100 Agatstons), or they’d get invasive angiography (catheterization) if their scores were 4 or higher (>70% occlusion). In-between, or non-diagnostic scans would get a nuclear stress test.

The 98 patients in the Standard of Care (SOC) arm received serial EKG’s and biomarker studies at 4h and 8hr after presentation. Troponins greater than 1.5 ng/mL, CK-MB greater than 5 ng/mL, or myoglobins over 98 ng/mL were considered abnormal. Patients received same-day SPECT (single photon emission CT) myocardial perfusion stress-tests or nuclear stress tests.

These SOC patients would go home if their EKG’s, biomarkers, and stress tests were normal. They’d get cathed if they had any abnormalities in EKG, enzymes, or stress test. (The final decision to cath, it should be noted, rested in the PMD’s hands).

It’s helpful to keep some concepts in mind: this study really just compared ways of diagnosing coronary artery disease, specifically,  CT vs. stress testing. There was no straight-up comparison to gold standard of PCI. And the enzymes/EKG portion was just a warmup to rule-out MI and stratify out the high-risk group, who would go straight to PCI anyway.

In terms of safety, well, there were no MACE within 6 months of the 88 MSCT patients (out of 99 total) that were discharged home from the ED (this is 67 patients with no or minimal coronary occlusion, plus 21 patients with intermediate or non-diagnostic MSCT who had negative stress tests). Similarly, there was no 6-month adverse events in the 95 (of the 9 SOC patients who went home.

In terms of diagnostic efficacy, MSCT alone was not adequate for diagnosis is 24 of 99 cases. Twelve of 99 underwent catheterization — eight of these were true positives, three were false positives, and one was a true negative. As the authors state, “96 of 99 patients were judged to have a clinically correct diagnosis.” Compare this to the SOC patients — only 7 of which (out of 9 underwent catheterization (one was a true positive, two were false positives, and four were false negatives). In total, “96 of the 98 SOC patients were judged to have a clinically correct diagnosis.” This stands as a pretty remarkable validation of standard-of-care risk stratification, based on the Goldman criteria.

Finally, in terms of efficiency, the time-to-diagnosis was found to be faster with MSCT (3.4 h vs. 15 hours) even though nuclear stress and MSCT were only available during daylight hours. Because of this reduced length-of-stay, the cost of care for patients in the MSCT arm was less ($1586 vs $1872 for SOC).

We noted that, while no negative outcomes in 6 months of followup is nice, it really suggests a larger trial is needed. Especially because we’re already starting with low-risk patients. Another way of knowing you need a bigger trial is calculating the positive and negative likelihood ratios of CAD with findings on MSCT. The positive LR was 4 (meaning, positive findings on the MSCT essentially quadrupled the odds the patient had significant occlusion), but the negative LR was 0… which just can’t be true. A larger sample is needed.

In the same issue, this journal also published editorial comments from de Fuyter and van Pelt. The editorial acknowledges that the real power of coronary CT might be in calcium scoring and total plaque burden calculation, but for now, we’re left wondering the value of the new tools we do have, especially in comparison to standbys like stress testing and PCI. The authors helpfully put some numbers on a concept we brought up in discussion: how much radiation are we talking about? (because, let’s not forget, some unfortunate patients had to undergo MSCT, nuclear stress, then PCI):

The editorialists also noted, wisely, that, ”A comprehensive evaluation of thoracic structures for noncardiac disease such as pneumonia, pleural calcification, and hiatal hernia might add to the usefulness of MSCT as a diagnostic tool when compared with other modalities such as nuclear and dobutamine stress testing.”

The ACEP clinical policy group just weighed in on NSTE ACS – but sadly does not mention the role of coronary CT in evaluating chest pain. Fortunately, EMCrit.org has a spectacular page on ACS — including likelihood ratios of physical exam findings, many important risk-stratification schemes, pathways for cases of renal insufficiency and cocaine (among others)… but this site, too, currently lacks guidance on the role of coronary CT. But because CT can visualize vessel walls and other sources of chest discomfort, we might someday look to CT as superior to PCI.