The Radioactive Heart

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For Journal Club this past week we covered what is undoubtably one of the more controversial diagnostic tests used in the evaluation of patients presenting to physicians with chest pain.  The most recent NICE guidelines recommend Coronary CT as the first line test for patients with stable angina symptoms but don't Coronary CT's lead to increased downstream testing? more radiation exposure? To investigate this topic we took a look at 3 articles focused on the utility of Coronary CT scans. Take a listen to the podcast and read the recap to learn for yourself.

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Hoffmann U, Truong QA, Schoenfeld DA, et al. Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain. N Engl J Med 2012;367(4):299–308. 

Methods

This was a multicenter, randomized controlled trial in an ED population.  The study compared coronary CTs to standard evaluation - exercise or nuclear stress testing - in 1000 patients with moderate risk chest pain whom ED physicians felt required further risk stratification after their initial ED evaluation.  The study population were men and women age 40-74 without a prior diagnosis of CAD, nonischemic and normal sinus EKG, negative troponin, normal creatinine, and BMI <40.  

The primary endpoint was ED length of stay - which was felt to be a proxy of aggregate medical decision making and an implication of efficacy and efficiency.  

Secondary endpoints looked at time to diagnosis, rate of discharge from the ED, cost, cumulative radiation  

Additionally, study investigators followed patients up to screen for missed ACS in 72 hours as well as complications of their testing.

Author’s Conclusions

The rate of ACS in this study population was 8%.  There was no increase in missed ACS or adverse effects with discharge from the ED after CCTA.  There was a statistically significant decrease in time to ED discharge (7.6 hours, p<0.001), as well as rate of ED discharge, in the CCTA group.  There was no statistically significant difference in the cost of CCTA vs standard evaluation.  There was a statistically significant increase in radiation exposure in the CCTA group.  More patients in the CCTA group underwent invasive testing after ED discharge.  

Our Conclusions

CCTA did allow earlier and increased rates of discharge from the ED - which, from a purely pragmatic and system-wide standpoint, could have huge ramifications for overall patient care.  However, patients who underwent CCTA then went on to receive increased rates of invasive testing - rather than preventing a coronary angiogram, does a CCTA merely defer it?  The cost data presented by Hoffman et al are also difficult to interpret, as it’s not entirely clear how that data was abstracted.  There was concern raised that coronary CTs exposed the patients to more radiation, though certainly that will depend on the local practice regarding noninvasive stress modalities - does everyone at your institution receive a nuclear stress, which carries a similar radiation load?  And ultimately, unfortunately, as much as the more pragmatic aspects of ED care are important, what about patient centered, clinical outcomes?  This study was not powered to detect differences in clinical outcomes such as MACE or mortality.

Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease. N Engl J Med 2015;372(14):1291–300.

Methods

Pragmatic comparative effectiveness design at 193 enrolling sites in North America looking at symptomatic outpatients without a history of CAD for whom the treating physicians believed that non urgent, noninvasive cardiovascular testing was deemed necessary.  The patients selected were >54 yo (if male), >64 yo (if female) with at least one cardiovascular risk factor.  Could not have an evaluation for CAD in the previous 12 months or a history of congenital, valvular, or cardiomyopathic heart disease.  After enrollment, patients were randomized either to receive a Coronary CT (CCTA) or functional-testing. 

Primary end point: Composite outcome of death, MI, admission for unstable angina and complications from major cardiovascular procedures or diagnostic testing.

Secondary end points

  • Composite of primary outcome or invasive catheterization showing no obstructive CAD.
  • Combinations of primary outcome + invasive catheterization with no obstructive CAD + cumulative radiation exposure (at 90 days)

Results

10,003 patients underwent randomization.  At 12 months, 95.1% of the CCTA group and 91.9% of the functional testing group completed the study protocol (the majority of this difference was made up of patients who withdrew their consent).

Who were these patients? Mean age was 61 yo, slightly over 50% of them were women, and 22.6% were part of a racial or ethnic minority.  They had a mean of 2.4 cardiovascular risk factors.  2/3rds of them had a 10 year risk of cardiovascular events >7.5% as calculated by the ACC-AHA 2013 Cardiovascular disease risk score.  Risk factors and baseline characteristics were equally distributed between the 2 groups.

Primary end point - HR 1.04 (0.83-1.29) - not just not significantly different but also upper bound exceeded pre-specified non-inferiority

  • CCTA group - 3.3%
  • Functional testing - 3.0%

Who got cathed? 12.2% of the CCTA group vs 8.1% of the functional testing group (within 90 days)

What did it show? Of the caths done in the CCTA 27.9% showed non-obstructive CAD.  Of the caths done in the functional testing group 52.% had non-obstructive CAD. More patients in the CTA group ended up with revascularization at 90 days as compared to the functional testing group (6.2% vs 3.2%, p<0.0001)

What about the radiation? It’s complicated…

32.6% of the patient in the functional testing group vs 4.0% of patients in the CTA group had NO ionizing radiation exposure.  

Median exposure was lower in the CTA group but mean exposure was higher in the CTA group.  Of the patients where their physician intended to refer them to nuclear stress testing, cumulative radiation exposure was lower in the CTA group (10.1 mSv vs 12.0 mSv, p<0.001)

What did the authors take from this?

“The strategy of anatomical testing with CTA compared to functional testing did not reduce the incidence of events over a median follow-up of 25 months”

CCTA strategy was associated with a lower incidence of non-obstructive cardiac catheterization at 90 days (though more patients underwent cardiac catheterization and revascularization).  However, the study wasn’t powered to detect the effect of additional diagnostic tests.

What should we take from this?

First, assuming that they are receiving standard outpatient care, patient’s with stable angina symptoms (which we do see in the ED) have a generally low rate of major cardiac events and death despite having cardiovascular risk factors.  

More patients who receive a CCTA will receive a cardiac catheterization as compared to the functional testing group.  More of these caths will be positive and you’ll be more likely to get revascularization (stenting) if you have a CCTA.  But, the real question is what does that mean for the patients?  Is it beneficial to stent a 70% occlusion in a patient with stable angina, or would aggressive medical management be as good or better?  Ultimately the answer to that question is outside of the scope of this article and will need additional study.

Morris JR, Bellolio MF, Sangaralingham LR, et al. Comparative Trends and Downstream Outcomes of Coronary Computed Tomography Angiography and Cardiac Stress Testing in Emergency Department Patients With Chest Pain: An Administrative Claims Analysis. Academic Emergency Medicine 2016;23(9):1022–30.

This paper utilizes a large database of claims data in order to analyze utilization of CCTA and functional stress testing in the evaluation of chest pain in the Emergency Department, and to assess associations between CCTA and functional stress testing with invasive downstream testing, hospital utilization, and acute MI. The database includes insured individuals in the United States presenting to the Emergency Department and given a primary diagnosis of chest pain, and was queried for an eight year time period ending in 2013. 

In terms of utilization, the authors found that use of CCTA is on the rise, increasing from 0.8% to 4.5% of all cardiac testing within 72 hours of patient presentation. However, it still accounts for only a small minority of testing. For example, in 2013, scintigraphy was ordered 1,300 times for every 10,000 patient visits, whereas CCTA was ordered only 88 for every 10,000 patient visits. 

With regard to outcomes and utilization, after propensity score matching, there was no difference between CCTA and other functional testing modalities in the rate of 30 day acute myocardial infarction. However, CCTA was associated with a higher likelihood of repeat cardiac stress testing. Moreover, compared to treadmill ECG, CCTA was associated with a greater likelihood of PCI. Compared to scintigraphy, CCTA was associated with higher rates of PCI and CABG. Finally, compared to stress echo, it was associated with higher rates of each of invasive angiography, PCI and CABG. Of note, this study was unable to assess mortality as an outcome.

Limitations of this study include the potential for coding errors or differences in coding between providers, exclusion of patients with anginal equivalents given primary diagnoses other than chest pain, and the inherent bias associated with choosing covariates for propensity matching.