This study set out to examine the downstream effects of negative ESE or CCTA when chosen as the initial noninvasive test for suspected CAD. As described in detail above, the choice of ESE was found to have a greater number of downstream tests, but was associated with a lower total cost. We originally hypothesized that CCTA would be associated with both total lower number of downstream tests and total cost due to the previously published negative predictive value of CCTA in RCTs.
In the past few years, two large RCTs, PROMISE and SCOT-HEART, have compared clinical outcomes between groups randomized to functional or anatomic testing with CCTA. As a result of these two and other studies, the European Society of Cardiology (ESC) guidelines for chronic coronary endorsed CCTA as a Class I recommendation for initial test to diagnose CAD [8]. As found in the PROMISE trial, there was no major difference between the CCTA and functional testing arms when comparing the primary composite outcome of death from any cause, nonfatal myocardial infarction (MI), hospitalization for unstable angina, or procedural complication. However, the CCTA arm showed statistically significant increases in total radiation, a 4.1% absolute increase in diagnostic cardiac catheterizations, and a 3.0% absolute increase in revascularization [6]. The SCOT-HEART trial remarkably showed that patients undergoing an anatomic evaluation with CCTA had a lower primary endpoint of death from CAD or nonfatal MI than the standard care group, predominately driven by nonfatal MI [9]. The authors hypothesized that this was due to increased preventive therapy for primary prevention of MI including statins, aspirin, lifestyle interventions, and revascularization when appropriate. They also hypothesized this may be due to increased patient motivation given objective measure of disease.
Notably, ESE was underrepresented in the functional imaging control group in both landmark studies. Specifically, only 22% of patients underwent ESE compared to 67% undergoing nuclear testing in the PROMISE trial [6]. Less than one percent of patients underwent ESE in the SCOT-HEART trial [5]. Furthermore, while the authors are aware of at least one prospective RCT comparing clinical outcomes between myocardial perfusion imaging (MPI) and CCTA we are unaware of any studies directly comparing ESE to CCTA in the outpatient setting, [10]. Upon our review of the literature, there has only been one RCT comparing ESE vs CCTA. Levsky et al. enrolled 400 patients without known CAD presenting with chest pain to the emergency department and showed that ESE and CCTA led to similar results in major adverse cardiac events (MACE), invasive angiography, and revascularization by one year. Patients in the CCTA arm were admitted more often and spent more days in the hospital than the patients in the ESE group [11].
Moreover, ESE possesses a few clear advantages when compared to CCTA. Despite the growing use of CCTA, ESE remains widely available in the clinic and emergency department settings with minimal equipment requirements. In addition to wall motion analysis, additional prognostic data can be derived, such as metabolic equivalents, heart rate response, and exercise induced hypertension. For patients being referred for cardiac testing with chief complaint of dyspnea, ESE can provide diagnostic information in nonischemic etiologies, including exercise-induced diastolic dysfunction, pulmonary hypertension, and severity of mitral valve disease. Importantly, ESE does not expose the patient to ionizing radiation. These advantages are in addition to the post cost savings discussed above.
Our study has several strengths. It benefits from the comprehensive electronic medical record available through the Department of Defense health system. As a result, over 11,000 patients were screened. Additionally, propensity matching was completed as outlined above, further strengthening the comparison between the two arms [12]. Our trial has some limitations. First, while the studied populations underwent propensity matching, this cannot eliminate all potential cofounders present in this retrospective analysis. Second, the results may lack generalizability given the population studied was Tricare beneficiaries. This is exemplified by the notable low pre-test probability noted in our study even after excluding very-low risk patients with a CAD consortium pretest probability of less than five percent. Lastly, it is retrospective and thus it should principally be viewed as hypothesis-generating.
This study demonstrates an association between ESE with higher total number of downstream tests as well as lower costs when compared to CCTA. These findings are unexpected and potentially worthwhile as the cardiology community moves towards CCTA as a first line test for suspected CAD. As these findings are retrospective, future RCTs specifically examining the financial and clinical outcomes of CCTA compared with ESE would bring further clarity to these questions.