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Coronary Computed Tomography Angiography Versus Radionuclide Myocardial Perfusion Imaging in Patients With Chest Pain Admitted to Telemetry: A Randomized TrialCCTA Versus Nuclear Stress for Chest Pain

Jeffrey M. Levsky, MD, PhD; Daniel M. Spevack, MD, MS; Mark I. Travin, MD; Mark A. Menegus, MD; Paul W. Huang, MD; Elana T. Clark, MD; Choo-won Kim, MD; Esther Hirschhorn, BS; Katherine D. Freeman, DrPH; Jonathan N. Tobin, PhD; and Linda B. Haramati, MD, MS
[+] Article, Author, and Disclosure Information

This article was published online first at www.annals.org on 9 June 2015.


From Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York.

Acknowledgment: The authors thank study coordinators Rizwan Aslam, Prameela Banoth, Shimon Farkas, Adina Haramati, Raphael Hulkower, David Kawior, Kristen Launier, Rikah Lerer, Shey Mukundan, Dieudonne Nonga, Paul O'Connor, Danny Nhan, Shayne Sebold, Samantha Selesny, Daniel Sova, Christian Stanton, and Shayna Vega. They thank Hannah Simons for help with statistical analyses and Nina Ackerman for help with analyzing socioeconomic status. They also acknowledge the contribution of the study's data and safety monitoring board members: Drs. Michael Farkouh, Gregory Pearson, Yungtai Lo, Michelle Johnson, and James Godbold.

Grant Support: By the American Heart Association Clinical Research Program (grant 0885024D) and the National Center for Advancing Translational Sciences (Clinical and Translational Science Award grants 1 UL1 TR001073-01), a component of the National Institutes of Health.

Disclosures: Dr. Travin reports a grant and other funds from GE Healthcare during the conduct of this study. Dr. Tobin reports receiving grants from National Institutes of Health, Agency for Healthcare Research and Quality, Patient-Centered Outcomes Research Institute, and Centers for Disease Control and Prevention during the conduct of the study. Dr. Levsky reports grants from American Heart Association during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=M14-2948.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Study protocol, data set, and statistical code: Available from Dr. Levsky (e-mail, jlevsky@montefiore.org). Statistical code: Not applicable.

Requests for Single Reprints: Jeffrey M. Levsky, MD, PhD, Department of Radiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467-2490; e-mail, jlevsky@montefiore.org.

Current Author Addresses: Drs. Levsky and Haramati: Division of Cardiothoracic Imaging, Department of Radiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467-2490.

Drs. Spevack and Menegus: Division of Cardiology, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467-2490.

Dr. Travin: Division of Nuclear Medicine, Department of Radiology, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467-2490.

Dr. Huang: Division of Hospital Medicine, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467-2490.

Dr. Clark: Cohen Children's Medical Center, 269-01 76th Avenue, New Hyde Park, NY 11040.

Dr. Kim: Department of Radiology, Stony Brook School of Medicine, 100 Nicolls Road, HSC L4 Room 120, Stony Brook, NY 11794-8460.

Ms. Hirschhorn: 1925 Eastchester Road, Apartment 6A, Bronx, NY 10461.

Dr. Freeman: Extrapolate Statistics, 1145 Harbor Drive, Suite 1A, Delray Beach, FL 33483.

Dr. Tobin: Clinical Directors Network, 5 West 37th Street, 10th Floor, New York, NY 10018.

Author Contributions: Conception and design: J.M. Levsky, D.M. Spevack, M.I. Travin, K.D. Freeman, J.N. Tobin, L.B. Haramati.

Analysis and interpretation of the data: J.M. Levsky, D.M. Spevack, M.I. Travin, M.A. Menegus, E. Hirschhorn, K.D. Freeman, J.N. Tobin, L.B. Haramati.

Drafting of the article: J.M. Levsky, M.A. Menegus, J.N. Tobin, L.B. Haramati.

Critical revision for important intellectual content: J.M. Levsky, D.M. Spevack, M.I. Travin, M.A. Menegus, E.T. Clark, C. Kim, E. Hirschhorn, K.D. Freeman, J.N. Tobin, L.B. Haramati.

Final approval of the article: J.M. Levsky, D.M. Spevack, M.I. Travin, M.A. Menegus, E.T. Clark, C. Kim, E. Hirschhorn, J.N. Tobin, L.B. Haramati.

Provision of study materials or patients: M.I. Travin, L.B. Haramati.

Statistical expertise: J.M. Levsky, K.D. Freeman, J.N. Tobin.

Obtaining of funding: J.M. Levsky, J.N. Tobin.

Administrative, technical, or logistic support: D.M. Spevack, M.A. Menegus, E.T. Clark, J.N. Tobin. L.B. Haramati.

Collection and assembly of data: J.M. Levsky, E.T. Clark, C. Kim, E. Hirschhorn, J.N. Tobin, L.B. Haramati.


Ann Intern Med. 2015;163(3):174-183. doi:10.7326/M14-2948
Text Size: A A A

Background: The role of coronary computed tomography angiography (CCTA) in the management of symptomatic patients suspected of having coronary artery disease is expanding. However, prospective intermediate-term outcomes are lacking.

Objective: To compare CCTA with conventional noninvasive testing.

Design: Randomized, controlled comparative effectiveness trial. (ClinicalTrials.gov: NCT00705458)

Setting: Telemetry-monitored wards of an inner-city medical center.

Patients: 400 patients with acute chest pain (mean age, 57 years); 63% women; 54% Hispanic and 37% African-American; and low socioeconomic status.

Intervention: CCTA or radionuclide stress myocardial perfusion imaging (MPI).

Measurements: The primary outcome was cardiac catheterization not leading to revascularization within 1 year. Secondary outcomes included length of stay, resource utilization, and patient experience. Safety outcomes included death, major cardiovascular events, and radiation exposure.

Results: Thirty (15%) patients who had CCTA and 32 (16%) who had MPI underwent cardiac catheterization within 1 year. Fifteen (7.5%) and 20 (10%) of these patients, respectively, did not undergo revascularization (difference, −2.5 percentage points [95% CI, −8.6 to 3.5 percentage points]; hazard ratio, 0.77 [CI, 0.40 to 1.49]; P  = 0.44). Median length of stay was 28.9 hours for the CCTA group and 30.4 hours for the MPI group (P = 0.057). Median follow-up was 40.4 months. For the CCTA and MPI groups, the incidence of death (0.5% versus 3%; P = 0.12), nonfatal cardiovascular events (4.5% versus 4.5%), rehospitalization (43% versus 49%), emergency department visit (63% versus 58%), and outpatient cardiology visit (23% versus 21%) did not differ. Long-term, all-cause radiation exposure was lower for the CCTA group (24 versus 29 mSv; P < 0.001). More patients in the CCTA group graded their experience favorably (P = 0.001) and would undergo the examination again (P = 0.003).

Limitation: This was a single-site study, and the primary outcome depended on clinical management decisions.

Conclusion: The CCTA and MPI groups did not significantly differ in outcomes or resource utilization over 40 months. Compared with MPI, CCTA was associated with less radiation exposure and with a more positive patient experience.

Primary Funding Source: American Heart Association.

Figures

Grahic Jump Location
Figure.

Study flow diagram.

CCTA was not performed in 13 patients because of patient refusal (n = 9), physician decision (n = 1), technical difficulty (n = 1), and safety concerns (n = 2); of these, 7 patients received MPI. MPI was not performed in 11 patients because of patient refusal (n = 6), physician decision (n = 4), and technical difficulty (n = 1); of these, 0 patients received CCTA. During hospitalization, 6 patients who received initial CCTA had additional MPI and 4 patients who received initial MPI had additional CCTA. Patients lost to follow-up could not be contacted by any means, including identification and inquiry of any treating physicians. All patients were included in the primary analysis (Cox proportional hazards model). CAD = coronary artery disease; CCTA = coronary computed tomography angiography; ICD = implantable cardioverter-defibrillator; MPI = radionuclide stress myocardial perfusion imaging.

* Based on admission to telemetry from the emergency department for chest pain and absence of acute myocardial infarction or ischemia.

† Recent imaging means CCTA, MPI, or cardiac catheterization within 6 mo.

‡ Managing physician had already chosen a noninvasive imaging modality and would not allow the patient to be randomly assigned.

§ Other reasons for exclusion are listed in the Appendix Table).

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Tables

References

Letters

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Comments

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Limitations of this study.
Posted on August 13, 2015
Wade Martin, MD, FACP
Washington University School of Medicine/St. Louis Veterans Administration Medical Center
Conflict of Interest: None Declared
The study by Levsky et al. (August 4th issue) on coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in telemetry patients with chest pain reported little or difference in outcome or other endpoints between these 2 modalities. However, a major limitation of this study is that the most important non-invasive information for evaluation of prognosis and outcome in patients with chest pain was not reported. Thus, there was no information in this paper on exercise capacity, heart rate or blood pressure responses to exercise, heart rate recovery, exercise-associated symptoms, ST-segment changes, dysrhythmias or other electrocardiographic (ECG) findings. There also was no data regarding how many participants even met appropriate use criteria for cardiac imaging. How many participants had resting ECG findings that would preclude interpretation of the stress ECG? How many underwent treadmill testing and how many were evaluated with pharmacologic evaluations? Unfortunately, anatomic and imaging information often has questionable functional and clinical relevance, necessitates exposure to significant radiation, is several times more expensive than exercise ECG stress testing, and fails to provide powerful prognostic and clinically important information on exercise capacity, symptomatic, cardiovascular, and ECG responses to the relevant physiologic stress of exercise. Exercise capacity is one of the most powerful predictors of all-cause and cardiovascular mortality1 and functional capacity is an important measure of quality of life. Heart rate recovery also has a strong inverse relationship with death,2 independent of exercise capacity. Peak heart rate and ventricular dysrhythmias are robust predictors of mortality3 and the Duke Treadmill Score is a well-validated and widely used marker of cardiovascular mortality.4 For patients who cannot perform treadmill or other leg exercise, we have reported that arm exercise capacity, heart rate recovery, and other responses are highly predictive of mortality.5 Exercise-induced ECG abnormalities, angina and other symptoms are clinically relevant findings that may result in coronary revascularization or changes in medical management that improve the length or quality of life, particularly in the context of the COURAGE trial. Although the approach described in this paper likely reflects clinical practice in the United States, it is Exhibit A for why per American capita health care costs are twice those of any other developed nation, yet our longevity is in the lowest 10% of those countries. Such an approach is doubtfully consistent with the Choosing Wisely initiative of the American Board of Internal Medicine, particularly for inner city hospitals.

1. Myers J, Prakash M, Froelicher V, et al. Exercise capacity and mortality among men referred for exercise testing. N Eng J Med 2002; 346:793-801.
2. Cole CR, Blackstone EH, Pashkow FJ, et al. Heart rate recovery immediately after exercise as a predictor of mortality. N Eng J Med 1999; 341:1351-1357.
3. Jouven X, Zureik M, Desnos M, et al. Long term outcome in asymptomatic men with exercise-induced premature ventricular depolarizations. N Eng J Med 2000; 343:826-833.
4. Mark DB, Shaw L, Harrell Jr. FE, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Eng J Med 1991; 325:849-853.
5. Martin WH III, Xian H, Chandiramani P, et al. Cardiovascular mortality prediction in veterans with arm exercise versus pharmacologic myocardial perfusion imaging. Am Heart J Published Online First 2015 doi: 10.1016/j.ahj.2015.05.004.
Wade H. Martin, III, M.D., F.A.C.P.
Associate Professor of Medicine, Washington University School of Medicine
Staff cardiologist, St. Louis Veterans Administration Medical Center
Wade.Martin@va.gov
Test Full Physiological Parameters, not only the Narrowing or Area of Hypoperfusion.
Posted on August 27, 2015
Neelesh Gupta
Univerity College of Medical Sciences & GTB Hospital (University of Delhi) New Delhi, India
Conflict of Interest: None Declared
Dear Editor:
I peruse with interest the randomized trial by Levsky JM et al.
The study showed no difference in the outcomes over 40.4 months among patients with chest pain admitted in the telemetry unit and underwent either CCTA or MPI.
No mention is made about how many percentage of patients met appropriate-use criteria for cardiac imaging with CCTA or MPI.
Moreover the details about the exercise parameters during MPI (though highly relevant to indicate prognosis) are conspicuous by their absence in the article.
As a matter of fact, both modalities even though used in developed countries, are hardly used in low-economy countries (with highly prevalent coronary artery disease, 11% at or > 20 years of age).(1)

The conventional treadmill exercise test with 12-lead ECG (TMT) is widely available (even in low-economy countries) popular, low- cost, easily reproducible, radiation-free, imaging-free, requiring less space, needing less-technology and man-power, user-friendly diagnostic technique is the standard-of-care.
Beside ST-T changes, this gives invaluable prognostic information (not obtained at pharmacological stress echocardiography and CCTA) like exercise capacity,(2)Duke treadmill score,(3)heart rate recovery,(4) peak heart rate,(5) and ventricular dysrhythmias .
Thus,TMT by knowledgeable practitioners could be at least noninferior or superior for outcome prediction and much more cost-effective than cardiac imaging in patients with an interpretable stress ECG who are able to exercise.
The study would have been more generalisable/useful if TMT could have been used in lieu of either MPI or CCTA.

References:
1. Mohan V, Deepa R, Rani SS, et al. Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India. J Am Coll Cardiol. 2001;38(3):682-687


2. Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002;346:793-801


3.Mark DB, Shaw L, Harrell FE Jr, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med 1991;325:849-853


4.Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999;341:1351-1357


5. Lauer MS, Francis GS, Okin PM, Pashkow FJ, Snader CE, Marwick TH. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA 1999;281:524-529
Inclusion and follow-up of patients without diagnostic testing: proof-of-pudding is in eating.
Posted on August 29, 2015
Rajeev Gupta, Wael Almahmeed
Kalba Hospital, Kalba, Sharjah, UAE. Cleveland Clinic , Abu Dhabi, UAE
Conflict of Interest: None Declared
Dear Editor:
The study is important as it has mean follow-up of 40.4 months.(1) Though the short-term and intermediate-term outcome studies have shown similar outcomes with two diagnostic modalities (CCTA and physiologic testing).(2) There is impending need for long-term outcomes driven randomized trial before a definite claim/conclusion of the superiority of one diagnostic technique over the other could be confirmed.

However like other study (3) conducted before, this study also did not include patients with medical therapy-only without undergoing testing. Moreover, the data from a third group of patients who received medical therapy without undergoing testing will also be useful, as we still do not know precisely, whether event rates are lowered by any interventions that are guided by positive test results.

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA;ClinicalTrials.gov number,NCT01471522),in which randomized therapy (invasive vs. medical) is guided by the presence of extensive ischemia on functional testing.This will help us to understand better and the study is timely.(4)

References:

1.Levsky JM,Spevack DM,Travin MI, et al.Coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in patients with chest pain admitted to telemetry: a randomized trial.Ann Intern Med 2015;163(3):174-183 doi:10.7326/M14-2948.

2.Douglas PS, Hoffman U, Patel MR, et al.Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med 2015;372: 1291-1300

3. Min JK,Dunning A, Lin FY, et al. Age-and-sex related differences in all-cause mortality risk based on coronary computed tomography angiography findings results from the international multicenter CONFIRM (coronary CT angiography evaluation for clinical outcomes: an international multicenter registry) of 23,854 patients without known coronary artery disease. J Am Coll Cardiol .2011;58(8):849-60 doi:10.1016/j.jacc.2011.02.074

4. Kramer CM.Cardiovascular imaging and outcomes-PROMISEs to keep (editorial).N Engl J Med 2015;372:1366-1367
IN RESPONSE
Posted on September 11, 2015
Jeffrey M. Levsky, Mark I. Travin, Linda B. Haramati
Departments of Radiology and Internal Medicine
Conflict of Interest: None Declared
We are active participants in efforts to reduce unnecessary testing (including Choosing Wisely and Image Wisely) and in no way wish to downplay the importance of performing imaging only when justified. All patients we enrolled in our recent trial comparing coronary CT angiography and stress radionuclide myocardial perfusion imaging had acute symptoms, clinical suspicion of acute coronary syndrome and intermediate pre-test probability of CAD (1). Per the most recent appropriate use criteria for cardiac radionuclide imaging (2, Table 1/indications 6-9) and cardiac computed tomography (3, Table 1/indications 6-8), all patients were ”appropriate” with scores of 7 or 8 out of 9. Both modalities we studied have the drawback of ionizing radiation exposure. We are therefore currently pursuing a randomized trial involving stress echocardiography in acute chest pain patients to assess the effectiveness of this non-radiation approach (4).

We agree that exercise treadmill electrocardiography would be an interesting comparison modality with the notable benefit of greater worldwide availability. Treadmill testing, however, is impractical in our practice primarily due to a very high prevalence of inability to exercise. To illustrate, although we strictly use treadmill exercise as the default stressor for myocardial perfusion imaging (1), a full two-thirds (126/189) of patients in our trial required pharmacologic stress. Unfortunately, sedentary lifestyle, co-morbid conditions and obesity – all highly prevalent in our population - curtail the success of exercise testing. Since only the minority of our patients underwent treadmill stress we did not describe the prognostically significant exercise parameters. Instead, we reported actual intermediate term prognosis by clinical follow-up.

We have also contemplated a randomized trial with a ”no imaging” arm as compared to non-invasive modalities. Tremendous advancements in medical management raise questions as to the added benefits of invasive treatments based on imaging findings. However, the great majority of clinicians are justifiably reluctant to prescribe empiric pharmacotherapy for presumed CAD in patients with undiagnosed chest pain, many of whom have a non-cardiac etiology for their symptoms.

We disagree in principle with the comparison of this work with the COURAGE and ISCHEMIA trials which involve patients with stable, established CAD. We do not dispute the importance of these studies, but we investigated a different population. All of our patients had acute presentations and were free of known CAD. Our results indicate that CT and radionuclide perfusion imaging are both reasonable initial options for the still challenging workup of these patients (1).


1. Levsky JM, Spevack DM, Travin MI, Menegus MA, Huang PW, Clark ET, et al. Coronary Computed Tomography Angiography Versus Radionuclide Myocardial Perfusion Imaging in Patients With Chest Pain Admitted to Telemetry: A Randomized Trial. Ann Intern Med. 2015;163(3):174-83.

2. Hendel RC, Berman DS, Di Carli MF, Heidenreich PA, Henkin RE, Pellikka PA, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/ SCMR/SNM 2009 appropriate use criteria for cardiac radionuclide imaging: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. Circulation. 2009;119(22):e561-87.

3. Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. Circulation. 2010; 122(21):e525-55.

4. Levsky JM, Haramati LB, Taub CC, Spevack DM, Menegus MA, Travin MI, et al. Rationale and design of a randomized trial comparing initial stress echocardiography versus coronary CT angiography in low-to-intermediate risk emergency department patients with chest pain. Echocardiography. 2014;31(6):744-50.
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