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      Asymptomatic myocardial ischemia forecasts adverse events in cardiovascular magnetic resonance dobutamine stress testing of high-risk middle-aged and elderly individuals

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          Abstract

          Background

          Current guidelines for assessing the risk of experiencing a hospitalized cardiovascular (CV) event discourage stress testing of asymptomatic individuals; however, these recommendations are based on evidence gathered primarily from those aged < 60 years, and do not address the possibility of unrecognized “silent myocardial ischemia” in middle aged and older adults.

          Methods

          We performed dobutamine cardiovascular magnetic resonance (CMR) stress testing in 327 consecutively recruited participants aged > 55 years without CV-related symptoms nor known coronary artery disease, but otherwise at increased risk for a future CV event due to pre-existing hypertension or diabetes mellitus for at least 5 years. After adjusting for the demographics and CV risk factors, log-rank test and Cox proportional hazards models determined the additional predictive value of the stress test results for forecasting hospitalized CV events/survival. Either stress-induced LV wall motion abnormalities or perfusion defects were used to indicate myocardial ischemia.

          Results

          Participants averaged 68 ± 8 years in age; 39% men, 75% Caucasian. There were 38 hospitalized CV events or deaths which occurred during a mean follow-up of 58 months. Using Kaplan-Meier analyses, myocardial ischemia identified future CV events/survival ( p <  0.001), but this finding was more evident in men (p <  0.001) versus women ( p = 0.27). The crude hazard ratio (HR) of myocardial ischemia for CV events/survival was 3.13 (95% CI: 1.64–5.93; p < 0.001). After accounting for baseline demographics, CV risk factors, and left ventricular ejection fraction/mass, myocardial ischemia continued to be associated with CV events/survival [HR: 4.07 (95% CI: 1.95–8.73) p < 0.001].

          Conclusions

          Among asymptomatic middle-aged individuals with risk factors for a sentinel CV event, the presence of myocardial ischemia during dobutamine CMR testing forecasted a future hospitalized CV event or death. Further studies are needed in middle aged and older individuals to more accurately characterize the prevalence, significance, and management of asymptomatic myocardial ischemia.

          Trial registration

          ( ClinicalTrials.gov identifier): NCT00542503 and was retrospectively registered on October 11th, 2007.

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          Most cited references23

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          Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences.

          To establish normal ranges of left ventricular (LV) and right ventricular (RV) dimensions as determined by the current pulse sequences in cardiac magnetic resonance imaging (MRI). Sixty normal subjects (30 male and 30 female; age range, 20-65) were examined; both turbo gradient echo (TGE) and steady-state free precession (SSFP) pulse sequences were used to obtain contiguous short-axis cine data sets from the ventricular apex to the base of the heart. The LV and RV volumes and LV mass were calculated by modified Simpson's rule. Normal ranges were established and indexed to both body surface area (BSA) and height. There were statistically significant differences in the measurements between the genders and between TGE and SSFP pulse sequences. For TGE the LV end-diastolic volume (EDV)/BSA (mL/m(2)) in males was 74.4 +/- 14.6 and in females was 70.9 +/- 11.7, while in SSFP in males it was 82.3 +/- 14.7 and in females it was 77.7 +/- 10.8. For the TGE the LV mass/BSA (g/m(2)) in males was 77.8 +/- 9.1 and in females it was 61.5 +/- 7.5, while in SSFP in males it was 64.7 +/- 9.3 and in females it was 52.0 +/- 7.4. For TGE the RV EDV/BSA (mL/m(2)) in males was 78.4 +/- 14.0 and in females it was 67.5 +/- 12.7, while in SSFP in males it was 86.2 +/- 14.1 and in females it was 75.2 +/- 13.8. We have provided normal ranges that are gender specific as well as data that can be used for age-specific normal ranges for both SSFP and TGE pulse sequences. Copyright 2003 Wiley-Liss, Inc.
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            ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

            The American College of Cardiology Foundation along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical presentations for stable ischemic heart disease (SIHD) to consider use of stress testing and anatomic diagnostic procedures. This document reflects an updating of the prior Appropriate Use Criteria (AUC) published for radionuclide imaging (RNI), stress echocardiography (Echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for SIHD. This is in keeping with the commitment to revise and refine the AUC on a frequent basis. A major innovation in this document is the rating of tests side by side for the same indication. The side-by-side rating removes any concerns about differences in indication or interpretation stemming from prior use of separate documents for each test. However, the ratings were explicitly not competitive rankings due to the limited availability of comparative evidence, patient variability, and range of capabilities available in any given local setting. The indications for this review are limited to the detection and risk assessment of SIHD and were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Eighty clinical scenarios were developed by a writing committee and scored by a separate rating panel on a scale of 1 to 9, to designate Appropriate, May Be Appropriate, or Rarely Appropriate use following a modified Delphi process following the recently updated AUC development methodology. The use of some modalities of testing in the initial evaluation of patients with symptoms representing ischemic equivalents, newly diagnosed heart failure, arrhythmias, and syncope was generally found to be Appropriate or May Be Appropriate, except in cases where low pre-test probability or low risk limited the benefit of most testing except exercise electrocardiogram (ECG). Testing for the evaluation of new or worsening symptoms following a prior test or procedure was found to be Appropriate. In addition, testing was found to be Appropriate or May Be Appropriate for patients within 90 days of an abnormal or uncertain prior result. Pre-operative testing was rated Appropriate or May Be Appropriate only for patients who had poor functional capacity and were undergoing vascular or intermediate risk surgery with 1 or more clinical risk factors or an organ transplant. The exercise ECG was suggested as an Appropriate test for cardiac rehabilitation clearance or for exercise prescription purposes. Testing in asymptomatic patients was generally found to be Rarely Appropriate, except for calcium scoring and exercise testing in intermediate and high-risk individuals and either stress or anatomic imaging in higher-risk individuals, which were all rated as May Be Appropriate. All modalities of follow-up testing after a prior test or percutaneous coronary intervention (PCI) within 2 years and within 5 years after coronary artery bypass graft (CABG) in the absence of new symptoms were rated Rarely Appropriate. Pre-operative testing for patients with good functional capacity, prior normal testing within 1 year, or prior to low-risk surgery also were found to be Rarely Appropriate. Imaging for an exercise prescription or prior to the initiation of cardiac rehabilitation was Rarely Appropriate except for cardiac rehabilitation clearance for heart failure patients.
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              ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).

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                Author and article information

                Contributors
                bstacey@wakehealth.edu
                tvera@wakehealth.edu
                tomorgan@wakehealth.edu
                jenjorda@wakehealth.edu
                mattwhitlockmd@gmail.com
                mehall@umc.edu
                crhamilt@wakehealth.edu
                dkitzman@wakehealth.edu
                336-716-6125 , ghundley@wakehealth.edu
                Journal
                J Cardiovasc Magn Reson
                J Cardiovasc Magn Reson
                Journal of Cardiovascular Magnetic Resonance
                BioMed Central (London )
                1097-6647
                1532-429X
                22 November 2018
                22 November 2018
                2018
                : 20
                : 75
                Affiliations
                [1 ]ISNI 0000 0001 2185 3318, GRID grid.241167.7, Department of Internal Medicine, Cardiovascular Medicine Section, , Wake Forest School of Medicine, ; Medical Center Boulevard, Winston-Salem, North Carolina 27157-1045 USA
                [2 ]ISNI 0000 0001 2185 3318, GRID grid.241167.7, Department of Public Health Sciences, , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [3 ]ISNI 0000 0001 2185 3318, GRID grid.241167.7, Department of Radiology (Division of Radiologic Sciences), , Wake Forest School of Medicine, ; Winston-Salem, NC USA
                [4 ]ISNI 0000 0004 1937 0407, GRID grid.410721.1, Department of Medicine (Cardiovascular Medicine), , University of Mississippi Medical Center, ; Jackson, MS USA
                [5 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Medicine (Cardiovascular Medicine), , Stanford University School of Medicine, ; Palo Alto, CA USA
                Article
                492
                10.1186/s12968-018-0492-5
                6249873
                30463565
                ddd7a2b4-878c-4b99-b830-ca851aeed83d
                © The Author(s). 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 March 2018
                : 9 October 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01HL076438
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Cardiovascular Medicine
                stress testing,cardiovascular events,aging,sex difference,cardiovascular magnetic resonance

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