Has anyone been listening? Post-SPECT MPI referral rates to catheterization

Journal of Nuclear Cardiology, Oct 2017

Elizabeth Hill DO, Rory Hachamovitch MD, MSc

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Has anyone been listening? Post-SPECT MPI referral rates to catheterization

Received May Has anyone been listening? Post-SPECT MPI referral rates to catheterization Elizabeth Hill 0 Rory Hachamovitch 0 0 Reprint requests: Rory Hachamovitch, MD, MSc, Section of Cardio- vascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic , J1-5, 9500 Euclid Avenue, Cleveland, OH 44195 1 Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic , Cleveland, OH - Radionuclide single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has retained its steadfast role in the assessment of suspected or known coronary artery disease (CAD). Both guidelines and appropriate use criteria continue to support its role in numerous clinical settings.1,2 At a time when there is increasing emphasis on quality and appropriateness in testing, there is an ongoing need to scrutinize the value of all cardiovascular imaging modalities. This scrutiny has encompassed the continuum from patient selection to correct image acquisition and interpretation of the reporting of results to referring physicians.3 Indeed, the importance of selecting the ‘‘right’’ patients for testing and the importance of considering how test results will change subsequent management have been embraced as a mantra. Although they are infrequently reported, patterns of post-SPECT MPI patient management are informative for this purpose and likely represent the most pragmatic insight we can gain with respect to the use of this modality in daily practice. To this end, prior studies have examined referral rates to catheterization, revascularization, and medical therapy after exercise stress testing and stress MPI, often focusing on whether systematic sex-related or age-related posttest differences in patient management were present.4–17 On the basis of these studies, a number of generalizations can be made. First, the likelihood of referral to catheterization after MPI is overwhelmingly driven by the results of the test. Further, the dominant drivers of this referral are markers of ischemia—predominantly the extent and severity of MPI-defined ischemia, but also presenting symptoms, stress-induced symptoms, and ST segment changes with stress. Other factors, of unclear appropriateness, also inform this decision. Referral rates vary among patient populations. Despite the widely reported issues with sex-related bias in cardiovascular care, catheterization rates remain greater in men compared to women. These differences remain after consideration of baseline patient characteristics, site-related practice differences, and other factors. Similarly, previous studies have also shown that in older patients, absolute catheterization rates were lower in patients aged [80 years compared to patients aged 50 to 64 years or 65 to 79 years.17 A 40 site prospective, multicenter study—the Study of myocardial Perfusion and coronary Anatomy imaging Roles in Coronary artery disease (SPARC)—examined posttest patient management in a cohort of 1703 patients with intermediate-tohigh pretest likelihood of CAD who were referred for a clinically ordered PET, SPECT, or CCTA in 40 sites.16,18 These results confirmed the impact of patient sex and age on catheterization referral rates. Men were found to have a significantly greater rate of referral to catheterization compared to women after all other factors were considered (odds ratio 1.82). Catheterization referral increased progressively with increasing age—patients in their 50s, 60s, and 70s had greater catheterization rates compared to patients aged younger than 40 years—but patients aged [80 had a lower odds ratio compared to patients \40 years of age. Hence, both these factors—patient age and sex—appear to impact catheterization referral rates. Whether the difference in referral rates related to these two factors are clinically appropriate or not is a challenging question. Undoubtedly the most concerning finding in studies to date is the relatively low absolute rate of referral to catheterization after moderate-to-severe test abnormalities. In the setting of the most profound test abnormalities (and the greatest risk for adverse events), the referral rates to 90-day catheterization are *40% to 60%.12,16,17 Although prior studies hypothesized that those patients who were not referred for catheterization were instead treated with aggressive medical management, thus obviating the need for an initial invasive approach, they did not collect pharmacotherapeutic data. This information, collected in SPARC, revealed that along with the *50% catheterization referral rate, referring physicians also did not prescribe aggressive medical therapy. Focusing on the use of aspirin, lipid lowering agents, and beta-blockers, only one in five patients with serious test abnormalities were on all three of these medications, most were on one or two of them, and there was no increase in the proportion of patients with increased number of medications after testing. Hence, half of the patients with the highest risk noninvasive test findings received a catheterization, half received a change in medical therapy, a quarter received neither, and a quarter received both. These practice patterns are difficult to comprehend and do not follow what most clinicians would believe to be the ‘‘appropriate’’ pattern.19 Of note, no studies to date have considered patient preferences, socioeconomic status, insurance status, or refusal of procedure. In the current issue of Journal of Nuclear Cardiology , Zeltser and colleagues present results from a study examining age and gender bias in catheterization referral rates after MPI at a tertiary referral center. Their hypothesis was that post-MPI referral bias associated with female patients and older patients result in lower referral catheterization rates. Their data suggest that the previously reported gender bias is not present, but that the age bias was present evident in their data. Full disclosure: What should be expected from publications in this area? A number of issues specific to this type of research must be considered. The greatest challenge facing investigators seeking to assess postMPI treatment patterns is that of bias and confounding. Due to the many potential applications of MPI, the cohorts referred to MPI are a remarkably diverse population. No clear conclusions can be reached from the collected data without careful risk adjustment for known or suspected confounders of treatment. Unfortunately, as the authors note in their limitations section, they did not collect data on clinical history, risk factors, stress test results, patient symptoms, and other key elements. What data were available are not entirely clear, as the authors were able to calculate an atherosclerosis risk score, but the necessary variables were not included in their analysis. The most striking aspect of this is the lack of symptom data. In the SPARC study the presence of angina was associated with a risk-adjusted odds ratio of 3.1 for catheterization referral. As symptom patterns differ between men and women presenting to testing, and the association of symptoms and CAD differ with sex and age, the absence of the data undermines the interpretation of the results. Although numerous catheterizations occurred on follow-up, only twelve degrees of freedom were used in the modeling (six covariates but three with four categories). This limited risk adjustment has been referred to as ‘‘underfitting’’ the model.20 The most striking aspect of the current study is the paucity of data presented. The authors inform us about the observed referral rates to catheterization in men and women, but do not describe the results as a function of the test result. In their solitary table, catheterization rates across categories of summed stress score but not summed difference score are presented, despite previous studies demonstrating the latter rather than the former to drive catheterization referral. Indeed, catheterization rates in patients without CAD with normal, mild, moderate, and severe summed score abnormalities are 6.7%, 51.5%, 57.1%, and 56.1%, respectively. It is disappointing that the authors do not mention that (in the absence of availability of ischemia data) physicians appear to use the MPI results in a dichotomous fashion and that these results confirm the previous reports of only *40% to 60% of patients referred to catheterization after abnormal testing. The authors do not refer to most of the studies in the area cited above. They interchange studies evaluating sex- and age-related treatment patterns in cohorts who did not undergo MPI. These populations differ considerably in makeup. Also, studies able to account for markers of extent of disease (coronary anatomy or MPI data) may differ in results compared to studies without this information. Finally, the authors conclude that their results may suggest that previously described sex-related referral biases may no longer be present. Unfortunately, the authors do not consider the results of the recent multicenter study that indicates that this bias is, unfortunately, still present. The authors highlight these issues in their limitations section, the section of a manuscript intended as an opportunity for the authors to address the challenges to internal and external validity (generalizability) due to study design and execution that may limit interpretation of the findings. What is unstated, but is understood, is that a flaw of design or execution may be sufficiently profound to compromise the study such that it is no longer a mere limitation—if a prognosis study followed only half the cohort, it would be problematic to refer to it as a limitation. Rather, the study is irretrievably compromised. The inability to acquire critical data relegates the study to, at best, a pilot study, potentially laying the groundwork for further, more complete, investigations. Nonetheless, the authors’ results remain important in that the underlying phenomenon of how we are using these test results remains largely undervalued. The results of a think tank on quality in cardiovascular imaging identified patient selection for testing, image acquisition and interpretation, and results communication to be the important components of imaging quality.3 In light of the results of studies to date, however, it is unclear whether a test result fulfilling these criteria would be considered a ‘quality’ study or clinically useful if its results are not considered appropriately in the formulation of subsequent treatment plans.16 Whether a test performed in an appropriate clinical setting that is performed, interpreted, and reported correctly is a quality study is questionable, if no action is taken by the referring physician, despite the presence of new abnormalities. In the context of increasing scrutiny of noninvasive testing, the monitoring of post-MPI resource utilization is a metric whose time has arrived. Disclosures The authors do not receive honoraria, have relationships with any companies or products, ownership of stock, membership on advisory councils, committees, or board of directors, thus, have no conflicts to disclose. 1. Hendel RC , Patel MR , Allen JM , Min JK , Shaw LJ , Wolk MJ , et al. Appropriate use of cardiovascular technology: 2013 ACCF appropriate use criteria methodology update: a report of the American College of Cardiology Foundation appropriate use criteria task force . J Am Coll Cardiol 2013 ; 61 : 1305 - 17 . 2. Klocke FJ , Baird MG , Lorell BH , Bateman TM , Messer JV , Berman DS , et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging-executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging) . J Am Coll Cardiol 2003 ; 42 : 1318 - 33 . 3. Douglas P , Iskandrian AE , Krumholz HM , Gillam L , Hendel R , Jollis J , et al. Achieving quality in cardiovascular imaging: proceedings from the American College of Cardiology-Duke University Medical Center Think Tank on Quality in Cardiovascular Imaging . J Am Coll Cardiol 2006 ; 48 : 2141 - 51 . 4. Shaw LJ , Miller DD , Romeis JC , Kargl D , Younis LT , Chaitman BR . Gender differences in the noninvasive evaluation and management of patients with suspected coronary artery disease . Ann Intern Med 1994 ; 120 : 559 - 66 . 5. Bateman TM , O'Keefe JH Jr, Dong VM , Barnhart C , Ligon RW . Coronary angiographic rates after stress single-photon emission computed tomographic scintigraphy . J Nucl Cardiol 1995 ; 2 : 217 - 23 . 6. Hachamovitch R , Berman DS , Kiat H , Bairey-Merz N , Cohen I , Cabico JA , et al. Gender-related differences in clinical management after exercise nuclear testing . J Am Coll Cardiol 1995 ; 26 : 1457 - 64 . 7. Nallamothu N , Pancholy SB , Lee KR , Heo J , Iskandrian AS . Impact on exercise single-photon emission computed tomographic thallium imaging on patient management and outcome . J Nucl Cardiol 1995 ; 2 : 334 - 8 . 8. Hachamovitch R , Berman DS , Kiat H , Cohen I , Cabico JA , Friedman J , et al. Exercise myocardial perfusion SPECT in patients without known coronary artery disease: Incremental prognostic value and use in risk stratification . Circulation 1996 ; 93 : 905 - 14 . 9. Amanullah AM , Kiat H , Hachamovitch R , Cabico JA , Cohen I , Friedman JD , et al. Impact of myocardial perfusion single-photon emission computed tomography on referral to catheterization of the very elderly. Is there evidence of gender-related referral bias ? J Am Coll Cardiol 1996 ; 28 : 680 - 6 . 10. Hachamovitch R , Berman DS , Kiat H , Cohen I , Lewin H , Amanullah A , et al. Incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography and impact on subsequent management in patients with or suspected of having myocardial ischemia . Am J Cardiol 1997 ; 80 : 426 - 33 . 11. Shaw LJ , Heller GV , Travin MI , Lauer M , Marwick T , Hachamovitch R , et al. Cost analysis of diagnostic testing for coronary artery disease in women with stable chest pain. Economics of Noninvasive Diagnosis (END) Study Group . J Nucl Cardiol 1999 ; 6 : 559 - 69 . 12. Hachamovitch R , Hayes SW , Friedman JD , Cohen I , Berman DS . Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography . Circulation 2003 ; 107 : 2900 - 7 . 13. Hachamovitch R , Hayes SW , Friedman JD , Cohen I , Kang X , Germano G , et al. Is there a referral bias against catheterization of patients with reduced left ventricular ejection fraction? Influence of ejection fraction and inducible ischemia on post-single-photon emission computed tomography management of patients without a history of coronary artery disease . J Am Coll Cardiol 2003 ; 42 : 1286 - 94 . 14. Hachamovitch R , Rozanski A , Hayes SW , Thomson LE , Germano G , Friedman JD , et al. Predicting therapeutic benefit from myocardial revascularization procedures: Are measurements of both resting left ventricular ejection fraction and stress-induced myocardial ischemia necessary ? J Nucl Cardiol 2006 ; 13 : 768 - 78 . 15. Hachamovitch R , Rozanski A , Shaw LJ , Stone GW , Thomson LEJ , Friedman JD , et al. Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy . Eur Heart J 2011 ; 32 : 1012 - 24 . 16. Hachamovitch R , Nutter B , Hlatky MA , Shaw LJ , Ridner ML , Dorbala S , et al. Patient management after noninvasive cardiac imaging results from SPARC (Study of myocardial perfusion and coronary anatomy imaging roles in coronary artery disease) . J Am Coll Cardiol 2012 ; 59 : 462 - 74 . 17. Nair SU , Ahlberg AW , Mathur S , Katten DM , Polk DM , Heller GV . The clinical value of single photon emission computed tomography myocardial perfusion imaging in cardiac risk stratification of very elderly patients ([/=80 years) with suspected coronary artery disease . J Nucl Cardiol 2012 ; 19 : 244 - 55 . 18. Hachamovitch R , Johnson JR , Hlatky MA , Cantagallo L , Johnson BH , Coughlan M , et al. The study of myocardial perfusion and coronary anatomy imaging roles in CAD (SPARC): Design, rationale, and baseline patient characteristics of a prospective, multicenter observational registry comparing PET, SPECT, and CTA for resource utilization and clinical outcomes . J Nucl Cardiol 2009 ; 16 : 935 - 48 . 19. Maron DJ , Stone GW , Berman DS , Mancini GB , Scott TA , Byrne DW , et al. Is cardiac catheterization necessary before initial management of patients with stable ischemic heart disease? Results from a Web-based survey of cardiologists . Am Heart J 2011 ; 162 : 1034 - 43 e13. 20. Hachamovitch R , Di Carli MF. Methods and limitations of assessing new noninvasive tests: Part II: Outcomes-based validation and reliability assessment of noninvasive testing . Circulation 2008 ; 117 : 2793 - 801 .


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Elizabeth Hill DO, Rory Hachamovitch MD, MSc. Has anyone been listening? Post-SPECT MPI referral rates to catheterization, Journal of Nuclear Cardiology, 2017, 1-4, DOI: 10.1007/s12350-016-0581-5