Initial Invasive or Conservative Strategy for Stable Coronary Disease.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis.

BACKGROUND: The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known. METHODS: We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained. RESULTS: Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer-determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to ≤5 at 101 (35.1%) laboratories, >5 to ≤10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays. CONCLUSIONS: There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.

The elusive role of myocardial perfusion imaging in stable ischemic heart disease: Is ISCHEMIA the answer?

The assessment of ischemia through myocardial perfusion imaging (MPI) is widely accepted as an index step in the diagnostic evaluation of stable ischemic heart disease (SIHD). Numerous observational studies have characterized the prognostic significance of ischemia extent and severity. However, the role of ischemia in directing downstream SIHD care including coronary revascularization has remained elusive as reductions in ischemic burden have not translated to improved clinical outcomes in randomized trials. Importantly, selection bias leading to the inclusion of many low risk patients with minimal ischemia have narrowed the generalizability of prior studies along with other limitations. Accordingly, an ongoing randomized controlled trial entitled ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) will compare an invasive coronary revascularization strategy vs a conservative medical therapy approach among stable patients with moderate to severe ischemia. The results of ISCHEMIA may have a substantial impact on the management of SIHD and better define the role of MPI in current SIHD pathways of care.

Temporal trends of single-photon emission computed tomography myocardial perfusion imaging in patients without prior coronary artery disease: A 22-year experience at a tertiary academic medical center.

BACKGROUND: Between 1990 and 2006, there was a large national increase in utilization of single-photon emission computed tomography myocardial perfusion imaging (SPECT) for assessment of coronary artery disease (CAD). We aim to examine the trends of SPECT test results and patients' characteristics at Mayo Clinic Rochester. METHODS: Using the Mayo Clinic nuclear cardiology database, we examined all SPECT tests performed between January 1, 1991, and December 31, 2012, in patients without prior CAD. The study cohort was divided into 5 time periods: 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2012. RESULTS: There were 35,894 eligible SPECT tests (mean age 62.5 ± 12 years, 54% men). Annual utilization of SPECT increased significantly in 1992-2002 but then decreased without evidence of test substitution with stress echocardiography. There were modest changes in CAD risk factors over time. Testing of asymptomatic patients doubled (21.9% in 1991-1995 to 40% in 2006-2010) but later decreased to 33.6% in 2011-2012. Tests on patients with typical angina decreased dramatically (18.3% in 1991-1995 to 6.7% in 2011-2012). Summed stress score, summed difference score, and high-risk SPECT tests all decreased over time in both symptomatic and asymptomatic patients regardless of stress modality (exercise vs pharmacologic). CONCLUSIONS: In Mayo Clinic Rochester, annual SPECT utilization in patients without prior CAD increased in 1992-2002 but then decreased. Despite similar CAD risk factors and decreased utilization after 2003, more tests were low risk; summed stress score, summed difference score, and high-risk tests all decreased. Our findings confirm previous observations that SPECT was increasingly used in patients with a lower prevalence of CAD.

Noninvasive Stress Testing for Coronary Artery Disease.

Stress testing remains the cornerstone for noninvasive assessment of patients with possible or known coronary artery disease (CAD). The most important application of stress testing is risk stratification. Most patients who present for evaluation of stable CAD are categorized as low risk by stress testing. These low-risk patients have favorable clinical outcomes and generally do not require coronary angiography. Standard exercise treadmill testing is the initial procedure of choice in patients with a normal or near-normal resting electrocardiogram who are capable of adequate exercise. Stress imaging is recommended for patients with prior revascularization, uninterpretable electrocardiograms, or inability to adequately exercise.

Assessing clinical impact of myocardial perfusion studies: ischemia or other prognostic indicators?

One of the major strengths of nuclear myocardial perfusion imaging (MPI) is the robust prognostic databases from observational studies demonstrating significantly different outcomes in patients with low-risk vs high-risk scans. The severity of the MPI defect can be semi-quantitated using the summed stress score (SSS) and summed difference score (SDS). SSS is more strongly associated with mortality, whereas SDS is the better predictor of subsequent coronary angiography and revascularization. The strength of MPI variables as prognostic indicators decreases when adjusted for prognostically important clinical and stress test variables. Nonetheless, most studies of general patient populations have demonstrated that MPI adds incremental prognostic value to clinical and stress test information. In contrast to these positive results from observational studies, the application of MPI ischemia as a treatment guide in several recent trials (DIAD, WOMEN, COURAGE, BARI 2D, STICH) has largely failed to identify patient subsets with improved outcome. This issue will continue to be investigated in the ongoing PROMISE and ISCHEMIA trials.

The safety of cardiopulmonary exercise testing in a population with high-risk cardiovascular diseases.

BACKGROUND: Cardiopulmonary exercise testing (CPX) with measurement of peak oxygen uptake (Vo(2)) is a powerful test for assessment and quantification of functional impairment resulting from cardiovascular disease. The safety of CPX has been established in patients with coronary artery disease and congestive heart failure, but clinical use of CPX in other cardiac diseases has been limited, in part because of a paucity of safety data. This study investigates the safety of CPX in a heterogeneous cohort of patients with a wide variety of underlying high-risk cardiac diagnoses. METHODS AND RESULTS: This single-center retrospective review examined 5060 CPX studies performed in 4250 unique patients, including 1748 (35%) female subjects and 686 (14%) subjects aged ≥75 years. The primary end point was major adverse event during stress testing. The study population included patients with a variety of high-risk cardiac diseases, including congestive heart failure (n=1289, 25.5%), hypertrophic cardiomyopathy (n=598, 11.8%), pulmonary hypertension (n=194, 3.8%), and aortic stenosis (n=212, 4.2%). This patient population generally had severe functional impairment, including 1192 (24%) patients with peak Vo(2)<14 mL/kg/min. Eight adverse events occurred during CPX, for an adverse event rate of 0.16%. The most common adverse event (n=6) was sustained ventricular tachycardia. There were no fatal events. CONCLUSIONS: CPX is generally a safe procedure, even in a population with underlying high-risk cardiovascular diagnoses.

Downstream clinical implications of abnormal myocardial perfusion single-photon emission computed tomography based on appropriate use criteria.

BACKGROUND: Appropriate use criteria (AUC) for single-photon emission computed tomography myocardial perfusion images (SPECT-MPI) were developed to address the growth of cardiac imaging studies. However, these criteria have not been vigorously validated. We sought to determine the rate of abnormal stress SPECT-MPI studies and subsequent revascularization procedures as categorized by AUC. METHODS: We retrospectively examined 280 patients who underwent stress SPECT-MPI and categorized these studies as appropriate, inappropriate, or uncertain based on AUC. Data regarding subsequent angiography and revascularization within 6 months after stress SPECT-MPI were collected from the electronic medical record. RESULTS: 280 patients met the inclusion criteria (mean age 67.3 ± 11.4 years, 36 % female). When categorized by AUC, 62.9 % (N = 176) of stress SPECT-MPI were considered appropriate, 13.6 % (N = 38) uncertain, and 23.6 % (N = 66) inappropriate. Appropriate stress SPECT-MPI studies were more likely to have intermediate or high risk results than uncertain or inappropriate studies [40 % (N = 71) vs. 21 % (N = 8) and 18 % (N = 12), respectively; P = 0.008)]. Appropriate studies were associated with an increased rate of coronary angiography [14 % (N = 25)] compared to the uncertain (0 %) and inappropriate [3 % (N = 2)] studies (P = 0.003). There was also an increased rate of revascularization after appropriate studies [9 % (N = 16)] compared to the uncertain (0 %) and inappropriate (0 %) studies (P = 0.006). CONCLUSIONS: Appropriate stress SPECT-MPI studies are more likely to result in abnormal results requiring subsequent revascularization compared to inappropriate and uncertain stress studies. Inappropriate and uncertain stress SPECT-MPI did not lead to subsequent revascularization.

Ischemia With Nonobstructive Coronary Arteries: Insights From the ISCHEMIA Trial.

BACKGROUND: Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown. OBJECTIVES: The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA. METHODS: Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia. RESULTS: Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]). CONCLUSIONS: Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

The impact of ordering provider specialty on appropriateness classification.

BACKGROUND: There is limited published data comparing the appropriateness use criteria for SPECT MPI with the specialty of the ordering provider. The aim of this study was to examine if the specialty of the ordering provider affected either the ordering indication or the appropriateness of stress SPECT MPI. METHODS AND RESULTS: The ordering provider's specialty was compared with the study indication and appropriateness rating. There were modest but significant differences in general indications by specialty. For example, the Emergency Department group ordered fewer studies in asymptomatic patients (3% compared to 14%-23% in the other four referral groups). In contrast, 43% of the studies ordered by Cardiovascular Division physicians and 39% of the studies ordered by the Registered Nurse group were on post-revascularization patients, compared to 23%-31% of those ordered by the other three groups. Overall appropriateness classification did not differ among the five specialty groups (P 5 0.19). CONCLUSION: In a clinical practice where pre-operative testing using SPECT is infrequent,the rate of inappropriate studies was similar for all ordering providers. Quality improvement efforts in similar practices will likely require a broad educational focus on all ordering providers.

Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association.

The management of low-risk patients presenting to emergency departments is a common and challenging clinical problem entailing 8 million emergency department visits annually. Although a majority of these patients do not have a life-threatening condition, the clinician must distinguish between those who require urgent treatment of a serious problem and those with more benign entities who do not require admission. Inadvertent discharge of patients with acute coronary syndrome from the emergency department is associated with increased mortality and liability, whereas inappropriate admission of patients without serious disease is neither indicated nor cost-effective. Clinical judgment and basic clinical tools (history, physical examination, and electrocardiogram) remain primary in meeting this challenge and affording early identification of low-risk patients with chest pain. Additionally, established and newer diagnostic methods have extended clinicians' diagnostic capacity in this setting. Low-risk patients presenting with chest pain are increasingly managed in chest pain units in which accelerated diagnostic protocols are performed, comprising serial electrocardiograms and cardiac injury markers to exclude acute coronary syndrome. Patients with negative findings usually complete the accelerated diagnostic protocol with a confirmatory test to exclude ischemia. This is typically an exercise treadmill test or a cardiac imaging study if the exercise treadmill test is not applicable. Rest myocardial perfusion imaging has assumed an important role in this setting. Computed tomography coronary angiography has also shown promise in this setting. A negative accelerated diagnostic protocol evaluation allows discharge, whereas patients with positive findings are admitted. This approach has been found to be safe, accurate, and cost-effective in low-risk patients presenting with chest pain.

Stress testing: the case for the standard treadmill test.

PURPOSE OF REVIEW: This review examines the diagnostic and prognostic performance of the standard exercise treadmill test (ETT) in comparison to stress imaging procedures. This topic is timely and relevant due to increasing healthcare expenditures and the substantially lower cost of the ETT. RECENT FINDINGS: The most important goal of noninvasive testing is to identify patients with left main or three-vessel coronary artery disease (CAD) or severely reduced left ventricular ejection fraction (LVEF) less than 35%. These patient subsets demonstrate a survival advantage when treated with coronary artery bypass grafting (severe CAD) or a defibrillator (LVEF <35%). This benefit is not present for patients with one-vessel or two-vessel CAD or preserved LVEF. For patients who have a normal resting ECG, studies have shown that the standard ETT is as accurate as imaging for identifying these high-risk patients. Outcome of patients with a low-risk exercise treadmill score is excellent. SUMMARY: The standard ETT should be the initial test in patients presenting for evaluation of CAD with the following characteristics: (1) ability to exercise adequately; (2) normal resting ECG; and (3) no prior revascularization. Applying this strategy should not sacrifice prognostic accuracy and should result in significant cost savings.

Early image acquisition using a solid-state cardiac camera for fast myocardial perfusion imaging.

BACKGROUND: A novel ultra-fast solid-state cardiac camera (Discovery NM 530c, General Electric) allows much shorter acquisition times compared to standard dual-detector SPECT cameras. This design enables investigation of the potential for early myocardial perfusion imaging (MPI) following a rest injection of technetium-99m (Tc-99m) rather than the conventional 45-60 minute delay in image acquisition. METHODS: A total of 30 patients underwent MPI at rest using Tc-99m sestamibi (n = 9) or tetrofosmin (n = 21). A 12 minute image acquisition in list mode was performed immediately following isotope injection. Patients also underwent a conventional delayed image acquisition 60 minutes following the rest isotope injection (image acquisition over 4 minutes). The immediate 12 minute acquisition was divided into three 4-minute intervals for image reconstruction (0-4, 4-8, and 8-12 minutes). The perfusion images were interpreted by two experienced physicians who evaluated each study for overall image quality (good, acceptable, or unacceptable) and graded each image using the summed rest score (SRS) and the standard 17-segment, 5-point scale model. RESULTS: The images acquired in the 0-8 minute time interval were predominantly uninterpretable due to excessive blood pool uptake. The images acquired in the 8-12 minute time interval were interpretable and compared to the conventional images obtained at 60 minutes. Overall image quality was better on the 60 minute image (17 good, 13 acceptable) compared with 8-12 minute image (3 good, 25 acceptable, 2 unacceptable). Sixteen of the 30 patients had an improvement in overall image quality by at least one category using the 60 minute delayed image. Nine of the 30 patients (2 Tc-99m sestamibi; 7 Tc-99m tetrofosmin) had at least one uninterpretable myocardial segment due to liver and/or bowel overlapping the myocardium on the 8-12 minute images vs 1 patient (1 myocardial segment) with this problem on the 60 minute delayed images (P = .005). Uninterpretable segments (total of 16) on the 8-12 minute images were confined to the apex and inferior wall. The mean SRS of the interpretable 8-12 minute images (n = 21) was 3.2 (95% confidence intervals; 1.0, 5.4) compared to 1.6 (95% confidence intervals; 0, 3.3) on the 60 minute delayed images in those patients (P = .005). CONCLUSIONS: Overall image quality was better with fewer uninterpretable studies and a lower SRS on the rest images obtained at 60 minutes compared to early image acquisition (8-12 minutes following isotope injection). These findings do not support the routine use of early image acquisition with this new solid-state ultra-fast camera system.

Temporal trends in compliance with appropriateness criteria for stress single-photon emission computed tomography sestamibi studies in an academic medical center.

BACKGROUND: The purpose of this study was to apply published appropriateness criteria for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in a single academic medical center to determine if the percentage of inappropriate studies was changing over time. In a previous study, we applied the American College of Cardiology Foundation/American Society of Nuclear Cardiology (ASNC) appropriateness criteria for stress SPECT MPI and reported that 14% of stress SPECT studies were performed for inappropriate reasons. METHODS: Using similar methodology, we retrospectively examined 284 patients who underwent stress SPECT MPI in October 2006 and compared the findings to the previous cohort of 284 patients who underwent stress SPECT MPI in May 2005. RESULTS: The indications for testing in the 2 cohorts were very similar. The overall level of agreement in characterizing categories of appropriateness between 2 experienced cardiovascular nurse abstractors was good (kappa = 0.68), which represented an improvement from our previous study (kappa = 0.56). There was a significant change between May 2005 and October 2006 in the overall classification of categories for appropriateness (P = .024 by chi(2) statistic). There were modest, but insignificant, increases in the number of patients who were unclassified (15% in the current study vs 11% previously), appropriate (66% vs 64%), and uncertain (12% vs 11%). Only 7% of the studies in the current study were inappropriate, which represented a significant (P = .004) decrease from the 14% reported in the 2005 cohort. CONCLUSIONS: In the absence of any specific intervention, there was a significant change in the overall classification of SPECT appropriateness in an academic medical center over 17 months. The only significant difference in individual categories was a decrease in inappropriate studies. Additional measurements over time will be required to determine if this trend is sustainable or generalizable.