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Exercise tomographic thallium-201 imaging in patients with severe coronary artery disease and normal electrocardiograms
Abstract
To assess the incremental value and cost-effectiveness of exercise tomographic thallium-201 imaging compared with clinical and exercise electrocardiographic variables for detecting three-vessel or left main coronary artery disease in patients with normal at-rest electrocardiograms.
Prospective cohort study.
411 patients (77 [19%] had three-vessel or left main disease) with normal at-rest electrocardiograms who underwent exercise tomographic thallium-201 studies and subsequently had coronary angiography.
Clinical, exercise, and thallium-201 variables; univariate followed by multivariate logistic regression analysis to determine predictors of three-vessel or left main disease (clinical variables; clinical and exercise electrocardiographic variables; and clinical, exercise, and thallium-201 variables). Patients were classified by each of these models into low-, intermediate-, and high-risk groups.
A tertiary referral center.
Among the clinical variables, diabetes mellitus, sex, age, and typical angina were independently associated with severe coronary disease (46% of patients were correctly classified into low- or high-risk groups). The peak exercise heart rate-blood pressure product and the magnitude of the exercise-induced ST depression added independent information to clinical variables. Among the thallium variables, the change in the global thallium-201 score (a measure of redistribution) added independent information to clinical and exercise variables, resulting in only 3% of the patients being reclassified regarding their predicted risk for severe coronary disease. The cost per additional reclassification was estimated to be $20,550. Twenty-one cardiac events occurred (7 cardiac deaths and 14 myocardial infarctions) after thallium study (follow-up, 2.8 +/- 1.0 years). Event-free survival was 94% to 97% regardless of the predicted probability of developing three-vessel or left main coronary artery disease by any model.
When the at-rest electrocardiogram is normal, thallium-201 scintigraphy adds little information to clinical and exercise variables in identifying patients with severe coronary artery disease. The high cost of this information may not justify the routine use of sophisticated imaging for this purpose.
... Other surrogates of exercise capacity have diagnostic and prognostic value, such as the ratepressure product (RPP), which predicts the probability of three-vessel or left main CAD. (28) Composite clinical scores, such as the Duke Treadmill Score (DTS), provide added prognostic information by combining multiple predictors into one measure. The DTS incorporates exercise duration, exercise-induced ST changes, and stress-induced angina. ...
... Stress myocardial perfusion imaging (MPI) provides minimal incremental value in patients with a low-risk exercise stress test, a low-risk Duke Treadmill Score, or a high rate-pressure product without ST-segment depression. (18,28,90,91) In addition, the low cardiac event rates in stable patients treated medically in recent landmark studies such as COURAGE and BARI-2D have challenged the paradigm of selecting coronary revascularization as the initial therapeutic strategy, potentially reducing the need for identification of low-levels of ischemia. (92,93) However, despite the low risk of events with negative ExECG, there continues to be widespread use of concurrent imaging.(9) ...
Exercise stress electrocardiography (ExECG) is underutilized as the initial test modality in patients with interpretable electrocardiograms who are able to exercise. Although stress myocardial imaging techniques provide valuable diagnostic and prognostic information, variables derived from ExECG can yield substantial data for risk stratification, either supplementary to imaging variables or without concurrent imaging. In addition to exercise-induced ischemic ST-segment depression, such markers as ST-segment elevation in lead aVR, abnormal heart rate recovery post-exercise, failure to achieve target heart rate, and poor exercise capacity improve risk stratification of ExECG. For example, patients achieving ≥10 metabolic equivalents on ExECG have a very low prevalence of inducible ischemia and an excellent prognosis. In contrast, cardiac imaging techniques add diagnostic and prognostic value in higher-risk populations (e.g., poor functional capacity, diabetes, or chronic kidney disease). Optimal test selection for symptomatic patients with suspected coronary artery disease requires a patient-centered approach factoring in the risk/benefit ratio and cost-effectiveness.
... Several studies have examined the incremental value of exercise imaging procedures compared with the exercise ECG in patients with a normal rest ECG who are not taking digoxin (Table 19). In analyses (397,398) that included clinical and exercise ECG parameters for the prediction of left main or three-vessel disease, the modest benefit of imaging does not appear to justify its cost, which has been estimated at $20,550 per additional patient correctly classified (397). For the prediction of subsequent cardiac events, four separate analyses have failed to demonstrate incremental value. ...
... Several studies have examined the incremental value of exercise imaging procedures compared with the exercise ECG in patients with a normal rest ECG who are not taking digoxin (Table 19). In analyses (397,398) that included clinical and exercise ECG parameters for the prediction of left main or three-vessel disease, the modest benefit of imaging does not appear to justify its cost, which has been estimated at $20,550 per additional patient correctly classified (397). For the prediction of subsequent cardiac events, four separate analyses have failed to demonstrate incremental value. ...
... However, stress tests such as ET, MPI and SE are limited in detecting and excluding the presence of high-risk CAD anatomy. ET is often used for risk stratification of symptomatic patients as a first-line diagnostic test, because it is widely available, does not use radiation and is inexpensive [8,34,35]. In ET the presence of high-risk CAD may be suspected with severe ST segment depression, short exercise duration or blood pressure drop during exercise [7,[35][36][37][38] but these parameters are not very sensitive. ...
... ET is often used for risk stratification of symptomatic patients as a first-line diagnostic test, because it is widely available, does not use radiation and is inexpensive [8,34,35]. In ET the presence of high-risk CAD may be suspected with severe ST segment depression, short exercise duration or blood pressure drop during exercise [7,[35][36][37][38] but these parameters are not very sensitive. ET diagnostic performance studies have shown sensitivities ranging from 74 % to 91 % for the detection of LM CAD [8,36] and from 63 % Data are presented as means with the number of patients in parentheses. ...
To determine the diagnostic performance of CT coronary angiography (CTCA) in detecting and excluding left main (LM) and/or three-vessel CAD ("high-risk" CAD) in symptomatic patients and to compare its discriminatory value with the Duke risk score and calcium score.
Between 2004 and 2011, a total of 1,159 symptomatic patients (61 ± 11 years, 31 % women) with stable angina, without prior revascularisation underwent both invasive coronary angiography (ICA) and CTCA. All patients gave written informed consent for the additional CTCA. High-risk CAD was defined as LM and/or three-vessel obstructive CAD (≥50 % diameter stenosis).
A total of 197 (17 %) patients had high-risk CAD as determined by ICA. The sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios of CTCA were 95 % (95 % CI 91-97 %), 83 % (80-85 %), 53 % (48-58 %), 99 % (98-99 %), 5.47 and 0.06, respectively. CTCA provided incremental value (AUC 0.90, P < 0.001) in the discrimination of high-risk CAD compared with the Duke risk score and calcium score.
CTCA accurately excludes high-risk CAD in symptomatic patients. The detection of high-risk CAD is suboptimal owing to the high percentage (47 %) of overestimation of high-risk CAD. CTCA provides incremental value in the discrimination of high-risk CAD compared with the Duke risk score and calcium score.
• Computed tomography coronary angiography (CTCA) accurately excludes high-risk coronary artery disease. • CTCA overestimates high-risk coronary artery disease in 47 %. • CTCA discriminates high-risk CAD better than clinical evaluation and coronary calcification.
... However, these assumptions are based on older, generally retrospective studies whose focus has been the sensitivity and predictive power of the exercise ECG as a diagnostic test, with the reference standard for significant disease being 50% or 70% coronary artery diameter stenosis on angiography. By design, these studies have included subjects with both false positive and false negative exercise ECG tests (2)(3)(4)(5)(6)(7)(8). Because false positive exercise tests are usually not strongly positive and because false negative tests tend to be associated with less severe disease (9,10), inclusion of such patients in a study cohort would suggest that more positive tests must signify more severe disease. ...
... A few previous studies have suggested that the correlation between these diagnostic modalities may be poorer than is generally assumed (24,26 -28). Their limitations as well as those of other studies correlating exercise with scintigraphy have been their retrospective design (24,26,27,29), use of a limited number of ECG leads during exercise (26), nonsystematic or biased use of scintigraphy or angiography (8,24,27,28) and use of planar rather than tomographic imaging, generally without quantification (8,24,26 -28). In a previous, smaller study, we were unable to find a correlation between exercise ECG and angiographic indexes of IHD severity (12). ...
We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings.
In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear.
We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized.
Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent.
In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.
... It is known that SPECT imaging has the higher accuracy in detecting the presence of significant CAD compared to exercise electrocardiography (7). However, it is also known that exercise electrocardiography can provide comprehensive information in some scenarios, limiting the contribution of the SPECT images (8). Consequently, the ECG results cannot simply be dismissed. ...
Both exercise single photon emission computed tomography (SPECT) imaging and myocardial perfusion imaging with positron emission tomography produce multiple outcome variables. These include the stress electrocardiogram (ECG), visual perfusion assessment and quantitative myocardial blood flow. Bayes’ analysis using conditional probability allows the distillation of multiple test results into a single probability of disease for individual patients. This paper examines the application of conditional probability analysis to two noninvasive modalities that generate multiple outcome results: exercise ECG combined with SPECT imaging and vasodilator RB-82 positron emission tomography perfusion imaging combined with quantitative measure of absolute myocardial blood flow. In this manner, a single probability of disease incorporating all the available data is generated for an individual patient.
... При почечной недостаточности такие высокие дозы могут вызвать токсические побочные эффекты. У пациентов с ИБС, получающих оптимальное лечение, аллопуринол уменьшил уровни сосудистого окислительного стресса [206], тогда как у пациентов с сердечной недостаточностью он сохранял уровни АТФ [324]. 7.1.3.3.9. ...
... 323 In renal impairment, such high doses may have toxic side-effects. In optimally treated SCAD patients, allopurinol reduced vascular oxidative stress, 206 while in heart failure patients it conserved ATP. 324 7.1.3.3.9 ...
... 323 In renal impairment, such high doses may have toxic side-effects. In optimally treated SCAD patients, allopurinol reduced vascular oxidative stress, 206 while in heart failure patients it conserved ATP. 324 7. 1.3.3.9 ...
ESC Committee for Practice Guidelines (CPG): Jose Luis Zamorano (Chairperson) (Spain), Stephan Achenbach (Germany), Helmut Baumgartner (Germany), Jeroen J. Bax (Netherlands), He ' ctor Bueno (Spain), Veronica Dean (France), Christi Deaton (UK), Cetin Erol (Turkey), Robert Fagard (Belgium), Roberto Ferrari (Italy), David Hasdai (Israel), ArnoW. Hoes (Netherlands), Paulus Kirchhof (Germany/UK), JuhaniKnuuti (Finland), PhilippeKolh (Belgium), Patrizio Lancellotti (Belgium), Ales Linhart (CzechRepublic), Petros Nihoyannopoulos (UK), Massimo F. Piepoli (Italy), Piotr Ponikowski (Poland), Per Anton Sirnes (Norway), Juan Luis Tamargo (Spain), Michal Tendera (Poland), AdamTorbicki (Poland), WilliamWijns (Belgium), StephanWindecker (Switzerland). Document Reviewers: Juhani Knuuti (CPG Review Coordinator) (Finland), Marco Valgimigli (Review Coordinator) (Italy), Hector Bueno (Spain), Marc J. Claeys (Belgium), Norbert Donner-Banzhoff (Germany), Cetin Erol (Turkey), Herbert Frank (Austria), Christian Funck-Brentano (France), Oliver Gaemperli (Switzerland), JoseR. Gonzalez-Juanatey (Spain), Michalis Hamilos (Greece), David Hasdai (Israel), Steen Husted (Denmark), Stefan K. James (Sweden), Kari Kervinen (Finland), Philippe Kolh (Belgium), Steen Dalby Kristensen (Denmark), Patrizio Lancellotti (Belgium), Aldo Pietro Maggioni (Italy), Massimo F. Piepoli (Italy), Axel R. Pries (Germany), Francesco Romeo (Italy), Lars Ryden (Sweden), Maarten L. Simoons (Netherlands), Per Anton Sirnes (Norway), Ph. Gabriel Steg (France), Adam Timmis (UK), William Wijns (Belgium), StephanWindecker (Switzerland), Aylin Yildirir (Turkey), Jose Luis Zamorano (Spain).
... 6 The concept of applying nuclear imaging for reclassifying patient risk is not new. [8][9][10] More recently, this concept has been popularized through the work of Pencina et al 11 and the introduction of the terms NRI and IDI. Only a handful of recent nuclear cardiology publications have applied this approach. ...
The role of stress testing in the noninvasive evaluation of patients with possible or known coronary artery disease has evolved from functioning as a diagnostic tool to serving primarily as an aid in risk stratification. The results of clinical assessment and stress testing can be combined to estimate individual patient risk and guide subsequent treatment. National guidelines recommend that stress imaging preferentially be performed instead of standard exercise testing in patients with characteristics consisting of inability to exercise adequately, uninterpretable exercise ECG, or previous coronary artery disease revascularization.1,2 Aside from these patient subsets, controversy persists concerning the selection of a stress test modality attributable to uncertainty concerning the incremental prognostic value of stress imaging compared with standard exercise testing.
Article see p 531
For nuclear myocardial perfusion gated SPECT (MPGS), patient risk can be determined simply by dichotomizing images as normal/abnormal,3 but risk stratification can be refined by categorizing the images on the basis of summed perfusion scores.4,5 These scores include the summed stress score, which is a reflection of the extent and severity of combined infarction and ischemia, and the summed different score, an indicator of the extent and severity of ischemia.
In this issue of Circulation: Cardiovascular Imaging , Candell-Riera et al6 report on the prognostic value of exercise MPGS in 5672 patients with known or suspected coronary artery disease. The authors apply the c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to examine the incremental prognostic value of MPGS compared with clinical and exercise test variables for predicting the end points of all-cause death and the major cardiovascular end point of combined cardiovascular death and nonfatal myocardial infarction. The authors report 2 major findings: (1) predictive accuracy significantly increased by adding exercise variables to clinical variables for …
... The incremental value of SPECT perfusion imaging in patients with normal resting ECGs is controversial. 6,15,16 Its incremental value in patients with normal exercise ECGs is limited to patients at high clinical risk. 17 In contrast, the incremental value of SPECT in intermediate-risk patients with abnormal resting ECGs (nonspecific ST-and T-wave abnormalities) is considerable. ...
The importance of risk stratification in the management of symptomatic patients with known or suspected coronary artery disease is well recognized. Risk stratification not only informs the clinician's response to queries regarding prognosis but also helps the clinician choose appropriate therapy.1 Cardiac computed tomographic angiography (CCTA) is a relatively new tool for this purpose. Single-center studies have suggested its potential utility in estimating the prognosis of patients with known or suspected coronary artery disease (CAD).2 In this issue of Circulation: Cardiovascular Imaging , Chow et al3 report the findings of a large international multi-center registry (CONFIRM) that examines the value of CCTA for risk stratification. The strengths of the study include its large size (27 125 patients), its multicenter nature (12 participating centers in 6 different countries), its prospective nature, and the use of all-cause mortality as an end point. Although the authors describe their use of all-cause mortality as a potential limitation, Lauer et al have argued that this end point is actually preferred.4
Article see p 463
To their credit, Chow et al performed a stepwise analysis incorporating first clinical variables, then clinical variables and the left ventricular ejection fraction (LVEF) by CCTA, and then clinical variables, LVEF, and CAD severity assessed by CCTA. The authors also calculated the net reclassification improvement. This approach tries to quantify the prevalence of clinically meaningful change in individual patients. Past studies considered this concept,5,6 but statistical rigor has recently been added.7 The authors conclude that CCTA measures of LVEF and CAD severity are incremental to clinical variables in predicting all-cause mortality. These results add significantly to the evidence base for CCTA. The remainder of this editorial will consider the implications of these data for the evidence-based clinician evaluating a symptomatic patient with suspected …
... Exercise thallium testing is often performed to aid the diagnosis, prognosis and functional evaluation of patients with known or suspected coronary artery disease. It has been suggested that radionuclide imaging provides little additional diagnostic or prognostic information for patients with severe coronary disease and normal rest ECGs (48). ...
We sought to determine the relative influence of estimated functional capacity and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) findings on prediction of short-term all-cause and cardiac-related mortality.
Decreased functional capacity and abnormal Tl-201 SPECT findings are predictive of increased cardiovascular risk and mortality. However, the relative importance of these variables as predictors of all-cause mortality is not well established.
Analyses were based on 3,400 consecutive adults undergoing symptom-limited exercise Tl-201 SPECT testing at the Cleveland Clinic Foundation between September 1990 and December 1993; none had previous invasive procedures, heart failure or valve disease. Estimated functional capacity, classified by age and gender, and thallium perfusion defects, expressed as a stress extent thallium score on a 12-segment scale, were analyzed to determine their relative prognostic importance during 2 years of follow-up.
Of 3,400 patients, 108 (3.2%) died during follow-up; 32 deaths were identified as cardiac related. On univariable analysis, estimated functional capacity was a strong predictor of death, with 62 (57%) deaths occurring in patients achieving < 6 metabolic equivalents (METs) (log-rank chi-square 86, p < 0.0001). On multivariable analysis, the strongest independent predictors of all-cause mortality were fair or poor functional capacity (adjusted relative risk [RR] 3.96, 95% confidence interval [CI] 2.36 to 6.64, chi-square 27, p < 0.0001) and age (adjusted RR for 10 years 2.25, 95% CI 1.80 to 2.80, chi-square 27, p < 0.0001). The presence of SPECT thallium perfusion defects was a less powerful predictor of death (for each two additional segments with defects, adjusted RR 1.21, 95% CI 1.03 to 1.43, chi-square 5, p = 0.02). Cardiac mortality was predicted by both fair or poor functional capacity (adjusted RR 4.37, 95% CI 1.59 to 12.00, chi-square 8, p = 0.004) and by stress extent thallium score (adjusted RR 1.62, 95% CI 1.25 to 2.11, chi-square 13, p = 0.0003).
In this clinically low risk group, estimated functional capacity was a strong and overwhelmingly important independent predictor of all-cause mortality among patients undergoing exercise Tl-201 SPECT testing. The extent of myocardial perfusion defects was of comparable importance for the prediction of cardiac mortality.
The accurate and cost effective evaluation of patients presenting with chest pain can be vexatious because it is a common symptom with an extensive differential diagnosis. Some etiologies are life threatening, others treatable if diagnosed early, and a few are aggravating but not serious. Although thorough attention to the details of the history and a careful examination often provide clues that narrow the diagnostic possibilities, further testing is frequently required. Laboratory studies are appropriately employed to confirm clinical suspicions, eliminate unlikely but dangerous processes, and to delineate the extent and functional severity of disease. However, the cost of pursuing a comprehensive investigation in complex cases can be staggering, rendering a prudent selection of testing modalities mandatory, tailored to the individual case.(1-4)
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.
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.
Background:
The incremental prognostic value of myocardial perfusion-gated single photon emission computed tomography (MPGS) compared with exercise test has not yet been properly evaluated.
Methods and results:
Five thousand six hundred seventy-two consecutive patients with known or suspected coronary disease undergoing exercise MPGS between 1997 and 2007 were included. Three-year predictive models for total death and death from cardiovascular causes or acute myocardial infarction (ie, major cardiovascular events [MCE]) were built using Cox-regression modeling, including only the clinical information. Then the exercise and MPGS information was sequentially added. The added discriminative ability of exercise test information and MPGS was assessed by net reclassification improvement and integrated discrimination improvement. The increase in predictive ability of exercise information for death and MCE was high as assessed by net reclassification improvement (0.199 and 0.263) and integrated discrimination improvement (0.042 and 0.021). The only variable of MPGS associated with total death was ejection fraction (hazard ratio, 0.84; 95% confidence interval, 0.79-0.89; P<0.001). Global stress ischemic score emerged as an additional variable associated with MCE (hazard ratio, 1.07; 95% confidence interval, 1.02-1.12; P=0.007). Adding MPGS information barely improved the prognostic value for total death (net reclassification improvement, 0.017; integrated discrimination improvement, 0.013), but it increased for MCE (net reclassification improvement, 0.122; integrated discrimination improvement, 0.033).
Conclusions:
Adding MPGS information to exercise information does not improve prediction of total death, although it allows a more accurate prediction of MCE.
Extensive data have demonstrated that radionuclide myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) yields independent, incremental prognostic value over demographic and clinical information ([1][1]). More recently, routine use of cardiac stress positron
Jeffrey L. Anderson, MD, FACC, FAHA, Chair
Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect
Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1]
Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1]
Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1]
Nancy M
A Report of the American College of Cardiology Foundation/AmericanHeart Association Task Force on Practice Guidelines, and the AmericanCollege of Physicians, American Association for Thoracic Surgery,Preventive Cardiovascular Nurses Association, Society for CardiovascularAngiography and Interventions, and Society of Thoracic Surgeons
Description:
The American College of Physicians (ACP) developed this guideline in collaboration with the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, and Society of Thoracic Surgeons to help clinicians diagnose known or suspected stable ischemic heart disease.
Methods:
Literature on this topic published before November 2011 was identified by using MEDLINE, Embase, Cochrane CENTRAL, PsychINFO, AMED, and SCOPUS. Searches were limited to human studies published in English. This guideline grades the evidence and recommendations according to a translation of the ACCF/AHA grading system into ACP's clinical practice guidelines grading system.
Recommendations:
This guideline includes 28 recommendations that address the following issues: the initial diagnosis of the patient who might have stable ischemic heart disease, cardiac stress testing to assess the risk for death or myocardial infarction in patients diagnosed with stable ischemic heart disease, and coronary angiography for risk assessment.
Exercise can be considered the most practical test of cardiac perfusion and function. Exercise testing is a noninvasive tool to evaluate the cardiovascular system’s response to exercise under carefully controlled conditions. Its main uses center around the diagnosis of coronary artery disease and the estimation of prognosis in a wide range of conditions. While there are important technological considerations and the need to be very knowledgable of the guidelines to insure its proper application, exercise testing remains one of the most widely used and valuable noninvasive tools to assess cardiovascular status.
Keywords:
exercise;
diagnostic;
prognostic;
ECG;
ventilatory oxygen;
consumption;
coronary artery disease;
scores;
clinical
It has recently been recognized that atherosclerosis in all stages of development and progression— from the fatty streak to
the ruptured plaque causing a myocardial infarction (MI) is a specialized inflammatory response. The central role of inflammation
in atherosclerosis is underscored by the last two papers authored by the late Russell Ross, whose pioneering research and
writing shaped much of our understanding of the pathology during the last 30 yr. Both of these reviews asserted unequivocally
that “atherosclerosis is an inflammatory disease” (1,2).
Background. The mortality of diagnostic catheterization is very low but still exists. Large series have documented left main disease as the most important anatomical risk factor but have not clarified the mechanism. Objectives. (1) To determine the mortality of diagnostic catheterization in a single high volume centre over a 9 year period and assess any change during this period. (2) To compare this experience with that of larger multicentre surveys (3) To identify the clinical and anatomical risk factors. (4) To investigate the mechanism of the event (5) To develope quidelines for prevention. Methods. Cardiac catheterization records were reviewed over a 9 year period and patients dying during or within 24 hours were identified. The clinical and anatomical profile of the patients who died were compared with the overall group to search for independent risk factors. The angiograms of the deaths were reviewed for a mechanism. Results. There were 30 deaths in 42,345 procedures (0.071%). There was no change in the incidence over the 9 years. Left main coronary disease was an overwhelming risk factor (incidence 0.7%, p
As a general rule, clinicians should attempt to isolate those patient subsets whose posttest patient management may be optimally changed by the test referral. Use of testing in a heterogeneous population will lead to an increase in the false-positive rate with a resultant increase in the rate of normal catheterization and higher costs of care.14,16 By providing imprecise test results to the clinician, a higher rate of cardiac events may be observed as a result of lack of care for these patients. In addition, a high rate of normal coronary angiograms in patients with positive test results or admissions for subsequent myocardial infarctions in patients with normal test results may result in a lack of confidence in the imaging results leading to a change in referral to newer, untested modalities.
Thus to integrate our knowledge of the benefits to exercise electrocardiography within the context of clinical decision making and the appropriate selection of a noninvasive test, it is clear that physicians may use aggregate indexes such as the Duke treadmill score to guide patient care, but they should not be relied on to provide definitive evidence. Nor can one make the statement that because of the risk stratification ability of the Duke treadmill score this modality may be used to supplant stress myocardial perfusion imaging. In fact, exercise electrocardiography should be the test of choice for lower risk patient populations.17 However, in more intermediate-risk populations (e.g., known coronary disease or abnormal resting electrocardiogram), stress perfusion imaging is of established diagnostic and prognostic value. Further, from the exercise treadmill test, patients with an intermediate Duke treadmill score would benefit from additional noninvasive testing with stress myocardial perfusion imaging. This strategy provides substantial prognostic information on which to guide subsequent patient care.
With the development of advanced imaging modalities, the regular exercise electro-cardiogram (ECG) test has come to be regarded
by some as passé. In large part, this is because of the low sensitivity and specificity for the diagnosis of coronary artery
disease (CAD). With newer methods of interpretation, however, exercise testing remains a powerful and inexpensive prognostic
tool. The use of the exercise test has important implications for risk stratification as a part of prevention strategies and
for after myocardial infarction (MI) management. This chapter focuses primarily on the prognostic implications of exercise
testing using cardiovascular events and mortality as endpoints. It examines all aspects of the exercise test, including functional
capacity, heart rate (HR) changes during exercise, blood pressure (BP) response, and more-recent methods of computerized interpretation
of the exercise ECG.
Coronary artery disease (CAD) is a chronic, multifactor disease that has powerful contributing genetic components as well
as strong lifestyle components that increase the risk for the development and progression of the disease. Risk factors for
CAD have been historically divided into nonmodifiable, primary modifiable, and secondary modifiable factors. The primary focus
of medicine has been on the treatment of established CAD, and preventive efforts have more aggressively addressed areas in
which direct pharmacological intervention is available (1) (see Table 1). This is especially evident with respect to hypertension, hyperlipidemia, and antiplatelet aggregation therapy.
Background
The purpose of this study was to compare the incremental value of clinical information, electrocardiographic data, myocardial perfusion imaging, and radionuclide angiography for predicting severe coronary artery disease at a single testing interval. Clinical information, treadmill exercise studies, radionuclide angiography, and myocardial perfusion imaging are important predictors of severe coronary artery disease. However, the relative and absolute diagnostic importance of each of these methods has not been addressed at a single testing interval.
Methods and Results
A same-day rest/treadmill exercise perfusion and function study was performed in 167 patients within 90 days of coronary angiography. A multivariable regression model was used to assess the independent informational content of these predictors. Clinical and electrocardiographic data were related strongly to the presence of severe coronary artery disease (χ2=12.2 and p<0.001; χ2=11.8 and p<0.001, respectively). Combined perfusion and functional studies contributed 31% of the diagnostic information beyond that provided by clinical and electrocardiographic data alone (p<0.05).
Conclusions
These data demonstrate that combined studies of myocardial perfusion and left ventricular function are able to improve prediction of the extent of coronary artery disease, even when clinical and electrocardiographic data are also available.
Objectives. This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cast implications. Background. The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored. Methods. We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/-SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered ''hard'' events, and coronary angioplasty and bypass surgery >60 days after testing were considered ''soft'' events. Results. Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (<0.15), intermediate (0.15 to 0.85) and high (>0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre ETT likelihood of coronary artery disease. Conclusions. Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.
Background
The goal was to assess the incremental diagnostic value of thallium single-photon emission computed tomographic (SPECT) imaging and lung/heart ratio (LHR) over other clinical and exercise electrocardiographic (ECG) variables concerning the presence and extent (three vessel/left main) of coronary artery disease.
Methods and Results
Multivariable logistic regression analysis that used an incremental study design was applied to clinical, exercise test, SPECT, LHR, and catheterization data from 323 patients with suspected coronary disease. The following variables were evaluated as predictors of presence and extent of disease: clinical (age, sex, symptoms, diabetes, and smoking), exercise ECG (millimeters of ST segment depression, slope of ST segment depression, peak heart rate, change in systolic blood pressure, and metabolic equivalents of the task), and thallium (defect reversibility and intensity of hypoperfusion and LHR). Discrimination and incremental value were assessed by receiver operating characteristic (ROC) curve analysis. SPECT imaging (segment hypoperfusion score) was an independent predictor of both presence and extent of disease (p<0.0001) irrespective of the percent stenosis criterion used. However, it added significant incremental diagnostic information over clinical and exercise ECG data only concerning presence (e.g., ROC curve areas: presence of disease — clinical plus exercise ECG=83±2 vs clinical, exercise ECG, plus SPECT=87±2, p<0.001; extent of disease — clinical plus exercise ECG=83+4 vs clinical, exercise ECG, plus SPECT=85±3, p=0.11). Thallium LHR was an independent predictor of both presence and extent of disease (p<0.05), but the incremental information added to SPECT data did not reach statistical significance (e.g., ROC curve areas: presence of disease — SPECT=87±2 vs SPECT plus LHR=88±2, p=0.24; disease extent — SPECT=85±2 vs SPECT plus LHR=86±2, p=0.24). However, when combined, LHR and SPECT data had significant incremental value over clinical and exercise ECG data alone concerning extent of disease (e.g., ROC curve areas: clinical plus exercise ECG=83±4 vs clinical, exercise ECG, SPECT and LHr=86±3, p=0.04).
Conclusion
SPECT thallium imaging variables are independent predictors of both presence and extent of coronary disease. However, they have significant incremental value over clinical and exercise ECG data concerning only presence of disease. Thallium LHR is an independent predictor of both presence and extent of disease but adds only a small insignificant amount of incremental diagnostic information over SPECT data. However, there was significant incremental value to the addition of LHR to SPECT data concerning extent of disease.
Objectives:
This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications.
Background:
The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored.
Methods:
We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered "hard" events, and coronary angioplasty and bypass surgery > 60 days after testing were considered "soft" events.
Results:
Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease.
Conclusions:
Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.
This review presents a brief overview of existing diagnostic and prognostic methodologies to be used for the evaluation of patients undergoing noninvasive testing. In part I of this review, we will present methods for use of logistic and Cox regression analyses in determining the diagnostic and prognostic value of nuclear imaging techniques. In part II of this review, we will present an outline for the integration of economic evaluations into the clinical decision-making process. This review will document how cost estimates may be defined as well as the differing type of cost analyses (i.e., cost efficiency versus cost-effectiveness).
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.
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.
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.
“Faux amis” or “false friends” (abbreviated hereafter as FF) are metalinguistic terms used to name word pairs that look alike in two languages, but that do not have the same meaning. The purpose of this paper is to identify and classify FF in a corpus of medical English prose. Our source material consists of twenty research papers randomly chosen and published between 1994 and 1996 in various leading medical journals. Every FF was identified by means of a contextual analysis. The deceptive cognates recorded were classified according to two groups of variables: FF types and word classes. The proportion of FF found in the corpus reached 5.3% of the number of total running words. This leads us to believe that they deserve special attention since it is well known that they represent an important problem for terminologists and are frequently misinterpreted by medical doctors and students. We thus believe that the elaboration of tables containing word pairs (English-Spanish, in our case) most frequently encountered, along with well designed exercises, could prove most helpful if presented at an early stage of reading comprehension and translation courses.
We sought to identify prospectively the prevalence of significant ischemia (> or =10% of the left ventricle [LV]) on exercise single-photon emission computed tomography (SPECT) imaging relative to workload achieved in consecutive patients referred for myocardial perfusion imaging (MPI).
High exercise capacity is a strong predictor of a good prognosis, and the role of MPI in patients achieving high workloads is questionable.
Prospective analysis was performed on 1,056 consecutive patients who underwent quantitative exercise gated (99m)Tc-SPECT MPI, of whom 974 attained > or =85% of their maximum age-predicted heart rate. These patients were further divided on the basis of attained exercise workload (<7, 7 to 9, or > or =10 metabolic equivalents [METs]) and were compared for exercise test and imaging outcomes, particularly the prevalence of > or =10% LV ischemia. Individuals reaching > or =10 METs but <85% maximum age-predicted heart rate were also assessed.
Of these 974 subjects, 473 (48.6%) achieved > or =10 METs. This subgroup had a very low prevalence of significant ischemia (2 of 473, 0.4%). Those attaining <7 METs had an 18-fold higher prevalence (7.1%, p < 0.001). Of the 430 patients reaching > or =10 METs without exercise ST-segment depression, none had > or =10% LV ischemia. In contrast, the prevalence of > or =10% LV ischemia was highest in the patients achieving <10 METs with ST-segment depression (14 of 70, 19.4%).
In this referral cohort of patients with an intermediate-to-high clinical risk of coronary artery disease, achieving > or =10 METs with no ischemic ST-segment depression was associated with a 0% prevalence of significant ischemia. Elimination of MPI in such patients, who represented 31% (430 of 1,396) of all patients undergoing exercise SPECT in this laboratory, could provide substantial cost-savings.
In the last decade, positron emission tomography (PET) myocardial perfusion imaging (MPI) has emerged as a valuable clinical tool for the management of patients with known or suspected coronary artery disease (CAD). Compared with single-photon emission computed-tomography (SPECT), PET provides
Our goal was to assess the incremental value of exercise testing in men and women for the diagnosis and extent of coronary artery disease. With data from one center, incremental logistic algorithms were developed and evaluated in a separate set of 865 patients from four centers. Variables included were pretest (age, sex, symptoms, diabetes, smoking, and cholesterol concentration); exercise electrocardiogram (ECG) (ST-segment depression [millimeters], ST-segment slope, peak heart rate, and change in systolic blood pressure); and thallium-201 scintigram (defect presence, reversibility, and intensity of hypoperfusion). End points were coronary disease presence (50% diameter stenosis) and extent (multivessel disease). Accuracy and incremental value were assessed by receiver operating characteristic (ROC) curve analysis. Incremental ROC curve areas for disease presence were pretest 0.75 +/- 0.02, post-exercise ECG 0.82 +/- 0.01, and post-thallium scintigram 0.85 +/- 0.01 and for disease extent were pretest 0.71 +/- 0.02, post-exercise ECG 0.76 +/- 0.02, and post-thallium scintigram 0.78 +/- 0.02 (p < 0.005 for all increments). Incremental increases in accuracy were similar for men and women. We conclude that when multivariable algorithms derived from one center were applied to a separate group, there was a significant incremental increase in accuracy associated with exercise testing for the presence and extent of coronary disease. This increase in accuracy was similar for men and women.
The hypothesis that a diagnostic evaluation performed by a generalist is less expensive than that performed by a specialist is untested. We retrospectively evaluated the indications and financial ramifications of radionuclide exercise stress testing by cardiologists and noncardiologists in 1,902 consecutive adults with normal resting electrocardiograms. Subjects completed radionuclide exercise tests for the diagnosis or management of coronary artery disease during a 14-month period. Tests were considered "indicated" or "not indicated" based on criteria determined from published reports and established practice guidelines. Savings in costs and charges were determined for a strategy of referral to a cardiologist before ordering tests. Non-cardiologists ordered more tests that were not indicated than cardiologists (69.6% vs 36.2%, chi-square = 209.07, p < 0.00001). Non-cardiologists also ordered tests that were not indicated in patients with (chi-square = 110.02, p < 0.00001) and without (chi-square = 110.02, p < 0.00001) and without (chi-square = 45.44, p < 0.00001) chest pain. Tests that were not indicated resulted in excess costs of $591,384 and excess charges of $1,082,400. Referral to a cardiologist before ordering tests could have saved $63,257 in costs and $169,800 in charges. Both cardiologists and non-cardiologists overutilized radionuclide exercise stress test; however, non-cardiologists were more likely to order tests that were not indicated. A strategy of referral to a cardiologist before ordering tests may be cost-effective in this population.
This study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders.
To minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women.
We identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women.
The patient population was followed up for 20 +/- 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 +/- 0.03 vs 0.71 +/- 0.03 in men, p < 0005). The odds ratio comparing event rates in patients with women than in men, suggesting superior stratification using nuclear testing in women.
Dual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men.
This study examined the prevalence of normal resting left ventricular function in 2,275 patients referred for technetium-99m sestamibi stress imaging. The strongest predictor of normal left ventricular function was a normal electrocardiogram at rest.
To demonstrate that a consensus approach for combining prediction equations based on clinical and exercise test variables derived from different populations can stratify patients referred for possible coronary artery disease (CAD) into low-, intermediate-, and high-risk groups.
Retrospective analysis of consecutive patients with complete data from exercise testing and coronary angiography referred for evaluation of possible CAD. After derivation of a logistic equation in our own training set of patients, this equation, along with two other equations developed independently by other investigators, was validated in a test set. The validation strategy for the consensus approach included the following: (1) calculation of probability scores for each patient using each logistic equation independently; (2) determination of probability thresholds in the training set to divide the patients into three groups-low risk (prevalence CAD <5%), intermediate risk (5 to 70%), and high risk (>70% prevalence of CAD); (3) using agreement among at least two of three of the prediction equations to generate "consensus" for each patient; and (4) application of the consensus approach thresholds to the test set of patients.
Two university-affiliated Veteran's Affairs medical centers.
We studied 718 consecutive men between 1985 and 1995 who had coronary angiography within 3 months of an exercise treadmill test for suspected CAD. The population was randomly divided into a training set of 429 patients and a test set of 289 patients. Patients with previous myocardial infarction or coronary artery bypass surgery, valvular heart disease, left bundle branch block, or any Q waves present on their resting ECG were excluded from the study.
Recording of clinical and exercise test data along with visual interpretation of the ECG recordings on standardized forms and abstraction of visually interpreted angiographic data from clinical catheterization reports.
We demonstrated that by using simple clinical and exercise test variables, we could improve on the standard use of ECG criteria during exercise testing for diagnosing CAD. Using the consensus approach divided the test set into populations with low, intermediate, and high risk for CAD. Since the patients in the intermediate group would be sent for further testing and would eventually be correctly classified, the sensitivity of the consensus approach is 94% and the specificity is 92%. The consensus approach controls for varying disease prevalence, missing data, inconsistency in variable definition, and varying angiographic criterion for stenosis severity. The percent of correct diagnoses increased from the 67% for standard exercise ECG analysis and from the 80% for multivariable predictive equations alone to >90% correct diagnoses for the consensus approach.
The consensus approach has made population-specific logistic regression equations portable to other populations. Excellent diagnostic characteristics can be obtained using simple data and measurements. The consensus approach is best applied utilizing a programmable calculator or a computer program to simplify the process of calculating the probability of CAD using the three equations.
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