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Background— Coronary artery disease is the main cause of mortality and morbidity in patients with impaired renal function. The aim of this study was to evaluate the prognostic implications of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with impaired renal function. Methods and Results— We included 7348 consecutive patients (mean age, 64�13 years; 51% men) referred for SPECT-MPI between March 2002 and October 2006. Renal function was estimated using the estimated glomerular filtration rate formula. Patients were followed up for the incidence of all-cause mortality. Patients with decreased glomerular filtration rate were more often older, with higher prevalence of conventional risk factors ( P P Conclusions— SPECT-MPI adds modest incremental prognostic information to identify patients at higher relative risk of death across a wide spectrum of renal function.

Background— The goal of this study was to assess the clinical value of stress myocardial perfusion scintigraphy (MPS) in elderly patients (≥75 years of age). Methods and Results— We followed up 5200 elderly patients (41% exercise) after dual-isotope MPS over 2.8±1.7 years (362 cardiac deaths [CDs], 7.0%, 2.6%/y) and a subset with extended follow-up (684 patients for 6.2±2.9 years; 320 all-cause deaths). Survival modeling of CD revealed that both MPS-measured ischemia and fixed defect added incrementally to pre-MPS data in both adenosine and exercise stress patients. Modeling a subset with gated MPS (n=2472) revealed that ejection fraction and perfusion data added incrementally to each other, further enhancing risk stratification. Unadjusted, annualized post–normal MPS CD rate was 1.3% but P Conclusions— Stress MPS effectively stratifies CD risk in elderly patients and may identify optimal post-MPS therapy. CD rates after normal MPS are low in all subsets in relative terms compared with the age-matched US population.

Cardiovascular imaging has become the focus of attention from both physicians and payers. The former see the potential of newer modalities to permit new and exciting insights into the diagnosis and management of coronary artery disease (CAD), that, in turn, may result in enhanced patient care strategies and new efficient clinical algorithms. On the other hand, payers have understandable concerns about the excessive use and enormous costs associated with cardiovascular imaging. These concerns have been exacerbated by the rapid expansion of the imaging devices used for the assessment of patients with known or suspected CAD. Cardiovascular stress imaging has long been the domain of stress single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) and stress echocardiography wall motion studies. At present, stress positron emission tomography (PET) MPI, cardiac computed tomography coronary angiography (CTA) (and, possibly, stress CT MPI), as well as cardiac magnetic resonance imaging (CMR) MPI and wall motion studies are utilized in daily practice. Whether all of these modalities will be reimbursed in the future is uncertain, but little doubt remains that their rigorous validation will be compulsory. Article see p 1390 Cardiac magnetic resonance imaging is an evolving technique with growing indications within the clinical cardiology setting. Whereas late gadolinium enhancement (LGE) has gained acceptance as an accurate approach for viability assessment, CMR stress imaging use is increasing as well. Nonetheless, stress CMR techniques are in their relative infancy, and evidence is only now beginning to accumulate justifying their use. Whereas several studies have examined the diagnostic accuracy of stress CMR, only recently have sufficient numbers of patients been collected to assess the prognostic value of this approach1–5 (Table).6 The validation of stress CMR is more complex than that of previous modalities, inasmuch as a routine study would include rest function and …

Section Editor: Christopher M. Kramer, MD imaging is presently in the crosshairs of policy makers in the U.S. government as the health care reform debate rages on. The era of proving cost effectiveness, not just efficacy, is upon us imagers whether we like it or not. Comparative effectiveness is

BACKGROUND The output of carbon dioxide (VCO2) is controlled by both hemodynamics and ventilation. To understand VCO2 in patients who have chronic heart failure (CHF), we studied 14 patients who had New York Heart Association functional class III failure by measurements of hemodynamics, ventilation, and arterial and venous blood gases at rest and at 50 W of cycle ergometry exercise. METHODS AND RESULTS Fick principle analysis of VCO2 showed that because of a limited increase in cardiac output, CHF patients widened their venoarterial CO2 content difference from 4.9 +/- 3.5 ml/dl at rest to 11.1 +/- 4.0 ml/dl with exercise (p less than 0.05). This increase in CO2 content difference was achieved with no change in venous CO2 content (from 54.3 +/- 3.3 ml/dl at rest to 54.5 +/- 4.8 ml/dl at exercise, p = NS); however, there was a decrease of arterial CO2 content (from 49.4 +/- 3.7 ml/dl at rest to 43.4 +/- 2.3 ml/dl with exercise, p less than 0.05). Modeling of the CO2 tension-content relation showed that there would have been a small, nonproportional increase of venous CO2 content as venous CO2 tension increased from 43.2 +/- 1.8 mm Hg at rest to 55.3 +/- 4.2 mm Hg during exercise (p less than 0.05); however, the development of metabolic acidosis during exercise entirely blunted the increase of CO2 content. In contrast, both the shape of the tension-content relation and the acidosis of exercise further influenced the decrease of arterial CO2 content as arterial CO2 tension decreased from 37.0 +/- 2.9 mm Hg at rest to 32.0 +/- 3.4 mm Hg during exercise (p less than 0.05) as a result of excess ventilation. CONCLUSIONS In CHF patients during exercise, the circulatory limitations imposed by a low cardiac output on VCO2 are compensated by a widened venoarterial CO2 content difference. The content difference is not widened through an increase of venous CO2 content but rather by a decrease of arterial CO2 content caused by arterial hypocapnia and metabolic acidosis.

Background: Combined adenosine stress perfusion (STRESS), myocardial delayed enhancement (MDE), and ventricular wall motion (WM) by cardiac magnetic resonance (CMR) is a promising approach to further risk stratification in patients with intermediate pre-test clinical cardiovascular risk. The prognosis conferred by normal (NL) STRESS, MDE, and WM CMR is unknown. Methods: 1,002 consecutive patients underwent combined CMR including STRESS by gadolinium first-pass perfusion, MDE, and cine WM for suspicion of coronary artery disease (CAD) or myocardial ischemia. 577 patients had NL STRESS, 607 had NL MDE, 544 had NL WM, and 448 had NL combined CMR. 70% had no history of CAD. Follow up was performed at a mean 31 (range 12– 62) months after CMR for cardiac death (CD) all-cause death (ACD) and non-fatal myocardial infarction (MI). Results: NL combined CMR resulted in 0.6% rate of CD per year of follow up (0.3% if no CAD history, and 1.4% with CAD history). Rates for ACD and ACD plus MI were 1.9% and 2.0%. Similar event rates were observed when each component of combined CMR was considered separately. Conclusion: Normal STRESS, MDE, and WM CMR, both singly or in combination, confer a low risk of subsequent cardiac events. Event Rate % per Year of Follow Up

Background. Evaluation of the intermediate risk patient (Pt) using combined cardiac magnetic resonance imaging (CMR) assessment of adenosine stress perfusion (STRESS), myocardial delayed enhancement viability (MDE), and ventricular wall motion imaging (WM) is a promising clinical approach. Whether this technique yields risk stratification and incremental prognostic value over pre-CMR data is uncertain. Methods. We identified 1,002 consecutive patients [Age 64±14, 58% male, 50% prior coronary artery disease (CAD)] undergoing combined CMR for suspicion of CAD or ischemia. STRESS first-pass gadolinium gradient echo pulse sequence, MDE, and steady state free precession WM were interpreted using 17-segment, 5 point scoring. Summed scores (SS) were calculated for each. The primary endpoint was all-cause death (ACD), the secondary endpoint cardiac death (CD). Incremental prognostic value was defined as an increased Cox proportional hazards model (CPH) global chi-square with the addition of CMR data after adjustment for clinical and historical data. Results: Follow-up (FU) at 2.6±1.2 years after CMR (2.4% lost to FU) identified 78 ACD (8.0%) and 38 CD (3.9%). Compared to pts with normal stress CMR (STRESS, MDE, and WM all normal), pts with abnormal results had greater ACD rates over FU (5.9% vs 11%, p=0.006). After adjusting for the most predictive pre-CMR data (dyspnea, rest heart rate, age, and known renal disease; global chi-square 55, p Conclusion : STRESS, MDE and WM all add incremental value for prediction of ACD and CD over pre-CMR data and can be combined to further enhance prognostication.

To design a multicenter study comparing the prognostic value and post-test resource utilization of PET, CT Coronary Angiography (CTA), and SPECT in clinical practice. Although PET, CTA, and SPECT are widely used, their relative clinical- and cost-effectiveness are undefined. The Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in CAD (SPARC) is a prospective, multicenter, observational registry that has enrolled 3019 patients undergoing clinically referred SPECT, PET, and CTA with the goal of comparing post-test resource utilization and comparative prognostic value. Resource utilization assessment will enroll intermediate-high likelihood patients without prior CAD, while prognostic assessment will include both these patients and patients with prior CAD. Secondary analyses include assessments of diagnostic accuracy, cost, and referral to revascularization. Sites recruited into at least two of the three imaging arms. Except for semi-quantitative interpretation, site protocols will be used for all imaging studies and images forwarded to an image repository. Follow-up for catheterization, revascularization, cardiac death, myocardial infarction, all-cause death and medication use changes will be performed at 90-day, 1, and 2 years. Standard statistical methods will be used to risk-adjust results within and between study arms. SPARC will have >85% power (two-sided test, α = 0.01) to detect a 5% catheterization rate difference at 90 days between the three arms and >90% power to detect a 2% difference in cardiac death, or nonfatal MI within 2 years of the index test. SPARC will be the first study comparing outcomes and resource utilization between SPECT, PET, and CTA in daily practice. In addition, the study design offers insights into inter-site and geographic differences in referral patterns and resource utilization.

Background - Although the value of coronary artery calcium (CAC) for atherosclerosis screening is gaining acceptance, its efficacy in predicting flow-limiting CAD remains controversial and its incremental prognostic value over myocardial perfusion is not well established. Methods and Results - We evaluated 621 consecutive patients undergoing combined rest-stress Rubidium-82 PET perfusion imaging and CAC scanning on a hybrid PET-CT scanner. The frequency of abnormal scans among patients with CAC ≥400 was higher than that in patients with CAC 1–399 (53.3% vs 30.0%, p Conclusions - Although increasing CAC scores are generally predictive of a higher likelihood of ischemia, its absence does not eliminate the possibility of flow-limiting CAD. Importantly, there is a stepwise increase in the risk of adverse events with increasing CAC scores in patients with and without ischemia on PET.

Little is known about incidence, threshold, and predictors of prognostically relevant silent ischemia (SI). The aim was to study these three aspects of silent coronary artery disease (CAD).In total, 3,664 consecutive asymptomatic patients without prior diagnosis of CAD undergoing myocardial perfusion SPECT (MPS) were evaluated and followed-upor = 1 year for Events (HE): cardiac death or myocardial infarction. MPS was interpreted using a 20 segment model to define summed stress, rest, and difference scores (the extent of % myocardium ischemic was derived). Prognostic high-risk ischemia was defined as ischemia consistent with a HE rateor = 3%.Overall,or = 7.5% myocardium ischemic was consistent with high risk. Twenty-one and six percent of patients had ischemia and high-risk ischemia, respectively. Patients with high-risk ischemia had a worse prognosis than patients with less SI, HE rate of 3.1 and 0.4%, respectively, (P = .0001). Sex, age, diabetes, hypertension, abnormal resting ECG, angina, peak heart rate, blood pressure during treadmill testing, ST-depression, and Duke treadmill score were independent predictors of relevant SI.In total,or = 7.5% myocardium ischemic revealed to be consistent with high risk. Six percent of patients had evidence of high-risk SI. Diagnostic scores are provided to most likely identify patients with high-risk SI.

Cardiac computed tomography (CT) and positron emission tomography (PET) are emerging as powerful noninvasive imaging tools for the evaluation of atherosclerosis in patients with known or suspected coronary artery disease (CAD). Unlike invasive coronary angiography, CT coronary angiography (CTA) not only assesses disease within the coronary lumen but can also provide direct qualitative and quantitative information about nonobstructive atherosclerotic plaque burden within the vessel wall. Thus, it is possible that CTA-based patient evaluation may provide more clinically relevant information on which to base risk assessments compared with conventional “lumenography.” On the other hand, PET is rapidly growing as a powerful and efficient alternative to conventional single-photon emission CT (SPECT) imaging to evaluate regional myocardial perfusion and metabolism in patients with CAD. In addition, PET scanners are now being converted to hybrid PET/CT devices, which, in the setting of CAD, offer the potential for a comprehensive noninvasive cardiac evaluation of anatomy and function. This review will discuss current and potential future applications of cardiovascular CT, PET, and hybrid PET/CT, with a particular focus on ischemic heart disease. The information provided by noninvasive imaging generally falls into 1 of 3 categories: myocardial perfusion, left ventricular (LV) function, or coronary artery anatomy. The clinical utility, value, and role of a noninvasive modality are based on 2 test characteristics: What type of information is provided (eg, stress perfusion, stress and/or rest LV function, coronary anatomy), and what is the accuracy of the information provided. For example, SPECT and PET both provide stress and rest perfusion information, but the latter will be a superior clinical tool if the imaging data better represent the actual defect size and are subject to less artifact. The advantage of PET over SPECT will be further enhanced, as will be discussed later, if it provides additional clinically relevant information not …

Noninvasive cardiac imaging has undergone a recent resurgence with the development of new approaches for imaging coronary atherosclerosis. Non-contrast computed tomography (CT) for imaging the extent of coronary artery calcification (CAC) and contrast CT for noninvasive coronary angiography (CTA) are developments with a growing evidence base regarding risk assessment and the diagnosis of obstructive coronary disease. This review discusses the role of CAC for risk assessment of asymptomatic individuals and for the use of coronary CTA in symptomatic patients. By comparison, gated myocardial perfusion scintigraphy (MPS) is a well-established noninvasive imaging modality that is a core element in evaluation of patients with stable chest pain syndromes. Stress MPS is the most commonly used stress imaging technique for patients with suspected or known coronary disease. In contrast to the nascent evidence noted with coronary CTA, MPS has a robust evidence base, including the support of numerous clinical guidelines. We highlight the current evidence supporting the diagnostic accuracy and risk stratification data for MPS for symptomatic patients with known or suspected coronary artery disease. It is likely that assessing the extent of atherosclerosis using CAC or coronary CTA will become an increasing part of mainstream cardiovascular imaging practices. In some patients, further ischemia testing with MPS will be required. Similarly, in some patients referred for MPS, anatomic definition of atherosclerosis using CAC by CT may be appropriate. Thus, this review also provides a synopsis of the available literature on imaging that integrates both CT and MPS in combined strategies for the assessment of atherosclerotic and obstructive coronary disease burden. We also propose possible risk-based strategies through which imaging might be used to identifying candidates for more intensive prevention and risk factor modification strategies as well as those who would benefit from referral to coronary angiography and revascularization.

This review has indicated that there is an interaction between the assessment of coronary anatomic abnormality — through the CCS or possibly even the non-invasive coronary angiogram — and the assessment of the functional consequences of atherosclerosis using gated MPS. Additional information of clinical importance may come from assessment of biomarkers of inflammation such as high-sensitivity CRP. It is considered likely that with an increased emphasis on prevention and a concomitant aging of the population, many forms of non-invasive cardiac imaging will continue to grow. The CCS and non-invasive CT coronary angiography approaches are likely to grow greatly in the preventive arena for the early detection of coronary atherosclerosis, in guiding the aggressiveness of medical therapy in these patients, and in detection of significant CAD. Gated MPS is likely to have its greatest growth in the increasing numbers of patients with known CAD, as the most effective method to identify which of these patients are most likely to benefit from medical therapy versus coronary revascularization or myocardial reshaping procedures.

This review deals with noninvasive imaging for risk stratification and with a conceptual approach to the selection of noninvasive tests in patients with suspected or known chronic coronary artery disease (CAD). Already widely acknowledged with SPECT, there is an increasing body of literature data demonstrating that CT coronary calcium assessment is also of prognostic value. The amount of coronary atherosclerosis, as can be extrapolated from CT coronary calcium score, has been shown to be highly predictive of cardiac events. The principal difference between myocardial perfusion SPECT (MPS) and CT coronary calcium for prognostic application appears to be that the former is an excellent tool for assessing short-term risk, thus effectively guiding decisions regarding revascularization. In contrast, the atherosclerosis imaging methods are likely to provide greater long-term risk assessment and, thus, are more useful in determination of the need for aggressive medical prevention measures. Although the more recent development of CT coronary angiography is promising for diagnosis, there has been no information to date regarding the prognostic value of the CT angiographic data. Similarly, cardiac MRI has not yet been adequately studied for its prognostic content. The selection of the most appropriate test for a given patient depends on the specific question being asked. In patients with a very low likelihood of CAD, no imaging test may be required. In screening the remaining asymptomatic patients, atherosclerosis imaging may be beneficial. In symptomatic patients, MPS, CT coronary angiography, and cardiac MRI play important roles. We consider it likely that, with an increased emphasis on prevention and a concomitant aging of the population, many forms of noninvasive cardiac imaging will continue to grow, with nuclear cardiology continuing to grow.

The clinical evidence discussed previously suggests that integrated PET-CT is a powerful noninvasive modality for diagnosing and managing CAD. The need for gated scans, the use of nephrotoxic contrast, and the potential limitations imposed by the presence of calcium bring into question the generalizability of CT alone to all patients with known or suspected CAD. Beyond diagnosis of CAD, CT coronary angiography may find its most important challenge in guiding management after the diagnosis of CAD is established. Thus the greatest strength of integrated PET-CT imaging is its ability to establish the diagnosis, define risk, and guide management with a single study.

Noninvasive cardiac imaging is now central to the diagnosis and management of patients with known or suspected chronic coronary artery disease (CAD). Although rest echocardiography has become the most common of the techniques, nuclear cardiology and more recently cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) play important roles in this regard. This review examines the current applications and interactions of noninvasive cardiac imaging approaches for the assessment of patients with suspected CAD. In addition to considering the strengths and weaknesses of each technique, this review attempts to provide a guide to the selection of a test (or tests) that is based on the question being asked and the ability of each test to answer this question. In patients with suspected CAD, the pretest likelihood of disease, a clinical assessment, becomes the most important determinant of the initial test. If the likelihood is very low, no testing is needed. However, if the likelihood is low, recent data suggest that assessment of early atherosclerosis is likely to be the most useful and cost-effective test. In patients who have an intermediate likelihood of CAD, nuclear cardiology with myocardial perfusion SPECT (MPS) becomes highly valuable; however, coronary CT angiography (CTA), with fast 16-slice or greater scanners, may emerge as the initial test of choice. MPS would then be used if the CTA is inconclusive or if there is a need to assess the functional significance of a stenosis defined by CTA. Coronary CTA, however, is not yet widely available and is limited in patients with dense coronary calcification. In older patients with a high likelihood of CAD, MPS may be the initial test of choice, since a high proportion of these patients have too much coronary calcium to allow accurate assessment of the presence of coronary stenoses. PET/CT or SPECT/CT could emerge as important modalities combining the advantages of each modality. While CMR has great promise as a radiation-free and contrast-free "one-stop" shop, it currently lags behind CTA for noninvasive coronary angiography. Nonetheless, CMR clearly has the potential for this application and has already emerged as a highly effective method for assessing ventricular function, myocardial mass, and myocardial viability, and there is increasing use of this approach for clinical rest and stress perfusion measurements. CMR is particularly valuable in distinguishing ischemic from nonischemic cardiomyopathy. While CT and CMR are likely to grow considerably in diagnostic evaluation over the next several years, MPS and PET will continue to be very valuable techniques for this purpose.

Although dyspnea is a common symptom, there has been only limited investigation of its prognostic significance among patients referred for cardiac evaluation.We studied 17,991 patients undergoing myocardial-perfusion single-photon-emission computed tomography during stress and at rest. Patients were divided into five categories on the basis of symptoms at presentation (none, nonanginal chest pain, atypical angina, typical angina, and dyspnea). Multivariable analysis was used to assess the incremental prognostic value of symptom categories in predicting the risk of death from cardiac causes and from any cause. In addition, the prognosis associated with various symptoms at presentation was compared in subgroups selected on the basis of propensity analysis.After a mean (+/-SD) follow-up of 2.7+/-1.7 years, the rate of death from cardiac causes and from any cause was significantly higher among patients with dyspnea (both those previously known to have coronary artery disease and those with no known history of coronary artery disease) than among patients with other or no symptoms at presentation. Among patients with no known history of coronary artery disease, those with dyspnea had four times the risk of sudden death from cardiac causes of asymptomatic patients and more than twice the risk of patients with typical angina. Dyspnea was associated with a significant increase in the risk of death among each clinically relevant subgroup and remained an independent predictor of the risk of death from cardiac causes (P0.001) and from any cause (P0.001) after adjustment for other significant factors by multivariable and propensity analysis.In a large series of patients, self-reported dyspnea identified a subgroup of otherwise asymptomatic patients at increased risk for death from cardiac causes and from any cause. Our results suggest that an assessment of dyspnea should be incorporated into the clinical evaluation of patients referred for cardiac stress testing.

The value of exercise-induced ST-segment depression for the prognostic evaluation of patients with 1 mm of ST depression or greater on the resting electrocardiogram is controversial.Patients who underwent exercise myocardial perfusion single photon emission computed tomography (MPS) and had resting ST depression of 1 mm or greater with a nondiagnostic exercise electrocardiographic response (n = 1122) were followed up for 3.4 +/- 2.3 years. Those with paced rhythm, pre-excitation, left bundle branch block, or myocardial revascularization within the first 60 days after MPS were excluded. Additional exercise-induced ST-segment depression was considered significant ifor = 2 mm MPS was scored semiquantitatively by use of a 20-segment model of the left ventricle; the percentage of myocardium involved with stress defects (% myo) was derived by normalizing to the maximal possible score of 80. Hard events were defined as nonfatal myocardial infarction or cardiac death. A Cox analysis was used to determine independent predictors of hard events among clinical, exercise, and nuclear variables. Hard event rates increased as a function of % myo for either patients with exercise-induced ST depression (1.4%/y for normal MPS vs 4.1%/y for % myo10%, P.03) or those without it (0.7%/y for normal MPS vs 3.0%/y for % myo10%, P = .0001). Age, diabetes mellitus, shortness of breath as the presenting symptom, and % myo were independent predictors of hard events. Exercise-induced ST depression was predictive of hard events only when it was 3 mm or greater. The presence and extent of perfusion defects, reflected in the % myo, had incremental prognostic value over clinical variables and also over all degrees of exercise-induced ST depression.Although MPS effectively risk-stratifies patients with resting ST depression of 1 mm or greater, the prognostic value of exercise-induced ST depression is limited in these patients, with a small added risk when severe (or = 3 mm).

The aim of our study was to derive and to validate the normal threshold for an automatically measured left ventricular transient ischemic dilation (TID) ratio in patients referred for adenosine stress myocardial perfusion SPECT (MPS) and to assess the value of integrating TID in detecting severe and extensive coronary artery disease (CAD).Normal limits for the TID ratio were derived using dual-isotope MPS data from 38 patients with a low (5%) likelihood of CAD. Criteria for abnormality were calculated on the basis of data from 179 consecutive patients who had undergone coronary angiography less than 3 mo after index adenosine MPS: 41 patients (23%) had severe and extensive CAD (or =90% stenosis) in the proximal left anterior descending artery or in 2 or more coronary arteries, 64 (36%) had no significant CAD (70% stenosis), and 74 (41%) had mild or moderate CAD. The criteria were then prospectively validated in a cohort of 177 patients, of whom 41 patients (23%) had severe and extensive CAD, 55 (31%) had no significant CAD, and 81 (46%) had mild or moderate CAD.By analysis of receiver-operating-characteristic curves, the best threshold for adenosine TID ratio abnormality was the mean adenosine TID ratio in the low-CAD-likelihood patients + 2 SDs (TID ratio1.36). Abnormal TID ratio using this threshold demonstrated high sensitivity and specificity for severe and extensive CAD (71% and 86%, respectively), and similar sensitivity and specificity were observed in the prospective validation group (73% and 88%, respectively). In the combined pilot and validation groups, the absence of both abnormal TID ratio and abnormal perfusion was highly specific for the absence of severe and extensive CAD; only one (1.3%) of 79 patients with severe and extensive CAD had neither of these abnormal findings on adenosine MPS. In patients with both abnormal TID ratio and abnormal perfusion, 55 of 84 (65%) had severe and extensive CAD. When patients had one but not both of these findings, 26 of 193 (13%) had severe and extensive CAD.The automatically measured TID ratio is a useful clinical marker that is sensitive and highly specific for identification of severe and extensive CAD in patients undergoing adenosine MPS. Integration of abnormal TID ratio into the dual-isotope MPS image interpretation algorithm improves the identification of severe and extensive CAD in adenosine MPS.

Recently, a 17-segment model of the left ventricle has been recommended as an optimally weighted approach for interpreting myocardial perfusion single photon emission computed tomography (SPECT). Methods to convert databases from previous 20- to new 17-segment data and criteria for abnormality for the 17-segment scores are needed.Initially, for derivation of the conversion algorithm, 65 patients were studied (algorithm population) (pilot group, n = 28; validation group, n = 37). Three conversion algorithms were derived: algorithm 1, which used mid, distal, and apical scores; algorithm 2, which used distal and apical scores alone; and algorithm 3, which used maximal scores of the distal septal, lateral, and apical segments in the 20-segment model for 3 corresponding segments of the 17-segment model. The prognosis population comprised 16,020 consecutive patients (mean age, 65 +/- 12 years; 41% women) who had exercise or vasodilator stress technetium 99m sestamibi myocardial perfusion SPECT and were followed up for 2.1 +/- 0.8 years. In this population, 17-segment scores were derived from 20-segment scores by use of algorithm 2, which demonstrated the best agreement with expert 17-segment reading in the algorithm population. The prognostic value of the 20- and 17-segment scores was compared by converting the respective summed scores into percent myocardium abnormal. Conversion algorithm 2 was found to be highly concordant with expert visual analysis by the 17-segment model (r = 0.982; kappa = 0.866) in the algorithm population. In the prognosis population, 456 cardiac deaths occurred during follow-up. When the conversion algorithm was applied, extent and severity of perfusion defects were nearly identical by 20- and derived 17-segment scores. The receiver operating characteristic curve areas by 20- and 17-segment perfusion scores were identical for predicting cardiac death (both 0.77 +/- 0.02, P = not significant). The optimal prognostic cutoff value for either 20- or derived 17-segment models was confirmed to be 5% myocardium abnormal, corresponding to a summed stress score greater than 3. Of note, the 17-segment model demonstrated a trend toward fewer mildly abnormal scans and more normal and severely abnormal scans.An algorithm for conversion of 20-segment perfusion scores to 17-segment scores has been developed that is highly concordant with expert visual analysis by the 17-segment model and provides nearly identical prognostic information. This conversion model may provide a mechanism for comparison of studies analyzed by the 17-segment system with previous studies analyzed by the 20-segment approach.

The purpose of this study was to evaluate the prognostic value of community-based myocardial perfusion imaging (MPI) and to assess the incremental value of individual components of (99m)Tc-sestamibi single photon emission computed tomography (SPECT).Although the most rapid growth of MPI has been in community outpatient laboratories, its prognostic value has not been validated in this setting.We prospectively followed 1,612 consecutive patients undergoing stress (99m)Tc-sestamibi SPECT in an outpatient community laboratory who experienced 71 hard events over 24 +/- 7 months (0.2% lost to follow-up).Patients whose scans were normal incurred an annualized event rate of 0.4%, compared with 2.3% for those with abnormal scans (p0.0001). Subset analysis demonstrated comparable risk stratification for women and men, diabetics, patients with normal resting ECGs, and those referred for pharmacologic and exercise stress. After adjusting for pre-test variables, multivariable Cox regression analysis found the most potent independent components of MPI to be, in order of importance, transient ischemic dilation, extent of reversibility, post-stress ejection fraction, extent and severity of the stress perfusion defect, and the overall test result (normal or abnormal). Each 1% decrement of ejection fraction predicted a 3% increase in risk (p = 0.0009). Post-MPI angiography and revascularization increased commensurate with the extent and severity of MPI result.The prognostic value of perfusion imaging is portable and transferable to the outpatient community setting, with multiple components of MPI providing incremental prognostic information.

Background— Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A 2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. Methods and Results— In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A 2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine ( P ≤0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine ( P Conclusions— The selective adenosine A 2A receptor agonist binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.

Coronary artery disease (CAD) is the number one cause of death for both men and women in the United States, causing 1 out of every 5 deaths.1 Stress single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) has been shown to effectively stratify risk of patients for cardiac death and nonfatal myocardial infarction (MI). At our institution, we advocate a semiquantitative scoring system to standardize the visual interpretation of stress MPS scans, providing semiquantitative global indices for overall assessment of extent and severity of perfusion abnormality.2,3 This approach is more systematic and reproducible than simple qualitative evaluation.

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

Objectives This study evaluated the prognostic value of transient ischemic dilation (TID) of the left ventricle (LV) in patients with normal stress myocardial perfusion single photon emission computed tomography (MPS). Background The prognostic value of TID in patients with an otherwise normal MPS has not been defined. Methods We identified 1,560 patients who had normal stress MPS (436 vasodilator and 1,124 exercise stress), and no rest LV enlargement (Population 1) and followed up for 2.30 ± 0.67 years for hard events (HE) (cardiac death or myocardial infarction) and soft events (SE) (revascularization). Prediction of first HE or SE (total events [TE]) was evaluated by multivariable Cox analysis, which was also applied to a broader group of 2,037 patients (including patients with minimal defects (Population 2). Results In Population 1, there were 13 HE, 36 SE, and 42 TE. Patients in the highest TID quartile (TID ≥1.21) had a higher TE rate than others, regardless of stress type. By multivariable analysis, highest TID quartile was predictive of TE (p = 0.008). Other independent predictors of TE were age, typical angina, and diabetes. In Population 2, TID was also predictive of TE. Conclusions An entirely normal stress MPS study does not always imply an excellent prognosis. In patients with otherwise normal MPS, TID is an independent and incremental prognostic marker of TE even after significant clinical variables—age, typical angina, and diabetes—are accounted for. When TID is present, caution in making low-risk prognostic statements may be warranted, especially in patients with typical angina, the elderly, and diabetics. Our findings also appear to apply to the broader population of “normal” MPS, which included patients with minimal perfusion defects.

PURPOSE OF REVIEW The purpose of this review is to review the recent published literature since 2002 for studies using stress myocardial perfusion single photon emission computed tomography for determination of the prognostic value of testing. RECENT FINDINGS A series of manuscripts dealing with myocardial perfusion single photon emission computed tomography have been published over the past 2 years that have altered a number of the most basic concepts defining risk stratification. These studies may have redefined the manner in which noninvasive stress imaging results will be interpreted and applied. SUMMARY Recent studies have expanded the understanding of how stress myocardial perfusion single photon emission computed tomography is helpful in the identification of risk, enhanced the means of identifying risk, and improved its use as a means to identify optimal posttest treatment.

The objective of this work was to define the relationship between left ventricular perfusion/ function measures and referral rates to catheterization and revascularization early after stress gated myocardial perfusion single-photon emission computed tomography (MPS).Although revascularization yields the greatest survival benefit in patients with low ejection fraction (EF) and extensive coronary artery disease, referral patterns to catheterization and revascularization after noninvasive testing are not well defined.We identified 3,369 patients without previous myocardial infarction or revascularization who underwent exercise or adenosine stress MPS and who were followed-up (97% complete) for occurrence of early (60 days) post-single-photon emission computed tomography (SPECT) revascularization. Multivariable logistic regression modeling was used to determine the association of various patient characteristics and test results with performance of catheterization and revascularization as separate end points.In the first 60 days after stress MPS, 445 catheterizations (13.2%) and 254 revascularizations (7.5%) occurred, including 140 coronary artery bypass graft surgeries (4.1%) and 114 percutaneous coronary interventions (3.4%). Both post-stress gated EF and percent of the myocardium ischemic by stress MPS were independent predictors of revascularization. Logistic regression revealed that the likelihood of catheterization increased with both increasing ischemia and decreasing EF (c-index = 0.94, chi-square = 590). Predicted referral rates to catheterization increased with decreasing EF except in patients with severe ischemia (15% of myocardium), where rates decreased with decreasing EF. Similar modeling of revascularization (c-index = 0.94, chi-square = 329) revealed that the likelihood of revascularization increased with increasing ischemia but, in general, decreased with decreasing EF.Although post-SPECT referral to both catheterization and revascularization is driven by ischemia, EF has the opposite effect on these two outcomes. Further studies evaluating the appropriateness of these referral patterns are warranted.

The clinician evaluating a woman with symptoms potentially indicative of coronary heart disease faces the challenge of choosing the appropriate diagnostic test. The use of noninvasive testing in women has been controversial due to a perception of diminished accuracy, limited female representation, and technical limitations that compromise efficacy. Recent meta-analyses and large observational series report marked improvements in accuracy for women undergoing exercise treadmill, echocardiography, and nuclear testing. Electron beam computed tomography is a relatively new technique, and the body of evidence is still developing. An adequate body of evidence supports the use of noninvasive testing for intermediate risk, symptomatic women and may result in improved diagnostic and therapeutic decision making.

The aim of this study was to determine the predictors of risk and the temporal characteristics of risk associated with normal myocardial perfusion single photon emission computed tomography (MPS).No empiric data exist regarding predictors of risk after normal MPS and their temporal characteristics.Follow-up (mean: 665 +/- 200 days, 96% complete) of 7,376 consecutive patients with normal exercise or adenosine MPS identified 78 hard events (HE) (45 cardiac deaths, 33 non-fatal myocardial infarction; 1.1% cumulative HE rate, 0.6%/year). Cox proportional hazards analysis was used to identify predictors of HE. Parametric survival analysis was used to model predicted time to HE.The HE rates were greater in patients with versus without previous coronary artery disease (CAD). The Cox proportional hazards model identified pharmacologic stress, known CAD, diabetes mellitus (DM), male gender, and increasing age, with interactions between stress type and previous CAD (lower risk in patients without previous CAD undergoing exercise stress vs. all others) and between DM and gender (higher risk in DM females vs. all others) as the model most predictive of HE. The highest risk subgroups had a maximal event rate of 1.4% to 1.8%/year. Parametric survival models revealed that in patients without previous CAD the level of risk was uniform with time, but in patients with known CAD, risk increased with time (e.g., risk in the first year was less than in the second year, hence, a dynamic temporal component of risk was present).Multiple clinical factors add incremental prognostic value in patients with normal MPS, affecting their risk and its temporal pattern, and may alter the appropriate timing of repeat testing, hence establishing the existence of a "warranty" period for normal MPS studies.

This study was designed to assess the incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography (MPS) in women versus men, and to explore the prognostic impact of diabetes mellitus.Limited data are available regarding the incremental value of adenosine stress MPS for the prediction of cardiac death in women versus men and the impact of diabetes mellitus on post-adenosine MPS outcomes. Of 6,173 consecutive patients who underwent rest thallium-201/adenosine technetium-99m sestamibi MPS, 254 (4.1%) were lost to follow-up, and 586 with early revascularizationor = 60 days after MPS were censored, leaving 2,656 women and 2,677 men.Women had significantly smaller adenosine stress, rest, and reversible defects than men. During 27.0 +/- 8.8 month follow-up, cardiac death rates were lower in women than men (2.0%/year vs. 2.7%/year, respectively, p0.05). Before and after risk adjustment, cardiac death risk increased significantly in both men and women as a function of MPS results. Multivariable models revealed that MPS results provided incremental prognostic value over pre-scan data for the prediction of cardiac death in both genders. Also, while comparative unadjusted rates of early (or =60 days post-test) coronary angiography (17% vs. 23%) and revascularization (8% vs. 12%) were significantly lower in women (p0.05), after adjusting for MPS, these rates were similar in men and women. Importantly, diabetic women had a significantly greater risk of cardiac death compared with other patients. Also, after risk adjustment, patients with insulin-dependent diabetes mellitus (IDDM) had higher risk of cardiac death for any MPS result than patients with non-insulin-dependent diabetes mellitus.The findings suggest that adenosine MPS has comparable incremental value for prediction of cardiac death in women and men and that MPS is appropriately influencing subsequent invasive management decisions in both genders. Diabetic women and patients with IDDM appear to have greater risk of cardiac death than other patients for any MPS result.

We sought to determine whether chronotropic incompetence (CI) adds incremental value in predicting cardiac death (CD) and all-cause mortality and to determine which marker of CI is superior.Chronotropic incompetence, defined by either a low percent heart rate (HR) reserve achieved or failure to achieve 85% maximal age-predicted heart rate (MA-PHR), is a predictor of mortality. These variables have not been examined together in a comprehensive myocardial perfusion single-photon emission computed tomographic (SPECT), or MPS, model.A total of 10,021 patients who underwent exercise MPS, evaluated by a summed stress score (SSS), were followed up for 719 +/- 252 days. Percent HR reserve = (peak HR - rest HR)/(220 - age - rest HR) x 100, with80% considered abnormal.A total of 2,956 patients (29.5%) had low %HR reserve; 1,331 (13.3%) achieved85% MA-PHR; and 1,296 (13.0%) had both. There were 234 deaths (93 CDs). On multivariate analysis, the SSS, %HR reserve, and inability to achieve 85% MA-PHR were predictors of all-cause mortality and CD (all p0.01). Myocardial perfusion SPECT was the most powerful predictor of CD (chi-square = 50). When the %HR reserve and ability to achieve 85% MA-PHR were considered, only the former remained a predictor of CD (p = 0.006 vs. p = 0.59).In a comprehensive MPS model, CI was an important predictor of CD and all-cause mortality. Percent HR reserve was superior to the ability to achieve 85% MA-PHR in predicting CD; MPS was superior to both. Combined with previous studies, the findings suggest that %HR reserve should become the standard for assessing the adequacy of HR response during exercise testing, and that it should be routinely incorporated in risk stratification algorithms.

Studies have indicated that the very early detection of a coronary artery burden is possible with electron-beam computed tomography (EBCT). However, both the Prevention Conference V and the ACC/AHA Expert Consensus Document on EBCT have recommended against the routine use of EBCT for screening for coronary artery disease in asymptomatic individuals. Moreover, there is no evidence so far to support using the results of EBCT in an asymptomatic patient to select a therapy or to guide referral to invasive investigations. The clinical role of EBCT is yet to be established in terms of screening for disease or risk assessment. EBCT is highly sensitive, but its specificity is low. In fact, when referral to angiography is based on the results of EBCT, referrals will be made for very few patients with normal results while many referrals will be made for those with abnormal results. The outcome will be that, in clinical practice, the observed sensitivity of EBCT will be increased, and the observed specificity will be reduced. To date, there are no well-conducted studies that clearly demonstrate the incremental value of calcium scoring over traditional assessments of risk factors, and the clinical role of EBCT is yet to be established in terms of screening for disease or risk assessment.

Background — The incremental value and cost-effectiveness of stress single photon emission computed tomography (SPECT) is of unclear added value over clinical and exercise treadmill testing data in patients with normal resting ECGs, a patient subset known to be at relatively lower risk. Methods and Results — We identified 3058 consecutive patients who underwent exercise dual isotope SPECT, who on follow-up (mean, 1.6±0.5 years; 3.6% lost to follow-up) were found to have 70 hard events (2.3% hard-event rate). Survival analysis used a Cox proportional hazards model, and cost-effectiveness was determined by the cost per hard event identified by strategies with versus without the use of SPECT. In this cohort, a normal study was associated with an exceedingly low hard-event rate (0.4% per year) that increased significantly as a function of the SPECT result. After adjusting for pre-SPECT information, exercise stress SPECT yielded incremental value for the prediction of hard events (χ 2 52 to 85, P Conclusions — Stress SPECT yields incremental prognostic value and enhanced risk stratification in patients with normal resting ECGs in a cost-effective manner. These findings are opposite those of previous studies examining anatomic end points in this same population and thus, if confirmed, have significant implications for patient management.

The application of cost-effective strategies for the diagnosis and risk stratification of patients with coronary artery disease (CAD) is a key issue in the practice of cardiology today. Although medical and surgical therapies have led to an overall decrease in mortality from acute coronary events since the 1960s1, myocardial infarction (MI) remains the Ieading cause of death in the United States.2 Significantly, 50% of men and 63% of women dying suddenly from acute coronary events have not previously been identified as having CAD.2 At the same time, many patients with clear signs and symptoms of CAD do not go on to experience acute coronary events.

Cardiac magnetic resonance (CMR) identifies important prognostic variables in ischemic cardiomyopathy (ICM) patients such as left ventricular (LV) volumes, LV ejection fraction (LVEF), peri-infarct zone, and myocardial scar burden (MSB). It is unknown whether Doppler-based diastolic dysfunction (DDF) retains its prognostic value in ICM patients, in the context of current imaging, medical, and device therapies. Methods: Diastolic function was evaluated in ICM patients (LVEF ≤40% and ≥70% stenosis in ≥1 coronary artery) who underwent transthoracic echocardiogram and delayed hyperenhancement CMR studies within 7 days. The association of DDF with the combined end point was assessed after risk-adjustment using Cox proportional hazards models. Results: A total of 360 patients with severe LV dysfunction (LVEF = 24±9%) and extensive MSB (31±17%) were evaluated; DDF was present in all patients (stage 1%-44%, stage 2%-25%, stage 3%-31%). There were 130 events (124 deaths and 6 heart transplants) over a median follow-up of 5.8 years (IQR, 3.7-7.4 years). On multivariable analysis, DDF > stage 1 (HR, 1.37; P = .007) was associated with the combined end-point, independent of clinical risk score (HR, 2.40; P < .0001), implantable cardioverter defibrillator implantation (HR, 0.60; P = .009), incomplete revascularization (HR, 1.32; P = .003), mitral regurgitation (HR, 3.37; P = .01), peri-infarct zone area (HR, 1.04; P = 0.02), and MSB (HR, 1.02; P = .01). DDF had incremental prognostic value for the combined end-point (model χ 2 increased from 89 to 95, P = .02). Conclusion: DDF is a powerful predictor of mortality in ICM patients with significant LV dysfunction, independent of clinical and CMR data. DDF assessment provides incremental value, improving risk stratification. © 2014 Mosby, Inc. All rights reserved.

Transmyocardial laser revascularization, a new strategy for the treatment of diffuse ischemic heart disease, uses laser technology for the theoretical purpose of forming transmyocardial channels in the heart to increase perfusion to ischemic zones. This report summarizes our initial clinical experience with the procedure.Excimer transmyocardial laser revascularization was performed in a reversibly ischemic region of the heart in 15 patients. Ischemia and myocardial viability were evaluated by assessment of symptoms and of results of radionuclide single photon emission computed tomography imaging, exercise tolerance testing, and 24-hour Holter monitoring.No adverse events occurred as a result of the laser revascularization, although 1 patient with preoperative ventricular arrhythmias died 48 hours postoperatively as a result of refractory ventricular tachycardia. Angina class decreased significantly from base line values in patients who had undergone the procedure (mean Canadian Cardiovascular Association angina class, 3.5+/-0.5 at base line, 1.6+/-0.6 at 1 month, 1.5+/-0.8 at 3 months, 1.9+/-0.9 at 6 months, 1.8+/-0.8 at 12 months; p0.002), and nitroglycerin requirements were similarly decreased in patients who had undergone laser revascularization (mean g/wk of sublingual nitroglycerin, 19+/-4 at baseline, 5+/-3 at 1 month, 4+/-2 at 3 months, 4+/-2 at 6 months, 2+/-1 at 12 months; p0.02). Exercise tolerance testing demonstrated increase in exercise duration compared with base line values (mean minutes, 7.4+/-3.1 at base line, 8.0+/-3.9 at 1 month, 8.5+/-4.4 at 3 months, and 9.0+/-3.9 at 12 months; p0.05); those increases were not large enough to be statistically significant, however.Our data are consistent with the concept that excimer transmyocardial laser revascularization in individuals with significant ischemic heart disease appears to be well tolerated, can be performed safely, and may lead to a reduction in ischemic symptomatology.