Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy.

AIMS: Although pre-revascularization ischaemia testing is recommended, the interaction between the extent of ischaemia and myocardial scar with performance of revascularization on patient survival is unclear. METHODS AND RESULTS: We identified 13 969 patients who underwent adenosine or exercise stress SPECT myocardial perfusion scintigraphy (MPS). The percent myocardium ischaemic (%I) and fixed (%F) were calculated using 5 point/20-segment MPS scoring. Patients lost to follow-up (2.8%) were excluded leaving 13 555 patients [35% with history (Hx) of known coronary artery disease (CAD), 65% exercise stress, 61% male, age 66 ± 12]. Follow-up was performed at 12-18 months for early revascularization and at >7 years for all-cause death (ACD) (mean follow-up 8.7 ± 3.3 years). All-cause death was modelled using Cox proportional hazards modelling adjusting for logistic-based propensity scores, MPS, revascularization, and baseline characteristics. During FU, 3893 ACD (29%, 3.3%/year) and 1226 early revascularizations (9.0%) occurred. After risk-adjustment, a three-way interaction was present between %I, early revascularization, and HxCAD, such that %I identified a survival benefit with early revascularization in patients without prior myocardial infarction (MI), whereas no such benefit was present in patients with prior MI (overall model χ(2)= 3932, P < 0.001; interaction P < 0.021). Further modelling revealed that after excluding patients with scar >10% total myocardium, %I identified a survival benefit in all patients. CONCLUSION: In this large observational series with long-term follow-up, patients with significant ischaemia and without extensive scar were likely to realize a survival benefit from early revascularization. In contrast, the survival of patients with minimal ischaemia was superior with medical therapy without early revascularization.

Prognostic implications of myocardial perfusion single-photon emission computed tomography in the elderly.

BACKGROUND: The goal of this study was to assess the clinical value of stress myocardial perfusion scintigraphy (MPS) in elderly patients (> or =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 <1% in patients with normal rest ECG, exercise stress, or age of 75 to 84 years and was 2.3% to 3.7% in patients > or =85 years of age or undergoing pharmacological stress. However, compared with age-matched US population CD rates (75 to 84 years of age, 1.5%; > or =85 years, 4.8%), normal MPS CD rates were approximately one-third lower than the baseline risk of US individuals (both P<0.05). Modeling of all-cause death in 684 patients with extended follow-up revealed that after risk adjustment, an interaction between early treatment and ischemia was present; increasing ischemia was associated with increasing survival with early revascularization, whereas in the setting of little or no ischemia, medical therapy had improved outcomes. 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.

Prognostic significance of dyspnea in patients referred for cardiac stress testing.

BACKGROUND: Although dyspnea is a common symptom, there has been only limited investigation of its prognostic significance among patients referred for cardiac evaluation. METHODS: 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. RESULTS: 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 (P<0.001) and from any cause (P<0.001) after adjustment for other significant factors by multivariable and propensity analysis. CONCLUSIONS: 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.

A prognostic score for prediction of cardiac mortality risk after adenosine stress myocardial perfusion scintigraphy.

OBJECTIVES: We sought to derive and validate a score to estimate risk after adenosine stress. BACKGROUND: Maximizing the prognostic information extracted from adenosine stress myocardial perfusion scintigraphy, a commonly performed test, is often challenging for referring physicians. METHODS: A split-set validation of a score predicting cardiovascular mortality was performed in 5,873 consecutive patients studied by adenosine stress, dual-isotope single-photon emission computed tomography (SPECT; follow-up 94% complete, mean 2.2 +/- 1.1 years). RESULTS: On follow-up, 387 cardiac deaths occurred (6.6%). The Cox proportional hazards model most predictive of cardiac death included age, % myocardium ischemic, % myocardium fixed, early revascularization, dyspnea, diabetes mellitus, rest and peak stress heart rates, abnormal rest electrocardiogram (ECG), and an interaction between % myocardium ischemic and early revascularization (chi-square = 376). The final prognostic score was calculated as follows: (age [decades] x 5.19) + (% myocardium ischemic [per 10%] x 4.66) + (% myocardium fixed [per 10%] x 4.81) + (diabetes mellitus x 3.88) + (if patient treated with early revascularization, 4.51) + (if dyspnea was a presenting symptom, 5.47) + (resting heart rate [per 10 beats] x 2.88) - (peak heart rate [per 10 beats] x 1.42) + (ECG score x 1.95) - (if patient treated with early revascularization, % myocardium ischemic [per 10%] x 4.47). Scores of <49, 49 to 57, and >57 identified low, intermediate, and high risk (0.9%, 3.3%, and 9.5% cardiac death/year, respectively). Score results further risk stratified patients with respect to cardiac death in all categories of SPECT abnormality. CONCLUSIONS: We derived and validated a score incorporating data available after adenosine stress perfusion SPECT. This score maximizes the prognostic information extracted from this test and may enhance the application of this test as part of an overall strategy.

Combined supine and prone quantitative myocardial perfusion SPECT: method development and clinical validation in patients with no known coronary artery disease.

UNLABELLED: Acquisition in the prone position has been demonstrated to improve the specificity of visually analyzed myocardial perfusion SPECT (MPS) for detecting coronary artery disease (CAD). However, the diagnostic value of prone imaging alone or combined acquisition has not been previously described using quantitative analysis. METHODS: A total of 649 patients referred for MPS comprised the study population. Separate supine and prone normal limits were derived from 40 males and 40 females with a low likelihood (LLk) of CAD using a 3 average-deviation cutoff for all pixels on the polar map. These limits were applied to the test population of 369 consecutive patients (65% males; age, 65 +/- 13 y; 49% exercise stress) without known CAD who had diagnostic coronary angiography within 3 mo of MPS. Total perfusion deficit (TPD), defined as a product of defect extent and severity scores, was obtained for supine (S-TPD), prone (P-TPD), and combined supine-prone datasets (C-TPD). The angiographic group was randomly divided into 2 groups for deriving and validating optimal diagnostic cutoffs. Normalcy rates were validated in 2 additional groups of consecutive LLk patients: unselected patients (n = 100) and patients with body mass index >30 (n = 100). RESULTS: C-TPD had a larger area under the receiver-operating-characteristic (ROC) curve than S-TPD or P-TPD for identification of stenosis >or=70% (0.86, 0.88, and 0.90 for S-TPD, P-TPD, and C-TPD, respectively; P < 0.05). In the validation group, sensitivity for P-TPD was lower than for S- or C-TPD (P < 0.05). C-TPD yielded higher specificity than S-TPD and a trend toward higher specificity than P-TPD (65%, 83%, and 86% for S-, P-, and C-TPD, respectively, P < 0.001; vs. S-TPD and P = 0.06 vs. P-TPD). Normalcy rates for C-TPD were higher than for S-TPD in obese LLk patients (78% vs. 95%, P < 0.001). CONCLUSION: Combined supine-prone quantification significantly improves the area under the ROC curve and specificity of MPS in the identification of obstructive CAD compared with quantification of supine MPS alone.

Predicting therapeutic benefit from myocardial revascularization procedures: are measurements of both resting left ventricular ejection fraction and stress-induced myocardial ischemia necessary?

BACKGROUND: We hypothesized that ejection fraction (EF) best predicts cardiovascular death but only measures of ischemia predict relative survival benefit from revascularization compared with medical therapy. METHODS AND RESULTS: We followed up 5366 consecutive patients without prior revascularization who underwent stress electrocardiography-gated myocardial perfusion single photon emission computed tomography (MPS) for 2.8 +/- 1.2 years, during which 146 cardiac deaths occurred (2.7%, 1.0%/y). The treatment received within 60 days after MPS was used to define the subgroups (revascularization in 402 patients, with cardiac death occurring in 6.2%, vs medical therapy in 4964 patients, with cardiac death occurring in 2.4%; P < .0001, chi2 = 18.7). Adjustment for nonrandomized treatment assignment used a propensity score based on logistic regression modeling of referral to revascularization. The percent of myocardium that was ischemic was the most important predictor of revascularization. The overall model (multivariate chi2 = 728, c index = 0.89, P < 10(-5)) was used as a propensity score. Cox proportional hazards analysis, assessing the relationship between MPS results, non-MPS covariates, and cardiac death, revealed that EF was superior to percent ischemic myocardium in the prediction of cardiac death after adjustment for pre-MPS data and the propensity score. However, an interaction between percent ischemic myocardium and revascularization was present such that, irrespective of EF, patients with little or no ischemia had an improved survival rate with medical therapy, whereas with increasing ischemia, progressive improvements in survival rate were noted with revascularization. CONCLUSIONS: Although EF predicts cardiac death, only inducible ischemia identifies which patients have a short-term benefit from revascularization.

Prognostic value of poststress left ventricular volume and ejection fraction by gated myocardial perfusion SPECT in women and men: gender-related differences in normal limits and outcomes.

BACKGROUND: Whether there are gender differences in the prognostic application of gated myocardial perfusion single photon emission computed tomography (SPECT) has not been assessed. METHODS AND RESULTS: Gender-specific normal limits of poststress volume and ejection fraction (EF) were obtained in 597 women and 824 men with a low likelihood of coronary artery disease and normal perfusion and were applied in a prognostic evaluation of 6713 patients (2735 women and 3978 men). Patients underwent rest thallium-201/stress technetium-99m sestamibi gated myocardial perfusion SPECT and were followed up for 35 +/- 14 months. The upper limit of the end-systolic volume (ESV) index was 27 mL/m2 in women and 39 mL/m2 in men, and the upper limit of the end-diastolic volume index was 60 mL/m2 in women and 75 mL/m2 in men. The lower limit of the EF was 51% in women and 43% in men. Gated SPECT variables provided incremental prognostic information in both genders. Women with severe ischemia and an EF lower than 51% or an ESV index greater than 27 mL/m2 were at very high risk of cardiac death or myocardial infarction (3-year event rates of 39.8% and 35.1%, respectively), whereas women with severe ischemia but an EF of 51% or greater or an ESV index of 27 mL/m2 or less were at intermediate or high risk (3-year event rates of 10.8% and 15.2%, respectively). CONCLUSION: Poststress EF and ESV index by gated myocardial perfusion SPECT provide comparable incremental prognostic information over perfusion in women and men. After separate criteria for abnormal EF and ESV index in women are used, the combination of severe ischemia and abnormal EF or ESV index identifies women at very high risk of cardiac events.

Left ventricular shape index assessed by gated stress myocardial perfusion SPECT: initial description of a new variable.

BACKGROUND: Ventricular remodeling is predictive of congestive heart failure (CHF). We aimed to automatically quantify a new myocardial shape variable on gated myocardial perfusion single photon emission computed tomography (SPECT) (MPS) and to evaluate the association of this new SPECT parameter with the risk of hospitalization for CHF. METHODS AND RESULTS: A computer algorithm was used to measure the 3-dimensional (3D) left ventricular (LV) shape index (LVSI), derived as the ratio of maximum 3D short- and long-axis LV dimensions, for end systole and end diastole. LVSI normal limits were obtained from stress technetium 99m sestamibi MPS images of 186 patients (60% of whom were men) (control subjects) with a low likelihood of CAD (< 5%). These limits were tested in a consecutive series of 93 inpatients (85% of whom were men) having MPS less than 1 week after hospitalization, of whom 25 were hospitalized for CHF exacerbation. Variables associated with CHF hospitalization were tested by receiver operating characteristic curve and multivariate logistic regression analyses. LVSI repeatability was assessed in 52 patients with ischemic cardiomyopathy who had sequential stress MPS within 60 days after the initial MPS without clinical events in the interval between MPS studies. Control subjects had lower end-systolic and end-diastolic LVSIs compared with patients with CHF and those without CHF (P < .001). Receiver operating characteristic curve areas for the prediction of hospitalization as a result of CHF were similar for LV ejection fraction and end-systolic LVSI. End-systolic and end-diastolic LVSIs were independent predictors of CHF hospitalization by multivariate analysis; however, end-systolic LVSI had the greatest added value among all tested variables. Repeatability was excellent for both end-systolic LVSI (R2 = 0.85, P < .0001) and end-diastolic LVSI (R2 = 0.82, P < .001). CONCLUSION: LVSI is a promising new 3D variable derived automatically from gated MPS providing highly repeatable ventricular shape assessment. Preliminary findings suggest that LVSI might have clinical implications in patients with CHF.

Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography.

BACKGROUND: The relationship between the amount of inducible ischemia present on stress myocardial perfusion single photon emission computed tomography (myocardial perfusion stress [MPS]) and the presence of a short-term survival benefit with early revascularization versus medical therapy is not clearly defined. METHODS AND RESULTS: A total of 10 627 consecutive patients who underwent exercise or adenosine MPS and had no prior myocardial infarction or revascularization were followed up (90.6% complete; mean: 1.9+/-0.6 years). Cardiac death occurred in 146 patients (1.4%). Treatment received within 60 days after MPS defined subgroups undergoing revascularization (671 patients, 2.8% mortality) or medical therapy (MT) (9956 patients, 1.3% mortality; P=0.0004). To adjust for nonrandomization of treatment, a propensity score was developed using logistic regression to model the decision to refer to revascularization. This model (chi2=1822, c index=0.94, P<10-7) identified inducible ischemia and anginal symptoms as the most powerful predictors (83%, 6% of overall chi2) and was incorporated into survival models. On the basis of the Cox proportional hazards model predicting cardiac death (chi2=539, P<0.0001), patients undergoing MT demonstrated a survival advantage over patients undergoing revascularization in the setting of no or mild ischemia, whereas patients undergoing revascularization had an increasing survival benefit over patients undergoing MT when moderate to severe ischemia was present. Furthermore, increasing survival benefit for revascularization over MT was noted in higher risk patients (elderly, adenosine stress, and women, especially those with diabetes). CONCLUSIONS: Revascularization compared with MT had greater survival benefit (absolute and relative) in patients with moderate to large amounts of inducible ischemia. These findings have significant consequences for future approaches to post-single photon emission computed tomography patient management if confirmed by prospective evaluations.

Value of stress myocardial perfusion single photon emission computed tomography in patients with normal resting electrocardiograms: an evaluation of incremental prognostic value and cost-effectiveness.

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 (chi2 52 to 85, P<0.001) and significantly stratified patients. In patients with intermediate to high likelihood of coronary artery disease after exercise treadmill testing, a cost-effectiveness ratio of $25 134 per hard event identified and a cost of $5417 per reclassification of patient risk were found. Subset analyses revealed similar prognostic, and cost results were present in men, women, and patients with and without prior histories of coronary artery disease. 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.

Prognostic impact of hemodynamic response to adenosine in patients older than age 55 years undergoing vasodilator stress myocardial perfusion study.

BACKGROUND: The prognostic importance of various hemodynamic responses to adenosine infusion in patients undergoing adenosine stress myocardial perfusion stress (MPS) has not been defined. METHODS AND RESULTS: We identified 3444 unique patients (53.5% women, mean age 74.0+/-8.4 years) who underwent adenosine (with no additional exercise) stress myocardial perfusion single photon emission computed tomography (MPS) and were followed up for 2.0+/-0.8 years. Multivariable Cox proportional hazards analysis was used to assess the prognostic value of hemodynamic variables in predicting cardiac death (CD). Two hundred twenty-four CDs (6.5%) occurred during follow-up. By multivariable analysis, higher rest heart rate (HR) and to a lesser extent lower peak HR were markers of CD. When added to the multivariable model in place of peak and rest HR, the peak/rest HR ratio was an independent predictor of CD. Peak/rest HR ratio additionally risk-stratified patients within each MPS category. A significant interaction was found between gender and peak systolic blood pressure (SBP), in which there was an increased risk associated with a low peak SBP (<90 mm Hg at end of adenosine infusion) in men but not in women. CONCLUSIONS: Patients undergoing adenosine stress MPS with high rest HR and low peak/rest HR ratio have increased risk of CD, as do male patients with a low peak SBP. Assessment of the hemodynamic response to adenosine adds incremental prognostic value to MPS results and enhances identification of patients at risk for CD.

Stress myocardial perfusion single-photon emission computed tomography is clinically effective and cost effective in risk stratification of patients with a high likelihood of coronary artery disease (CAD) but no known CAD.

OBJECTIVES: We sought to evaluate the prognostic and cost implications of stress myocardial perfusion single-photon emission computed tomography (SPECT), or MPS, in patients with a high pretest likelihood (>0.85) of coronary artery disease (CAD) with no previous CAD. BACKGROUND: Sparse data are available regarding the prognostic performance characteristics of MPS in this patient group. METHOD: We followed up 1,270 consecutive patients with no previous revascularization or myocardial infarction (MI), with a pre-exercise tolerance test (ETT) likelihood of CAD > or =0.85, who underwent exercise or adenosine stress MPS (follow-up 94.4% complete; 2.2 +/- 1.2 years; 60 hard events [5.9%, 2.6%/year]). Risk adjustment of survival data was done using Cox proportional hazards analysis. Costs per reclassification of risk were calculated using assumed costs and threshold analyses. RESULTS: In patients treated medically after MPS, normal MPS had a low risk of cardiac death and hard events (0.6% and 1.3% per year, respectively). With increasing extent and severity of MPS defects, the risk of both cardiac death and hard events increased significantly (p < 0.05). Cox models indicated that the addition of MPS data resulted in incremental prognostic value over pre-MPS data (chi-square increase 48 to 87, p < 0.0001). Compared with strategies of initial referral to ETT in patients able to exercise, initial referral to MPS appeared to be a more cost-effective strategy. Similarly, compared with a strategy of direct referral to catheterization in patients with a high likelihood of CAD, initial referral to MPS is a cost-saving approach. CONCLUSIONS: In patients with a high likelihood of CAD but without known CAD, stress MPS yields incremental value and achieves risk stratification in a cost-effective manner. The current results support a strategy of initial stress imaging in this patient cohort, as a reasonable alternative to direct referral to catheterization or initial ETT.

Determinants of risk and its temporal variation in patients with normal stress myocardial perfusion scans: what is the warranty period of a normal scan?

OBJECTIVES: 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). BACKGROUND: No empiric data exist regarding predictors of risk after normal MPS and their temporal characteristics. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Is there a referral bias against catheterization of patients with reduced left ventricular ejection fraction? Influence of ejection fraction and inducible ischemia on post-single-photon emission computed tomography management of patients without a history of coronary artery disease.

OBJECTIVES: 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). BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 incremental prognostic value of percentage of heart rate reserve achieved over myocardial perfusion single-photon emission computed tomography in the prediction of cardiac death and all-cause mortality: superiority over 85% of maximal age-predicted heart rate.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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, with <80% considered abnormal. RESULTS: A total of 2,956 patients (29.5%) had low %HR reserve; 1,331 (13.3%) achieved <85% 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 p < 0.01). 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). CONCLUSIONS: 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.

Adenosine myocardial perfusion single-photon emission computed tomography in women compared with men. Impact of diabetes mellitus on incremental prognostic value and effect on patient management.

OBJECTIVES: 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. BACKGROUND: 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 revascularization < or = 60 days after MPS were censored, leaving 2,656 women and 2,677 men. RESULTS: 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, p < 0.05). 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 (p < 0.05), 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. CONCLUSION: 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.

Transient ischemic dilation ratio of the left ventricle is a significant predictor of future cardiac events in patients with otherwise normal myocardial perfusion SPECT.

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 > or =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.

Prognostic implications of combined prone and supine acquisitions in patients with equivocal or abnormal supine myocardial perfusion SPECT.

UNLABELLED: Although acquisition of (99m)Tc-sestamibi myocardial perfusion SPECT (MPS) with the patient in the prone position is commonly used to minimize attenuation artifacts, the impact of combined prone and supine imaging on the prognostic evaluation of coronary artery disease (CAD) has not been determined. The prognostic implications of MPS obtained in both prone and supine positions in patients with perfusion defects on supine MPS were evaluated. METHODS: We studied 3,834 patients who were monitored for 24.2 +/- 6.0 mo after rest (201)Tl/stress (99m)Tc-sestamibi MPS acquired during 1994-1995, when prone acquisition was performed only in patients with inferior wall perfusion defects that might represent attenuation or motion artifact. RESULTS: During follow-up, there were 132 hard events (cardiac death or myocardial infarction) and 375 total events (hard events or late myocardial revascularization). Overall, patients who underwent prone and supine acquisitions had similar characteristics to those who underwent supine-only imaging, with the exception of being more commonly male. In multivariable analysis, there were similar independent predictors for hard events and total events; the type of acquisition (prone and supine or supine-only) was not a significant predictor of either of these outcome events. After risk adjustment, the predicted event rates were nearly identical for patients undergoing prone and supine compared with supine-only studies. Both observed and predicted hard event rates of patients with normal prone and supine versus supine-only imaging were very low (observed, 0.7%/y and 0.5%/y, respectively; predicted, 1.5% over 24 mo for both). There was no reduction in the higher rates of events associated with abnormal scan results with the combination of prone and supine imaging. CONCLUSION: Patients with inferior wall defects on supine MPS that are not present on prone MPS have a low risk of subsequent cardiac events, similar to that of patients with normal supine-only studies.

Integration of automatically measured transient ischemic dilation ratio into interpretation of adenosine stress myocardial perfusion SPECT for detection of severe and extensive CAD.

UNLABELLED: 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). METHODS: 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. RESULTS: 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 ratio > 1.36). 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. CONCLUSION: 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.

Stress thallium-201/rest technetium-99m sequential dual isotope high-speed myocardial perfusion imaging.

OBJECTIVES: Our purpose was to describe a novel, rapid stress thallium-201 (Tl-201)/rest technetium-99m (Tc-99m) agent myocardial perfusion imaging (MPI) protocol (Tl/Tc) with a high-speed MPI scanner and to compare this protocol with a standard rest/stress Tc-99m agent protocol (Tc/Tc) with respect to image quality and radiation dosimetry. BACKGROUND: Recent advances in gamma camera technology have provided opportunity for improved SPECT MPI protocols. A rapid Tl/Tc protocol that could improve image information while maintaining a low radiation burden for the patient would be desirable. METHODS: We compared high-speed SPECT MPI studies in 374 consecutive patients undergoing exercise or pharmacologic Tl/Tc protocol to those of 262 patients undergoing rest/stress Tc/Tc protocol. RESULTS: Tl/Tc imaging was accomplished in <20 min. Overall image quality was good to excellent in 96% and 98% of patients with the Tl/Tc and the Tc/Tc protocols, respectively (p = ns). Beginning rest imaging within 2 min after rest injection with the Tl/Tc protocol did not result in reduced confidence in image interpretation. Early rest Tc images of the Tl/Tc protocol showed less extracardiac activity than was observed on standard rest imaging used in the Tc/Tc protocol (84% vs. 61%), respectively (p < 0.01). The normalcy rate was high in both groups (100% vs. 92%). Radiation burden was similar between the Tl/Tc and Tc/Tc protocols. CONCLUSIONS: A rapid stress Tl-201/rest Tc-99m protocol for use with high-speed SPECT MPI has image quality and radiation dosimetry similar to those observed with a conventional rest/stress Tc-99m protocol. The Tl/Tc protocol offers promise as an efficient and relatively low radiation dose method, in which the superior qualities of Tl-201 for stress imaging and of the Tc-99m agents for rest imaging can be preserved. The findings also suggest that with rapid imaging rest MPI immediately after Tc-99m agent injection may be superior to standard delayed image initiation.