Denny D. Watson

Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three-vessel coronary artery disease

OBJECTIVESnWe hypothesized that combining functional assessment to perfusion enhances the ability of electrocardiographic gating Tc-99m sestamibi single photon emission computed tomography (gated SPECT) myocardial perfusion imaging (MPI) to detect defects in multiple vascular territories in patients with severe three-vessel coronary artery disease (3VD).nnnBACKGROUNDnIn patients with 3VD, perfusion defects in multiple vascular territories may not always be evident due to globally reduced perfusion.nnnMETHODSnGated SPECT MPIs were interpreted sequentially with perfusion first, followed by combined perfusion/function, in 143 patients with angiographic 3VD and a control group of 112 non-3VD patients. All patients underwent coronary arteriography within one month of MPI.nnnRESULTSnIn 3VD patients, combined perfusion/function analysis yielded significantly greater numbers of abnormal segments/patient (6.2 +/- 4.7 vs. 4.1 +/- 2.8, p < 0.001) and more defects in multiple vascular territories (60% vs. 46%, p < 0.05) than perfusion alone. In the control group, there were no differences between the combined perfusion/function and perfusion alone interpretations. Multivariate analysis of 15 different clinical, stress, and scintigraphic variables in all patients revealed age (p < 0.0001) and number of abnormal vascular territories by combined perfusion/function (p < 0.0001) to be the most powerful predictors of 3VD. Addition of functional data to clinical, stress, and perfusion yielded a significant increase in the predictive value of 3VD (global chi-square: 131.7 vs. 89.8, p < 0.00001). Specificity of combined perfusion/function analysis was not lower than perfusion alone (72% vs. 69%, p = NS). CONCLUSIONS; Adjunctive assessment of function with perfusion by gated SPECT MPI enhances the detection of defects in multiple vascular territories in patients with severe 3VD, without adversely affecting its specificity.

Achieving an Exercise Workload of ≥10 Metabolic Equivalents Predicts a Very Low Risk of Inducible Ischemia : Does Myocardial Perfusion Imaging Have a Role?

OBJECTIVESnWe sought to identify prospectively the prevalence of significant ischemia (> or =10% of the left ventricle [LV]) on exercise single-photon emission computed tomography (SPECT) imaging relative to workload achieved in consecutive patients referred for myocardial perfusion imaging (MPI).nnnBACKGROUNDnHigh exercise capacity is a strong predictor of a good prognosis, and the role of MPI in patients achieving high workloads is questionable.nnnMETHODSnProspective analysis was performed on 1,056 consecutive patients who underwent quantitative exercise gated (99m)Tc-SPECT MPI, of whom 974 attained > or =85% of their maximum age-predicted heart rate. These patients were further divided on the basis of attained exercise workload (<7, 7 to 9, or > or =10 metabolic equivalents [METs]) and were compared for exercise test and imaging outcomes, particularly the prevalence of > or =10% LV ischemia. Individuals reaching > or =10 METs but <85% maximum age-predicted heart rate were also assessed.nnnRESULTSnOf these 974 subjects, 473 (48.6%) achieved > or =10 METs. This subgroup had a very low prevalence of significant ischemia (2 of 473, 0.4%). Those attaining <7 METs had an 18-fold higher prevalence (7.1%, p < 0.001). Of the 430 patients reaching > or =10 METs without exercise ST-segment depression, none had > or =10% LV ischemia. In contrast, the prevalence of > or =10% LV ischemia was highest in the patients achieving <10 METs with ST-segment depression (14 of 70, 19.4%).nnnCONCLUSIONSnIn this referral cohort of patients with an intermediate-to-high clinical risk of coronary artery disease, achieving > or =10 METs with no ischemic ST-segment depression was associated with a 0% prevalence of significant ischemia. Elimination of MPI in such patients, who represented 31% (430 of 1,396) of all patients undergoing exercise SPECT in this laboratory, could provide substantial cost-savings.

Prognostic value of dobutamine stress technetium-99m-sestamibi single-photon emission computed tomography myocardial perfusion imaging: stratification of a high-risk population

OBJECTIVESnThis work was undertaken to define the intrinsic cardiac risk of the patient population referred for dobutamine stress perfusion imaging and to determine whether dobutamine technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography (SPECT) imaging is capable of risk stratification in this population.nnnBACKGROUNDnIn animal models, dobutamine attenuates the myocardial uptake of (99m)Tc-sestamibi resulting in underestimation of coronary stenoses. Therefore, we hypothesized that the prognostic value of dobutamine stress (99m)Tc-sestamibi SPECT myocardial perfusion imaging might be impaired, owing to reduced detection of coronary stenoses.nnnMETHODSnWe reviewed the clinical outcome of 308 patients (166 women, 142 men) who underwent dobutamine stress SPECT (99m)Tc-sestamibi imaging at our institution from September 1992 through December 1996.nnnRESULTSnDuring an average follow-up of 1.9 +/- 1.1 years, there were 33 hard cardiac events (18 myocardial infarctions [MI] and 15 cardiac deaths) corresponding to an annual cardiac event rate of 5.8%/year, which is significantly higher than the event rate for patients referred for exercise SPECT imaging at our institution (2.2%/year). Event rates were higher after an abnormal dobutamine (99m)Tc-sestamibi SPECT study (10.0%/year) than after a normal study (2.3%/year) (p < 0.01), even after adjusting for clinical variables. In the subgroup (n = 29) with dobutamine-induced ST-segment depression and abnormal SPECT imaging, the prognosis was poor, with annual cardiac death and nonfatal MI rates of 7.9% and 13.2%, respectively.nnnCONCLUSIONSnPatients referred for dobutamine perfusion imaging are a high-risk population, and dobutamine stress (99m)Tc-sestamibi SPECT imaging is capable of risk stratification in these patients.

Prognosis in patients achieving ≥10 METS on exercise stress testing: Was SPECT imaging useful?

BackgroundThe benefit of myocardial perfusion imaging (MPI) over exercise ECG stress testing alone is unclear in individuals attaining a workload of ≥10 METS. The purpose of this prospective study is to determine mortality and nonfatal cardiac events in patients at either intermediate pretest risk for CAD or patients with known CAD, achieving ≥10 METS regardless of peak exercise heart rate. The authors previously reported a low prevalence of significant ischemia in this patient cohort.MethodsBaseline characteristics, ECG stress test findings, and perfusion and function results from quantitative gated 99mTc-SPECT MPI were compared by achievement of a maximum age-predicted heart rate ≥85% in 509 consecutive patients who reached ≥10 METS. Events including all-cause and cardiac mortality, non-fatal myocardial infarction (MI), and late revascularization (>4xa0weeks after MPI) were prospectively collected.ResultsOf the 509 patients achieving ≥10 METS, follow-up for mortality was obtained in 463 (91%). Those lost to follow-up were older and had higher rates of tobacco use. The prevalences of CAD risk factors, prior known CAD, and MPI abnormalities were higher for the 68 patients failing to reach 85% of their target heart rate. The rate of ≥10% left-ventricular (LV) ischemia by MPI remained very low irrespective of attained heart rate (0.6% (3/463)). Six (1.2%) had an LVEFxa0<xa040%. Death occurred in 12 (2.6%) patients, one of which was classified as cardiac (0.1%/year). The other 11 deaths were related to cancer. Additionally, there were three nonfatal MIs (0.7 %) and one late revascularization (0.2%). Only one of these patients had any ischemia on MPI. No cardiac event patient had exercise ST depression or ≥5% LV ischemia.ConclusionsThus, patients at intermediate risk for CAD or known CAD achieving ≥10 METS have a very low prevalence of ≥10% LV ischemia and very low rates of cardiac mortality, nonfatal MI, and late revascularization, irrespective of heart rate achieved. Cardiac events did not correlate with abnormalities on the index MPI study. These results suggest that patients who attain ≥10 METS during exercise stress have an excellent prognosis over an intermediate term of follow-up, regardless of peak exercise heart rate achieved. The added value of MPI to standard exercise ECG testing in this population is questionable.

Elevated serum levels of S-100 after deep hypothermic arrest correlate with duration of circulatory arrest

OBJECTIVEnCerebral damage is a major problem after reconstructive surgery of the aortic arch and the descending aorta. Current protective strategies, including deep hypothermia and retrograde cerebral perfusion, are used to prolong the tolerated duration of circulatory arrest, and the latter may also decrease the possibility of air/particle embolization. The aim of the current study was to investigate whether the neurochemical marker S-100 is related to the duration of circulatory arrest, when the influence of embolic injury has been minimized by the use of retrograde cerebral perfusion during the last part of circulatory arrest.nnnMETHODSnArterial serum levels of S-100 were followed before, during and after reconstructive surgery of the thoracic aorta during deep hypothermic arrest in ten adults. Retrograde cerebral blood perfusion was used during the latter part of the arrest period in eight of the ten patients. Neurologic status was followed daily.nnnRESULTSnAll patients survived the operation. The median (range) duration of cardiopulmonary bypass (CPB) was 184.5 (121-386) min. The median duration of circulatory arrest and retrograde cerebral perfusion was 50 (3-118) min and 16 (0-84) min, respectively. S-100 increased from 0.10 (0.02-0.18) microg/l preoperatively to 2.37 (0.64-10.80) microg/l after CPB (P<0.01), followed by a decrease to 0.79 (0.21-2.64) microg/l on the first postoperative day (P<0.01). The duration of circulatory arrest correlated with S-100 levels after CPB (r(S) = 0.71, P<0.05) and even better with the S-100 levels on the first postoperative day (r(S) = 0.83, P<0.01). However, there was no significant correlation between duration of arrest and duration of CPB. The duration of circulatory arrest without retrograde cerebral perfusion correlated well with S-100 levels on the first postoperative day (r(S) = 0.88, P<0.01), but not significantly with S-100 levels after CPB.nnnCONCLUSIONSnS-100 levels after aortic surgery with deep hypothermic arrest correlate with the duration of circulatory arrest, indicating that the duration of circulatory arrest is damaging to the brain despite the use of deep hypothermia and partial retrograde cerebral perfusion. The highest correlation between S-100 and duration of arrest was seen on the first postoperative day. S-100 appears to perform well under clinical circumstances as a sensitive and discriminative marker for neuronal injury.

Influence of propranolol, enalaprilat, verapamil, and caffeine on adenosine A2A-receptor–mediated coronary vasodilation

OBJECTIVESnThe study was done to determine the effects of propranolol, enalaprilat, verapamil, and caffeine on the vasodilatory properties of the adenosine A(2A)-receptor agonist ATL-146e (ATL).nnnBACKGROUNDnATL is a new adenosine A(2A)-receptor agonist proposed as a vasodilator for myocardial stress perfusion imaging. Beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium blockers are commonly used for the treatment of coronary artery disease (CAD), and their effect on ATL-mediated vasodilation is unknown. Dietary intake of caffeine is also common.nnnMETHODSnIn 19 anesthetized, open-chest dogs, hemodynamic responses to bolus injections of ATL (1.0 microg/kg) and adenosine (60 microg/kg) were recorded before and after administration of propranolol (1.0 mg/kg, ATL only), enalaprilat (0.3 mg/kg, ATL only), caffeine (5.0 mg/kg, ATL only), and verapamil (0.2 mg/kg bolus, ATL and adenosine).nnnRESULTSnNeither propranolol nor enalaprilat attenuated the ATL-mediated vasodilation (225 +/- 86% and 237 +/- 67% increase, respectively, p = NS vs. control). Caffeine had an inhibitory effect (97 +/- 28% increase, p < 0.05 vs. control). Verapamil blunted both ATL- and adenosine-induced vasodilation (63 +/- 20% and 35 +/- 7%, respectively, p < 0.05 vs. baseline), and also inhibited the vasodilation induced by the adenosine triphosphate-sensitive potassium (K(ATP)) channel activator pinacidil.nnnCONCLUSIONSnBeta-blockers and ACE inhibitors do not reduce the maximal coronary flow response to adenosine A(2A)-agonists, whereas verapamil attenuated this vasodilation through inhibition of K(ATP) channels. The inhibitory effect of verapamil and K(ATP) channel inhibitors like glybenclamide on pharmacologic stress using adenosine or adenosine A(2A)-receptor agonists should be evaluated in the clinical setting to determine their potential for reducing the sensitivity of CAD detection with perfusion imaging.

The prevalence and predictive accuracy of quantitatively defined transient ischemic dilation of the left ventricle on otherwise normal SPECT myocardial perfusion imaging studies.

AimTID in the setting of otherwise normal MPI has been suggested as a marker of high risk CAD. In this study we estimate the variance of TID in a normal population and the statistical frequency of false positive TID. This will provide an indirect measurement of predictive accuracy (PA) in a mixed referral population.ObjectiveTo study the PA of TID in otherwise normal MPI.Methods688 consecutive patients were studied. We defined TID according to the standard method at 2 cut-off values; 1SD and 2SD, and also by a BSA normalized volume difference with gender-specific 2SD limits (NrVD).Results457 patients with otherwise normal MPI were analyzed. PA of TID at 1SD was 4% and 26% at 2SD. PA was slightly higher (42%) using the NrVD, however, still too low to be clinically useful as a high-risk marker. PA of TID in patients with perfusion abnormalities was 58% at 1SD, 80% at 2SD and slightly higher (93%) by NrVD.ConclusionsIn the setting of otherwise normal MPI, elevated TIDr has a low prevalence and poor predictive accuracy and should not be considered summarily as a marker of high risk CAD.

Prevalence and Predictors of Ischemia and Outcomes in Outpatient Diabetic Patients Referred for SPECT Myocardial Perfusion Imaging

Background— The prevalence of ischemia and its prediction of events are unclear in outpatients with diabetes mellitus in the modern era of intensive medical management. We sought to identify the prevalence of ischemia, subsequent cardiac events, and impact of sex, stress type, and symptom status on these findings in a cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging (MPI). Methods and Results— The study cohort included 575 consecutive outpatients with diabetes mellitus who underwent quantitative, gated single-photon emission computed tomography MPI. Clinical information, stress MPI variables, and cardiac events were prospectively collected and analyzed. The study population was at intermediate risk of coronary artery disease or had known coronary artery disease (40.3%); 29% of patients were asymptomatic at the time of stress testing. Scintigraphic ischemia and significant (≥10%) left ventricular ischemia were present in 126 patients (21.9%) and 29 patients (5.0%), respectively, and <1% of patients had early revascularization. The risk of ischemia was increased >2-fold by male sex (P<0.001), but was not impacted by pharmacological stress (P=0.15) or presence of symptoms (P=0.89). During a median 4.4 years follow-up, the rate of cardiac death/nonfatal myocardial infarction was moderate at 2.6%/y (cardiac death 0.8%/y) in the total cohort, but was 5.7%/y in those with ischemia (P<0.001). Pharmacological stress predicted a higher cardiac event rate (P<0.001) but symptoms did not (P=0.55). Conclusions— This cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography had low rates of significant ischemia and early revascularization; an initially low cardiac event rate increased after 2 years. Independent predictors of cardiac death/nonfatal myocardial infarction were known coronary artery disease, pharmacological stress, and MPI ischemia. Nearly one third of those with events had a normal MPI, indicating a need for improved risk stratification.Background nThe prevalence of ischemia and its prediction of events are unclear in outpatient diabetic patients in the modern era of intensive medical management. We sought to identify the prevalence of ischemia, subsequent cardiac events, and impact of gender, stress type, and symptom status on these findings in a cohort of outpatient, stable diabetic patients referred for SPECT myocardial perfusion imaging (MPI).

Incidence and Significance of Ischemic ST-Segment Depression Occurring Solely During Recovery After Exercise Testing

Although ischemic ST-segment depression (ST2) during exercise testing is an accepted finding suggesting the presence of coronary artery disease (CAD), the significance of ST2 that appears solely during the recovery period is less well defined. There have been only a few studies 1‐5 addressing this issue. Only 1 study correlated ST2 in recovery with scintigraphic incidence of ischemia, and that study used planar thallium-201 (Tl-201) imaging. 3 Tl-201 imaging usually begins as soon as possible after exercise testing, making it difficult to perform careful postexercise electrocardiographic (ECG) monitoring. Technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) is superior to Tl-201 in this regard because Tc-99m sestamibi does not rapidly redistribute. This yields ample time for poststress ECG monitoring before acquiring postexercise images. Therefore, the purpose of this study was to comprehensively investigate this uncommon ECG response of recovery ST2 using ECG-gated SPECT Tc-99m sestamibi imaging for determining the incidence of ischemic exercise test responses. ••• Patients were selected from a group of 1,507 consecutive patients who underwent Tc-99m sestamibigated SPECT combined with exercise testing. Patients who had a normal exercise Tc-99m sestamibi-gated SPECT were included in the study only if they reached

A Welcomed New Myocardial Perfusion Imaging Agent for Positron Emission Tomography

85% of their maximal predicted heart rate and if they did not have known CAD. Patients with only nonreversible defects on SPECT imaging were excluded. Patients included in the study had either normal SPECT or at least 1 reversible or partly reversible perfusion defect. A reversible defect was considered as the criterion for inducible ischemia. Pa