The present role of nuclear cardiology in clinical practice.

Many advances have been made in the field of nuclear cardiology in the past decade for enhancing the diagnostic and prognostic value of stress myocardial perfusion imaging and the assessment of myocardial viability using SPECT technology. Gated SPECT for determining regional and global function have provided incremental diagnostic and prognostic information in the evaluation of patients with suspected or known coronary artery disease. Left ventricular ejection fraction and regional myocardial wall thickening can now be simultaneously evaluated with regional perfusion particularly with the use of the (99m)Tc-labeled perfusion agents such as sestamibi and tetrofosmin. Many studies have shown that the extent and severity of stress-induced perfusion defects have incremental prognostic value over exercise electrocardiographic stress test variables alone. Patients with normal perfusion scans have <1% combined cardiac death and myocardial infarction rates per year and thus have an excellent prognosis. Diabetics are particularly benefited from stress perfusion imaging for detection of coronary artery disease and risk assessment. Diabetics have a worse prognosis than nondiabetics for the same amount of hypoperfusion on stress SPECT studies. Quantitative rest perfusion imaging with (201)Tl or with one of the (99m)Tc-labeled imaging agents, or PET imaging with (18)F-deoxyglucose can accurately distinguish viable from irreversibly injured myocardium providing useful information for identifying which patients with ischemic cardiomyopathy benefit most from coronary revascularization with a subsequent improvement in left ventricular function and enhanced survival. Finally, serial stress perfusion imaging can be employed to monitor the efficacy of medical therapy that improves endothelial function and myocardial blood flow reserve.

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

OBJECTIVES: This 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. BACKGROUND: In 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. METHODS: We 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. RESULTS: During 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. CONCLUSIONS: Patients 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.

Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection.

BACKGROUND: Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A(2A) Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5'-N-ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. METHODS AND RESULTS: In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A(2A) over the A(1) and A(3) receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 normal) or bolus injection (ATL-146e; n=9 critical left anterior descending coronary artery stenosis), and hemodynamic responses were compared with those of Ado. Both agonists produced dose-dependent coronary flow (CF) elevation without provoking the hypotension observed with Ado. After an ATL-146e bolus, the CF increase was sustained for several minutes, providing ample time for injection and myocardial uptake of (99m)Tc-sestamibi, and CF returned to baseline within 20 minutes. The CF increase was completely blocked by the selective A(2A) antagonist ZM241385 (3 microgram. kg(-1). min(-1)). CONCLUSIONS: ATL-193 and ATL-146e are highly potent and selective Ado A(2A) receptor agonists with excellent potential for use as vasodilators for myocardial perfusion imaging. An important advantage of ATL-146e is the ability to administer it by bolus injection.

Assessment of residual coronary stenoses using 99mTc-N-NOET vasodilator stress imaging to evaluate coronary flow reserve early after coronary reperfusion in a canine model of subendocardial infarction.

UNLABELLED: Reperfusion is often incomplete after recanalization therapy because of the presence of residual coronary stenoses. Detecting mild to moderate stenoses requires assessing coronary flow reserve with vasodilator stress. 99mTc-(N-ethoxy-N-ethyl-dithiocarbamato)nitrido (N-NOET) is a viability-independent flow tracer and thus may be well suited for assessing coronary flow reserve in the acute phase of reperfusion. METHODS: Twelve open-chest dogs underwent 60 min of total left anterior descending artery (LAD) occlusion followed by either full reperfusion (group 1; n = 4) or reperfusion through a residual critical stenosis (group 2; n = 8). 99mTc-N-NOET was given during peak vasodilator stress 165 min after reperfusion, and initial and 60-min delayed images were acquired. Regional blood flow was assessed with radiolabeled microspheres. RESULTS: Infarct size was similar in both groups (9% +/- 2% vs. 8% +/- 2% of left ventricle). Both initial (0.61 +/- 0.02 vs. 0.73 +/- 0.01; P < 0.01) and 60-min (0.67 +/- 0.02 vs. 0.80 +/- 0.01; P < 0.01) defect count ratios (LAD/left circumflex coronary artery [LCx]) differentiated between the 2 groups, reflecting the greater diminution in coronary flow reserve in group 2 dogs (LAD/LCx flow ratios = 0.37 +/- 0.04 vs. 0.57 +/- 0.09; P < 0.01). Interestingly, coronary flow reserve in the reperfused zone of group 1 was diminished despite the absence of a stenosis. Thus, the difference in 99mTc-N-NOET uptake between the 2 groups was less than expected. CONCLUSION: In this canine myocardial infarction model with some coronary flow reserve preservation, 99mTc-N-NOET imaging can detect residual coronary stenoses. However, with more prolonged occlusion resulting in more severe endothelial or microvascular dysfunction, it may be difficult to distinguish varying degrees of vessel patency using any coronary flow reserve technique.

Clinical benefit of noninvasive viability studies of patients with severe ischemic left ventricular dysfunction.

The population of patients who have congestive heart failure of ischemic origin is large and growing. It imposes a heavy burden on human suffering and economic costs such as the chronic use of costly medications, recurrent hospital admissions, and, eventually, death or the necessity of heart transplantation. Therefore, the development of methods for detecting viable myocardium may allow the accurate selection of those patients with coronary artery disease with severe left ventricular dysfunction who are most likely to benefit from revascularization, but also excludes patients who are unlikely to obtain any improvement with revascularization techniques. The presence of reversible dysfunctional myocardium that may improve after revascularization implies the concepts of stunned and hibernating myocardium. Recent evidence suggests that hibernation may not be a stable condition since it might evolve toward an irreversible dysfunction if it is not revascularized at the right moment. The techniques available for viability studies are single-photon emission computed tomography using thallium-201 or compounds labeled with technetium-99m, positron emission tomography, and dobutamine stress echocardiography. Newer and promising techniques are magnetic resonance imaging and contrast echocardiography, whose definitive roles are not clear yet. There is abundant evidence from several important studies showing that patients with a significant amount of viable myocardium have a poor outcome if they are treated medically. Conversely, if these patients are revascularized, their outcomes improve and their symptoms significantly decrease, with less necessity of medication, fewer admissions to the hospital, and even in some cases avoiding heart transplantation. On the other hand, patients with poor or no viability who are revascularized do not obtain significant benefit.

Relationship between extent of residual myocardial viability and coronary flow reserve in patients with recent myocardial infarction.

BACKGROUND: The presence of viability in an infarct zone implies an intact microvasculature. We hypothesized that coronary flow reserve (CFR), which assesses the microcirculation, would correlate with the extent of viability in infarction zones. METHODS: CFR was measured after stenting in 17 patients with single vessel disease >48 hours from infarction. Viability was determined with use of single-photon emission computed tomography sestamibi imaging. RESULTS: Sestamibi uptake in the infarct zone correlated with CFR in the infarct artery (r = 0.62, P =.008) and sestamibi uptake in the infarct zone was greater in patients with normal CFR than in patients with abnormal CFR (61.9 +/- 9.1% vs 46.3 +/- 9.6%, P =.004). In addition, CFR was greater in patients with viability compared with patients without viability (2.4 +/- 1.3 vs 1.4 +/- 0.4, P =.015). CONCLUSIONS: CFR correlates with the extent of viability after infarction. Preserved CFR in an infarct-related artery implies preserved viability.

Tc-99m sestamibi defect magnitude predicts the amount of viable myocardium after coronary reperfusion despite the presence of severe residual stenosis.

BACKGROUND: Whether technetium-99m-labeled methoxyisobutyl isonitrile (Tc-99m sestamibi) imaging early after reperfusion can detect the amount of salvaged viable myocardium in the presence of a severe residual stenosis remains controversial. METHODS AND RESULTS: Nine dogs underwent total left anterior descending coronary artery (LAD) occlusion for 40 to 180 minutes followed by reperfusion through a flow-limiting stenosis. They were divided into 2 groups based on infarct size (group 1, <15% of risk area; group 2, > or =15%). Triphenyl tetrazolium chloride infarct size was measured by planimetry, and regional flow was quantified by radiolabeled microspheres. Mean infarct size was 9.3% +/- 3.0% of risk area in group 1 versus 51.1% +/- 4.8% in group 2 (P <.01). Tc-99m sestamibi was injected 30 minutes after reperfusion, when the LAD flows were comparable for group 1 (9 +/- 2 mL. min(-1)) and group 2 (9 +/- 1 mL. min(-1)). Left circumflex coronary artery flows were 33 +/- 5 and 32 +/- 9 mL. min(-1) for groups 1 and 2, respectively. Despite administration of Tc-99m sestamibi during diminished residual LAD flow after reperfusion, defect magnitude on ex vivo images in group 1 was significantly less severe than that in group 2, which had larger infarcts (0.71 +/- 0.02 vs 0.42 +/- 0.05, P <.01). This reflects greater salvage and more viability in group 1. CONCLUSION: Resting perfusion imaging with Tc-99m sestamibi accurately determined viability of the infarct zone despite reperfusion through a residual stenosis. Tc-99m sestamibi imaging may prove useful in the clinical setting for the prediction of the amount of salvaged myocardium.