Background-Disturbances of autonomic function after infarction are associated with both total mortality and sudden death. Although many imaging techniques for assessing the cardiac autonomic nervous system have been studied, the clinical usefulness of these techniques remains uncertain. This exploratory pilot study examined the relationship between abnormalities of ventricular sympathetic innervation delineated by scintigraphic imaging with Clinical Perspective see p 140123 I-mIBG is a norepinephrine analogue, and myocardial uptake reflects the extent of sympathetic innervation. Reduced myocardial uptake of 123 I-mIBG is observed in asso- ciation with most diseases that result in left ventricular (LV) dysfunction and potentially lethal ventricular arrhythmias. [5][6][7][8][9][10][11][12][13][14][15] In small observational studies, dysfunction of the myocardial autonomic nervous system as evaluated by using 123 I-mIBG has been shown to be associated with the occurrence of arrhythmias. 16 -18 However, the explanation for this association is not yet clear. One potential link between abnormalities of sympathetic innervation and the occurrence of potentially lethal ventricular arrhythmias is the fact that denervated myocardium may be viable and hyperresponsive to circulating catecholamines. 3 It is also possible that denervated but viable myocardium on the border zone of infarctions is prone to the development of reentrant ventricular tachycardia circuits. Both single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging have been used to demonstrate the presence of denervated but still viable myocardium (as can be observed after myocardial infarction) that could contribute to the development of ventricular arrhythmias. 18 -26 The present exploratory pilot study was designed to examine whether alterations in cardiac sympathetic innervation as measured by 123 I-mIBG scintigraphy were related to the inducibility of ventricular arrhythmias during EP testing in patients with previous infarction. The primary objective was to evaluate results by using planar 123 I-mIBG imaging and the combination of SPECT 123 I-mIBG innervation and 99m Tctetrofosmin perfusion imaging (providing information on extent of denervated myocardium and infarct size, respectively). Methods Patient SelectionThis was a phase 2, open-label, multicenter exploratory study conducted at 13 centers in Europe and one center in the United States, investigating the association between findings on planar and SPECT 123 I-mIBG imaging and the results of cardiac EP testing. The protocol was approved by the ethical committees or institutional review boards at each participating institution. All patients provided written informed consent before the performance of any study procedures.Primary inclusion criteria at the inception of the study included a history of myocardial infarction, LV dysfunction (left ventricular ejection fraction [LVEF]Յ40%, measured within 30 days of study entry), and referral for a clinically indicat...

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for the WOMEN Trial InvestigatorsBackground-There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. Methods and Results-We randomized symptomatic women with suspected CAD, an interpretable ECG, and Ն5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; Pϭ0.59).Compared with ETT, index testing costs were higher for exercise MPI (PϽ0.001), whereas downstream procedural costs were slightly lower (Pϭ0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI (PϽ0.001). Conclusions-In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. Clinical Trial Registration-http://www.clinicaltrials.gov.

These data indicate that same-day rest/stress sestamibi imaging will incorrectly identify 36% of myocardial regions as being irreversibly impaired and nonviable compared with both thallium redistribution/reinjection and PET. However, the identification of reversible and viable myocardium can be greatly enhanced with sestamibi if an additional redistribution image is acquired after the rest sestamibi injection or if the severity of reduction in sestamibi activity within irreversible defects is considered.

The central nervous system (CNS) effects of mental stress in patients with coronary artery disease (CAD) are unexplored. The present study used positron emission tomography (PET) to measure brain correlates of mental stress induced by an arithmetic serial subtraction task in CAD and healthy subjects. Mental stress resulted in hyperactivation in CAD patients compared with healthy subjects in several brain areas including the left parietal cortex [angular gyrus͞parallel sulcus (area 39)], left anterior cingulate (area 32), right visual association cortex (area 18), left fusiform gyrus, and cerebellum. These same regions were activated within the CAD patient group during mental stress versus control conditions. In the group of healthy subjects, activation was significant only in the left inferior frontal gyrus during mental stress compared with counting control. Decreases in blood f low also were produced by mental stress in CAD versus healthy subjects in right thalamus (lateral dorsal, lateral posterior), right superior frontal gyrus (areas 32, 24, and 10), and right middle temporal gyrus (area 21) (in the region of the auditory association cortex). Of particular interest, a subgroup of CAD patients that developed painless myocardial ischemia during mental stress had hyperactivation in the left hippocampus and inferior parietal lobule (area 40), left middle (area 10) and superior frontal gyrus (area 8), temporal pole, and visual association cortex (area 18), and a concomitant decrease in activation observed in the anterior cingulate bilaterally, right middle and superior frontal gyri, and right visual association cortex (area 18) compared with CAD patients without myocardial ischemia. These findings demonstrate an exaggerated cerebral cortical response and exaggerated asymmetry to mental stress in individuals with CAD.

Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomy's Role in Coronary Artery [CAD] [SPARC]; NCT00321399).

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These data indicate that one of two imaging modalities, either stress-redistribution-reinjection or rest-redistribution imaging, may be used for identifying viable myocardium. However, if there are no contraindications to stress testing, stress-redistribution-reinjection imaging provides a more comprehensive assessment of the extent and severity of coronary artery disease by demonstrating regional myocardial ischemia without jeopardizing information on myocardial viability.