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Considerable awareness has been raised of late of the need to reduce radiation exposure and control costs of x-ray and radionuclide imaging procedures. PET/CT cameras are now widely available and in conjunction with appropriate radionuclides and commercially available software make quantitative measurement of absolute MBF feasible for routine clinical practice. Quantitative measurement of absolute MBF under condition of coronary vasodilation permits independent assessment of the functional status of each of the three major coronary perfusion zones and so obviates the need for rest MBF determination in the great majority of cases. Coronary microvascular function also may be assessed in this same way. Thus, the stress-only protocol with quantitative PET measurement of MBF provides essential information required for clinical decision making related to need for catheterization and intervention for patients with known or suspected ischemic heart disease. Moreover, the single PET determination of maximal MBF in contrast to the usual rest/stress procedure addresses both safety and cost concerns. The present review focuses on: (1) quantitative PET measurements of myocardial blood flow for physiological assessment of the coronary circulation and (2) the value and potential limitations of performing stress only imaging in the clinical context.

Introduction: We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis., Methods: Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores., Results: On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall gamma = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest., Conclusions: CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress.

Objectives: This study sought to determine the feasibility of performing a comprehensive cardiac computed tomographic (CT) examination incorporating stress and rest myocardial perfusion imaging together with coronary computed tomography angiography (CTA)., Background: Although cardiac CT can identify coronary stenosis, very little data exist on the ability to detect stress-induced myocardial perfusion defects in humans., Methods: Thirty-four patients who had a nuclear stress test and invasive angiography were included in the study. Dual-source computed tomography (DSCT) was performed as follows: 1) stress CT: contrast-enhanced scan during adenosine infusion; 2) rest CT: contrast-enhanced scan using prospective triggering; and 3) delayed scan: acquired 7 min after rest CT. Images for CTA, computed tomography perfusion (CTP), and single-photon emission computed tomography (SPECT) were each read by 2 independent blinded readers., Results: The DSCT protocol was successfully completed for 33 of 34 subjects (average age 61.4 +/- 10.7 years; 82% male; body mass index 30.4 +/- 5 kg/m(2)) with an average radiation dose of 12.7 mSv. On a per-vessel basis, CTP alone had a sensitivity of 79% and a specificity of 80% for the detection of stenosis > or =50%, whereas SPECT myocardial perfusion imaging had a sensitivity of 67% and a specificity of 83%. For the detection of vessels with > or =50% stenosis with a corresponding SPECT perfusion abnormality, CTP had a sensitivity of 93% and a specificity of 74%. The CTA during adenosine infusion had a per-vessel sensitivity of 96%, specificity of 73%, and negative predictive value of 98% for the detection of stenosis > or =70%., Conclusions: Adenosine stress CT can identify stress-induced myocardial perfusion defects with diagnostic accuracy comparable to SPECT, with similar radiation dose and with the advantage of providing information on coronary stenosis.

Objectives: This study tests the hypothesis that absolute measurement of adenosine (Ado)-stimulated myocardial blood flow (MBFado) is superior to measurement of relative tracer uptake for identification of hemodynamically significant coronary artery disease (CAD)., Background: Positron emission tomography measurement of absolute myocardial blood flow (MBF) ((13)N-ammonia) with Ado has the capability to more accurately assess hemodynamic severity of CAD than measurement of relative tracer content (TC) (nCi/ml) during Ado, which by definition depends on at least 1 normal zone to which others are compared., Methods: A total of 27 patients (20 male, 58 +/- 11 years, mean +/- SD) with known or suspected CAD and 21 normal subjects (13 male, 38 +/- 10 years) were studied. Parametric (K1) MBF images and TC sum images were analyzed. A stenosis > or =70% defined significant CAD. The receiver-operator characteristic curve (ROC) analysis area under the curve (AUC) compared MBF and TC results. Cut-point analysis for sensitivity, specificity, and accuracy showed the best MBF criteria for CAD as MBFado <1.85 ml/min/g and the best TC as <70% maximum. The myocardial blood flow reserve ratio (MBFR) (optimal <2.0x) also was studied., Results: The ROC analysis of PET parameters showed that MBFado was superior to <70% maximum uptake for CAD detection (n = 144 vessels; AUC 0.900 vs. 0.690, respectively, p < 0.0001) and was marginally greater than MBFR (0.856; p = 0.10). For CAD cut-point analysis, MBFado accuracy exceeded TC (0.84 vs. 0.72, respectively, p = 0.005), as did sensitivity (0.81 vs. 0.48, respectively; p = 0.001). Specificity of MBFado for CAD classification (0.85) was comparable to TC (0.82; p = NS). Sensitivity, specificity, and predictive accuracy for MBFR were 0.62, 0.85, and 0.79, respectively. The difference in specificity was not significant versus MBFado. However, MBFado was more sensitive than MBFR (p = 0.01). The difference in predictive accuracy was borderline (p = 0.06) in favor of MBFado., Conclusions: Measurement of Ado-stimulated absolute MBF is superior to relative measurement of myocardial tracer retention for identification of CAD and can be accomplished with a single MBFado measurement.

Background: Delayed heart rate (HR) recovery after treadmill exercise testing predicts mortality. Patients with suspected ischemic heart disease who cannot perform adequate treadmill exercise are typically evaluated with pharmacological stress myocardial perfusion imaging (MPI) studies, but little prognostic significance has been attributed to the hemodynamic response to vasodilator stress testing with low-level exercise. We hypothesized that a delay in HR recovery after adenosine stress testing with arm exercise is associated with increased mortality., Methods and Results: Technetium 99m-Sestamibi MPI was performed in 1,455 consecutive patients (70 +/- 12 years, 50.2% men) with adenosine stress and supplemental arm exercise. HRs were recorded at rest, continuously during infusion, and then 5 minutes post-infusion. Delayed HR recovery was defined as a decline of < or = 12 bpm from peak HR at 5 minutes after discontinuation of the infusion. Of 1,356 patients during 5 years of follow up, there were 135 deaths (10%). Delayed HR recovery was strongly predictive of all-cause mortality (16.5% vs 5.3% in those with normal HR recovery, P < .001) with an adjusted hazard ratio of 2.5 (95% CI, 1.7-3.6; P < .001)., Conclusion: Delayed HR recovery after adenosine stress testing with arm exercise is a readily available and powerful predictor of all-cause mortality.

Objectives: We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function., Background: Hyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary circulation is not known., Methods: Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA) (0.3 mg/kg/min intravenously)., Results: Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 +/- 1.00 ml/min/g vs. 0.58 +/- 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 +/- 2.6% vs. 2.6 +/- 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of l-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of l-NMMA (2.08 +/- 1.34 ml/min/g vs. 1.48 +/- 1.32 ml/min/g, placebo vs. l-NMMA, p < 0.05)., Conclusion: The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability.

To test the hypothesis that adenosine is required to mediate the sustained increase in myocardial flow evoked by isoproterenol haemodynamic indices, myocardial blood flow (microspheres), and regional myocardial oxygen consumption were measured in eight closed chest, sedated pigs (a) at control, (b) after isoproterenol (6.9(2.8) ng·kg−1·min−l (mean (SD)) infused into the left anterior descending coronary artery, (c) repeat control, and (d) after a simultaneous infusion of the same dose of isoproterenol and adenosine deaminase (10 U·kg−1·min−1). Data were acquired at one and 10 minutes after each infusion and compared with control measurements. Heart rate was held constant by atrial pacing. Peak left ventricular dP/dt (mm Hg·s−1) increased significantly (control 2190(32) mean (SD)) at both one (2900(302)) and 10 minutes (3010(391)) of isoproterenol infusion alone. At one minute of simultaneous infusion there was no change (control 1970(447)) in left ventricular dP/dt (2290(521)), although dP/dt was significantly increased at 10 minutes of simultaneous infusion (2790(483)). Transmural flow (ml·min−1·g−1) increased significantly (control 1.49(0.46)) in the distal left anterior descending zone at one (1.94(0.48)) and 10 minutes (2.07(0.27)) of isoproterenol infusion alone. In contrast, flow failed to increase (control 1.65(0.27)) during the first minute of simultaneous infusion (1.73(0.38)), although it did increase significantly by 10 minutes (1.91(0.21). Finally, although myocardial oxygen consumption (ml·min−1·100 g−1) increased significantly (control 16.4(4.7)) at both one (20.1(4.7)) and 10 minutes (19.4(3.6)) of isoproterenol infusion alone, it failed to increase (control 18.2(3.8)) at one (19.3(4.6)) and 10 minutes (19.1(3.8)) of simultaneous infusion.The data indicate that destruction of interstitial adenosine by adenosine deaminase initially impairs the ability of the myocardium to adjust to an abrupt increase in myocardial oxygen demand induced by isoproterenol. Within 10 minutes, however, the absence of adenosine is compensated for by some other mediator(s) and so flow increases despite the destruction of the nucleoside. Accordingly, adenosine appears to play a role in mediating the immediate but not the sustained flow response to isoproterenol. [ABSTRACT FROM PUBLISHER]

Data from experiments in isolated cardiac muscle preparations indicate that adenosine in high concentration (10−3 mol·litre−1) exerts a negative inotropic effect on the myocardium under basal conditions. The following study was performed to test the hypothesis that adenosine exerts a similar negative inotropic effect when administered in an intact animal model in a dose sufficient to cause maximal coronary vasodilatation. Six open chest anaesthetised pigs were studied as follows. Ultrasonic length sensors were placed in the endocardium of the free wall of the left ventricle in a region perfused by the left anterior descending (LAD) coronary artery. Large increases in endocardial blood flow in response to adenosine administration, which could enhance segmental function (“garden hose effect”), were prevented by inserting an artificial stenosis (73% reduction in lumenal diameter) in the proximal third of the LAD. Measurements of haemodynamics, regional myocardial blood flow (microsphere technique), and regional systolic function were made at control 1, at the end of 10 min of intracoronary adenosine infusion (3.0 μmol·min−1) at a dose which exceeded that previously shown to cause maximal coronary vasodilatation and at second control 20 to 40 min after discontinuation of adenosine infusion. In response to drug infusion there was no significant change (versus control 1) in heart rate (82±15 to 90±17 min−1, mean±1 SD), systolic arterial pressure (132±20 to 128±16 mmHg [17.6±2.6 to 17.0±2.1 kPa]), mean left atrial pressure (6±2 to 8±4 mmHg [0.8±0.3 to 1.1±0.5 kPa]) and endocardial blood flow (0.94±0.24 to 1.06±0.46 ml·min−1·g−1). Adenosine in LAD plasma attained an estimated concentration of 1.09 × 10−4 ± 5.16 × 10−5 mol·litre−1 during infusion. Regional systolic function (assessed by fractional shortening (FS), mean velocity of circumferential fibre shortening (Vcf, s−1), and end diastolic length (EDL, mm)) did not change significantly versus control 1 in response to adenosine infusion. Values for each parameter (control 1 to adenosine) were as follows: FS=0.17±0.03 to 0.16±0.20; Vcf=0.43±0.09 to 0.43±0.10; and EDL=17.4±4.0 to 16.9±4.2. Thus, contrary to the proposed hypothesis, under basal conditions adenosine does not exert a negative inotropic effect on the myocardium of an intact animal when administered in a dose sufficient to cause maximal coronary vasodilatation. [ABSTRACT FROM PUBLISHER]