Henry Gewirtz

Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography.

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.

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Transient defects of resting thallium scans in patients with coronary artery disease.

Defects on resting thallium-201 (201T1) scans in patients who do not have evidence of acute myocardial ischemia have been thought to represent myocardial scar. Our study of 20 patients with stable but severe coronary artery disease (CAD), including nine with ECG evidence of myocardial scar, was undertaken to reexamine the significance of such defects. Imaging was performed in two views, beginning within 10 minutes after Tl administration and repeated over a 2-4-hour period. Images in each of the two projections were divided into three zones, for a total of 120 zones in 20 patients. An initial defect was present in 43 zones in 15 patients, while five patients demonstrated totally normal studies. On later scans 18 defects persisted while 25 filled in. Twelve of 18 persistent defects were associated with ECG evidence of infarction, compared with only six of 25 transient defects (p>0.01). Correlation with angiographic left ventricular wall motion was possible for 12 of 18 persistent defects and 18 of 25 transient defects. Six of 12 persistent defects, compared with only one of 18 transient defects, were associated with akinesia/dyskinesia (p>0.01). In addition, 17 of 18 transient defects were associated with either normal left ventricular wall motion (12 defects) or hypokinesia (five defects). Finally, 23 of 25 transient defects, compared with only 41 of 77 normal zones, were associated with severe CAD (p>0.001).Thus, in resting patients with stable CAD: 1) serial imaging reveals that many initial defects fill in over time; 2) initial resting defects on TI scans may not indicate myocardial scar; and 3) transient defects are usually associated with severe CAD, but normal or only mildly abnormal left ventricular wall motion.

Effects of Short-Term Treatment of Hyperlipidemia on Coronary Vasodilator Function and Myocardial Perfusion in Regions Having Substantial Impairment of Baseline Dilator Reverse

BACKGROUND We tested the hypothesis that correction of hyperlipidemia improves coronary vasodilator response and maximal perfusion in myocardial regions having substantial impairment of pretreatment vasodilator capacity. METHODS AND RESULTS Measurements of myocardial blood flow were made with PET [13N]ammonia in 12 patients with ischemic heart disease (11 men; age, 65+/-8 years [mean+/-SD]) at rest and during adenosine at 70 and then 140 microg . kg-1 . min-1 for 5 minutes each before and approximately 4 months after simvastatin treatment (40 mg daily). Simvastatin reduced LDL (171+/-13 before versus 99+/-18 mg/dL after simvastatin, P<0.001) and increased HDL (39+/-8 versus 45+/-9 mg/dL, P<0.05). Myocardial segments were classified on the basis of pretreatment blood flow response to 140 microg . kg-1 . min-1 adenosine as normal (flow >/=2 mL . min-1 . g-1) or abnormal (flow <2 mL . min-1 . g-1). In normal segments, baseline myocardial blood flow (0.95+/-0.32) increased (P<0.001) at both low- (1.62+/-0.81) and high- (2.63+/-0.41) dose adenosine and was unchanged both at rest and with adenosine after simvastatin. In abnormal segments, myocardial blood flow at rest (0. 73+/-0.19) increased at low- (1.06+/-0.59, P<0.02) and high- (1. 29+/-0.33, P<0.01) dose adenosine. After simvastatin, myocardial blood flow increased more compared with pretreatment at both low- (1. 37+/-0.66, P<0.05 versus pretreatment) and high- (1.89+/-0.79, P<0. 01 versus pretreatment) dose adenosine. CONCLUSIONS Short-term lipid-lowering therapy increases stenotic segment maximal myocardial blood flow by approximately 45%. The mechanism involves enhanced, flow-mediated dilation of stenotic epicardial conduit vessels and may account at least in part for the efficacy of lipid lowering in secondary prevention trials and in reducing ischemic episodes in ambulatory patients.

The effect of intraaortic balloon counterpulsation on regional myocardial blood flow and oxygen consumption in the presence of coronary artery stenosis in patients with unstable angina.

To determine whether a reduction in myocardial oxygen demand or an increase in coronary blood flow or both are responsible for the salutory effect of intraaortic balloon counterpulsation (IABP) in relieving medically refractory angina, we assessed these variables in six patients in whom IABP was required for relief of myocardial ischemia. IABP decreased the rate7pressure product and aortic enddiastoliczpressure, and the peak systolic aortic pressure and regional myocardial oxygen consumption declined in- all but one patient. Peak and mean aortic diastolic pressures increased. Changes in regional coronary blood flow paralleled changes in peak systolic aortic pressure (r = 0.92, p < 0.007). Thus, relief of angina during IABP could not be ascribed to an increase in regional coronary blood flow. Reduction of myocardial oxygen consumption is the most likely mechanism by which IABP relieves myocardial ischemia in patients with unstable angina pectoris.

Positron emission tomographic measurements of absolute regional myocardial blood flow permits identification of nonviable myocardium in patients with chronic myocardial infarction

OBJECTIVES This study tested the hypothesis that nonviable myocardium can be identified by quantitative measurements of regional myocardial blood flow obtained using positron emission tomography in conjunction with a mathematical model of nitrogen-13 (N-13) ammonia tracer kinetics. BACKGROUND Under steady state basal conditions there is a minimal level of blood flow required to sustain myocardial viability. Therefore, the hypothesis predicts that regions with flow below a certain threshold are likely to be composed primarily of scar. METHODS Studies were conducted in 26 patients with chronic myocardial infarction. Positron emission tomographic measurements of basal regional myocardial blood flow (N-13 ammonia) and fluorine-18 (F-18) fluorodeoxyglucose uptake were made and correlated with information about coronary anatomy and regional wall motion to assess myocardial viability. RESULTS In patients with chronic myocardial infarction, normal zone blood flow (0.81 +/- 0.32 ml/min per g [mean +/- SD]) was greater (p < 0.02) than that of border zones (0.59 +/- 0.29 ml/min per g), which in turn exceeded (p < 0.001) that of infarct zone flow (0.27 +/- 0.17 ml/min per g). Good correlation was noted between relative F-18 fluorodeoxyglucose uptake and relative regional myocardial blood flow in all zones (r = 0.63, p < 0.001). Mismatch between blood flow and F-18 fluorodeoxyglucose uptake, with a single exception, was not observed in any segment with blood flow < 0.25 ml/min per g. All dyskinetic segments (n = 5) also had blood flow < 0.25 ml/min per g. In contrast, 43 of 45 myocardial segments (23 patients) with normal contraction or only mild hypokinesia had flow > or = 0.39 ml/min per g (average flow 0.78 +/- 0.35 ml/min per g). CONCLUSIONS In patients with chronic myocardial infarction, myocardial viability is unlikely when basal regional myocardial blood flow is < 0.25 ml/min per g. Average basal flow in segments with normal or nearly normal wall motion is 0.78 +/- 0.35 ml/min per g. Thus, positron emission tomographic measurement of regional myocardial blood flow is helpful in identifying nonviable myocardium in these patients.

Comparison of Positron Emission Tomography Measurement of Adenosine-Stimulated Absolute Myocardial Blood Flow Versus Relative Myocardial Tracer Content for Physiological Assessment of Coronary Artery Stenosis Severity and Location

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.

Effect of a reduction in blood viscosity on maximal myocardial oxygen delivery distal to a moderate coronary stenosis.

This study tested the hypothesis that a reduction in blood viscosity by means of isovolumetric hemodilution will permit an increase in maximal oxygen delivery to myocardium distal to a moderate coronary arterial stenosis. It is known that blood viscosity is a determinant of resistance to blood flow at both the stenotic and the arteriolar levels. Accordingly, a reduction in blood viscosity could exert a favorable influence on maximal myocardial oxygen delivery in the setting of stenosis, provided that the oxygen-carrying capacity of the blood is not compromised excessively. Closed-chest, sedated domestic swine (n = 8) were instrumented with an artificial coronary arterial stenosis that reduced vessel diameter by 64%. Measurements of hemodynamics, regional myocardial blood flow (microspheres), lactate and oxygen metabolism, and whole blood viscosity were made at control and after two successive 10 min intracoronary infusions of adenosine (400 and 800 micrograms/min) distal to the stenosis. Next, albumin/saline solution was given intravenously to reduce the animals hematocrit by approximately 50%. Repeat measurements of all experimental variables were then made at a second control and again after two successive 10 min intracoronary infusions of adenosine (400 and 800 micrograms/min) distal to the stenosis. Myocardial blood flow (ml/min/g) distal to the stenosis increased from 1.52 +/- 0.21 (mean +/- 1 SD) to 4.10 +/- 0.86 in response to adenosine (peak dose) before hemodilution (p less than .01) and from 2.07 +/- 0.59 to 4.08 +/- 0.93 (p less than .01) after hemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the role of coronary angioplasty in patients with unstable angina pectoris

Seventeen patients presenting with unstable angina pectoris underwent percutaneous transluminal coronary angioplasty (PTCA). Despite vigorous medical therapy, all patients were disabled with 10 experiencing refractory in-hospital angina. PTCA was judged successful in 13 patients and resulted in decreased coronary diameter narrowing from 80 +/- 16% to 34 +/- 13% and reduced transstenotic pressure gradient from 69 +/- 13 to 23 +/- 12 mm Hg. Regional coronary blood flow (CBF) and myocardial metabolism were assessed at rest and during pacing tachycardia in six patients with left anterior descending coronary stenosis. Prior to PTCA, neither regional CBF increased nor coronary vascular resistance declined during rapid pacing; myocardial lactate extraction fell, indicating a shift from aerobic to anerobic metabolism. Following PTCA, however, rapid pacing resulted in increased regional CBF, decreased coronary vascular resistance, and preservation of aerobic metabolism. Following PTCA, successfully dilated patients demonstrated marked relief of angina symptoms, increase in functional capacity, and objective exercise ECG and thallium scintigraphic evidence of relief of previously ischemic myocardium. This investigation demonstrates that PTCA, when combined with medical therapy, can be performed safely and successfully in selected patients who present with otherwise refractory unstable angina, and indicates the procedure deserves further study as a therapeutic alternative in this condition.

Homocysteine impairs coronary microvascular dilator function in humans.

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.