Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

Purpose Tetrahydrobiopterin (BH₄) is an essential co-factor for the synthesis of nitric oxide (NO), and BH₄ deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH₄ deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia.Methods Myocardial blood flow (MBF; ml min^–1 g^–1) was measured at rest, during adenosine-induced (140 g kg^–1 min^–1 over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using ¹⁵O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH₄ (10 mg kg^–1 body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress.Results BH₄ increased exercise-induced hyperaemia in controls (2.96±0.58 vs 3.41±0.73 ml min^–1 g^–1, p<0.05) and hypercholesterolaemic subjects (2.47±0.78 vs 2.70±0.72 ml min^–1 g^–1, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52±1.10 vs 4.85±0.45 ml min^–1 g^–1, p=NS) or hypercholesterolaemic subjects (4.86±1.18 vs 4.53±0.93 ml min^–1 g^–1, p=NS). Flow reserve utilisation remained unchanged in controls (70±17% vs 71±19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53±15% vs 66±14%, p<0.05).Conclusion BH₄ restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH₄ deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.The first two authors have contributed equally to the present project.An erratum to this article can be found at     

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

Purpose The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation.Methods The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6±1.8 months after atorvastatin therapy, ¹³N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine 2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF.Results LDL cholesterol decreased after atorvastatin therapy from 186±43 mg/dl to 101±26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy.Conclusion The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.P. Wielepp and D. Baller contributed equally to the study     

Estimation of coronary flow reserve by sestamibi imaging in type 2 diabetic patients with normal coronary arteries

Background  We assessed coronary flow reserve (CFR) by sestamibi imaging in patients with type 2 diabetes without coronary artery disease and normal coronary vessels. Methods and Results  Dipyridamole/rest technetium 99m sestamibi imaging was performed in 33 patients with type 2 diabetes without a history of coronary artery disease and normal coronary vessels at angiography and in 12 control subjects. Myocardial blood flow (MBF) was estimated by measuring first-transit counts in the pulmonary artery and myocardial counts from tomographic images. Estimated CFR was expressed as the ratio of stress MBF to rest MBF. Rest MBF and CFR were corrected for rate-pressure product and expressed as normalized MBF and normalized CFR. At rest, estimated MBF and normalized MBF were not different in control subjects versus patients (0.98±0.4 counts·pixel⁻¹·s⁻¹ vs 1.42±0.9 counts·pixel⁻¹·s⁻¹ and 1.14±0.5 counts·pixel⁻¹·s⁻¹ vs 1.61±0.9 counts·pixel⁻¹·s⁻¹, respectively). Conversely, stress MBF was higher in control subjects than in patients (2.34±0.8 counts·pixel⁻¹·s⁻¹ vs 1.55±0.8 counts·pixel⁻¹·s⁻¹, P<.01). Thus estimated CFR was higher in control subjects than in patients (2.40±0.3 vs 1.36±0.8, P<.0001). After correction for the rate-pressure product, normalized CFR was still higher in control subjects than in patients (2.10±0.5 vs 1.28±0.8, P<.001). Conclusions  Sestamibi imaging may detect impaired coronary vascular function in response to dipyridamole in type 2 diabetic patients withou a history of coronary artery disease and with normal coronary arteries.     

Quantification of myocardial blood flow using dynamic 320-row multi-detector CT as compared with 15O-H2O PET

Objectives

This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against ¹⁵O-H₂O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients.

Methods

Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n?=?7).

Results

Correlation between MBF of MDCT and PET was strong (r?=?0.95, P?<?0.0001). CFR showed good correlation between dynamic CTP and PET (r?=?0.67, P?=?0.0126). CFR_CT in the CAD group (2.3?±?0.8) was significantly lower than that in the validation group (5.2?±?1.8) (P?=?0.0011).

Conclusions

We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP.

Key Points

? MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. ? MBF and CFR showed good correlation between dynamic CTP and PET. ? Lower CFR was well demonstrated in CAD patients by dynamic CTP.     

Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

Purpose Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means.Methods One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF 40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with ¹⁵O-labelled water (H₂¹⁵O) and ¹⁸F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (0.6 ml min^–1 g^–1) were classified as stunned, and segments with reduced MBF (<0.6 ml min^–1 g^–1) as hibernating if MRG was 0.25 mol min^–1 g^–1. Segments with reduced MBF and MRG <0.20 mol min^–1 g^–1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 mol min^–1 g^–1 as non-transmural scars.Results Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 mol min^–1 g^–1) and 233 (39%) reduced MRG (0.16±0.05 mol min^–1 g^–1). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 mol min^–1 g^–1) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min^–1 g^–1), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min^–1 g^–1 and 0.48±0.08 ml min^–1 g^–1, respectively), and lowest in transmural scars (0.40±0.14 ml min^–1 g^–1, P<0.01). MRG was comparable in hibernating and stunned myocardium with preserved MRG (0.40±0.19 mol min^–1 g^–1 vs 0.46±0.20 mol min^–1 g^–1, NS), and lowest in stunned myocardium with reduced MRG and transmural scars.Conclusion Chronic stunning is more prevalent than expected. The degree of MRG reduction in stunned myocardium may disclose segments at higher risk of permanent damage.     

Combined evaluation of regional coronary artery calcium and myocardial perfusion by <Superscript>82</Superscript>Rb PET/CT in the identification of obstructive coronary artery disease

Purpose

Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD).

Methods

We analyzed 113 patients with suspected CAD referred to ⁸²Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD.

Results

Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6?±?6.2 vs. 0.6?±?1.3) and lower hyperemic MBF (1.01?±?0.5 vs. 1.75?±?0.6 ml/min/g) and CFR (1.56?±?0.6 vs. 2.38?±?0.7; all p?<?0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p?<?0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365–1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64–1.26) for the CAC/ITPD/CFR model.

Conclusion

Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD.

     

The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve

BackgroundA diminished coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive disease on invasive coronary angiography (ICA).MethodsPatients underwent CCTA, and positron emission tomography (PET) prior to ICA. Matched global V/M, global, and vessel specific hyperaemic MBF (hMBF), coronary flow reserve (CFR), and, FFR were available for 431 vessels in 152 patients. The median V/M (20.71 mm³/g) was used to divide the population into patients with either a low V/M or a high V/M.ResultsOverall, a higher percentage of vessels with an abnormal hMBF and FFR (34% vs. 19%, p = 0.009 and 20% vs. 9%, p = 0.004), as well as a lower FFR (0.93 [interquartile range: 0.85–0.97] vs. 0.95 [0.89–0.98], p = 0.016) values were observed in the low V/M group. V/M was weakly associated with vessel specific hMBF (R = 0.148, p = 0.027), and FFR (R = 0.156, p < 0.001). Among vessels with non-obstructive CAD on ICA (361 vessels), no association between V/M and vessel specific hMBF nor CFR was noted. However, in the absence of obstructive CAD, V/M was associated with (R = 0.081, p = 0.027), and independently predictive for FFR (p = 0.047).ConclusionOverall, an abnormal vessel specific hMBF and FFR were more prevalent in patients with a low V/M compared to those with a high V/M. Furthermore, V/M was weakly associated with vessel specific hMBF and FFR. In the absence of obstructive CAD on ICA, V/M was weakly associated with notwithstanding independently predictive for FFR.     

Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123±7/65±9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8±0.6 vs 2.5±1.0 ml min^–1 g^–1; P<0.05), and perfusion reserve was also lower, at borderline significance (2.7±1.0 vs 3.6±1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9±0.9 (P<0.001) due to normalisation of maximal perfusion (2.3±0.5 ml min^–1 g^–1, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH.     

PET心肌灌注显像测定心肌血流量及冠状动脉血流储备的研究进展

PET心肌灌注显像可绝对定量测定局部心肌血流量（MBF）和冠状动脉血流储备（CFR）。由于显像剂半衰期短,允许在短时间内重复进行PET心肌灌注显像,获得静息态、冷加压试验和药物负荷试验等不同状态下的MBF,进而评价冠状动脉血管内皮依赖性和非依赖性的CFR功能。在早期诊断冠心病,准确诊断冠状动脉多支病变,评价微血管病变,早期检测冠状动脉内皮细胞功能异常及CFR功能的异常,估测预后,帮助临床治疗方案的制定以及检测疗效等方面,PET心肌灌注显像有重要的临床价值。该文将介绍PET心肌灌注显像相关知识及其在心血管领域的主要应用。     

Electron beam CT and cost-efficient diagnosis of coronary artery disease

Summary Background: Electron beam CT (EBCT) can acquire rapid, multiple thin-section tomograms of the beating heart in synchrony with the electrocardiogram and quantify coronary calcification without intravenous contrast. Coronary calcification is an active process exclusively associated with atherosclerotic plaque formation and regulated in a manner similar to the calcification of bone. Clinical studies have demonstrated that EBCT coronary calcification (1) follows a pattern similar to the epidemiology of coronary artery disease (CAD), (2) has a high sensitivity (90–95 %) for coronary plaque and significant angiographic coronary stenoses, and (3) has the potential to assess the prognosis of patients with coronary atherosclerotic disease. Coronary calcium area or “score” correlates best with overall plaque burden within the coronary system. However, coronary calcium is of limited value in distinguishing coronary stenosis on a segment-by-segment basis. EBCT and CAD: Due to spiraling health care costs, there is a need for cost-efficient strategies in the diagnosis and stratification of patients with known or suspected CAD. There are two major patient groups in which EBCT calcium scanning has a potential for cost-efficient application: (1) in asymptomatic, high-risk patients, identification of significant plaque burden may direct judicious use of long-term drug therapy or further investigation to those individuals most likely to benefit from an aggressive risk factor modification and medical program; (2) in patients with chest pain syndromes but no prior CAD, EBCT calcium scanning compares favorably with conventional diagnostic methods. In particular, using receiver operating characteristic analysis, the sensitivity and specificity of an EBCT calcium score of 80 in detecting obstructive CAD are both about 85 %. Using a theoretical model, EBCT calcium scanning was found to be the most cost-effective approach to diagnosis in populations with a low-to-moderate likelihood of obstructive CAD when compared with treadmill exercise, stress thallium, and stress echocardiography. Conclusions: EBCT calcium scanning is not a substitute for coronary angiography, but it has clear advantages over other more traditional diagnostic methods for CAD. In particular, it can be performed conveniently and inexpensively in most patients. Additionally, the site and extent of calcification are intimately related to the atherosclerotic plaque burden. The analyses presented suggest that it may also provide a cost-effective clinical alternative in specific subsets of the population. Eingegangen am 15. Januar 1996 Angenommen am 27. Februar 1996     

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [¹³N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min^–1·100 g^–1; group B, 124±30 ml·min^–1·100 g^–1 normal subjects, 105±21 ml·min^–1·100 g^–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.     

Coronary vasodilator reserve and Framingham risk scores in subjects at risk for coronary artery disease

Background  The relationship between coronary vasodilator reserve and risk of coronary heart disease (CHD) in subjects without coronary artery disease (CAD) is not well known. Methods and Results  We studied 289 subjects (mean age, 58 ± 10 years) without overt CAD and at low (<10%) to intermediate risk (10%–20%) for CHD based on Framingham risk scores (RAMPART [Relative and Absolute Myocardial Perfusion changes as measured by Positron Emission Tomography to Assess the Effects of ACAT Inhibition: A Double-Blind, Randomized, Controlled, Multicenter Trial]). Coronary flow reserve (CFR) and coronary vascular resistance (CVR) were calculated from rest and adenosine nitrogen 13 ammonia positron emission tomography studies. Framingham-estimated CHD risk was used to as a surrogate for outcomes. Compared with subjects with low-risk scores (n = 150), those with intermediate-risk scores (n = 139) had a higher minimal CVR (49.3 ± 17.41 mm Hg · mL^-1 · min^-1 · g^-1 vs 52.4 ± 16.4 mm Hg · mL^-1 · min^-1 · g^-1, P = .05) and lower CFR (2.8 ± 1.0 vs 2.5 ± 0.8, P = .02). CFR was inversely related to CHD risk (R=-0.2, P = .006), and CVR was directly related to CHD risk (R = 0.2, P < .001). The mean CFR was significantly lower in patients in the first quartile of CHD risk compared with those in the fourth quartile (2.3 ± 0.7 vs 2.8 ± 1.0, P = .02), and the minimal CVR was significantly higher (44 ± 15 mm Hg · mL^-1 · min^-1 · g^-1 vs 53 ± 14 mm Hg · mL^-1 · min^-1 · g^-1, P < .05). Conclusions  In subjects without clinical CAD and at low to intermediate risk, CFR assessed by positron emission tomography is inversely related to estimated 10-year CHD risk.     

Myocardial sympathetic innervation in patients with chronic coronary artery disease: is reduction in coronary flow reserve correlated with sympathetic denervation?

Purpose Higher sensitivity of sympathetic nerves to ischaemia in comparison with myocytes has been observed and has been claimed to contribute to poor prognosis in patients with coronary artery disease (CAD). The aim of this study was to evaluate the dependency of myocardial sympathetic innervation on restrictions in coronary flow reserve (CFR). Methods We analysed 27 non-diabetic patients with advanced CAD. We determined quantitative myocardial blood flow using ¹³N-ammonia PET, myocardial viability with ¹⁸F-FDG PET and cardiac innervation with ¹¹C-HED PET. Scarred segments were excluded from analysis. We investigated the relationship between regional HED retention, blood flow and CFR. Results There was no correlation between rest perfusion and HED retention within a flow range from approximately 30 to 120 ml/(100 ml·min). A slight correlation was observed between stress perfusion values and HED retention (p<0.001), and between CFR and HED retention (p<0.001). Conclusion In non-diabetic CAD patients, HED retention in vital myocardium does not correlate with myocardial rest perfusion over a large flow range. The observed relation between HED retention and CFR indicates that sympathetic innervation can be preserved even when there is major impairment of myocardial blood supply. Most probably the occurrence of denervation depends not only on reductions in CFR, but also on the duration and severity of resulting ischaemic episodes.     

Comparison of myocardial blood flow and coronary flow reserve during dobutamine and adenosine stress: implications for pharmacologic stress testing in coronary artery disease

BACKGROUND: Mechanistic differences between pharmacologic stressors may offer different clinical benefits. Therefore the effects of dobutamine and adenosine on absolute myocardial blood flow (MBF) and coronary flow reserve (CFR) were compared. METHODS AND RESULTS: We divided 36 patients (mean age, 61 +/- 8 years) with coronary artery disease into 2 groups based on stenosis severity as follows: greater than 50% but less than 75% (n = 16) and greater than 75% (n = 20). In addition, 18 normal volunteers (mean age, 46 +/- 7 years) served as control subjects. Groups of equal sizes received either dobutamine or adenosine. MBF at rest and peak MBF were measured by use of positron emission tomography in territories subtended by the stenosis (ischemic) and remote myocardium (remote), whereas left ventricular MBF was used in control subjects. CFR was calculated as peak MBF divided by MBF at rest. CFR was significantly greater with adenosine than with dobutamine stress in control subjects and remote CFR. Ischemic CFR was blunted to a similar degree with each stressor. Therefore adenosine achieved flow heterogeneity across all coronary stenosis severities greater than 50%. However, dobutamine achieved flow heterogeneity only in the presence of a severe coronary stenosis greater than 75% despite provoking a greater ischemic stimulus. CONCLUSION: Adenosine stress demonstrated a higher sensitivity and dobutamine demonstrated a higher specificity with quantitative perfusion imaging. Therefore adenosine is superior for diagnostic perfusion imaging, whereas dobutamine is better suited in combination with visual imaging and in the functional assessment of a known coronary stenosis.     

Assessment of coronary flow reserve by sestamibi imaging in patients with typical chest pain and normal coronary arteries

Purpose We assessed coronary flow reserve (CFR) by sestamibi imaging in patients with typical chest pain, positive exercise stress test and normal coronary vessels. Methods Thirty-five patients with typical chest pain and normal angiogram and 12 control subjects with atypical chest pain underwent dipyridamole/rest ^99mTc-sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first transit counts in the pulmonary artery and myocardial counts from SPECT images. Estimated CFR was expressed as the ratio of stress to rest MBF. Rest MBF and CFR were corrected for rate–pressure product (RPP) and expressed as normalised MBF (MBF_n) and normalised CFR (CFR_n). Coronary vascular resistances (CVR) were calculated as the ratio between mean arterial pressure and estimated MBF. Results At rest, estimated MBF and MBF_n were lower in controls than in patients (0.98 ± 0.4 vs 1.30 ± 0.3 counts/pixel/s and 1.14 ± 0.5 vs 1.64 ± 0.6 counts/pixel/s, respectively, both p < 0.02). Stress MBF was not different between controls and patients (2.34 ± 0.8 vs 2.01 ± 0.7 counts/pixel/s, p=NS). Estimated CFR was 2.40 ± 0.3 in controls and 1.54 ± 0.3 in patients (p < 0.0001). After correction for the RPP, CFR_n was still higher in controls than in patients (2.1 ± 0.5 vs 1.29 ± 0.5, p < 0.0001). At baseline, CVR values were lower (p < 0.01) in patients than in controls. Dipyridamole-induced changes in CVR were greater (p < 0.0001) in controls (−63%) than in patients (−35%). In the overall study population, a significant correlation between dipyridamole-induced changes in CVR and CFR was observed (r = −0.88, p < 0.0001). Conclusion SPECT might represent a useful non-invasive method for assessing coronary vascular function in patients with angina and a normal coronary angiogram.     

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.     

Coronary calcium score scans for attenuation correction of quantitative PET/CT 13N-ammonia myocardial perfusion imaging

Purpose  

The aim of this study was to evaluate whether ECG-triggered coronary calcium scoring (CCS) scans can be used for attenuation correction (AC) to quantify myocardial blood flow (MBF) and coronary flow reserve (CFR) assessed by PET/CT with ¹³N-ammonia.     

Detection and quantification of coronary artery calcification with electron-beam and conventional CT

To identify patients with increased risk of having coronary artery disease (CAD), electron-beam computed tomography (EBCT) was used for years for quantifying calcifications of the coronary arteries. The first direct comparison between EBCT and conventional CT was performed to determine the reliability of widely available conventional CT for the assessment of the coronary calcium score. Fifty male patients with suspected CAD were investigated with both modalities, EBCT and conventional 500-ms non-spiral partial scan CT. Scoring of the coronary calcification was performed according to the Agatston method. Forty-two of these patients underwent coronary angiography for the assessment of significant luminal narrowing. The correlation coefficient of the score values of both modalities was highly significant (r = 0.982, p < 0.001). The variability between the two modalities was 42 %. Mean calcium score in patients with significant coronary luminal narrowing (n = 37) was 1104 ± 1089 with EBCT and 1229 ± 1327 with conventional CT. In patients without luminal narrowing (n = 5) mean calcium score was 73 ± 57 with EBCT and 26 ± 35 with conventional CT. Although images of the heart from conventional CT may suffer from cardiac motion artifacts, conventional CT has the potential to identify patients with CAD with accuracy similar to EBCT. Received: 13 July 1998; Revision received: 11 October 1998; Accepted: 14 October 1998     

Dobutamine 99mTc-MIBI single-photon emission tomography: non-exercise-dependent detection of haemodynamically significant coronary artery stenoses

Dobutamine pharmacological stress testing in conjunction with technetium-99m methoxyisobutylisonitrile single-photon emission tomography (MIBI SPET) may be a useful alternative to convential exercise stress MIBI SPET for the detection and localisation of coronary artery stenoses. Therefore, 35 patients with stenoses ( 50% diameter reduction) of one or more coronary arteries were selected for dobutamine MIBI SPET. Each patient underwent MIBI injection at rest and during dobutamine infusion with incremental doses (5, 10, 15 and 20 g kg^–1 min^–1). A conventional exercise stress test (EST) was performed in all patients. Peak double product during steady-state dobutamine infusion (18 200 ± 4200 mmHg min^–1) was lower (P = 0.0001) than during EST (21 700 ± 4900 mmHg min^–1). Image quality was good in all but one patient, who had to be excluded from data analysis due to excessive hepatobiliary MIBI activity. Dobutamine-induced perfusion abnormalities were observed in 30/34 MIBI SPET studies, resulting in an overall detection rate for coronary artery disease of 88%. A pathological EST was observed in 23/34 patients (68%). The detection rate of individual coronary artery stenoses was 85% (28/33) for stenosess with a severe diameter reduction (>70%) and 50% (12/24) for stenoses with a moderate diameter reduction ( 50–70%). In particular, sensitivity and specificity for the detection of moderate and severe stenoses ( 50%) were 75%/100% for left anterior descending, 67%/95% for left circumflex and 67%/69% for right coronary artery stenoses. Dobutamine MIBI SPET is a well-tolerated, non-exercise-dependent test for detection and localisation of haemodynamically significant coronary artery stenoses. The use of dobutamine allows a stepwise increase in pharmacological stress similar to EST and is especially useful in patients who are unable to exercise. Correspondence to: E. Voth     

Interobserver and interstudy variability of myocardial blood flow and flow-reserve measurements with nitrogen 13 ammonia-labeled positron emission tomography

Background  

Experimental studies have shown that positron emission tomography (PET) with ¹³N-labeled ammonia provides accurate quantification of regional myocardial blood flow (MBF) under rest and stress conditions. To establish the clinical utility of this method, the interobserver variability and the temporal variability of serial measurements of blood flow and coronary flow reserve (CFR) must be known. This study investigated the interobserver and temporal reproducibility of ¹³N-labeled PET for measurement of MBF and CFR.