Regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing: a comparison with stress echocardiography and perfusion scintigraphy.

OBJECTIVES: We evaluated regional diastolic function by pulsed Doppler myocardial mapping for the detection of left ventricular ischemia during pharmacologic stress testing. BACKGROUND: Evaluation and quantification of diastolic myocardial function remain a challenge for imaging techniques in stress tests. METHODS: A prospective study compared the detection of coronary artery stenosis: 1) by pulsed Doppler myocardial mapping, 2) by two-dimensional echocardiographic dobutamine stress test, and 3) by perfusion scintigraphy in 64 patients using coronary angiography for reference. An age matched subgroup of 10 patients with normal angiograms and two-dimensional echocardiographic stress test served as control group. Peak myocardial contraction velocity (Vc) and lengthening rate during early diastolic left ventricular (LV) filling (VE) were measured in 12 LV segments from three apical views. RESULTS: In controls, myocardial velocities increased during stress by > or =3.6 cm/s (p < 0.001). In LV segments depending on a stenosed artery (n = 70), VE decreased by > or =1 cm/s and, thus, was different from control segments (n = 112, p < 0.001) and from scar segments (n = 13, p < 0.01), whereas the change of Vc was similar to that in scar segments. A stress induced 2 cm/s reduction of VE discerned the best diagnostic accuracy (sensitivity 84%, specificity 93%) in comparison with two-dimensional echocardiography (78% and 71%) and perfusion scintigraphy (61% and 86%). Using receiver operating curves at incremental levels of luminal narrowing, these relations persisted. CONCLUSIONS: Quantification of diastolic myocardial function by pulsed Doppler myocardial mapping during dobutamine stress test was shown to be a feasible, accurate, reproducible, noninvasive technique that should be considered to be a sensitive alternative to the present echocardiographic and scintigraphic imaging techniques for stress tests.

Early recovery of coronary flow reserve after stent implantation as assessed by positron emission tomography.

OBJECTIVES: The aim of this study was to quantitatively evaluate myocardial flow reserve in patients early after coronary stent implantation using positron emission tomography. BACKGROUND: Delayed restoration of coronary flow reserve after percutaneous transluminal coronary angioplasty (PTCA) has been observed using a variety of techniques. Altered distal vasoregulation as well as residual stenosis have been considered possible explanations for this phenomenon. Although the implantation of stents may influence some of these mechanisms, little data are available characterizing coronary flow reserve early after stent placement. METHODS: In 14 patients 1.6 +/- 0.6 days after stenting, N-13-ammonia positron emission tomographic studies were performed at rest and during adenosine-induced vasodilation. Myocardial blood flow was quantified using a three-compartment model. Rest and stress flow data, as well as coronary flow reserve of stented vascular territories, were compared with that of remote areas. RESULTS: The stenosis decreased from 72.1 +/- 7.3% to 3.7 +/- 6.7% after stent implantation. Coronary flow in the stented areas did not differ significantly from that in remote areas either at rest (76.1 +/- 18.5 and 75.7 +/- 17.7 ml/min/100 g, respectively), or during maximal vasodilation (205.5 +/- 59.9 and 179.4 +/- 47.4 ml/min/100 g, respectively). In addition, there was no significant difference in the calculated values of coronary reserve of these two regions (2.74 +/- 0.64 and 2.43 +/- 0.55, respectively). CONCLUSIONS: The mechanical support of dilated arteries by a stent not only restores the macroscopic integrity of epicardial arteries, but also results, in contrast to conventional PTCA procedures, in early recovery of flow reserve.

Myocardial perfusion scintigraphy to evaluate patients after coronary stent implantation.

UNLABELLED: Coronary stent implantation is an increasingly accepted revascularization method. The 20%-30% restenosis rate during the first 6 mo requires a close follow-up of the patients. Since there is very little data available defining the role of perfusion scintigraphy in the management of this population, the aim of this study was to assess the diagnostic performance of stress myocardial perfusion imaging for detecting restenosis in patients after coronary stent implantation. METHODS: In 82 patients, 93 rest or stress SPECT studies were performed using 201Tl and 99mTc-hexakis-2-methoxyisobutyl isonitrile to evaluate 99 vascular territories with implanted coronary stents. The average interval between the stent implantation and the scintigraphic study was 210.5 +/- 129.6 days. The scintiscans were visually evaluated. A stress-induced perfusion defect with reversibility at rest was used as the criterion for stent restenosis. RESULTS: Coronary angiography revealed a stenosis of > 50% diameter in the region of the stent in 19 arteries, while in 80 arteries there was no evidence of restenosis angiographically. With perfusion scintigraphy, 15/19 vascular territories with restenosed stents showed stress-induced perfusion abnormalities (sensitivity = 79%), while 62/80 territories without restenosis did not (specificity = 78%). In territories without a myocardial infarction (n = 48), sensitivity and specificity values were 8/8 (100%) and 36/44 (82%), and in territories with a myocardial infarction (n = 47) 7/11 (64%) and 26/36 (72%), respectively. Side branch stenosis was fairly frequent in patients without stent restenosis but with a reversible perfusion pattern on their scintiscan (8/18); however, these stenoses were induced infrequently by the stents (3 cases). CONCLUSION: Using the criterion of defect reversibility, stress perfusion SPECT can accurately detect restenoses of coronary artery stents. This method is most accurate for evaluating patients without a previous myocardial infarction in the stented vascular territory.

Regional myocardial wall thickening and global ejection fraction in patients with low angiographic left ventricular ejection fraction assessed by visual and quantitative resting ECG-gated 99mTc-tetrofosmin single-photon emission tomography and magnetic resonance imaging.

We investigated the use of visual and quantitative technetium 99m tetrofosmin ECG-gated single-photon emission tomography (SPET) for the assessment of regional myocardial wall thickening (WT) and left ventricular (LV) ejection fraction (EF) in comparison with gated magnetic resonance imaging (MRI) in patients with a low angiographic LVEF. Gated SPET using 99mTc-labelled flow tracers offers potential for simultaneous assessment of myocardial perfusion and LV function. Few data are available on the use of visual and quantitative gated SPET in patients with low LVEF. In this study 21 patients with low angiographic LVEF (mean 37%+/-5%) were studied. Resting gated 99mTc-tetrofosmin SPET and gated MRI were performed within 48 h. WT was assessed by visual interpretation (five point score) and quantitative analysis based on count increase. There was good agreement for EF measurements by MRI and gated SPET (mean EF: 33%+/-12% vs 35%+/-11%, r = 0.86, P<0.001). Areas under receiver operator characteristic curves (AUC) for differentiation between MRI WT score points ranged from 0.60 to 0.66 for visual SPET WT analysis, from 0.59 to 0.71 for delta count increase values and from 0.46 to 0.60 for % WT, indicating substantial overlap between WT categories. Absolute agreement for visual WT between MRI and gated SPET ranged from 25% to 57% (kappa 0.03-0.25) depending on tracer uptake, and was limited in areas with moderate to severe perfusion defects (kappa 0.03-0.13). It is concluded that gated SPET provided reliable estimates of regional WT and global function in patients with low angiographic LVEF.

Perfusion-contraction mismatch during inotropic stimulation in hibernating myocardium.

UNLABELLED: The aims of this study were to assess the value of dobutamine echocardiography in identifying myocardial hibernation versus stunning and to elucidate the underlying pathophysiological mechanism of the contractile impairment. METHODS: Twenty-one patients with isolated stenosis of the left anterior descending artery were evaluated 1 mo after thrombolysed acute anterior infarction. Regional function and blood flow were measured using echocardiography and PET at rest and during dobutamine administration (10 microg/kg/min). RESULTS: Defined by [18F]fluorodeoxyglucose uptake, 36 of 102 dyssynergic segments were necrotic, and 66 were viable. The latter segments were subdivided according to their [13N]ammonia flow distribution: 30 hibernating regions with perfusion defects (flow of <80% of maximum) and 36 stunned areas with preserved resting perfusion (flow of > or =80% of maximum). Resting flows were similar in necrosis and hibernation (0.43 +/- 0.18 versus 0.47 +/- 0.16 ml x min(-1) x g(-1); not significant), and both resting values were lower than those seen in stunning (0.79 +/- 0.24; p < 0.05). Flow response to dobutamine was markedly reduced in necrosis (dobutamine/resting flow = 1.16 +/- 0.27), whereas it was maintained in hibernation (1.65 +/- 0.54) and stunning (1.42 +/- 0.57). Dobutamine improved function in a higher number of stunned (55%) than hibernating (16%) or necrotic (11%) segments. CONCLUSION: Dobutamine improves function mainly in stunned myocardium and does not reliably identify hibernation. The lack of functional response in hibernation is not related to an exhausted vasodilating capacity.

Homogeneously reduced versus regionally impaired myocardial blood flow in hypertensive patients: two different patterns of myocardial perfusion associated with degree of hypertrophy.

OBJECTIVES: The aim of this study was to quantitatively measure regional and global myocardial blood flow and coronary reserve in hypertensive patients without coronary artery disease and to assess the correlation with left ventricular mass. BACKGROUND: The effect of left ventricular hypertrophy on regional vasodilating coronary capability in arterial hypertension is controversial, and no quantitative method has been applied to assess a possible correlation. METHODS: Positron emission tomography was performed in 50 untreated hypertensive patients and 13 normotensive subjects. Blood flow at baseline and after dipyridamole was globally and regionally measured by using nitrogen-13 ammonia; coronary reserve and resistance were calculated. Left ventricular mass was assessed by two-dimensional echocardiography. RESULTS: In hypertensive patients, flow at baseline was similar to that of normotensive subjects (p = 0.21), but values were reduced after pharmacologic vasodilation (p < 0.05). This impairment of maximal coronary flow was not correlated with left ventricular mass (p = 0.13). Among hypertensive patients, we identified a group with a homogeneous distribution of perfusion and a group with a heterogeneous flow pattern. Flow was globally reduced in the former group, but it was abnormal only at the site of perfusion defects in the latter. Patients with regional defects showed the highest likelihood of having an increased left ventricular mass. CONCLUSIONS: In arterial hypertension, left ventricular mass is not correlated with global myocardial blood flow. Nevertheless, patients with ventricular hypertrophy are likely to show a heterogeneous flow pattern with regional defects and almost normal blood flow in nonaffected regions. In hypertensive patients with a homogeneous perfusion pattern during stress, myocardial blood flow frequently shows a diffuse reduction.

Coronary vasoconstriction during myocardial ischemia induced by rises in metabolic demand in patients with coronary artery disease.

BACKGROUND: In patients with coronary artery disease, a maximal vasodilation of the coronary microcirculation is generally assumed to occur during myocardial ischemia induced by rises in metabolic demand. However, vasoconstriction has been documented during severe prolonged ischemia in animals. The aim of this study was to investigate coronary vasomotor tone during pacing-induced ischemia in humans. METHODS AND RESULTS: The study included 11 patients with exercise-induced ischemia and single-vessel disease of the left anterior descending artery and 7 control subjects with normal coronary arteries. Blood flow velocity was monitored with a Doppler catheter in the left anterior descending artery. Coronary resistance index was calculated as the ratio between mean arterial pressure and flow velocity. Measurements were obtained at baseline, after intracoronary adenosine (2 mg), and during maximal atrial pacing in the absence and presence of adenosine. After adenosine administration at rest, coronary resistance decreased more in control subjects than in patients (25 +/- 7% of baseline versus 61 +/- 19%; P < .01). Coronary resistance decreased in all control subjects (P < .01) both at maximal pacing (60 +/- 17% of baseline) and after administration of adenosine during tachycardia (31 +/- 13% of baseline). By contrast, all 10 ischemic patients displayed increased coronary resistance at maximal heart rate (221 +/- 131% of baseline; P < .01 versus baseline, P < .01 versus control subjects). At this stage, adenosine decreased coronary resistance to 44 +/- 20% of values observed before injection. Additionally, it reduced ST-segment depression in 5 of 8 patients. CONCLUSIONS: In patients with coronary artery disease, transient myocardial ischemia induced by increased metabolic demand is not associated with maximal vasodilation. Rather, an inappropriate severe microvascular vasoconstriction is present that can be abolished by intracoronary adenosine.

Assessment of tissue viability with fluorine-18-fluoro-2-deoxyglucose (FDG) and carbon-11-acetate PET imaging.

Positron emission tomography allows noninvasive assessment of myocardial metabolic processes and perfusion. Myocardial F-18-2 deoxyglucose (FDG) uptake as assessed by PET imaging has been established as a metabolic tracer indicating myocardial viability, whereas N-13 ammonia uptake reflects myocardial perfusion. Furthermore, it has been shown that the clearance of C-11-acetate in normal and ischemic myocardium correlates closely with overall myocardial oxygen consumption (MVO2). Therefore, C-11-acetate PET imaging has been proposed as a tracer for myocardial viability. In contrast with myocardial FDG uptake, the clearance of C-11-acetate is independent from overall substrate utilization. In the present time the highly expensive PET studies should only be performed in patients with chronic advanced coronary artery disease resulting in severely impaired left ventricular function. Moreover, coronary anatomy has to be suitable for revascularization and there has to be an absence of reversible perfusion abnormalities on Tl-201-chloride reinjection SPECT scans. This review focuses on clinical studies employing C-11-acetate and FDG PET imaging in patients with advanced chronic coronary artery disease, acute myocardial infarction and after heart transplantation. Clinical applications of FDG and C-11-acetate PET imaging and prognosis of PET flow-metabolic imaging regarding recovery of myocardial function and clinical outcome after revascularization and thrombolytic therapy are summarized. Furthermore, PET results are compared to SPECT imaging with Tl-201 and Tc-99m-MIBI.

[The effect of acute cellular rejection on liver function following orthoptic liver transplantation. Quantitative functional studies with the 14C-aminopyrine breath test]. / Einfluss der akuten zellulären Abstossung auf die Leberfunktion nach orthotoper Lebertransplantation. Quantitative Funktionsuntersuchungen mit dem 14C-Aminopyrin-Atemtest.

To test the effect of acute cellular rejection on liver function as represented by cytochrome-P-450 enzyme activity, the 14C-aminopyrine breath test (ABT) was performed prospectively in 46 patients (31 men, 15 women; mean age 48 [15-66] years) who had undergone a total of 50 orthotopic liver transplantations. Routine biochemical tests were performed daily until the 30th postoperative day, while the ABT was done daily on days 1-10 and three times weekly on days 11-30, and liver puncture biopsies were obtained once weekly or more often if there was clinical suspicion of rejection. Histologically confirmed cellular rejection occurred within the stated period of observation in eight patients (five women, three men; median age 45 [18-59] years). Results of routine laboratory tests (transaminases, bilirubin, thromboplastin time), as well as bile-flow and body temperature, did not vary uniformly. On the other hand, results of ABT at the time of rejection showed a decrease in all patients by an average of 65% (P < 0.01). Changes in the ABT preceded those in other tests by 1-2 days in four patients, being the only measurable functional abnormality in one. All rejection episodes responded to glucocorticoid pulse-treatment (three times 1 g methyl-prednisolone). Using ABT results as criterion, liver function became normal after the glucocorticoid injection within 4-11 days. These data indicate that the ABT is suitable in the routine monitoring of transplant function, thus facilitating early diagnosis and controlled treatment of acute cellular rejection.

Direct evidence of a functional separation of alloreactive T lymphocytes from bystander cells infiltrating rat allografts. Interleukin 2 receptor-positive cells reacting with the monoclonal antibody ART 18 mediating second-set rejection.

In this study we examined the functional capacity of unseparated, IL-2R positive and IL-2R negative leukocytes infiltrating BN rat hearts or kidneys grafted into allogeneic LEW rats. Upon adoptive transfer into syngeneic LEW recipients, splenocytes or day-3 graft infiltrate cells of either cardiac or renal transplants were ineffective to alter BN cardiac test graft survival (controls 7.8 +/- 0.8 day). However, adoptive transfer of day-5 heart infiltrate cells resulted in a delay of test graft rejection (9.4 +/- 0.7 day, P less than 0.001), while day-5 kidney-graft-infiltrating cells produced second set rejection (6.2 +/- 0.5, P less than 0.001). Specificity controls of day-5 cells infiltrating DA heart or kidney grafts rejected at 7.8 +/- 0.8 or 7.7 +/- 0.5 days. Following separation into IL-2R positive and negative subpopulations by use of the mAB ART 18, IL-2R positive but not IL-2R negative cells caused second set rejection in both the renal and the cardiac model (6.2 +/- 0.4, respectively, 6.3 +/- 0.5 days, P less than 0.001 or P less than 0.005). Furthermore, in the kidney model IL-2R positive nylon-wool nonadherent cells also caused second set rejection (6.2 +/- 0.4, P less than 0.005) suggesting that IL-2R positive T cells present in the graft at maximal infiltration are the mediators of rejection. Thus, it appears that these cells can be phenotypically and functionally separated from bystander cells.