M. G. Niemeyer

Comparison of adenosine and high-dose dipyridamole both combined with low-level exercise stress for 99Tcm-MIBI SPET myocardial perfusion imaging

SummaryIntravenously administered adenosine and high-dose dipyridamole, both combined with low-level exercise stress, were compared in a head-to-head fashion using 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) single photo emission tomography (SPET) myocardial perfusion imaging. Thirty-nine consecutive patients who had undergone coronary arteriography underwent 99Tcm-MIBI (740 Mbq) SPET after dipyridamole (0.84 mg kg-1) and after adenosine (0.84 mg kg-1), both combined with low-level exercise (30 W load), and under resting conditions. Our results demonstrate that adenosine and dipyridamole combined with exercise have comparable haemodynamic effects, with a low incidence of side-effects. The time of recovery from the stress protocol was not significantly different: adenosine, 5.7 ± 3.9 min; dipyridamole, 6.6 ± 4.9 min. However, aminophylline was significantly (P < 0.05) more often administered to reverse side-effects using the dipyridamole protocol (36% of patients) compared with the adenosine protocol (8% of patients). The results of 99Tcm-MIBI SPET imaging were highly concordant and demonstrated a high diagnostic accuracy for identifying coronary artery disease (CAD). The sensitivity was 90% (95% confidence intervals 79–100%) with adenosine SPET and 93% (95% confidence intervals 84–100%) with dipyridamole SPET for identifying patients with CAD (i.e. luminal stenosis > 50%); their specificities were both 100% (95% confidence intervals 66–100%). The sensitivity of identifying angiographically diseased vessels was 81% (95% confidence intervals 70–92%) using adenosine SPET and 85% (95% confidence intervals 75–95%) using dipyridamole; the specificity for both stress modalities was 94% (95% confidence intervals 89–100%). The combination of exercise with adenosine and high-dose dipyridamole appears to be a feasible and safe method to alleviate some of the undesirable Al -receptor-mediated side-effects of adenosine. The choice of the pharmacological stress will depend on local expertise and availability.

T-Channel-Selective Calcium Channel Blockade: A Promising Therapeutic Possibility, Only Preliminarily Tested So Far

Basic studies as well as short-term clinical trials of the T-channel-selective calcium channel blocker, mibefradil, are reviewed. The compound reduced afterload and was effective for the symptomatic treatment of hypertension and stable angina pectoris. It did not display any relevant negative inotropic or positive chronotropic effect. Mibefradil has been withdrawn by the manufacturer because of drug interaction at the cytochrome P-450 3A4 enzyme. It is hoped that new T-channel-selective calcium channel blockers will be developed to explore further this promising but so far only preliminarily tested therapeutic possibility.

The clinical impact of thallium-201 reinjection scintigraphy for detection of myocardial viability

In a clinical study, the value of thallium-201 reinjection was studied in 139 patients with suspected or known coronary artery disease who showed one or more persistent defects after conventional stress-redistribution imaging. Fifty-nine (42%) patients had sustained a Q-wave myocardial infarction. Sixty-eight (49%) patients showed a reversible defect in at least one myocardial segment at redistribution, while 71 (51%) had persistent defects only. Following reinjection additional segmental filling-in was seen in 95 (68%) patients, including 50 of the 68 (74%) patients with reversible defects and 45 of the 71(63%) with persistent defects only. On the immediately post-exercise images, 458 (47%) of 973 segments showed perfusion defects. At redistribution 105 (23%) of the 458 defects showed filling-in, whereas of the remaining 353 persistent defects 164 (46%) resolved additionally after reinjection. Thirteen (10%) of 133 Q-wave related defects showed filling-in at redistribution compared with 22 (27%) of 82 remote defects (P = 0.001). After reinjection additional filling-in of defects was seen in 47 (39%) of 120 Q-wave related defects compared with 35 (58%) or 60 remote defects (P = 0.015). Overall, 60 (45%) of 133 Q-wave related defects resolved compared with 57 (70%) of 82 remote defects (P = 0.005). Thus reinjection of thallium-201 (1) revealed reversible defects in 63% of patients with only persistent defects at redistribution, (2) demonstrated additional filling-in in 74% of patients who already showed reversible defects at redistribution, (3) showed viability in 46% of segments initially classified as persistent, and (4) demonstrated filling-in in 39% of Q-wave related segments, although this was less conspicuous than in remote segments.

99Tcm-SESTAMIBI for planar myocardial perfusion imaging; not as ideal as the physical properties

99Tcm-methoxyisobutyl isonitrile (Tc-SESTAMIBI) has recently been introduced as a new myocardial perfusion agent which exhibits ideal physical properties for imaging with the gamma camera. To assess the diagnostic accuracy of planar Tc-SESTAMIBI, myocardial perfusion imaging was performed in 60 consecutive patients at rest and during exercise. The results were compared with coronary angiographie findings, obtained within 3 months of the exercise test. Planar 201Tl images were also performed on the same day and to the same level of stress as the Tc-SESTAMIBI exercise. Exact segmentai agreement between Tc-SESTAMIBI and 201Tl was 77%. Nineteen per cent of all 900 segments demonstrated ischaemia with Tc-SESTAMIBI and 20% with 201Tl.The overall sensitivity for detecting haemodynamically significant coronary artery disease with Tc-SESTAMIBI was 86% and specificity was 78%; with 201Tl the values were 89 and 78%, respectively (differences not significant). Vessel-specific comparative detection rates revealed no statistical significant differences between both radiopharmaceuticals. Intra-observer variability for Tc-SESTAMIBI images was 12% and for 201Tl it was 14%. Inter-observer variability for Tc-SESTAMIBI was 14% and for 2O1T117%.Although the physical characteristics of Tc-SESTAMIBI allow crisp and clear high-count density imaging, no significant differences are found when planar images are compared with 201Tl and are well within observer variabilities.

Infarct sizing by scintigraphic techniques and nuclear magnetic resonance imaging

Assessment of myocardial infarct size is the cornerstone in the evaluation of interventions designed to salvage myocardium, such as thrombolytic therapy and urgent coronary angioplasty. Enzymatic methods have probably the highest accuracy but can only be used in the very early phase of infarction. The electrocardiogram allows a reasonable estimate of infarct size, but its confidence limits are wide, and in inferior wall infarction the estimates are unreliable. In recent years, radionuclide techniques have been successfully used to identify, localize and determine infarct size in the course of acute myocardial infarction. These scintigraphic measurements have provided important diagnostic, therapeutic and prognostic information based on the extent of myocardial damage. Nuclear magnetic resonance imaging, particularly with contrast enhancement, is one of the methods that have the greatest potential in accurately delineating myocardial infarct size. Nuclear medicine procedures, on the other hand, employ more biologically oriented tracers and offer promise in view of their ability to monitor biochemical alterations as an effect of therapy in the course of myocardial infarction.

Tc-99m tetrofosmin myocardial SPECT perfusion imaging: comparison of rest-stress and stress-rest protocols

Aim. The purpose of this study was to evaluate the diagnostic value of Tc-99m tetrofosmin SPECT myocardial perfusion scintigraphy rest/stress and stress/rest protocols for the assessment of coronary artery disease (CAD). Methods. 65 patients underwent both rest and stress SPECT imaging in a one-day protocol and coronary angiography within 2 months before or after scintigraphy. Scintigraphic data was obtained according to two different protocols; 1) rest-stress (n=18) and 2) stress-rest (n=47). Results. Scintigraphic evidence for myocardial ischaemia was found in 36 patients (55%). The overall sensitivity to detect CAD (>50% luminal stenosis) was 94% (34/36), specificity 66% (19/24), positive predictive value 77%, negative predictive value 90%. The sensitivity to detect CAD for protocols 1 and 2 were 100% and 93%, specificity 56% and 70%, positive predictive value 69% and 81% and negative predictive value 100% and 88%, respectively. The left anterior descending coronary artery showed a sensitivity (overall, protocol 1 & 2) of 78%, 75% (3/4) and 79% (15/19) and a specificity of 71%, 64% (9/14) and 75% (21/28). The right coronary artery showed a sensitivity (overall, protocol 1 & 2) of 91%, 100% (6/6) and 88% (14/16) and a specificity of 70%, 92% (11/12) and 61% (19/31). The left circumflex coronary artery showed a sensitivity (overall, protocol 1 & 2) of 50%, 67% (2/3) and 46% (6/13) and a specificity of 94%, 100% (15/15) and 91% (31/34). Conclusion. Tc-99m tetrofosmin appears to be a valuable tool in predicting significant CAD. The sensitivity and the positive predictive value are high, making this test highly appropriate for the diagnosis of CAD. The diagnostic value of the individual coronary arteries is high to moderate. No significant differences were found between both protocols.

Long-term efficacy of diltiazem controlled release versus metoprolol in patients with stable angina pectoris.

In a randomized, double-blind, multicenter study, the efficacy of diltiazem controlled-release (CR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 56 patients with stable exertional angina pectoris. Fifty-one patients (28 receiving diltiazem CR. 23 receiving metoprolol), completed a follow-up period of 8 weeks. Thirty-nine patients (20 receiving diltiazem CR. 19 receiving metoprolol). completed a follow-up period of 32 weeks. Maximal exercise testing was performed at baseline and after 8, 20, and 32 weeks of treatment. Most exercise parameters were not significantly different between the patients on diltiazem CR and those on metoprolol. However, exercise duration was longer and maximal work load was higher in patients on diltiazem CR than in patients on metoprolol, and significant differences were observed at 20 weeks of treatment (p = 0.006 and p = 0.008. respectively). At all times during treatment, heart rate at maximal exercise and rate-pressure product at maximal exercise were significantly lower in the patients treated with metoprolol. In conclusion, monotherapy with diltiazem CR is at least as effective as monotherapy with metoprolol in patients with stable angina pectoris. As compared to metoprolol, diltiazem CR has a minor depressing effect on rate-pressure product, resulting in a favorable effect on exercise duration.

Myocardial Imaging Using Thallium 201 Scintigraphy after Dipyridamole Infusion: A Case History

Coronary artery disease frequently occurs in combination with peripheral vascular disorders and is an important cause of morbidity and mortality during or after peripheral vascular surgery. However, the detection of coronary artery disease in patients with peripheral vascular disease may be complicated, since most of these patients are unable to perform conventional exercise testing. The authors report a sixty-two-year-old man with an infrarenally located aneurysm of the abdominal aorta who underwent thallium 201 scintigraphy combined with dipyridamole infusion as an alternative exercise test. The subsequent thallium 201 images showed perfusion defects indicative of severe coronary artery disease. Coronary angiography showed an occluded right coronary ar tery and a significant proximal stenosis in the left anterior descending coronary artery. The patient underwent successful aortocoronary bypass surgery, and two months later, the aortic aneurysm was operated on without complications. As a result, dipyridamole thallium 201 scintigraphy should be considered as a valuable diagnostic test to detect coronary artery disease in patients with pe ripheral vascular disorders.

99Tcm-sestamibi SPECT with combined dipyridamole and exercise stress in coronary artery disease

In order to evaluate the clinical value of 99Tcm-methoxyisobutylisonitrile (sestamibi) single photon emission computed tomography (SPECT) after dipyridamole infusion in combination with low level bicycle exercise for the assessment of the presence, localization and extent of coronary artery disease (CAD), myocardial perfusion imaging was performed in 76 patients. Low level bicycle exercise was used to supplement the standard dipyridamole infusion protocol because of the lower incidence of non-cardiac side effects. The results were compared to arteriographic findings obtained within 3 months of the SPHCT studies. The overall sensitivity of detection of coronary artery disease (i.e. a luminal stenosis >50%) was 81%, specificity 80%, positive predictive value 96%, negative predictive value 40% and accuracy 82%. The diagnostic values for the detection of significant stenoses in the three major coronary arteries were: left anterior descending artery sensitivity 72%, specificity 87% and accuracy 76%; right coronary artery sensitivity 75%, specificity 90% and accuracy 80%; left circumflex coronary artery sensitivity 57%, specificity 85% and accuracy 71%. Scintigraphic evidence of multivessel disease was found in 31 (65%) patients with two- or three-vessel involvement assessed by arteriography. False negative test results were mainly found in patients with relatively mild CAD (one-vessel disease, branch and distal disease). 99Tcm-sestamibi SPECT after dipyridamole infusion in combination with low level bicycle exercise is shown to be a valuable diagnostic tool for the evaluation of CAD.

Quantitative thallium-201 myocardial exercise scintigraphy in normal subjects and patients with normal coronary arteries

Quantitative thallium-201 myocardial exercise scintigraphy was tested in two patient populations representing alternative standards for cardiac normality: group I comprised 18 male uncatheterized patients with a low likelihood of coronary artery disease (CAD); group II contained 41 patients with normal coronary arteriograms. Group I patients were younger, they achieved a higher rate-pressure product than group II patients; all had normal findings by physical examination and electrocardiography at rest and exercise. Group II patients comprised 21 females, 11 patients showed abnormal electrocardiography at rest, and five patients showed ischemic ST depression during exercise. Twelve patients had signs of minimal CAD. Twelve patients revealed abnormal visual and quantitative thallium findings, three of these patients had minimal CAD. Profiles of uptake and washout of thallium-201 were derived from both patient groups, and compared with normal limits developed by Maddahi et al. Furthermore, low likelihood and angiographically normal patients may differ substantially, and both sets of normal patients should be considered when establishing criteria for abnormality in exercise thallium imaging. When commercial software containing normal limits for quantitative analysis of exercise thallium-201 imaging is used in clinical practice, it is mandatory to compare these with normal limits of uptake and washout of thallium-201, derived from the less heterogeneous group of low-likelihood subjects, which should be used in selecting a normal population to define normality.