Localization of epileptic foci with postictal single photon emission computed tomography.

Effective surgical treatment of patients with intractable complex partial seizures depends on accurate preoperative seizure focus localization. We evaluated seizure localization with interictal and immediate postictal single photon emission computed tomographic images of cerebral perfusion using technetium-99m-hexamethyl-propyleneamineoxime (99mTc-HMPAO) in comparison with conventional ictal electroencephalographic (EEG) localization. Thirty-two patients with intractable complex partial seizures were studied. The mean delay from seizure onset to injection was 6.3 +/- 5.3 (SD) minutes. Independent blinded observers assessed the scans for interictal hypoperfusion and postictal focal hyperperfusion. Interictal scans alone were unreliable, indicating the correct localization in 17 patients (53%) and an incorrect site in 3 (9%). When interictal and postictal scans were interpreted together, the focus was correctly localized in 23 patients (72%). There was 1 false-positive study, and 8 patients had inconclusive changes, including 2 with inconclusive depth EEG studies. Postictal hyperperfusion was predominantly mesial temporal and frequently associated with hypoperfusion of lateral temporal cortex. Secondarily generalized seizures tended to show focal hyperperfusion less often than complex partial seizures did (Fisher's exact test p = 0.09). Combined interictal and immediate postictal single photon emission computed tomography with 99mTc-HMPAO is a useful noninvasive technique for independent confirmation of electrographic seizure localization. It may provide a suitable alternative to the use of depth electrode studies for confirmation of surface EEG findings in many patients with complex partial seizures.

Silent myocardial ischemia in asymptomatic survivors of unrecognized myocardial infarction and matched controls.

Although silent myocardial ischemia (SI) occurs frequently in patients with angina and is of prognostic significance, little is known of its occurrence in other subgroups. We assessed the incidence of SI in offspring of Framingham Heart Study (FHS) patients following unrecognized myocardial infarction (UMI) and in controls without MI but who were matched for age, sex, hypertension, diabetes, smoking, and total cholesterol at entry into the FHS. Of the 20 UMI patients, six had died and one with left bundle branch block was excluded. The remaining 13 UMI patients and 26 control patients underwent 24-hour ambulatory electrocardiographic monitoring (AECG) for SI. Two patients (one from each group) with angina were excluded from the AECG analysis. Only two (15.4%) of the UMI patients and two (7.7%) of the control patients had any AECG evidence of SI. These preliminary results suggest that routine monitoring for SI is not indicated in asymptomatic long-term survivors of UMI or in asymptomatic patients without prior MI but with otherwise similar risk profiles.

Costs and effectiveness of routine therapy with long-term beta-adrenergic antagonists after acute myocardial infarction.

We analyzed the costs and effectiveness of routine therapy with beta-adrenergic antagonists in patients who survived an acute myocardial infarction. On the basis of data pooled from the literature, this form of therapy resulted in a 25 percent relative reduction annually in the mortality rate for years 1 to 3 and a 7 percent relative reduction for years 4 to 6 after a myocardial infarction. The estimated cost of six years of routine beta-adrenergic-antagonist therapy to save an additional year of life was $23,400 in low-risk patients, $5,900 in medium-risk patients, and $3,600 in high-risk patients, assuming that the entire benefit of earlier treatment is lost immediately after six years. Under a more likely assumption--that the benefit of six years of treatment wears off gradually over the subsequent nine years--the estimated cost of therapy per year of life saved would be $13,000 in low-risk patients, $3,600 in medium-risk patients, and $2,400 in high-risk patients. As compared with coronary-artery bypass grafting and the medical treatment of hypertension, routine beta-adrenergic-antagonist therapy has a relatively favorable cost-effectiveness ratio.

The utilization of technetium-99m CPI as a myocardial perfusion imaging agent in exercise studies.

Myocardial perfusion imaging with Tc-99m carbomethoxyisopropylisonitrile (CPI) was compared with Tl-201 imaging in 22 patients who were assessed for coronary artery disease. There was agreement between Tc-99m CPI and Tl-201 imaging for detecting segmental myocardial ischemia and fixed defects in 185/198 (93%) of left ventricular segments. There was also an excellent correlation between the two tracers for the detection of coronary artery disease (18/22 patients). Myocardial clearance of the isonitrile complex was slow, and there was no redistribution into ischemic regions; the normal to ischemic myocardial ratio remained relatively constant over time. Reinjection at rest was used to distinguish transient ischemia from infarction. The isonitrile complex was excreted rapidly via the hepatobiliary system. After 3 hours, background activity was reduced to about 20% of the initial activity. Tc-99m CPI appears comparable to Tl-201 thallous chloride for detecting coronary artery disease. Tc-99m CPI may be useful as a myocardial imaging agent because there is no myocardial redistribution, myocardial clearance is slow, and clearance from background tissues is rapid.

Myocardial imaging with technetium-99m CPI: initial experience in the human.

The hexakis(isonitrile)technetium(I) analog [99mTc]carbomethoxyisopropyl isonitrile (CPI) has high myocardial uptake and rapid lung and liver clearance in most animal species. To evaluate [99mTc]CPI as a myocardial imaging agent in the human, we evaluated this tracer in three normals and in six patients with coronary artery disease (CAD). In normals, [99mTc]CPI cleared quickly from the lungs and accumulated in the liver and heart. The liver activity peaked at 10-15 min and cleared through the hepatobiliary system. Planar images were of excellent technical quality with high myocardial to background ratios as early as 10 min after injection. Myocardial activity fell gradually to 76.1 +/- 2.9 (s.d.)% of initial activity by 60 min after injection. In six patients with CAD, myocardial defects were present on planar images up to 2 hr after exercise and injection. In one out of six patients, the defect was not seen 3 hr after injection. In five of the six patients, normal perfusion patterns were observed 1 hr after reinjection of CPI at rest (4 hr after the initial injection). In one patient who developed spontaneous angina prior to reinjection, the perfusion defects persisted. The repeat study 3 days later with injection of [99mTc]CPI at rest was normal. Technetium-99m CPI appears to have excellent physical and biologic properties for use in association with myocardial imaging with exercise.

Perhexiline maleate treatment for severe angina pectoris--correlations with pharmacokinetics.

Perhexiline maleate, which causes inhibition of myocardial fatty acid catabolism with a concomitant increase in glucose utilization, is particularly useful in the management of patients with severe angina pectoris. While perhexiline exerts no significant negative inotropic or dromotropic effects, its short- and long-term use has hitherto been restricted because of complex pharmacokinetics and the eventual development, in many patients, of hepatitis and peripheral neuropathy. Correlations between perhexiline dose, plasma drug concentrations, efficacy and development of toxicity were examined prospectively in 3 groups of patients. The first group (n = 29) were patients in whom perhexiline was added to previously prescribed anti-anginal medication for short-term (pre-surgical or post-myocardial infarction) control of angina pectoris. Over a mean treatment period of 18 +/- 2 (SEM) days, 13 patients experienced a marked reduction in frequency and severity of attacks. No adverse effects occurred. A second group of patients (n = 19) were treated chronically with 50-400 mg/day of perhexiline, dosage being adjusted to minimize symptoms. Over a mean treatment period of 8.8 +/- 1.7 months, 5 patients became asymptomatic, while 9 developed evidence of hepatitis or neurotoxicity, with concomitant plasma perhexiline concentrations of 720-2680 ng/ml. Subsequently, a further group of similar patients (n = 22) were treated for 12.4 +/- 2.6 months, perhexiline dosage being adjusted to maintain plasma perhexiline concentrations below 600 ng/ml. Nine patients became asymptomatic, while none developed adverse effects. It is concluded that perhexiline is useful both as a short-term adjunct to anti-anginal therapy and in the long-term management of patients unsuitable for coronary artery bypass grafting. The risk of long-term toxicity can be reduced markedly by maintenance of plasma drug concentrations below 600 ng/ml without significantly compromising anti-anginal efficacy.

Nuclear scanning in the diagnosis and localization of parathyroid adenomas.

Technetium-thallium nuclear scanning was performed in 17 patients whose clinical and biochemical findings were suggestive of the presence of hyperparathyroidism. An adenoma was located by scanning in 12 patients. Ten of these 12 patients underwent surgery; the scan had located the adenoma correctly in all these patients. One patient with a negative result of a scan examination subsequently had an adenoma removed at operation. Thyroid pathology interfered with the interpretation of the scan. This technique is recommended as a useful preoperative procedure for the detection of parathyroid adenomas, and its role in the rapid evaluation of hypercalcaemia seems promising. A prospective study to compare the sensitivity and specificity of this technique with computerized tomographic scanning and ultrasound is warranted.

Short-term myocardial uptake of lidocaine and mexiletine in patients with ischemic heart disease.

Determination of short-term myocardial drug uptake and subsequent redistribution was performed in 27 patients with ischemic heart disease for the antiarrhythmic agents lidocaine and mexiletine, using frequent simultaneous measurements of drug concentration in aortic and coronary sinus blood, combined with measurement of coronary sinus blood flow after intravenous bolus injection of the drug. Maximal myocardial drug content per unit resting coronary sinus blood flow (MDC:F) was significantly greater in patients in whom coronary sinus pacing at 100 beat/min was performed during the initial period of drug uptake. Maximal myocardial drug content occurred after 2.4 +/- 0.2 (SEM) for lidocaine and after 5.5 +/- 0.6 min for mexiletine (p less than .001), and pacing did not affect time to maximum myocardial drug content. In nonpaced, but not paced, patients maximal MDC:F was greater in the lidocaine group than that in the mexiletine group. The subsequent efflux of lidocaine from the myocardium was more rapid that that of mexiletine in both paced and nonpaced groups.

Usefulness of early exercise testing after non-Q-wave myocardial infarction in predicting prognosis.

The value of an early symptom-limited maximal exercise test in predicting coronary anatomy, left ventricular ejection fraction and hemodynamics was assessed prospectively in 64 patients after an acute non-Q-wave myocardial infarction (MI). Exercise tests and cardiac catheterization were performed at a median of 6 and 7 days, respectively, after non-Q MI. Forty-one percent of the patients had a negative exercise test response (no angina, less than 1 mm of ST depression and normal blood pressure responses). Twenty-five percent had a positive response (1 to 1.9 mm of ST depression or angina); 34% had a "strongly positive" exercise test response (at least 2 mm of ST depression or abnormal blood pressure responses). A negative response predicted the absence of 3-vessel disease (at least 70% stenosis) or critical stenoses (at least 90% stenosis) involving major coronary arteries (negative predictive accuracy 92%), whereas a strongly positive response predicted their presence (positive predictive value 77%, specificity 88%). Cardiac index and mean pulmonary artery wedge pressure did not vary significantly among the 3 exercise groups, whereas left ventricular ejection fraction was slightly higher in the exercise test group with a positive response (p less than 0.025). Thus, in patients who have had a non-Q MI, early exercise testing can be used to predict the extent and severity of coronary artery disease, and the decision to perform coronary angiography should be guided by the exercise test results.

The utilization of Tc-99m-TBI as a myocardial perfusion agent in exercise studies: comparison with Tl-201 thallous chloride and examination of its biodistribution in humans.

Twenty-four patients were studied with both 201Tl-thallous chloride and 99mTc-TBI scintigraphy following exercise. Comparison of the two agents in detecting segmental myocardial ischemia and scar was made in 18 patients with evidence of coronary artery disease on 201Tl-thallous chloride scintigraphy. Agreement between the two studies was observed in 77% (125 of 162) of left ventricular segments, suggesting that 99mTc-TBI can be used as a myocardial perfusion agent. Limitations were related to early high background activity from lungs and liver. The high lung activity and early myocardial redistribution within the 1st hour contributed to the failure of 99mTc-TBI to detect 16 segmental defects seen in the immediate post-exercise thallous chloride scan. Persistently high liver activity additionally affected accurate interpretation in the left ventricular segments close to the diaphragm. Improvement in the accuracy of 99mTc-TBI stress studies might be achieved with tomographic imaging to reduce the problem of background activity or by the development of 99mTc-labeled isonitrile analogues with rapid lung and liver clearance.

Aggravation of myocardial ischaemia by nifedipine.

Three cases in which myocardial ischaemia was possibly precipitated by the administration of nifedipine are reported. It is suggested that the initial administration of nifedipine should be undertaken with caution in patients with unstable ischaemic heart disease.