Greater diagnostic sensitivity of treadmill versus cycle exercise testing of asymptomatic men with coronary artery disease.

Maximal hemodynamic and ventilatory responses using cycle and treadmill ergometer were compared in 52 asymptomatic patients with angiographically proved coronary artery disease. Moreover, test sensitivity with respect to ST-segment depression and typical angina pectoris were compared between exercise modes used. Exercise tests were performed on different days in randomized order. In 42 patients, exercise-induced myocardial ischemia, expressed as a fraction of left ventricular circumference, was assessed by thallium-201 scintigraphy. The main finding of this study was a significantly higher maximal oxygen uptake (1.87 +/- 0.4 vs 2.2 +/- 0.5 liters/min; p less than 0.001), heart rate (148 +/- 19 vs 158 +/- 18 beats/min; p less than 0.001) and rate-pressure product (28.3 +/- 5 x 10(3) vs 30.7 +/- 5 x 10(3); p less than 0.001) during treadmill walking than during cycling. Therefore, stress-induced myocardial ischemia was significantly more extensive after treadmill walking (31 +/- 37 degrees vs 45 +/- 40 degrees; p less than 0.001). Moreover, there were significantly more patients with signs of myocardial ischemia (ST-segment depression or typical angina pectoris, or both) during treadmill than during cycle ergometry (35 vs 25 patients; p less than 0.05). However, lactate levels measured at peak exercise (4.07 +/- 2.0 vs 4.38 +/- 1.9 mmol/liter) and 3 minutes into the recovery period (5.60 +/- 2.2 vs 5.80 +/- 2.2 mmol/liter) were comparable between both methods, indicating no significant difference in anaerobic energy production. These findings suggest that walking on a treadmill represents an exercise method with a greater ability than cycling to detect coronary artery disease.     

Myocardial scintigraphy with Tc-99m-teboroxime: its feasibility and the evaluation of its diagnostic reliability. A comparison with thallium-201 and coronary angiography]

BACKGROUND. Tc-99m-teboroxime is a new tracer for myocardial perfusion scintigraphy. Its more remarkable features are the high myocardial extraction fraction, which is well correlated with the coronary blood flow, and the extremely rapid myocardial washout. This makes it necessary to complete the image collection shortly after the injection; on the other hand, repeated scans can be easily performed by renewed Tc-99m-teboroxime administrations. The aim of the present study was to test the feasibility of Tc-99m-teboroxime imaging and to evaluate its accuracy by comparing it with thallium-201 (TI-201) scintigraphy and coronary angiography. METHODS. The patient population included 16 male patients (mean age 57.8 +/- 6.3 years) affected by suspect effort angina and/or with signs of exercise-induced ischemia; 12 of them had history of previous myocardial infarction. They underwent effort TI-201 and Tc-99m-teboroxime myocardial scintigraphy within 48 hours; left heart catheterization and coronary angiography were performed within 5 days. Scintigraphic images were collected in 3 planar views; each projection was divided in 3 segments, with the apical one shared by all views, for a total of 7 segments/study. Tracer uptake was qualitatively assessed and graduated according to a scoring scheme (from 0 = normal through 4 = absent uptake). RESULTS. Tc-99m-teboroxime scans could be accomplished without major problems in all subjects. The image quality was comparable to TI-201 in 8 patients and poorer in the remaining 8. Coronary angiography showed 50% obstructions in 15 patients; of them 1 subject had a normal scintigraphic pattern with both TI-201 and Tc-99m-teboroxime. The presence of previous infarction was recognized by both tracers in the 12 patients with infarct history. The number of abnormal segments and the uptake score were not significantly different in the Tc-99m-teboroxime rest and in the TI-201 redistribution images (segments: 2.8 +/- 1.4 vs 2.8 +/- 1.6; score: 5.6 +/- 4.2 vs 6 +/- 4.5). The diagnosis of effort ischemia was made in 13 patients with Tc-99m-teboroxime and in 12 patients with TI-201. The number of abnormal segments in the exercise Tc-99m-teboroxime and TI-201 myocardial scintigraphy was not significantly different (3.3 +/- 1.3 vs 3.3 +/- 1.5); on the contrary the defect score was significantly higher with Tc-99m-teboroxime than with TI-201 (9.5 +/- 4.3 vs 8.4 +/- 4.6, p < 0.03). Therefore the ischemic score (exercise defect score minus rest defect score) of Tc-99m-teboroxime was significantly higher than that of TI-201 (3.9 +/- 2.8 vs 2.4 +/- 2.2, p < 0.02). The two tracers gave comparable results in terms of recognition of patients with one-vessel or multi-vessel coronary artery disease. CONCLUSIONS. Planar myocardial scintigraphy with Tc-99m-teboroxime can be performed without major problems. In terms of clinical reliability the results are comparable to those of TI-201 scans. On the other hand, taking into account the poor image quality of Tc-99m-teboroxime scintigraphy, it is still impossible to predict its future role in the radionuclide imaging of coronary artery disease.     

Quantitative analysis of thallium-201 uptake and washout before and after transluminal coronary angioplasty

Transluminal coronary angioplasty has become an important therapeutic modality in the treatment of coronary artery disease. The effects of coronary angioplasty on regional myocardial perfusion have been reported in only a small series of patients, employing subjective analysis of thallium-201 perfusion scintigrams. Thus, we studied 61 patients with quantitative analysis of thallium-201 uptake and washout before and after undergoing angioplasty. Prior to angioplasty, there were 105 areas in 47 patients with abnormal thallium-201 uptake during exercise, with a mean uptake of 49 +/- 1.3%. The uptake of thallium-201 in these same areas increased to 71.3 +/- 1.9% post angioplasty (P less than 0.0001), and 68 (65%) of the areas showing abnormal uptake returned to normal. Abnormalities in washout of thallium-201 before angioplasty were seen more frequently than in uptake (150 vs 105 areas, P less than 0.05), with 8 patients having abnormal washout in the presence of totally normal uptake. Thallium-201 washout in the abnormal areas improved from 16 +/- 2.8 pre angioplasty to -23 +/- 1.8% post angioplasty (P less than 0.001). Normalization resulted in 6 of the 8 patients with exclusively washout abnormality. Residual abnormalities in uptake and/or washout were seen in 53% of the patients, usually in areas with prior myocardial infarction or supplied by a vessel with significant stenosis which did not undergo angioplasty. Improved thallium-201 uptake and washout corresponded to reductions in percent coronary area stenosis (89 +/- 1.0 to 36 +/- 2.0%, P less than 0.001) and transstenotic pressure gradient (42 +/- 3.0 to 9.0 +/- 2.0 mm Hg, P less than 0.001). Thus, quantitative analysis of thallium-201 uptake and washout provided objective evidence for improved myocardial perfusion after coronary angioplasty. Due to a fairly high prevalence of residual perfusion abnormalities after this procedure, optimal assessment of benefits requires quantitative comparison of thallium uptake and washout before and after coronary angioplasty.     

Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia

The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 [69 to 304] mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and "usual medical care" was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress.     

Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy

BACKGROUND. Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. METHODS AND RESULTS. Fifty patients with hypertrophic cardiomyopathy underwent exercise 201Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more 201Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial 201Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible 201Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing (myocardial lactate extraction of 0 mmol/l or less) compared with four of 13 patients (31%) with normal 201Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only 201Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal 201Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of 201Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible 201Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible 201Tl abnormalities, and 55% had pacing-induced ischemia. CONCLUSIONS. Reversible 201Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium. In contrast, ST segment changes with exercise and systolic compression of coronary arteries on angiography are unreliable markers of inducible myocardial ischemia in hypertrophic cardiomyopathy. Apparent cavity dilatation during 201Tl scintigraphy may indicate ischemia-related changes in left ventricular filling, with elevation in diastolic pressures and endocardial compression.     

Exercise myocardial perfusion scintigraphy with technetium-99m methoxy isobutylisonitrile: a comparative study with thallium-201

The evaluation of technetium-99m methoxy isobutylisonitrile for the diagnosis of coronary artery disease requires comparative validation against thallium-201, the established perfusion imaging agent. We have compared myocardial and lung uptake of both radiotracers following maximal exercise in 52 patients: 40 with angiographically proven coronary disease. Qualitative and quantitative image analysis showed the diagnostic sensitivity of technetium-99m methoxy isobutylisonitrile to compare favourably with that of thallium-201 as reflected by the mean number of ischaemic segments identified: 5.6 +/- 2.5 vs 4.8 +/- 2.1 by qualitative analysis, and 5.7 +/- 3.2 vs 5.0 +/- 2.6 segments by quantitative analysis. More reversibly ischaemic segments per patient were identified with technetium-99m methoxy isobutylisonitrile than with thallium-201: 3.6 +/- 2.3 vs 1.8 +/- 1.9. There was a higher exercise myocardial to background count ratio with technetium-99m methoxy isobutylisonitrile: 3.16:1 vs 2.58:1, and the mean exercise lung uptake normalised to left ventricular uptake ('lung index'), was lower for technetium-99m methoxy isobutylisonitrile than for thallium-201 (36 +/- 8% vs 40 +/- 10%). Five of the six patients with abnormal elevation of the thallium-201 exercise lung index also had elevation of the technetium-99m methoxy isobutylisonitrile exercise lung index, and all had extensive coronary artery disease. These results indicate that technetium-99m methoxy isobutylisonitrile is at least as effective as thallium-201 for detecting exercise induced myocardial ischaemia. However, technetium-99m methoxy isobutylisonitrile provides a better image quality and may be a more sensitive marker of defect reversibility. For both radiotracers lung uptake is increased with extensive coronary artery disease and measurement of this variable provides prognostic information.     

Spectrum of exercise thallium-201 myocardial perfusion imaging in patients with chest pain and normal coronary angiograms.

Twenty-seven consecutive patients with chest pain and no significant obstructive coronary lesions on arteriography were studied with thallium-201 myocardial imaging during exercise and at rest. Fifteen of the patients had typical and 12 atypical angina pectoris. All underwent treadmill exercise electrocardiographic testing; the results were abnormal in 10 patients (37 percent), normal in 14 (52 percent) and uninterpretable in 3 (11 percent). The exercise and resting thallium-201 myocardial images were normal in 23 patients (85 percent); the results of exercise testing were normal in 12 of these patients, abnormal in 8 and uninterpretable in 3. Four patients had a perfusion defect on exercise thallium-201 myocardial imaging; the defect filled in by 4 hours in two patients but persisted in the other two. In contrast, when thallium-201 myocardial imaging was performed in 28 consecutive patients with angiographic coronary artery disease, only 5 patients (16 percent) had normal exercise and resting thallium-201 myocardial images. Therefore, thallium-201 myocardial imaging offers a more effective means of identifying patients with chest pain and no obstructive coronary artery disease than the clinical history or the exercise electrocardiographic test, or both. However, 15 percent of these patients will have abnormal exercise thallium-201 myocardial images because of factors that have not yet been identified.     

Prognostic value of dipyridamole thallium-201 imaging in elderly patients.

The prognostic value of intravenous dipyridamole myocardial perfusion imaging has not been studied in a large series of elderly patients. Patients greater than or equal to 70 years of age with known or suspected coronary artery disease were evaluated to determine the predictive value of intravenous dipyridamole thallium-201 imaging for subsequent cardiac death or nonfatal myocardial infarction. Of the 348 patients, 207 were symptomatic and 141 were asymptomatic; 52% of the asymptomatic group had documented coronary artery disease. During 23 +/- 15 months of follow-up, there were 52 cardiac deaths, 24 nonfatal myocardial infarctions and 42 revascularization procedures (percutaneous transluminal coronary angioplasty in 20; coronary artery bypass surgery in 22). Clinical univariate predictors of a cardiac event included previous myocardial infarction, congestive heart failure symptoms, hypercholesterolemia and diabetes (all p less than 0.05). The presence of a fixed, reversible or combined thallium-201 defect was significantly associated with the occurrence of cardiac death or myocardial infarction during follow-up (p less than 0.05). Cardiac death or nonfatal myocardial infarction occurred in only 7 (5%) of 150 patients with a normal dipyridamole thallium-201 study (p less than 0.001). Stepwise logistic regression analysis of clinical and radionuclide variables revealed that an abnormal (reversible or fixed) dipyridamole thallium-201 study was the single best predictor of cardiac events (relative risk 7.2, p less than 0.001). As has been demonstrated in younger patients, previous myocardial infarction (relative risk 1.8, p less than 0.001) and symptoms of congestive heart failure at presentation (relative risk 1.6, p = 0.02) were also significant independent clinical predictors of cardiac death or myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thallium-201 myocardial scintigraphy in patients with Wolff-Parkinson-White syndrome

Wolff-Parkinson-White syndrome (WPW) is known to cause abnormal rest electrocardiogram and stress test. Thallium-201 myocardial scintigraphy has been particularly indicated for the noninvasive evaluation of coronary artery disease in these patients. The study group consisted of 11 WPW patients with abnormal ST-segment depression at rest electrocardiogram and/or stress test, with the absence of signs or symptoms of coronary artery disease. All the patients underwent exercise thallium-201 imaging associated with stress test by bicycle ergometer: 7 of them had ST-segment depression, but without other signs or symptoms of coronary artery disease. Transient and moderate myocardial perfusion defects were found in 5 of 11 patients. Perfusion defects in patients with WPW could derive from dyssynergy of ventricular activation, which could modify myocardial perfusion scintigraphy despite the absence of angiographic coronary stenosis. Previous reports and our data concluded that transient perfusion defects during exercise thallium-201 testing in WPW patients without cardiovascular disease may be observed. Thus, thallium-201 myocardial scintigraphy could present some limitations as a helpful adjunctive method for assessment of coronary artery disease in WPW patients.     

Myocardial bridging of the left anterior descending artery: Evaluation using exercise thallium-201 myocardial scintigraphy

Seven patients with myocardial bridging of the left anterior descending coronary artery were evaluated by means of thallium-201 exercise scintigraphy. The degree of systolic narrowing was 60–70% in five patients and 75–80% in two patients. All patients had presented with chest pain. The resting electrocardiogram was normal in six patients; there were ST segment and T-wave abnormalities in one patient. No patient complained of chest pain during exercise. The exercise electrocardiogram was negative in six patients and inconclusive in one patient. Exercise myocardial scans were negative in all seven patients. We conclude that no evidence of ischemia was demonstrated in patients with myocardial bridging of the left anterior descending coronary artery as determined by exercise electrocardiography and stress thallium-201 scintigraphy.     

Use of exercise thallium-201 imaging for risk stratification of elderly patients with coronary artery disease

Although coronary artery disease (CAD) may be asymptomatic, it is the most common cause of death in elderly patients in the U.S. This study examined the prognosis of 449 patients with a mean age of 65 years using exercise thallium-201 imaging. At a follow-up of 25 months, 45 patients underwent coronary artery revascularization, 8 died of cardiac causes and 10 had nonfatal acute myocardial infarctions (AMIs). Thus the total of patients with "hard" events was 18. The events included 12 of 276 patients with atypical or non-anginal symptoms versus 6 of 128 with typical angina (p = not significant); 7 of 51 patients (14%) with Q-wave AMI versus 11 of 353 (3%) without Q-wave AMI (p less than 0.001); 1 of 183 patients (1%) with normal versus 17 of 221 (8%) with abnormal exercise thallium-201 images (p less than 0.002); 10 of 76 patients (13%) with multi vessel thallium-201 abnormality vs 8 of 328 (2%) with no or 1-vessel thallium-201 abnormality (p less than 0.001) and 10 of 96 patients (10%) with greater than or equal to 3 abnormal segments by thallium-201 imaging (total segments = 9) versus 8 of 308 patients with no or less than 3 abnormal segments (p less than 0.001). The number of segments with thallium-201 defects was 1 +/- 2 patients without and 3 +/- 2 in patients with hard events (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nicardipine improves myocardial perfusion in systemic sclerosis

Primary scleroderma myocardial disease may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. We evaluated the effect of the calcium channel blocker nicardipine on myocardial perfusion assessed by thallium-201 scanning in 16 patients with systemic sclerosis. Thallium-201 single photon emission computerized tomography was performed at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SD) number of left ventricular segments with perfusion defects significantly decreased from 6.0 +/- 2.0 at baseline to 4.1 +/- 2.3 after nicardipine (p less than 0.01). The mean global perfusion score significantly increased from 10.2 +/- 1.9 at baseline to 11.9 +/- 2.6 after nicardipine (p less than 0.02). Our study demonstrates short-term improvement in thallium-201 myocardial perfusion with nicardipine in patients with systemic sclerosis.     

Merits of stress thallium-201 myocardial perfusion imaging in patients with inconclusive exercise electrocardiograms: Correlation with coronary arteriograms

Stress thallium-201 myocardial perfusion images were obtained in 65 patients with an inconclusive exercise electrocardiogram. All 65 patients underwent coronary angiographic studies. The exercise electrocardiogram was judged inconclusive in 35 patients (54 percent) because submaximal exercise had been performed and in 30 patients (46 percent) who manifested ST-T segment abnormalities at rest. Exercise thallium-201 myocardial perfusion images were abnormal in 20 patients and normal in 45. Nineteen (95 percent) of the 20 patients with abnormal exercise images had severe disease of one or more major coronary arteries. Thirty-seven (82 percent) of the 45 patients with normal exercise images had no significant coronary artery disease; the remaining 8 patients had coronary artery disease. Therefore, 19 of 27 patients with coronary artery disease had abnormal exercise images (sensitivity 70 percent), and 37 of 38 patients without coronary artery disease had normal exercise images (specificity 97 percent). Thallium-201 imaging predicted the correct diagnosis in 56 patients (86 percent). Thus, exercise myocardial imaging with thallium-201 appears to be a useful diagnostic aid in patients with an inconclusive exercise electrocardiogram.     

Prognostic value of exercise thallium scintigraphy in patients with good exercise tolerance and a normal or abnormal exercise electrocardiogram and suspected or confirmed coronary artery disease.

Exercise thallium scintigraphy is widely used to assess prognosis in patients with suspected or proven coronary artery disease. The incremental prognostic value of this technique in patients who have good exercise tolerance has not been well studied. Two hundred ninety-nine patients with known or suspected coronary artery disease without prior myocardial infarction or revascularization procedure referred for exercise myocardial perfusion imaging and able to exercise to greater than or equal to stage III of the Bruce protocol were included. After a mean follow-up of 50 +/- 10 months, there were 15 cardiac events (5%). The incidence of cardiac events was 10 versus 3% (p less than 0.001) in patients with an abnormal versus normal thallium-201 scan, and 9 versus 3% (p = 0.03) for an abnormal versus normal exercise electrocardiogram. When the 185 patients with a normal exercise electrocardiogram were examined, the incidence of cardiac events was 3% (5 of 150) in patients with a normal scan versus 0% (0 of 35) in patients with an abnormal scan. In the 114 patients with an abnormal exercise electrocardiogram, an abnormal thallium-201 scan was predictive of cardiac events (18% [8 of 44] versus 3% [2 of 70]; p = 0.006). Stepwise logistic regression analysis selected an abnormal thallium-201 scan and abnormal exercise electrocardiogram, low peak exercise heart rate, and male gender as independent variables associated with a significant increased risk of cardiac events. Thus, in patients with known or suspected coronary artery disease and good exercise tolerance, the addition of thallium-201 imaging in patients with an abnormal exercise electrocardiogram provides useful prognostic information.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recommendations for the use of LDL apheresis

Plasma exchange has been shown to increase life-expectancy in homozygous familial hypercholesterolaemia (FH) but increasingly is being replaced by LDL apheresis. Several methods are now available for undertaking this procedure, which lowers LDL cholesterol and Lp(a) efficiently and safely when performed weekly or bi-weekly and causes only slight decreases in HDL cholesterol. Hitherto the main clinical indication has been homozygous FH, including children and pregnant women, but there are limited data showing that LDL apheresis has effects on the progression of cardiovascular disease in FH heterozygotes which are similar to those of maximal lipid-lowering drug therapy. Hence it has the potential to be beneficial in hypercholesterolaemic patients with overt coronary disease who are refractory to or intolerant of drugs. It is therefore recommended that LDL apheresis should be the treatment of choice for: (1) all FH homozygotes from the age of seven onwards unless their serum cholesterol can be reduced by >50% and/or decreased to 5.0mmol/l or is decreased by <40% with maximal drug therapy. Apheresis may also occasionally be indicated on a case-by-case basis for patients with lower levels of LDL. (3) LDL apheresis should also be considered for patients with aggressive progressing coronary disease and Lp(a)>60mg/l whose LDL cholesterol remains >3.2mmol/l despite maximal drug therapy.     

Prognostic value of dipyridamole thallium-201 scintigraphy in patients with stable chest pain.

The usefulness of dipyridamole testing with planar thallium-201 scintigraphy for assessing risk of subsequent cardiac events was evaluated in 373 patients with stable chest pain. Follow-up information was complete in 362 patients (mean age 64 +/- 9 years). During an average follow-up period of 18 months, cardiac events occurred in 59 patients--unstable angina in 27, nonfatal acute myocardial infarction in 11, and death from cardiac causes in 21. A history of previous myocardial infarction, congestive heart failure, or coronary bypass surgery before the study, or the presence of an abnormal scan or one with a fixed perfusion defect was associated with a significantly increased frequency of subsequent cardiac events (p less than 0.05). However, the presence of a reversible perfusion defect was not associated with increased risk (p = 0.1872). Stepwise logistic regression showed that a history of coronary artery bypass surgery before the study and the presence of a fixed perfusion defect were the only variables with independent predictive value for occurrence of a subsequent cardiac event (p less than 0.05). Survival analysis revealed a significantly increased cardiac event rate in patients with abnormal scans compared with those with normal scans over a 30-month follow-up period (p less than 0.01). We conclude that dipyridamole testing with thallium-201 scintigraphy can provide prognostic information concerning risk of future cardiac events in patients with stable chest pain. The presence of a fixed perfusion defect in particular identifies patients at increased risk.     

Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels

OBJECTIVES: We sought to evaluate whether pravastatin treatment increases myocardial perfusion, as assessed by thallium-201 single-photon emission computed tomographic (SPECT) dipyridamole testing, in patients with coronary artery disease (CAD) and average cholesterol levels. BACKGROUND: Previous studies in hypercholesterolemic patients have demonstrated that cholesterol reduction restores peripheral and coronary endothelium-dependent vasodilation and increases myocardial perfusion. METHODS: This was a randomized, placebo-controlled study with a cross-over design. Twenty patients with CAD were randomly assigned to receive 20 mg of pravastatin or placebo for 16 weeks and then were crossed over to the opposite medication for a further 16 weeks. Lipid and lipoprotein analysis and dipyridamole thallium-201 SPECT were performed at the end of each period. The SPECT images were visually analyzed in eight myocardial segments using a 4-point scoring system by two independent observers. A summed stress score and a summed rest score were obtained for each patient. Quantitative evaluation was performed by the Cedars-Sinai method. The magnitude of the defect was expressed as a percentage of global myocardial perfusion. RESULTS: Total and low density lipoprotein cholesterol levels during placebo were 214 +/- 29 mg/dl and 148 +/- 25 mg/dl, respectively. These levels with pravastatin were 170 +/- 23 mg/dl and 103 +/- 23 mg/dl, respectively. The summed stress score and summed rest score were lower with pravastatin than with placebo (7.2 +/- 2.3 vs. 5.9 +/- 2.3, p = 0.012 and 3.2 +/- 1.6 vs. 2.4 +/- 2.2, p = 0.043, respectively). Quantitative analysis showed a smaller perfusion defect with pravastatin (29.2%) as compared with placebo (33.8%) (p = 0.021) during dipyridamole stress. No differences were found at rest. CONCLUSIONS: Reducing cholesterol levels with pravastatin in patients with CAD improves myocardial perfusion during dipyridamole stress thallium-201 SPECT.     

Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia

OBJECTIVES: The present study evaluates the impact of total cholesterol (TC) and its subfractions on coronary flow reserve (CFR), an index of the integrated function of the coronary circulation, in asymptomatic subjects. BACKGROUND: Endothelial dysfunction of the coronary microcirculation has been reported in asymptomatic subjects with hypercholesterolemia. METHODS: Using oxygen-15-labeled water and positron emission tomography, myocardial blood flow (MBF, in ml/min per g) was measured at rest and during intravenous adenosine (140 microg/kg body weight per min) in 80 asymptomatic nonsmoking men: group 1 (n = 61; age 45 +/- 7 years) had normal TC (< or =6.5 mmol/liter or < or =250 mg/dl) and group 2 (n = 19; age 48 +/- 10 years) had elevated TC. RESULTS: Total cholesterol were 5.1 +/- 0.8 and 7.2 +/- 0.7 mmol/liter in groups 1 and 2 (p < 0.0005), respectively; low density lipoprotein (LDL) cholesterol levels were 3.2 +/- 0.8 and 4.9 +/- 0.7 mmol/liter (p < 0.0005); high density lipoprotein (HDL) cholesterol levels were 1.1 +/- 0.3 and 1.0 +/- 0.4 mmol/liter (p = NS); and triglyceride levels were 1.8 +/- 1.3 and 3.0 +/- 1.8 mmol/liter (p < 0.005). Groups 1 and 2 did not differ with regard to MBF at rest (0.87 +/- 0.14 vs. 0.84 +/- 0.14), MBF during adenosine (3.63 +/- 1.02 vs. 3.30 +/- 0.86) or CFR (4.23 +/-1.29 vs. 3.95 +/- 0.93). A significant but weak correlation was found between CFR and HDL in group 1 (r = 0.29, p < 0.05), but not in group 2. In contrast, a significant inverse correlation between LDL and CFR was found in group 2 (r = -0.61, p < 0.05), but not in group 1. CONCLUSIONS: Low density lipoprotein cholesterol but not TC correlated inversely with CFR in hypercholesterolemic subjects. Thus, LDL-induced coronary microvascular dysfunction could play an important role in the pathogenesis of coronary artery disease and its complications.     

Beta-methyl-15-P-[123I] iodophenyl-pentadecanoic acid and thallium-201 in the assessment of myocardial perfusion defects

The purpose of this investigation was to examine the ability of beta-methyl-15-P-[123I]-iodophenyl-pentadecanoic acid (beta 123IPPA) and thallium-201 to assess the ischemic risk zone associated with myocardial infarction. The hearts of mongrel dogs were infarcted by ligating the left anterior descending coronary artery and at 6 h post infarction injected with thallium-201 (2 mCi; scanning time 30 mins) followed by beta 123IPPA (3 to 5 mCi; scanning time 30 mins). Scintigraphic assessment of the perfusion defect yielded perfusion defect size (percentage of whole slice), which was then compared to the defect when assessed by tetrazolium staining. Myocardial ratios were calculated to assess differences in localization between tracers. Any differences noted may affect identification of the area at risk following acute myocardial infarction. A slice-by-slice comparison of perfusion defect size for scintigraphic methods and histochemical method showed no significant difference between beta 123IPPA and thallium-201. The mean ratio for myocardial defect size expressed as beta 123IPPA/thallium-201 was 1.03 +/- 1.29. Enzymatic analysis demonstrated significant increases in creatine kinase (160.33 +/- 46.44 to 5030.6 +/- 2238 U) and creatine kinase-MB% (31.85 +/- 15.11 to 82.99 +/- 8.14%) post infarction (P less than 0.05 in both cases). Elevated ST segments were also seen in all dogs post infarction. It can be concluded that the combined use of beta 123IPPA and thallium-201 does not allow the identification of the ischemic risk zone (percentage area at risk) often associated with myocardial perfusion defects. Problems continue to exist with image resolution and border demarcation.     

Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity.

Recent evidence suggests that high-density lipoprotein (HDL) cholesterol has important vasoactive properties which may contribute to its beneficial effects on atherosclerotic coronary artery disease. The endothelium-dependent vasodilator acetylcholine has been used in a number of experimental studies to assess endothelial function. The relation between serum lipoproteins and acetylcholine-induced coronary vasoreactivity was investigated in patients (n = 27) undergoing elective coronary arteriography. Mean serum cholesterol, low-density lipoprotein cholesterol, HDL cholesterol and triglyceride levels were 189 +/- 7 (4.84 +/- 0.18 mmol/liter), 134 +/- 6 (3.47 +/- 0.15 mmol/liter), 41 +/- 3 (1.06 +/- 0.08 mmol/liter) and 106 +/- 30 mg/dl (1.20 +/- 0.03 mmol/liter), respectively. After a baseline arteriogram, acetylcholine was infused into the left main coronary artery and percent change from baseline dimension was determined in 27 angiographically smooth coronary artery segments and in 14 arterial segments with evidence of mild atherosclerotic disease. Intact vascular smooth muscle function was then confirmed in all segments by dilation to intracoronary nitroglycerin. Acetylcholine produced significant vasoconstriction of both angiographically smooth (13 +/- 4%, p less than 0.05 vs baseline) and diseased (19 +/- 4%, p less than 0.05 vs baseline) coronary segments. A positive correlation was observed between HDL cholesterol and normal acetylcholine-induced coronary vasoreactivity in both angiographically smooth (r = 0.59, p less than 0.001) and diseased (r = 0.62, p less than 0.02) coronary segments. No significant correlation was observed, however, between total and low-density lipoprotein cholesterol, or between total cholesterol to HDL ratio and the response of coronary artery diameter to acetylcholine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)