The quality of life of patients on the lung transplantation waiting list.

INTRODUCTION: Lung transplantation (LTx) candidates present incapacitating symptoms related to their mobility and activities of daily living, thereby affecting their work, social and emotional relations, and quality of life (QoL). OBJECTIVE: To study the QoL of LTx candidates, seeking to identify domains that suffer the greatest impact and verify if there are differences among these impairments according to the original lung disease. METHODS: We applied the Short Form-36 questionnaires and St George's Respiratory Questionnaire (SGRQ). All data were analyzed by one-way analysis of variance and the Kruskal Wallis test for the probability with significance at P < 0.05. RESULTS: Fifty patients were divided into groups of emphysema (n = 16), bronchiectasis (n = 12), idiopathic pulmonary fibrosis (n = 7), and cystic fibrosis (n = 15). The functional capacity, physical aspects, general status, and vitality domains showed average values below 50 points. The cystic fibrosis group showed higher functional capacity scores (46 +/- 23) than the emphysema (12 +/- 13) or idiopathic pulmonary fibrosis cohort (7 +/- 5). The limitation caused by pain affected the bronchiectasis more than the cystic fibrosis group (52 +/- 28 vs 81 +/- 25, respectively). The SGRQ scores showed impairment among all groups in all domains with average values over 50. The activities domain shows the highest score value; the emphysema (92 +/- 10) and idiopathic pulmonary fibrosis cohorts (91 +/- 9) were extremely affected compared with the cystic fibrosis (69 +/- 21) and bronchiectasis subjects (79 +/- 16). The impact domain show that subjects with cystic fibrosis were less emotionally affected by the disease. CONCLUSION: LTx candidates showed great impairment of their QoL due to their health problems, above all in the physical-functional aspects; the cystic fibrosis patients were the least affected by their health status.

Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation.

AIM: Based upon a microarray assay, we have identified that triiodothyronine (T3) upregulates MDM2 gene expression in the rat skeletal muscle. As MDM2 protein is an E3 ligase, we hypothesized that this enzyme could play a role in T3 effects on skeletal muscle mass control. METHODS: To test our hypothesis, male rats (2 months old) were randomly assigned into the following groups: intact controls, treated with 20 physiological doses of T3 for 0.5, 1 and 7 days, or with 5, 20 and 50 physiological doses of T3 for 7 days. For in vitro experiments, myotubes and C2C12 cells were treated with T3 for 3 days. RESULTS: After validation of the microarray finding throughout RT-PCR and confirmation that T3 induces increases in MDM2 protein expression in a dose-dependent manner, we observed that MDM2 was upregulated by T3 exclusively in fibre type I. Moreover, detailed histological evaluation showed that MDM2 overexpression distributes punctiformily along the cross section of the fibre and also inside nuclei. MDM2 colocalizes with PAX7 in control muscle and T3 downregulates this myogenic factor. Pharmacological inhibition of MDM2 in cultured myotubes caused a severe decrease in their diameter (~35%, P < .001 vs Control), enhancing the effect of T3 (from ~12% to ~35%, P < .001) alone upon myotube diameter and mRNA levels of atrogenes. Finally, we observed that FOXO3 (MDM2 target) is kept outside the nucleus under T3 stimulation. CONCLUSION: Our results indicate that MDM2 might be involved in the pro-trophic effects of T3 in skeletal muscle.

Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.

Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

Comparison of physiologic ejection fraction responses to activities of daily living: implications for clinical testing.

The recent development of the VEST, an ambulatory radionuclide detector, to measure left ventricular ejection fraction may enhance the detection of ischemia during daily activities in patients with coronary artery disease. The normal range and determinants of ejection fraction responses to stimuli other than physical exercise, however, are not adequately characterized. Therefore, ejection fraction responses to various activities were measured in 18 normal subjects utilizing the VEST. Uniform increases (greater than 5%) in ejection fraction were seen during physical exercise, uniform decreases were seen during cold pressor testing and modest changes (including decreases greater than 5%) were seen in ejection fraction during mental stress, micturition and hyperventilation. Different forms of stress produced significantly different changes in ejection fraction, even when values were controlled for changes in heart rate. Ventricular loading conditions in the form of enhanced blood pressure responses during mental stress may have contributed to the relatively smaller changes in ejection fraction compared with those during exercise. Subjects demonstrating a decrease in ejection fraction during mental stress did not differ from other subjects in hemodynamic reactivity during mental testing but did have evidence of increased parasympathetic tone during cold pressor and bicycle exercise testing. The results reveal that normal ejection fraction response differs among varying physiologic stimuli. These changes are in part related to changes in heart rate and blood pressure; however, other factors, such as neurohumoral regulation, may also play a role. These findings indicate that the patient's activity and the setting in which it occurs must be considered when interpreting ambulatory ejection fraction responses.

Late reversibility of tomographic myocardial thallium-201 defects: an accurate marker of myocardial viability.

Twenty-one patients were studied who underwent thallium-201 stress-redistribution single photon emission computed tomography (SPECT) both before and after coronary artery bypass grafting (n = 15) or transluminal coronary angioplasty (n = 6). All patients underwent thallium imaging 15 min, 4 h and late (18 to 72 h) after stress as part of the preintervention thallium-201 scintigram. In a total of 201 tomographic myocardial segments with definite post-stress thallium-201 perfusion defects in which the relevant coronary arteries were subsequently successfully reperfused, the 4 h redistribution images did not predict the postintervention scintigraphic improvement: 67 (85%) of the 79 4 h reversible as well as 88 (72%) of the 122 4 h nonreversible segments improved (p = NS). The 18 to 72 h late redistribution images effectively subcategorized the 4 h nonreversible segments with respect to postintervention scintigraphic improvement: 70 (95%) of the 74 late reversible segments improved after intervention, whereas only 18 (37%) of the 48 late nonreversible segments improved (p less than 0.0001). The frequency of late reversible defects and the frequency of postrevascularization improvement of late nonreversible defects are probably overestimated by this study because of referral biases. The cardiac counts and target to background ratios from late redistribution studies resulted in satisfactory cardiac images for visual interpretation. For optimal assessment of the extent of viable myocardium by thallium-201 scintigraphic studies, late redistribution imaging should be performed when nonreversible defects are observed on 4 h redistribution images.

Analysis of the degree of pulmonary thallium washout after exercise in patients with coronary artery disease.

An abnormal increase in pulmonary thallium activity may be visualized on post-stress thallium images in patients with coronary artery disease. Because this increased pulmonary thallium activity usually disappears by the time of redistribution imaging, this study was designed to assess whether measurement of the degree of pulmonary thallium washout between stress and redistribution might improve the detection of increased pulmonary thallium activity in patients with coronary artery disease. Quantitative analysis revealed abnormal (that is, greater than 2 standard deviations of normal values) pulmonary thallium washouts in 59 (64%) of 92 patients with coronary artery disease, but in only 2 (25%) of 8 subjects with angiographically normal arteries (p less than 0.06). By comparison, the visual analysis of pulmonary thallium washout and use of initial pulmonary to myocardial thallium ratio were significantly (p less than 0.05) less sensitive in detecting abnormality in patients with coronary artery disease. Abnormal pulmonary thallium washout was related to both the anatomic extent and functional severity of disease: it occurred with greatest frequency in patients with multivessel disease and in those with exercise-induced left ventricular dysfunction (p less than 0.005). When added to the quantitative analysis of myocardial scintigraphy, the analysis of pulmonary thallium washout increased the detection of coronary artery disease from 84 to 93% (p less than 0.05), but the sample size was too small to assess specificity. Thus, the analysis of pulmonary thallium washout is a useful diagnostic variable because it: 1) provides an objective measurement of abnormal pulmonary thallium activity and is more sensitive than other methods; 2) correlates with both the extent of coronary artery disease and the degree of exercise-induced left ventricular dysfunction, and 3) improves the sensitivity of quantitative myocardial thallium scintigraphy to detect the presence of coronary artery disease.

Effect of beta-blockade on low heart rate-related ischemia during mental stress.

To explore the effect of beta-adrenergic blockade on low heart rate-related (mental stress) ischemia, 19 patients with coronary artery disease were randomized into a double-blind crossover trial of metoprolol, 100 mg twice daily, and underwent serial mental stress/bicycle exercise studies. Mental stress-induced wall motion abnormalities occurred at a lower heart rate than exercise-induced wall motion abnormalities during placebo administration (81 +/- 16 vs. 123 +/- 20 beats/min, p less than 0.05). Metoprolol reduced the mean magnitude of exercise-induced wall motion abnormalities (2.8 +/- 2.0 vs. 1.6 +/- 2.4, p = 0.003); improvement was related to the magnitude of hemodynamic beta-blockade effect. Metoprolol did not significantly reduce the mean magnitude of mental stress-induced wall motion abnormalities (3.0 +/- 2.2 vs. 2.6 +/- 2.2), although individual responses predominantly either improved (50%) or worsened (29%). Unlike exercise, the magnitude of hemodynamic beta-blockade did not predict mental stress response and metoprolol did not block mental stress-induced blood pressure elevations. Patients with abolition of exercise-induced ischemia were more likely to have reduction of mental stress-induced ischemia. Patients whose ischemia worsened with metoprolol during mental stress had more easily inducible ischemia, as assessed by exercise-induced placebo wall motion abnormality, chest pain and prior myocardial infarction. Beta-blockade was associated with a lowering of ischemia-related hemodynamic thresholds compared with placebo. These results suggest that beta-blockade has a variable effect on low heart rate-related ischemia that may be due to a lack of effect on mental stress-induced blood pressure elevation in patients with easily induced ischemia or to effects on coronary vasomotor tone, or both.

Reversal of rest myocardial asynergy during exercise: a radionuclide scintigraphic study.

UNLABELLED: While exercise-induced segmental left ventricular wall motion abnormalities are well described, the phenomenon of improvement in certain asynergic segments during exercise in some patients remains a curiosity. To assess this unexpected finding, results were analyzed in 85 patients with wall motion abnormalities at rest who underwent two view (45 degrees left anterior oblique and anterior) exercise radionuclide ventriculography and exercise thallium-201 myocardial perfusion imaging. Wall motion was scored with a 5 point system (from 3 [normal] to - 1 [dyskinesia]); normalization or increase of 2 or more points with exercise signified improvement. Forty-eight patients (56%) had no change or further deterioration of wall motion at peak exercise, 15 (18%) showed both improvement of wall motion and deterioration and 22 (26%) showed only improvement of wall motion. Wall motion improvement during exercise was found in 57 (20%) of 279 segments with asynergy at rest. Of these 57 segments improving with exercise, 45 (79%) showed mild and 12 (21%) showed severe asynergy at rest. Only seven segments (12%) were associated with pathologic Q waves. Thallium-201 perfusion was normal in 44 segments (77%) while only 6 segments (11%) had reversible and only 7 (12%) had nonreversible thallium-201 defects. IN CONCLUSION: 1) wall motion that is abnormal at rest can sometimes improve with exercise; 2) this phenomenon generally occurs in zones without a Q wave or nonreversible thallium-201 defect. Hence, segments with abnormal wall motion at rest that show improvement with exercise appear to represent viable nonischemic segments.

Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with suspected coronary artery disease.

The ability of exercise-induced myocardial hypoperfusion on thallium scintigraphy to predict coronary events was assessed in 1,689 patients with symptoms suggestive of coronary artery disease but without prior myocardial infarction or coronary artery bypass surgery. A total of 74 patients had a coronary event in the year after testing (12 cardiac deaths, 20 nonfatal infarctions and 42 referrals for bypass surgery more than 60 days after testing). Stepwise logistic regression identified only three independent predictors: the number of myocardial regions with reversible hypoperfusion (an index of the extent of hypoperfusion), the maximal magnitude of hypoperfusion (an index of the severity of hypoperfusion) and the achieved heart rate (an index of exercise performance). Both extent and severity were exponentially correlated with event rate (r greater than 0.97 and p less than 0.01 for each), whereas achieved heart rate was linearly correlated with event rate (r = 0.79 and p less than 0.05). On the basis of these data, a prognostic model was defined that employs extent and severity as stress-dependent orthogonal variables. Using this model, the predicted coronary event rate ranged over two orders of magnitude--from a low of 0.4% in patients able to exercise adequately without developing severe and extensive hypoperfusion at a low heart rate (less than 85% of their maximal predicted heart rate). Extent and severity of myocardial hypoperfusion, therefore, are important independent variables of prognosis in patients with suspected coronary artery disease.

Should the intent of testing influence its interpretation?

A test is often interpreted as "normal" or "abnormal" by a single criterion, regardless of the intent of testing. The discriminate accuracy of this convention was critically analyzed using information content (I), likelihood ratio and the area under the receiver-operating characteristic curve. Three ejection fraction variables were assessed--ejection fraction at rest, exercise ejection fraction and the change in ejection fraction from rest to exercise--each relative to three intentional goals: diagnosis of coronary artery disease in 929 patients without previous myocardial infarction, prediction of multivessel disease in these same 929 patients and prediction of multivessel disease in 507 patients with previous myocardial infarction. The information content of exercise ejection fraction (IEX) was higher than for ejection fraction at rest (IR) or for the change from rest to exercise (IEX-R), and was relatively constant regardless of the goal of testing. In contrast, neither IR nor IEX-R was constant. IR was lowest for diagnosis of coronary artery disease, whereas IEX-R was highest for this same goal. These empiric observations are consistent with the quantitative relation predicted by information theory: IEX = IR + IEX-R. Thus, ejection fraction at rest has little discriminate value relative to the diagnosis of coronary artery disease, but does have value in evaluating the extent of disease in patients after myocardial infarction. Exercise ejection fraction and change in ejection fraction are nearly equally useful for purposes of diagnosis, whereas the former is most useful for functional evaluation in postinfarction patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of silent myocardial ischemia with mental stress testing: relation to the triggers of ischemia during daily life activities and to ischemic functional severity.

OBJECTIVES: This study examined the relations among the triggers of ischemia during the activities of daily life, mental stress-induced ischemia in the laboratory and functional severity of ischemia on exercise testing. BACKGROUND: Myocardial ischemia is readily induced with exercise testing, but most episodes of ischemia in daily life occur during relatively sedentary activities. Although mental and emotional arousal are known to trigger myocardial ischemia, mental stress testing induces ischemia in only approximately 50% of patients with active coronary disease. It is not known whether such patients are particularly susceptible to nonexertional ischemia during daily activity. METHODS: We studied 45 men (mean age +/- SD 58 +/- 9 years) with coronary artery disease by means of 48-h Holter ambulatory electrocardiography for ST segment analysis and quantification of physical and mental activity with a structured diary system. These data were cross-tabulated with new left ventricular dyssynchrony (detected on two-dimensional echocardiography) induced by two mental stressors and by bicycle exercise. RESULTS: During mental stress testing, 24 patients (53%) (Group I) had a new wall motion abnormality; the other 21 patients (Group II) did not. The average wall motion dyssynchrony score increased from 1.20 +/- 0.29 to 1.34 +/- 0.36 (p = 0.001), but the increase was less than that with exercise stress (1.52 +/- 0.41, p = 0.001). The total duration of ischemia during sedentary activities was greater in Group I (22.9 +/- 24.5 min) than in Group II (3.6 +/- 3.9 min, p = 0.025). Group I had more ischemic events while sedentary (23 of 290 diary entries) than did Group II (8 of 256 diary entries, p = 0.015). The magnitude of dyssynchrony with mental stress and the number of mental stressors capable of triggering ischemia were related to severity of ischemia with exercise. CONCLUSIONS: Patients with ischemia during mental stress testing also have increased ischemia during sedentary activities in daily life. This finding may reflect greater functional severity of coronary artery disease or a propensity toward coronary vasoconstriction while sedentary.

Triggers of myocardial ischemia during daily life in patients with coronary artery disease: physical and mental activities, anger and smoking.

OBJECTIVES: This study assessed the potency of physical and mental activities and emotions (anger and anxiety) and smoking and other substance use as proximate triggers of ischemia in patients with coronary artery disease during daily life. BACKGROUND: Myocardial ischemia occurs during a wide variety of activities in patients with coronary artery disease, but frequency and relative potency of physical and mental activities, smoking and use of caffeine and alcohol as triggers of ischemia during daily life have not been established. METHODS: Patients (n = 63) with coronary artery disease and evidence of out-of-hospital ischemia kept a validated structured diary of physical and mental activities and psychologic states while undergoing ambulatory electrocardiographic monitoring for 24 to 48 h. RESULTS: Ischemia occurred most frequently during moderately intense physical and mental activities. Patients spent the largest proportion of time engaged in low intensity physical and mental activities (p < 0.05), but the likelihood of ischemia was greatest during intense physical (p < 0.0001) and stressful mental activities (p < 0.03). The percentage of time in ischemia was elevated and approximately equivalent for high intensity physical and high intensity mental activities (5%) compared with 0.2% when patients were engaged in low intensity activities. Strenuous physical activity (e.g., effortful walking, p < 0.05) and the experience of intense anger were potent ischemic triggers, and heart rates at onset of ischemia increased with the intensity of physical and mental activity and with anger. Among smokers, ischemia was more than five times as likely when patients smoked than when they did not (during 24% vs. 5% of diary entries, p < 0.0001). Coffee and alcohol consumption were also related to ischemia (p < 0.05), but this association disappeared after controlling for concurrent cigarette smoking. CONCLUSIONS: Triggers of ischemia in patients with coronary artery disease during daily life include not only strenuous exercise, but also activities involving low levels of exertion, such as anger and smoking. Mental activities appear to be as potent as physical activities in triggering daily life ischemia. Coffee and alcohol consumption are related to ischemia only by virtue of their associations with smoking.

The frequency of late reversibility in SPECT thallium-201 stress-redistribution studies.

The frequency of thallium-201 late reversibility was prospectively assessed in 118 patients who had stress-redistribution thallium-201 studies by single photon emission computed tomography (SPECT). These patients demonstrated two or more segments with nonreversible defects at 4 h imaging and underwent late (18 to 72 h) redistribution imaging. When the criterion of late reversibility was defined as greater than or equal to 1 segment with 4 h nonreversible defects demonstrating late reversibility, it was present in 62 (53%) of the 118 patients and 164 (22%) of 762 segments. When the criterion of greater than or equal to 2 segments was used, late reversibility was found in 41 (35%) of 118 patients and 143 (19%) of 762 segments. The frequency of detected reversible defects increased from 27% at 4 h imaging to 43% at combined 4 h and late imaging (p less than 0.0001) and was significantly increased in all myocardial regions. In comparing the efficacy of initial and late imaging alone versus performing initial, 4 h and late imaging for the identification of reversible defects, 421 (94%) of 449 segments classified as reversible by the latter protocol were also correctly identified by the early and late imaging only approach, with the remaining 6% (28 segments) comprising those segments demonstrating the reversible pattern at 4 h and the nonreversible pattern at late imaging. No major differences were noted with respect to clinical, stress electrocardiographic and scintigraphic variables between the 118 patients undergoing late imaging and 98 additional randomly selected patients with two or more nonreversible defects at 4 h, who did not have late imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

A format for integrating the interpretation of exercise ejection fraction and wall motion and its application in identifying equivocal responses.

The conventional interpretation of ejection fraction change with exercise may be limited because it does not consider the rest value, define equivocal responses or integrate wall motion data reproducibly. Thus, a format was developed for combined interpretation of rest and exercise radionuclide ejection fraction and wall motion by reviewing the reported data for the exercise responses of patients without prior myocardial infarction. The ejection fraction data of 202 normal patients and of 259 patients with coronary artery disease were first fitted to beta distributions. The true positive and false positive rates for coronary disease for each combination of rest and exercise ejection fraction were then determined directly from these distributions. A given rest/exercise ejection fraction combination was "normal" if the false positive rate was greater than the true positive rate, or "abnormal" if the true positive rate was greater than the false positive rate, and "equivocal" when the rates were similar (within a 50% confidence interval). This analytic format, which predicted an inverse relation between rest ejection fraction and the change required with exercise, was then validated prospectively in 854 patients without myocardial infarction (557 with and 297 without angiographic coronary artery disease). Using the conventional criterion of an abnormal test result (less than 0.05 absolute rise in ejection fraction with exercise or a wall motion abnormality), sensitivity was 85 +/- 2% and specificity only 42 +/- 3%. The statistical format had a sensitivity of 70 +/- 2% and specificity of 70 +/- 3%, resulting in a twofold increase in information content. This format has at least two advantages over conventional interpretation: 1) it provides an explicit definition of equivocal responses; and 2) it reproducibly integrates discordant ejection fraction and wall motion responses and allows for the combined analysis of other nonscintigraphic observations, such as age and sex.

The secondary prevention of coronary artery disease.

Randomized clinical trials demonstrate the efficacy of medical secondary prevention in coronary disease patients. The magnitude of risk reduction with exercise, diet, lipid modification, and smoking cessation is similar to other medical therapies for coronary disease such as aspirin, beta blockers, as well as coronary bypass surgery, (Table VI) In contrast to these therapies, however, secondary prevention stabilizes angiographic progression in about 50% of patients and induces regression in about 25% of patients. Both symptoms and perceived quality of life also are beneficially altered by secondary prevention programs, although possibly not by the magnitude reported for bypass surgery. These clinical trial results have led the American Heart Association, and the American College of Cardiology to strongly endorse secondary prevention. A reasonable projection based on these clinical trial data is that widespread use of these recommendations in the 12 million established coronary disease patients would significantly reduce coronary mortality and morbidity.

Using gated technetium-99m-sestamibi SPECT to characterize fixed myocardial defects as infarct or artifact.

UNLABELLED: Perfusion-scan fixed defects may result from soft tissue attenuation, decreasing test specificity for coronary disease and myocardial infarction (MI). Gated 99mTc-sestamibi SPECT may help differentiate MI from artifact since fixed defects with decreased function (wall motion and thickening) probably represent MI, whereas attenuation artifacts either have normal function or at least do not demonstrate markedly reduced function. METHODS: Ungated resting and gated stress 99mTc-sestamibi SPECT was performed in 551 consecutive patients referred for evaluation of coronary disease. From resting and summed gated stress images, 180 patients (33%) were identified with isolated fixed defects. Function of the defects was assessed subjectively from gated stress images and results were correlated with clinical (history and/or ECG Q-waves) evidence of MI. RESULTS: Of 102 patients with fixed defects and clinical MI, 98 (96%) had abnormal defect function. Of 78 patients with no clinical MI, 18 (23%) had decreased function of the defect, possibly indicating silent MI. In 60 of the 78 patients (77%) with no clinical MI, defect function was normal. Because most (91%) of fixed defects with normal systolic function occurred in women with anterior fixed defects (48%) or men with inferior fixed defects (43%), these were most likely attenuation artifacts. By reclassifying patients with fixed defects and normal function as normal, patients with unexplained fixed defects (no clinical MI) decreased from 14% to 3%. CONCLUSION: Gating provides a valuable adjunct to 99mTc-sestamibi SPECT in characterizing fixed defects and potentially improving test specificity.

Effect of motion on thallium-201 SPECT studies: a simulation and clinical study.

Although patient motion on 201Tl SPECT studies has been reported as a source of artifacts, systematic studies on motion patterns and resultant artifacts are lacking. Accordingly, we simulated 74 motion patterns upon a normal study. The tomograms were assessed for presence of defects: The "motion pixel area index" ranged from 1 to 83; 26 of 30 (87%) simulations with an index > or = 21 had defects, whereas 38 of 44 (86%) simulations with an index < 21 were normal. Defect location was dependent on motion direction; defect intensity was dependent on its magnitude and timing. Review of data acquisition in 164 recent normal patient studies revealed motion in 42 (26%). Motion was generally minimal and caused defects in only seven (4%). Thus, mild motion is unlikely to produce defects. In our laboratory, motion is now an infrequent source of artifacts; severe motion produces recognizable patterns that depend on its direction, magnitude and timing.

Development and application of normal limits for left ventricular ejection fraction and volume measurements from 99mTc-sestamibi myocardial perfusion gates SPECT.

UNLABELLED: Gated SPECT is a reproducible method for assessing left ventricular volume (LVV) and left ventricular ejection fraction (LVEF) from 99mTc-sestamibi myocardial perfusion imaging studies. LVV and LVEF measurements by this approach correlate well with those obtained from other cardiovascular imaging techniques. Nevertheless, the lack of criteria for abnormal test findings has limited the potential clinical application of this new imaging technique. METHODS: Gated SPECT measurements were evaluated for 214 patients with a low Bayesian likelihood (< 10%) of coronary artery disease (CAD) before performance of 99mTc-sestamibi stress-rest myocardial perfusion SPECT. The patients were grouped into normotensive patients (n = 98), hypertensive patients without left ventricular hypertrophy (LVH) (n = 80), and hypertensive patients with LVH on resting electrocardiography (n = 36). Gated SPECT measurements for left ventricular end-diastolic volume (LVEDV) index, left ventricular end-systolic volume (LVESV) index, and LVEF were obtained according to a published method, using a modified Simpson's rule technique. RESULTS: Similar results were obtained for mean LVV and LVEF measurements between normotensive patients and hypertensive patients without LVH. Hence, these groups were combined (as group 1). By contrast, hypertensive patients with LVH (group 2), had significantly lower LVEF values (P = 0.01) and higher mean LVESV index values than normotensive patients (P = 0.03). Sex differences were marked: women had significantly higher mean resting LVEF values than men (P < 0.0001) and significantly lower mean resting LVEDV index values (P < 0.0001). A significant relationship was seen between LVEDV index and LVEF (r = -0.60; P < 0.0001) and between LVEDV index and heart rate (r = -0.26; P < 0.001). The normal limits were LVEF > or = 41% in men and > or = 49% in women, LVEDV index < or = 76 mL/m2 in men and < or = 57 mL/m2 in women, and LVESV index < or 38 mL/m2 in men and < or =26 mL/m2 in women. Among hypertensive patients, 22% with LVH had an abnormally low LVEF and 19% had an increased LVEDV index according to these test criteria. By contrast, no hypertensive patients without LVH had an abnormally low LVEF, and only 6% had volume abnormalities. CONCLUSION: Using a cohort of low-likelihood patients, we generated sex-specific normal limits for LVV and LVEF for myocardial perfusion gated SPECT. Application of these findings resulted in the detection of occult left ventricular dysfunction in approximately one fifth of hypertensive patients for whom concomitant LVH was found through resting electrocardiography. These normal limits can now be evaluated prospectively for their potential clinical value.

Image enhancement of severely hypoperfused myocardia for computation of tomographic ejection fraction.

UNLABELLED: Ejection fractions computed from 99mTc-sestamibi myocardial perfusion gated tomograms have demonstrated a high degree of accuracy and reproducibility. Although automated algorithms appear to provide reasonable endocardial outlines for patients over a broad spectrum of cardiac diseases, in cases of severe hypoperfusion, it is necessary to manually adjust contrast and brightness to judge whether borders are correct or must be altered. METHODS: Midventricular horizontal and vertical long axis gated tomograms were generated for 116 studies chosen on the basis of extensive, severe myocardial perfusion defects. Automated software transformed cinematic tomograms into images demonstrating uniform appearance of the myocardium throughout the cardiac cycle. Transformed images were introduced to edge detection algorithms for subsequent calculation of ventricular volumes and ejection fractions. RESULTS: Linear regression analysis demonstrated excellent intraobserver reproducibility for ejection fractions (r = 0.95) and volumes (r = 0.98). There was also good agreement of ejection fractions (r = 0.86) and volumes (r = 0.94) with values derived from an expert's manual drawings. In a subgroup of 22 patients, automated ejection fractions from transformed images demonstrated better agreement with independent first-pass values (r = 0.90) than did manual measurements derived from original data (r = 0.85). CONCLUSION: Image enhancement algorithms succeeded in providing accurate, reproducible gated SPECT ejection fractions in the most difficult class of patients exhibiting severe hypoperfusion.

Influence of arrhythmias on gated SPECT myocardial perfusion and function quantification.

UNLABELLED: Despite the importance of R-wave gating myocardial perfusion tomography for ventricular function assessment, neither prevalence of gating errors nor their influence on quantified cardiac parameters has been studied. METHODS: Arrhythmia-induced anomalies in curves of counts versus projection angle for each R-wave segment were detected visually and algorithmically. Arrhythmia prevalence was tabulated for 379 patients (group 1) with prospective coronary artery disease (mean age 63+/-13 y, 47% male). Myocardial counts were analyzed from all reconstructed cinematic midventricular slices to assess arrhythmia effects on percentage of systolic count increase, generally assumed to equal percentage of wall thickening. In a separate retrospective analysis of 41 patients (group 2), with coronary artery disease (mean age 64+/-12 y, 68% male) having no significant arrhythmias, 36 of whom also underwent equilibrium radionuclide angiography, original projection data were altered to simulate arrhythmia-induced aberrant count patterns to evaluate effects on ventricular function and perfusion measurements. RESULTS: Group 1 patients consisted of 26% without gating errors, 32% with count losses only in the last R-wave interval due to inconsistent transient increase of heart rate, 24% with count decreases in several late intervals due to consistently variable rates, 8% with early interval count increases paired with late interval count decreases due to ectopic beats and 9% with erratic count changes due to atrial fibrillation. Observed count patterns were strongly associated (P < 10(-3)) with arrhythmias detected by electrocardiogram monitoring. In group 2 simulations, ventricular volumes changed by only 2%+/-9% and ejection fraction (EF) by only 1%+/-4% from control values and correlated linearly (r> or = 0.96) with control values for all simulated arrhythmias. SPECT and equilibrium radionuclide angiography EFs correlated similarly (r = 0.85-0.89) for control and all simulations. Percentage changes from control in perfusion defect extent and severity were larger than processing reproducibility limits, the largest change being for atrial fibrillation. Control wall thickening was 38%+/-17%, significantly lower (P < 10(-6)) than for simulated arrhythmias, reflecting similar observations for group 1 patients. CONCLUSION: Even though ventricular volumes and EFs were affected minimally by arrhythmias, both perfusion analysis and wall thickening were compromised. Consequently, quality assurance of gating may be critically important for obtaining accurate quantified parameters.