Combined assessment of myocardial perfusion and left ventricular function with exercise technetium-99m sestamibi gated single-photon emission computed tomography can differentiate between ischemic and nonischemic dilated cardiomyopathy

The purpose of this study was to determine whether exercise technetium-99m sestamibi gated single-photon emission computed tomography (SPECT) accurately distinguishes between patients with ischemic cardiomyopathy and patients with nonischemic left ventricular systolic dysfunction. Noninvasive tests have previously failed to accurately separate patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Technetium-99m gated SPECT imaging offers advantages that have the potential to overcome the limitations of previous studies. Thirty-seven adults with a left ventricular ejection fraction < or = 35%, including 24 patients with nonischemic cardiomyopathy and 13 patients with ischemic cardiomyopathy, were prospectively evaluated using symptom-limited metabolic exercise treadmill testing with technetium-99m sestamibi gated SPECT imaging. Interpretation of myocardial perfusion and regional wall motion was performed, using a 17-segment model. Summed stress, rest, and reversibility perfusion defect scores were determined, and the variance of segmental wall motion scores was computed. Summed stress, rest, and reversibility perfusion defect scores were significantly lower in nonischemic cardiomyopathy patients, compared with those with ischemic cardiomyopathy (summed stress defect score: 6.9 +/- 3.8 vs 32.9 +/- 7.7, respectively, p <0.001). Variability in segmental wall motion was also significantly lower in patients with nonischemic cardiomyopathy compared with those with ischemic cardiomyopathy (variance: 0.3 +/- 0.3 vs 1.2 +/- 0.8, respectively, p <0.001). Thus, assessment of myocardial perfusion and regional ventricular function with exercise technetium-99m sestamibi gated SPECT imaging can reliably distinguish between patients with ischemic cardiomyopathy and patients with nonischemic dilated cardiomyopathy.     

Repeatability of treadmill exercise ejection fraction and wall motion using technetium 99m-labeled sestamibi first-pass radionuclide ventriculography

Bacterial antibodies were studied in acute, intermediate and convalescent phase sera (mean duration from first to last sample 36 days) of 121 children hospitalized for acute lower respiratory tract infection. Antibody responses were observed in 45% of all cases and in 29% of the 21 children < 1 year old. A total of 15 responses to Streptococcus pneumoniae (pneumolysin), 20 to Haemophilus influenzae, 9 to Moraxella catarrhalis, 3 to chlamydiae and 8 to Mycoplasma pneumoniae were found. In 79 patients with 4 consecutive samples available, 52% of the 31 responses were measurable within 5 days from admission. Overall the responses were not associated with upper respiratory tract bacterial findings or acute otitis media. Significantly more responses were found in the 121 children with acute lower respiratory tract infection than in healthy controls (P < 0.007). We conclude that bacterial antibody assays provide a useful tool in the study of the etiology of acute lower respiratory tract infection in young children, even if the interval between paired serum samples is short.     

ECG-gated dual-isotope myocardial SPECT with 201Tl and 99mTc-tetrofosmin: simultaneous assessment of stress/rest myocardial perfusion and left ventricular function

ECG-gated dual-isotope acquisition protocol involving rest imaging with 201Tl and stress 99mTc-tetrofosmin (TF) SPECT was designed for the simultaneous assessment of rest/stress myocardial perfusion and rest ventricular systolic function. This study assessed the feasibility and diagnostic accuracy of this protocol. Forty-five patients underwent the dual-isotope SPECT protocol. Twenty minutes after resting injection of 111 MBq of 201Tl, 370 MBq of 99mTc-TF was administered at a peak exercise. The dual-isotope gated SPECT acquisition was performed 1 hour later. Then, the regional count increase rate (%WT) of 99mTc-TF from end-diastole end-systole was calculated using an automated method which was developed for quantification of regional wall thickening based on circumferential profile analysis in our laboratory. Myocardial perfusion and contractility analysis was carried out using 8 segments of left ventricle with comparison of coronary angiographical findings. The sensitivity and specificity for the detection of diseased coronary vessels (> = or 75% stenosis) were 76% and 94%, respectively. Infarcted regions showing reversible defect had significantly greater %WT as compared with those with fixed defects (63 seg; 12.7 +/- 6.1% vs. 36 seg; 8.9 +/- 7.2%, p < 0.01). In conclusion, this dual-isotope protocol has some advantages; i.e., shortening an examination time, having the exact registration of stress/rest perfusion, and simultaneous evaluation of resting regional wall thickening.     

False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy

Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had "significant" (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH.     

Validation of left ventricular volume measurements by gated SPECT 99mTc-labeled sestamibi imaging

BACKGROUND: Originally, the authors used a combined transcranial-transmalar approach for removal of sphenoorbital tumors. METHODS: More recently, when computed tomography (CT) scanning became available, surgical management of sphenoorbital meningiomas included resection of the hyperostosis in the pterional region, orbital roof and lateral wall, and middle fossa floor. Thereafter, intradural and intraorbital components are removed, as well as infiltrated dura mater. Finally, a periosteal flap is placed over the dural defect and bone reconstructed with methylmethacrylate. RESULTS: Of 25 patients, there was only one death and all but one showed very good to moderate response to treatment. Four recurrences were observed. CONCLUSIONS: Surgical management cannot be uniform in all cases, but must be adapted to each form of presentation. On the basis of the satisfactory results achieved, we feel justified in advising the technique described above with its current modifications.     

MRI-derived ventricular volume curves for the assessment of left ventricular function

To assess the utility of double oblique, ECG-gated 1H magnetic resonance (MR) derived volume curves for assessing LV function, cardiac short axis images were acquired with a fast field echo technique. We applied this methodology to assess left ventricular function in three groups: normals, patients with left ventricular hypertrophy, and dilated cardiomyopathy. Six slices with 16-20 phases per RR interval were analyzed, representing the initial 75-80% of the cardiac cycle. For each slice, the endocardial border of the left ventricular (LV) chamber was manually traced. Using Simpson's rule, the total LV volume at a given phase was determined considering the traced area, thickness and position in three-dimensional space of each of the six constituent slices. The calculated volumes were plotted against time and the stroke volume, ejection fraction and cardiac output were determined. The volume vs time plots for the systolic and diastolic portions of the curve were individually fit to third degree polynomials using a least squares approximation. From the fit curves, the following data were extracted: the mean slope (dV/dT) during filling and emptying, and the time to 1/4, 1/3 and 1/2 filling and emptying. These parameters are valuable indices of the functional status of the myocardium; thus, accurate and useful estimates of LV function can be obtained using MRI derived volume curves in normal and abnormal states.     

Evaluation of the automatic quantification of left ventricular function using ECG gated 99mTc-MIBI myocardial SPECT

OBJECTIVE: To compare temporal changes in body mass index (BMI) (kg/m2) and prevalence of obesity (BMI > 25 and > 30 kg/m2) among adult Kuwaitis between two periods 14 y apart. DESIGN: Comparison of two independent cross-sectional samples of Kuwaitis studied in 1980-1981 and 1993-1994. SUBJECTS: 2067 (896 men and 1171 women) and 3435 (1730 men and 1705 women) adult Kuwaitis (aged > or = 18 y), drawn from primary health care (PHC) clinics and studied for nutritional assessment and for prevalence of obesity in 1980-1981 and 1993-1994, respectively. MEASUREMENTS: BMI, which is the weight in kilograms divided by the height in meters squared (kg/m2), was based on measured weight and height. Obesity was defined as BMI > 25 kg/m2 (grade 1) and BMI > 30 kg/m2) (grade 2). RESULTS: Mean BMI increased significantly (P < 0.001) by 10.0% and 6.2% (2.5 and 1.7 kg/m2) among men and women, respectively. Prevalence of obesity (BMI > 25 and > 30 kg/m2) increased by 20.6% and 15.4% and by 13.7% and 8.4% among men and women, respectively. After controlling for sociodemographic differences between the two study periods, BMI was 2.0 and 1.6 kg/m2 higher in 1993-1994 than in 1980-1981 among men and women respectively. The risk of obesity (BMI > 25 and > 30 kg/m2) also increased among both genders between the two periods (OR = 2.1, 95% CI 1.7-2.7 and OR = 1.9, 95% CI 1.5-2.4, for men and OR = 2.2, 95% CI 1.6-3.0 and OR = 1.4, 95% CI 2.2 CI-1.0-1.9, for women). CONCLUSION: BMI and prevalence of obesity increased among Kuwaitis between 1980-1981 and 1993 and 1994 probably due to the effects of modernization, affluence, increased food consumption and the concomitant changes to sedentary lifestyles. The rate of temporal changes in BMI and obesity were higher, by comparison, in Kuwait than in selected other countries.     

Adenosine technetium-99m sestamibi single-photon emission tomography for the assessment of jeopardized myocardium early after acute myocardial infarction. Paradoxical scintigraphic underestimation of jeopardized myocardium in patients with a severe infarct-related stenosis

This study investigated the value of technetium-99m sestamibi scintigraphy in identifying patients at risk for post-infarct ischaemia (=jeopardized myocardium), especially within the reperfused infarct region. In 51 patients with a recent (<1 month) myocardial infarction, adenosine 99mTc-sestamibi single-photon emission tomography (SPET) and dobutamine stress echocardiography (DSE) were performed and correlated with the presence of significant coronary artery stenosis [% diameter stenosis (DS) >50%] on quantitative coronary angiography. Regional perfusion activity was analysed semi-quantitatively (score 0-4) on a 13-segment left ventricular model. DSE was used for the estimation of the infarct size (low-dose DSE) and for concomitant evaluation of ischaemia (high-dose DSE). A reversible perfusion defect within the infarct region was observed in 20 of the 37 patients with a significant infarct-related lesion (sensitivity of 54%) and only in one patient without a significant infarct-related lesion (specificity of 93%). Further analysis revealed that the scintigraphic assessment of jeopardized myocardium was fairly good in patients with a moderate (DS 51%-64%) infarct-related stenosis but was inadequate in patients with a severe (DS>/=65%) infarct-related stenosis (sensitivity of 80% vs 36%, P<0.01), while the echocardiographic detection of ischaemia was not influenced by stenosis severity (sensitivity of 73% in both subgroups). This scintigraphic underestimation of jeopardized myocardium was mainly related to a severely impaired myocardial perfusion under baseline conditions, as was evidenced by a significantly more severe rest perfusion score in the infarct region in patients with a severe stenosis as compared to those with a moderate stenosis (average score: 1.5+/-0.7 vs 2.1+/-0.6, P<0.01), while infarct size on echocardiography was similar for both subgroups. It may be concluded that early after an acute myocardial infarction, adenosine 99mTc-sestamibi SPET may underestimate reperfused but still jeopardized myocardium, particularly in patients with a severe infarct-related stenosis. In these patients the evaluation of the ischaemic burden on rest-stress scintigraphy is hampered by the presence of a severely impaired myocardial perfusion in resting conditions.     

Comparison of left and right ventricular function in acute myocardial infarction

Pulmonary arterial end-diastolic and mean right atrial pressures were compared in 25 patients with acute myocardial infarction and in one patient with unstable angina. No consistent relationship was observed between these pressures. Simultaneous ventricular function curves relating the stroke work of each ventricle to its respective filling pressure were constructed on 34 occasions, dextran infusion or diuresis being used to alter the filling pressure. The curves from each ventricle were described mathematically by a quadratic (parabolic) function as well as by a straight line function and then compared by canonical correlation analysis. Alterations in the left ventricular function curves occurred with and without depression or right ventricular function curves. These hemodynamic measurements demonstrate that acute myocardial infarction can alter the relationship between left and right ventricular function.     

Steps forward in the assessment of myocardial viability in left ventricular dysfunction

Molecular chaperones protect proteins against environmental and physiologic stress and from the deleterious consequences of an imbalance in protein homeostasis. Many of these stresses, if prolonged, result in defective development and pathologies associated with a diverse array of diseases due to tissue injury and repair including stroke, myocardial reperfusion damage, ischemia, cancer, amyloidosis, and other neurodegenerative diseases. We discuss the molecular nature of the stress signals, the mechanisms that underlie activation of the heat shock response, the role of heat shock proteins as cytoprotective molecules, and strategies for pharmacologically active molecules as regulators of the heat shock response.     

Doppler echocardiographic assessment of left ventricular diastolic function in myotonic dystrophy

To determine the increased production and release of vascular endothelial growth factor (VEGF) from the retina in the eye with non-angiogenic retinal detachment in which relative blood supply disturbance may be present, the concentration of VEGF in subretinal fluid and vitreous fluid collected from the eyes was investigated by enzyme linked immunospecific assay. The average concentration of VEGF was 0.5 +/- 1.1 ng/ml (mean +/- standard deviation) in nine samples of vitreous fluid collected from proliferative retinal detachment, and was 1.2 +/- 1.2 ng/ml in eleven samples of subretinal fluid from rhegmatogenous retinal detachment. The concentration of VEGF in six samples of vitreous fluid from angiogenic diabetic eyes (5.0 +/- 2.8 ng/ml) was significantly higher than in the samples from eyes with retinal detachment. The results suggest that the relative ischemic insult to the detached retina increases the release of VEGF into the vitreous cavity and subretinal space. The increased concentration of VEGF does not induce remarkable angiogenesis since the concentration is lower than the biological threshold, or the effect is modulated by inhibitors.     

Integrated MRI assessment of regional function and perfusion in canine myocardial infarction

A single integrated examination using regional measurements of perfusion from contrast-enhanced MRI and three-dimensional (3D) strain from tissue-tagged MRI was developed to differentiate infarcted myocardium from adjacent tissue with functional abnormalities. Ten dogs were studied at baseline and 10 days after a 2-hour occlusion of the left anterior descending coronary artery (LAD). Strain was determined using a 3D finite element model. Two-dimensional measurements of hypoenhancing regions were highly correlated with myocardial viability (r = 0.96). Signal intensity versus time curves obtained from contrast-enhanced MRI were used for quantitative perfusion analysis. The remote and adjacent noninfarcted tissue of the dogs with LAD occlusion, as well as the infarcted tissue, exhibited abnormal deformation patterns as compared to normal dogs (positive predictive value (PPV) of strain determination of infarction = 66%). Integration of contrast-enhanced MRI results with 3D strain analysis enabled the delineation of the myocardial infarction (PPV = 100%) from functionally compromised myocardium. This integrated cardiac examination shows promise for noninvasive serial assessment of potentially jeopardized noninfarcted myocardium to study the process of infarct remodeling and expansion.     

Effects of transdermal nitroglycerin on left ventricular function after acute myocardial infarction

Progressive left ventricular dysfunction in acute myocardial infarction patients is associated with a poor prognosis. It has been shown that some therapeutic measures which have the potential for limiting the infarct size and preserving ventricular function, are also able to reduce the incidence of congestive heart and improve survival. The aim of this protocol was to assess the effects of transdermal nitroglycerin administered within 72 hours after the onset of acute myocardial infarction and for the following 6 months, on left ventricular function. A total of 98 consecutive acute myocardial infarction patients were randomly allocated, within 72 hours of onset of symptoms, to a double-blind 6-month-therapy with either 10 mg/24 hour transdermal nitroglycerin or placebo. Patients underwent two-dimensional echocardiography at entry, after 2 weeks, 3 months and 6 months. In the nitroglycerin group, end-diastolic volume increased during the follow-up (+6.7%, p < 0.05) while end-systolic volume remained nearly unchanged; ejection fraction and stroke volume increased progressively (+6.3%, p < 0.05, +14.2%, p < 0.05, respectively) and a important reduction of percent of dyssynergic segments was present (-19.2%, p < 0.005). In the placebo group end-diastolic volume and end-systolic volume slightly increased during the follow-up (+2% and +4.9% respectively); ejection fraction and stroke volume remained nearly unchanged during the study; percent of dyssynergic segments showed an important decrease after 2 weeks and 6 months (-21.3%, p < 0.005). A clinically relevant increase (> 20%) in ejection fraction was present more frequently in the nitroglycerin than in the placebo group (p < 0.001). In conclusion, the early (within 72 hours) and prolonged (6 months) administration of transdermal nitroglycerin in acute myocardial infarction improves ejection fraction and stroke volume but does not modify ventricular remodeling.     

Clinical implications of left ventricular function in patients with acute myocardial infarction

Correlation of left ventricular filling pressure (55 patients) with the left ventricular stroke work index (61 patients) provided a rapid means of objectively determining ventricular performance after myocardial infarction. Pressure was monitored by means of the Swan-Ganz balloon-tipped catheter and thermal indicators were used for measuring cardiac output. A hemodynamic grouping of these myocardial infarction patients on the basis of the stroke work index showed close correlation with morbidity and mortality and provided a more accurate prognostic indicator than did the commonly used clinical predictors. Serial assessment of ventricular function further aided in defining the prognosis when it was not clear on admission. Thus, the levels of normal or abnormal ventricular function and the effect of therapeutic measures can be rapidly evaluated by determining the pressures and flows in patients with acute myocardial infarction.     

Evaluation of myocardial perfusion and ventricular shape in hypertrophic cardiomyopathy using 99mTc-tetrofosmin scintigraphy: comparison with 201Tl myocardial scintigraphy

Hypertrophic cardiomyopathy (HCM) is known to have the impairment of myocardial perfusion as well as irregularly hypertrophic myocardium. To evaluate myocardial perfusion and ventricular shape in HCM, 99mTc-Tetrofosmin scintigraphy was performed after exercise (Ex) and at resting state (Re) in 10 patients with HCM and was compared with early image (Ea) and delayed image (De) of 201Tl scintigraphy performed after exercise. SPECT images of both 99mTc-Tetrofosmin and 201Tl scintigraphy were analyzed with five scaled visual scores set in 18 segments. The complete concordance ratio between 99mTc-Tetrofosmin (Ex and Re) and 201Tl (Ea and De) images in segmental analysis was 75%. Image quality of 99mTc-Tetrofosmin was seemed to be superior to that of 201Tl scintigraphy. In 9 patients with HCM, 99mTc-Tetrofosmin scintigraphy was performed under the ECG gating and the thickness of septal and free wall was measured. Good correlation was observed with the data by ultrasound cardiography (r = 0.79, p < 0.002 in wall thickness, r = 0.84, p < 0.01 in the ratio of septal wall thickness to free wall thickness). Left ventricular shape (ventricular long axis) was closely resemble to that of left ventriculography by contrast medium. In conclusion, 99mTc-Tetrofosmin scintigraphy is useful for the evaluation of myocardial morphology as well as perfusion abnormality.     

Doppler echocardiographic assessment of left atrial and left ventricular function during right bundle branch block]

Electrocardiographic, echocardiographic and Doppler echocardiographic studies were performed in 44 patients with coronary heart disease and complete right bundle branch block. The patients were found to have an impaired phase pattern of left ventricular systole and diastole as more prolonged length of its isometric relaxation and contraction, lower economic feasibility and efficiency of its contraction, moderate dilation and hypertrophy. Hemodynamic abnormalities in the left heart in these patients are closely correlate with the changes in the phase pattern of right ventricular systole and they turn out to be so greater as the degree of its hypertrophy is. In complete right bundle branch block, left ventricular pump dysfunction leads to decreased cardiac output and cardiac index, increased total peripheral vascular resistance, thus predisposing to impaired greater circulation.     

Determinants of left ventricular diastolic function during myocardial ischemia: influence of myocardial structure and pericardial constraint

The genotoxic activities of 8-methoxypsoralen (8-MOP) and 4,4',5'-trimethylazapsoralen (4,4',5'-TMAP) on plasmid DNA have been compared. In a previous work, 4,4',5'-TMAP, a methyl derivative of a psoralen isoster, had shown potential photochemotherapeutic activity. The mutagenic activity of mono- and bifunctional lesions caused by these compounds was evaluated both after UVA irradiation, which causes the formation of both kinds of lesions, and after a two-step irradiation procedure of the psoralen-plasmid DNA complex, which allowed monoadducts and interstrand crosslinks to be studied separately. Furthermore, we used a procedure that allowed us to evaluate both the mutagenic and recombinogenic activity of the two compounds. Results indicate that the most important difference between 8-MOP and 4,4',5'-TMAP consists in their mode of photoreaction with DNA rather than in their mutagenic potential. In fact, in all of the experimental procedures, 4,4',5'-TMAP shows a lower ability than 8-MOP to generate interstrand crosslinks. However, when comparable toxicity levels are reached, the two compounds show the same mutagenic potentiality.