Chronic fatigue syndrome in women assessed with combined cardiac magnetic resonance imaging.

OBJECTIVE: In chronic fatigue syndrome (CFS), only a few imaging and histopathological studies have previously assessed either cardiac dimensions/function or myocardial tissue, suggesting smaller left ventricular (LV) dimensions, LV wall motion abnormalities and occasionally viral persistence that may lead to cardiomyopathy. The present study with cardiac magnetic resonance (CMR) imaging is the first to use a contrast-enhanced approach to assess cardiac involvement, including tissue characterisation of the LV wall. METHODS: CMR measurements of 12 female CFS patients were compared with data of 36 age-matched, healthy female controls. With cine imaging, LV volumes, ejection fraction (EF), mass, and wall motion abnormalities were assessed. T2-weighted images were analysed for increased signal intensity, reflecting oedema (i. e. inflammation). In addition, the presence of contrast enhancement, reflecting fibrosis (i. e. myocardial damage), was analysed. RESULTS: When comparing CFS patients and healthy controls, LVEF (57.9 ± 4.3 % vs. 63.7 ± 3.7 %; p < 0.01), end-diastolic diameter (44 ± 3.7 mm vs. 49 ± 3.7 mm; p < 0.01), as well as body surface area corrected LV end-diastolic volume (77.5 ± 6.2 ml/m2 vs. 86.0 ± 9.3 ml/m2; p < 0.01), stroke volume (44.9 ± 4.5 ml/m2 vs. 54.9 ± 6.3 ml/m2; p < 0.001), and mass (39.8 ± 6.5 g/m2 vs. 49.6 ± 7.1 g/m2; p = 0.02) were significantly lower in patients. Wall motion abnormalities were observed in four patients and contrast enhancement (fibrosis) in three; none of the controls showed wall motion abnormalities or contrast enhancement. None of the patients or controls showed increased signal intensity on the T2-weighted images. CONCLUSION: In patients with CFS, CMR demonstrated lower LV dimensions and a mildly reduced LV function. The presence of myocardial fibrosis in some CFS patients suggests that CMR assessment of cardiac involvement is warranted as part of the scientific exploration, which may imply serial non-invasive examinations.

Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin.

Adipose-derived stem cells (ASCs) are promising candidates for therapy in myocardial infarction (MI). However, the frequency of human ASCs that differentiate towards cardiomyocytes is low. We hypothesized that adherence to extracellular matrix molecules that are upregulated after MI might increase human stem cell differentiation towards cardiomyocytes. We analysed putative ASC differentiation on fibronectin-coated, laminin-coated and uncoated culture plates. Expression of cardiac markers in cells was analysed 1, 3 and 5 weeks after stimulation with 5-aza-2-deoxycytidine. After 1 week, mRNA expression of myosin light chain-2alpha (MLC-2alpha), an early marker in cardiomyocyte development, was increased significantly in treated cells, independent of coating. At 5 weeks, however, mRNA expression of the late cardiomyocyte development marker SERCA2alpha was only significantly increased in 5-aza-2-deoxycytidine-treated cells cultured on laminin. Significantly higher numbers of cells were immunopositive for MLC-2alpha in cultures of treated cells grown on laminin-coated wells, when compared with cultures of treated cells grown on uncoated wells, both at 1 week and at 5 weeks. Furthermore, after 3 weeks, significantly more alpha-actinin- and desmin-positive cells were detected after treatment with 5-aza-2-deoxycytidine, but only in uncoated wells. After 5 weeks, however, the number of desmin-positive cells was only significantly increased after treatment of cells with 5-aza-2-deoxycytidine and culture on laminin (61% positive cells). Thus, we have found that a high percentage of human ASCs can be differentiated towards cardiomyocytes; this effect can be improved by laminin, especially during late differentiation.

N(epsilon)-(carboxymethyl)lysine depositions in intramyocardial blood vessels in human and rat acute myocardial infarction: a predictor or reflection of infarction?

OBJECTIVE: Advanced glycation end products (AGEs), such as N(epsilon)-(carboxymethyl)lysine (CML), are implicated in vascular disease. We previously reported increased CML accumulation in small intramyocardial blood vessels in diabetes patients. Diabetes patients have an increased risk for acute myocardial infarction (AMI). Here, we examined a putative relationship between CML and AMI. METHODS AND RESULTS: Heart tissue was stained for CML, myeloperoxidase, and E-selectin in AMI patients (n=26), myocarditis patients (n=17), and control patients (n=15). In AMI patients, CML depositions were 3-fold increased compared with controls in the small intramyocardial blood vessels and predominantly colocalized with activated endothelium (E-selectin-positive) both in infarction and noninfarction areas. A trend of increased CML positivity of the intima of epicardial coronary arteries did not reach significance in AMI patients. In the rat heart AMI model, CML depositions were undetectable after 24 hours of reperfusion, but became clearly visible after 5 days of reperfusion. In line with an inflammatory contribution, human myocarditis was also accompanied by accumulation of CML on the endothelium of intramyocardial blood vessels. CONCLUSIONS: CML, present predominantly on activated endothelium in small intramyocardial blood vessels in patients with AMI, might reflect an increased risk for AMI rather than being a result of AMI.

Rationale of the SEAS study: Serial Echocardiography After Subarachnoid haemorrhage, a prospective national, multicentre, multidisciplinary, cohort study to evaluate cardiac abnormalities following intracranial haemorrhage.

The SEAS study is a prospective national, multicentre, multidisciplinary, cohort study in which the cardiac abnormalities following aneurysmal subarachnoid haemorrhage are studied. Incidence, clinical implications and predictive variables of cardiac abnormalities following aneurysmal subarachnoid haemorrhage will be studied. Cardiac abnormalities are defined as ECG changes, echocardiographic function abnormalities, and biochemical changes. A total of 350 patients will be included over a period of three years including follow-up.

Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue.

OBJECTIVE: Cardiac energetics and performance depend on the expression level of the fast (alpha-) and slow (beta-) myosin heavy chain (MHC) isoform. In ventricular tissue, the beta-MHC isoform predominates, whereas in atrial tissue a variable mixture of alpha- and beta-MHC is found. In several cardiac diseases, the slow isoform is upregulated; however, the functional implications of this transition in human myocardium are largely unknown. The aim of this study was to determine the relation between contractile properties and MHC isoform composition in healthy human myocardium using the diversity in atrial tissue. METHODS: Isometric force production and ATP consumption were measured in chemically skinned atrial trabeculae and ventricular muscle strips, and rate of force redevelopment was studied using single cardiomyocytes. MHC isoform composition was determined by one-dimensional SDS-gel electrophoresis. RESULTS: Force development in ventricular tissue was about 5-fold more economical, but nine times slower, than in atrial tissue. Significant linear correlations were found between MHC isoform composition, ATP consumption and rate of force redevelopment. CONCLUSION: These results clearly indicate that even a minor shift in MHC isoform expression has considerable impact on cardiac performance in human tissue.

Time course of functional recovery of stunned and hibernating segments after surgical revascularization.

BACKGROUND: Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation. It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium. Accordingly, the time courses of functional recovery in hibernating and stunned myocardium were compared. METHODS AND RESULTS: Patients (n=26) with ischemic cardiomyopathy undergoing surgical revascularization were studied; regional perfusion (resting (201)Tl single-photon emission CT), glucose utilization ((18)F-2-deoxyglucose single-photon emission CT), and contractile function (2D echocardiography) were assessed before revascularization. Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned, and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating. Contractile function was reevaluated 3 months (early) and 14 months (late) after revascularization. Of the 266 dysfunctional segments, 57 (22%) were stunned, 62 (23%) were hibernating, and 147 (55%) were scar tissue. In stunned myocardium, contractile function improved significantly at 3 months, without further improvement at 14 months; 61% of the stunned segments improved at 3 months, and 9% improved at 14 months. In hibernating myocardium, contractile function improved at 3 months, with a further improvement at 14 months; 31% of the hibernating segments improved at 3 months, and 61% showed (additional) recovery at 14 months. CONCLUSIONS: Stunned myocardium is likely to demonstrate early recovery of function, whereas hibernating myocardium may take a longer time to (fully) recover in function after revascularization.

Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts.

BACKGROUND: During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca(2+), P(i), and pH. METHODS AND RESULTS: Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added P(i) to 0.33+/-0.02 of the control force (pH 7.1, 0 mmol/L P(i)) at 30 mmol/L P(i) and increased with pH from 0.64+/-0.03 at pH 6.2 to 1.27+/-0.02 at pH 7.4. Force dependency on P(i) and pH did not differ between donor and failing hearts. Incubation of myocytes in a P(i)-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca(2+)]. Ca(2+) sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca(2+) responsiveness of force and myosin light chain 2 phosphorylation. CONCLUSIONS: Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca(2+) responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its P(i) and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [P(i)] at submaximal [Ca(2+)] may even be less than in donor hearts because of the increased Ca(2+) responsiveness.

Accuracy of currently available techniques for prediction of functional recovery after revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease: comparison of pooled data.

OBJECTIVES: This study evaluated the relative merits of the most frequently used techniques for predicting improvement in regional contractile function after coronary revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease. BACKGROUND: Several techniques have been proposed for predicting improvement in regional contractile function after revascularization, including thallium-201 (Tl-201) stress-redistribution-reinjection, Tl-201 rest-redistribution, fluorine-18 fluorodeoxyglucose with positron emission tomography, technetium-99m sestamibi imaging and low dose dobutamine echocardiography (LDDE). METHODS: A systematic review of all reports on prediction of functional recovery after revascularization in patients with chronic coronary artery disease (published between 1980 and March 1997) revealed 37 with sufficient details for calculating the sensitivity and specificity of each imaging modality. From the pooled data, 95% and 99% confidence intervals were also calculated. RESULTS: Sensitivity for predicting regional functional recovery after revascularization was high for all techniques. The specificity of both Tl-201 protocols was significantly lower (p < 0.05) and LDDE significantly higher (p < 0.01) than that of the other techniques. CONCLUSIONS: Pooled analysis of 37 studies showed that although all techniques accurately identify segments with improved contractile function after revascularization, the Tl-201 protocols may overestimate functional recovery. The evidence available thus far indicates that LDDE appears to have the highest predictive accuracy.

Prediction of recovery of myocardial dysfunction after revascularization. Comparison of fluorine-18 fluorodeoxyglucose/thallium-201 SPECT, thallium-201 stress-reinjection SPECT and dobutamine echocardiography.

OBJECTIVES: We compared three techniques to predict functional recovery after revascularization. BACKGROUND: Recently, fluorine-18 (F-18) fluorodeoxyglucose in combination with single-photon emission computed tomography (SPECT) has been proposed to identify viable myocardium, Thallium-201 reinjection and low dose dobutamine echocardiography are used routinely for this purpose. METHODS: Seventeen patients (mean [+/- SD] left ventricular ejection fraction 36 +/- 11%) were studied. Regional and global ventricular function were evaluated before and 3 months after revascularization by echocardiography and radionuclide ventriculography, respectively. Myocardial F-18 fluorodeoxyglucose uptake (during hyperinsulinemic glucose clamping) was compared with rest perfusion assessed with early thallium-201 SPECT. On a separate day, low dose dobutamine echocardiography and post-stress thallium-201 reinjection SPECT were simultaneously performed. RESULTS: The sensitivities for F-18 fluorodeoxyglucose/thallium-201, thallium-201 reinjection and low dose dobutamine echocardiography to assess recovery were 89%, 93% and 85%, respectively; specificities were 77%, 43% and 63%, respectively. Stepwise logistic regression indicated that F-18 fluorodeoxyglucose/ thallium-201 was the best predictor. In hypokinetic segments, the combination of F-18 fluorodeoxyglucose/thallium-201 and low dose dobutamine echocardiography was the best predictor. Global function improved (left ventricular ejection fraction increased > 5%) in 6 patients and remained unchanged in 11. All three techniques correctly identified five of six patients with improvement. Fluorine-18 fluorodeoxyglucose/thallium-201 identified all patients without improvement; low dose dobutamine echocardiography identified 9 of 11 without improvement; and thallium-201 reinjection identified 6 of 11 patients without improvement. CONCLUSIONS: Fluorine-18 fluorodeoxyglucose/thallium-201 SPECT was superior to the other techniques in assessing functional recovery. Integration of metabolic and functional data is necessary, particularly in hypokinesia, for optimal prediction of improvement of regional function.

Prediction of improvement of contractile function in patients with ischemic ventricular dysfunction after revascularization by fluorine-18 fluorodeoxyglucose single-photon emission computed tomography.

OBJECTIVES: We evaluated the use of fluorine-18 fluorodeoxyglucose (FDG) and single-photon emission computed tomography (SPECT) to predict improvement of left ventricular ejection fraction (LVEF) after revascularization. BACKGROUND: FDG SPECT has recently been proposed for assessment of myocardial viability. However, FDG SPECT still awaits validation in terms of predicting improvement of contractile function after revascularization in patients with poor left ventricular (LV) function. METHODS: Fifty-five patients with contractile dysfunction (including 22 with LVEF < 30%) underwent FDG SPECT during hyperinsulinemic glucose clamping and early thallium-201 SPECT (to assess perfusion). Improvement of LV function was evaluated 3 months after revascularization with echocardiography and radionuclide ventriculography. RESULTS: The 55 patients were arbitrarily classified into two groups: 19 with three or more viable, dysfunctional segments on FDG SPECT and 36 with less than three viable, dysfunctional segments. LVEF increased significantly in the first group, from 28 +/- 8% (mean +/- SD) before to 35 +/- 9% (p < 0.01) after revascularization. In the second group, LVEF remained unchanged after revascularization (45 +/- 14% vs. 44 +/- 14%, p = NS). The 22 patients with severely depressed LV function were similarly classified into two groups: 14 with three or more viable segments on FDG SPECT in whom LVEF improved significantly (25 +/- 6% vs. 32 +/- 6%) and 8 with less than three viable segments in whom LVEF remained unchanged (24 +/- 6% vs. 25 +/- 6%). CONCLUSIONS: This study shows that FDG SPECT can identify patients in whom LV function improves after revascularization. Because SPECT is widely available, this technique may contribute to more routine use of FDG for determination of viability.

Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure.

Isometric force production and ATPase activity were determined simultaneously in single human skeletal muscle fibers (n = 97) from five healthy volunteers and nine patients with chronic heart failure (CHF) at 20 degrees C. The fibers were permeabilized by means of Triton X-100 (1% vol/vol). ATPase activity was determined by enzymatic coupling of ATP resynthesis to the oxidation of NADH. Calcium-activated actomyosin (AM) ATPase activity was obtained by subtracting the activity measured in relaxing (pCa = 9) solutions from that obtained in maximally activating (pCa = 4.4) solutions. Fiber type was determined on the basis of myosin heavy chain isoform composition by polyacrylamide SDS gel electrophoresis. AM ATPase activity per liter cell volume (+/-SE) in the control and patient group, respectively, amounted to 134 +/- 24 and 77 +/- 9 microM/s in type I fibers (n = 11 and 16), 248 +/- 17 and 188 +/- 13 microM/s in type IIA fibers (n = 14 and 32), 291 +/- 29 and 126 +/- 21 microM/s in type IIA/X fibers (n = 3 and 5), and 325 +/- 32 and 205 +/- 21 microM/s in type IIX fibers (n = 7 and 9). The maximal isometric force per cross-sectional area amounted to 64 +/- 7 and 43 +/- 5 kN/m(2) in type I fibers, 86 +/- 11 and 58 +/- 4 kN/m(2) in type IIA fibers, 85 +/- 6 and 42 +/- 9 kN/m(2) in type IIA/X fibers, and 90 +/- 5 and 59 +/- 5 kN/m(2) in type IIX fibers in the control and patient group, respectively. These results indicate that, in CHF patients, significant reductions occur in isometric force and AM ATPase activity but that tension cost for each fiber type remains the same. This suggests that, in skeletal muscle from CHF patients, a decline in density of contractile proteins takes place and/or a reduction in the rate of cross-bridge attachment of approximately 30%, which exacerbates skeletal muscle weakness due to muscle atrophy.

Force production in mechanically isolated cardiac myocytes from human ventricular muscle tissue.

OBJECTIVE: The expression of contractile isoforms changes during various pathological conditions but little is known about the consequences of these changes for the mechanical properties in human ventricular muscle. We investigated the feasibility of simultaneous determination of protein composition and isometric force development in single cardiac myocytes from human ventricular muscle tissue obtained from small biopsies taken during open heart surgery. METHODS: Small biopsies of about 3 mg wet weight were taken during open heart surgery from patients with aortic valve stenosis. These biopsies were divided in two parts. One part (approximately 2 mg) was used for mechanical isolation of single myocytes and subsequent force measurement while the remaining part was used, in aliquots of 1 microgram dry weight, for protein analysis by polyacrylamide gel electrophoresis. The myocytes were attached with silicon glue to a sensitive force transducer and a piezoelectric motor, mounted on an inverted microscope and permeabilized by means of Triton X-100. Force development was studied at various free calcium concentrations. RESULTS: From all biopsies, myocytes could be obtained and the composition of contractile proteins could be determined. The average isometric force (+/- s.e.m.) at saturating calcium concentration obtained on 20 myocytes from 5 patients amounted to 51 +/- 8 kN/m2. Force was half maximal at a calcium concentration of 2.47 +/- 0.10 microM. CONCLUSION: These measurements indicate that it is possible to study the correlation between mechanical properties and protein composition in small biopsies from human ventricular muscle.

Isometric tension development and its calcium sensitivity in skinned myocyte-sized preparations from different regions of the human heart.

OBJECTIVE: In this study we investigated whether differences exist or develop in patients with aortic or mitral valve disease in myofibrillar contractile function and contractile protein composition between subendo- and subepicardial human ventricular tissue. Isometric tension, its calcium sensitivity and contractile protein composition were studied in left ventricular subendo- and subepicardial and in atrial biopsies obtained during open heart surgery from 24 patients with mitral or aortic valve disease. METHODS: Isometric tension was measured in mechanically isolated skinned myocyte-sized preparations at different free calcium concentrations at 15 degrees C. Protein composition was analysed by one-dimensional gel electrophoresis. A comparison was made between the results of subendo- and subepicardial ventricular tissue within each New York Heart Association class and within the different hemodynamically overloaded groups. RESULTS: Maximal isometric tension was significantly lower in atrial than in ventricular preparations. The concentration of calcium required for half-maximal activation was significantly higher in atrial than in ventricular preparations. Within the ventricle no differences were found in contractile protein composition, isometric tension and its calcium sensitivity between subendo- and subepicardial tissue when all patients were treated as one group or when patients were subdivided according to severity of heart disease or hemodynamic overload. CONCLUSIONS: In this group of patients with ventricular volume or pressure overload no regional differences exist or develop during cardiac disease in left ventricular myofibrillar protein composition and force production. Maximal isometric tension and its calcium sensitivity are smaller in atrial than in ventricular preparations.

Comparison of 17-iodine-131 heptadecanoic acid kinetics from externally measured time-activity curves and from serial myocardial biopsies in an open-chest canine model.

The relation between the externally measured myocardial time-activity curve and the radiochemically determined kinetics of iodine-131(131I) heptadecanoic acid was studied in an open-chest canine model under different metabolic interventions. Kinetics were assessed by analysis of 12 biopsies taken in an assay period of 90 min. Time-activity curves were fitted with a monoexponential plus constant. The halftime value of the exponential of the external curve corresponded well with the elimination rate of 131I from the myocardium: 14.6 +/- 4.5 min vs. 14.6 +/- 5.3 min. The constant was build up of three components: free 131I in cardiac tissue, the almost constant activity of the radiolabeled free fatty acid (FFA) in the myocardial lipid pool, and the radioactivity of blood and noncardiac tissues. The contribution of blood and noncardiac tissue to the constant amounted to a mean value of 77%. These findings support the analysis of externally measured time-activity curves with a monoexponential plus constant curve fit, in which background correction is not necessary. In cases where lipid storage is predominantly present, high T1/2 values, both internally and externally, were found, which were fitted with a monoexponential curve. It can be concluded that externally measured time-activity curves reflect satisfactorily the kinetics of radioiodinated heptadecanoic acid.

Increased uptake of iodine-123-BMIPP in chronic ischemic heart disease: comparison with fluorine-18-FDG SPECT.

UNLABELLED: To evaluate the potential role of 15-p-[123I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP) for the assessment of myocardial viability, the patterns of BMIPP versus 18F-fluorodeoxyglucose (FDG) uptake were evaluated in patients with chronic ischemic heart disease. METHODS: Twenty-one patients with stable chronic coronary artery disease underwent resting TI SPECT to delineate myocardial perfusion followed by FDG SPECT to detect residual viability in regions showing perfusion defects. Resting BMIPP SPECT was obtained on a separate day. SPECT images were displayed as polar maps (13 segments) and analyzed semiquantitatively. A total of 273 segments were analyzed. RESULTS: In 87 (32%) of the segments, a perfusion defect was observed. In perfusion defects, the distributions of BMIPP/TI (mis)matches were significantly different (p < 0.0001) between the FDG viable (n = 42) and nonviable (n = 45) segments. A BMIPP/TI mismatch (BMIPP uptake higher than perfusion) was found in 74% of FDG viable segments, whereas a BMIPP/TI match (BMIPP uptake equal or lower than perfusion) was found in 69% of FDG nonviable segments. Agreement between matching or mismatching of segments was assessed to be 71%. Agreement was 81% when the data were analyzed on a patient basis. The observed frequency of BMIPP/TI mismatches was significantly higher (p < 0.05) in segments with an old myocardial infarction (20 of 36; 55%) than it was in subacute infarcted myocardium (5 of 21; 24%). CONCLUSION: In chronically hypoperfused myocardium, an increased BMIPP uptake relative to perfusion was detected, which is different from the decreased BMIPP uptake often reported in (sub)acute myocardial ischemia. Therefore, the interval from infarction may be an important factor in the interpretation of BMIPP scintigraphic data. Increased BMIPP uptake was associated with FDG/TI mismatches and may, therefore, confirm myocardial viability. Some segments with a FDG/TI mismatch, however, revealed a BMIPP/TI match. These segments may contain viable but more severely damaged tissue. Further studies on functional recovery are warranted to assess the significance of a BMIPP/perfusion (mis)match for tissue viability.

Fluorine-18-fluorodeoxyglucose cardiac imaging using a modified scintillation camera.

Conventional 201TI and hexakis 2-methoxy-2-isobutyl isonitrile studies are less accurate as compared to FDG PET in the prediction of functional recovery after revascularization in patients with injured but viable myocardium. The introduction of a dual-head variable-angle-geometry scintillation camera equipped with thicker crystals (5/8 in.) and high-resolution, ultrahigh-energy collimators capable of 511 keV imaging has permitted FDG SPECT to provide information equivalent to that of PET for the detection of injured but viable myocardium in patients with chronic ischemic heart disease. The development of standardized glucose-loading protocols, including glucose-insulin-potassium infusion and the potential use of nicotinic acid derivatives, has simplified the method of obtaining consistently good-to-excellent quality FDG SPECT cardiac studies. FDG SPECT may become the modality of choice for evaluating injured but viable myocardium because of enhanced availability of FDG, logistics, patient convenience, accuracy and cost-effectiveness compared to PET.

Metabolism of radioiodinated fatty acid analogs in ischemic and hypoxic canine myocardium.

UNLABELLED: Myocardial metabolism of 17-[123I]-iodoheptadecanoic acid (IHDA), 15-(p-[131I]-iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[125I]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) was assessed during ischemia and hypoxia. The simultaneous investigation allowed us to evaluate differences in metabolic handling of these three fatty acids. METHODS: In 17 open-chest dogs, the left ascending coronary artery was cannulated and extracorporeal bypass (ECB) perfused. In 3 dogs, ECB flow was kept normal, and these control experiments showed that kinetics of the radioiodinated fatty acids were not affected by the ECB technique itself. In 9 dogs, ECB flow was reduced to one third (ischemia), and in 5 dogs, the ECB area was perfused with venous blood and was kept at control values (hypoxia). After simultaneous intravenous injection of IHDA, pIPPA and DMIPP, seven paired biopsy specimens from the native and ECB-perfused myocardium were taken over an assay period of 35 min. Total activity and the distribution in the aqueous phase and lipid fractions were determined, and time-activity curves were constructed. RESULTS: In ischemic (Is) but not in hypoxic (Hy) myocardium, peak total activity of IHDA, pIPPA and DMIPP decreased significantly versus normal (N) myocardium (IHDA: N = 700 +/- 267 versus Is = 335 +/- 158 dpm/mg/mCi; pIPPA: N = 988 +/- 318 versus Is = 438 +/- 180 dpm/mg/mCi; DMIPP: N = 352 +/- 146 versus Is = 179 +/- 82 dpm/mg/mCi; all P values < 0.001). The relative decrease was similar for IHDA, pIPPA or DMIPP. Half-time values of total activity were prolonged for IHDA and pIPPA but were shortened for DMIPP in ischemic and hypoxic myocardium (IHDA: N = 22, Is = 44 and Hy = 50 min; pIPPA: N = 24, Is = 95 and Hy = 169 min; DMIPP: N = 528, Is = 409 and Hy = 115 min). The aqueous phase activity for IHDA, pIPPA and DMIPP decreased significantly versus normal myocardium in both ischemic (IHDA: N = 71% +/- 9% versus Is = 36% +/- 9%, P < 0.001; pIPPA: N = 62% +/- 10% versus Is = 25% +/- 8%, P < 0.001; DMIPP: N = 26% +/- 11% versus Is = 18% +/- 3%, P < 0.05) and hypoxic (IHDA: N = 76% +/- 8% versus Hy = 62% +/- 8%, P < 0.05; pIPPA: N = 66% +/- 8% versus Hy = 46% +/- 10%, P < 0.05; DMIPP: N = 32% +/- 6% versus Hy = 24% +/- 4%, P < 0.05) myocardium. The relative decrease was significantly highest for pIPPA and lowest for DMIPP. Incorporation into triacylglycerols increased significantly for IHDA, pIPPA and DMIPP in both ischemic and hypoxic myocardium. In normal myocardium, DMIPP was already mainly incorporated into triacylglycerols. Activity of IHDA and pIPPA in acylcarnitine increased significantly in ischemic and hypoxic myocardium. CONCLUSION: Kinetics of the radioiodinated fatty acid analogs in myocardium are altered during oxygen deprivation in a similar fashion as documented in literature for natural fatty acids. However, the changes were different between IHDA, pIPPA and DMIPP, suggesting different metabolic handling and thus reflecting different aspects of myocardial fatty acid metabolism.

Image-derived input functions for determination of MRGlu in cardiac (18)F-FDG PET scans.

UNLABELLED: Image-derived input functions (IDIF) are frequently used in cardiac (18)F-FDG PET studies for determination of the myocardial metabolic rate of glucose (MRGlu). The purpose of this study was to assess which vascular structure is most suited for defining the IDIF, using online arterial blood sampling (AS) as the gold standard. METHODS: In 18 patients with ischemic heart disease, 370 MBq FDG were injected during a hyperinsulinemic euglycemic clamp. Studies were performed with a Siemens/CTI HR+ PET scanner using a dynamic scanning protocol. A fully automated blood-sampling device was used for continuous AS. IDIF were obtained using regions of interest (ROIs) of 3 different sizes defined on the left ventricle (LV), left atrium (LA), ascending aorta (AA), and descending aorta (DA). MRGlu was calculated with all input functions. Ratios between MRGlu obtained with IDIF and AS were calculated for each patient. RESULTS: Time-activity curves from smaller ROIs suffered more from statistical noise with only a modest reduction of spillover effects, which led to more variation in calculated MRGlu. Mean ratios of MRGlu obtained with IDIF and AS were close to 1 when AA and DA (0.97 +/- 0.07 and 1.00 +/- 0.11, respectively) were used to define the input function. However, when LA and LV were used, mean ratios were 0.81 +/- 0.06 and 0.79 +/- 0.08, respectively, reflecting a significant underestimation of MRGlu. The use of AA for defining the input function resulted in the best agreement with AS and the smallest interobserver variation. CONCLUSION: The ascending aorta is the structure of choice for defining IDIF and a large ROI (diameter, approximately 15 mm) should be used to minimize the effects of statistical noise.

Relationship between preoperative viability and postoperative improvement in LVEF and heart failure symptoms.

UNLABELLED: The presence of myocardial viability is predictive of improvement in regional left ventricular (LV) function after revascularization. Studies on predicting improvement in global LV function are scarce, and the amount of viable myocardium needed for improvement in LV ejection fraction (LVEF) after revascularization is unknown. Moreover, whether the presence of viability is associated with relief of heart failure symptoms after revascularization is uncertain. Hence, the aims were to define the extent of viable myocardium needed for improvement in LVEF and to determine whether preoperative viability testing can predict improvement in heart failure symptoms. METHODS: Patients (n = 47) with ischemic cardiomyopathy (mean LVEF +/- SD, 30% +/- 6%) undergoing surgical revascularization were studied with 18F-FDG SPECT to assess viability. Regional and global function were measured before and 3-6 mo after revascularization. Heart failure symptoms were graded according to the New York Heart Association (NYHA) criteria, before and 3-6 mo after revascularization. RESULTS: The number of viable segments per patient was directly related to the improvement in LVEF after revascularization (r = 0.79, P < 0.01). Receiver operating characteristic curve analysis revealed that the cutoff level of four viable segments (representing 31% of the left ventricle) yielded the highest sensitivity and specificity (86% and 92%, respectively) for predicting improvement in LVEF. Furthermore, the presence of four or more viable segments predicted improvement in heart failure symptoms after revascularization, with positive and negative predictive values of 76% and 71%, respectively. CONCLUSION: The presence of substantial viability (four or more viable segments, 31% of the left ventricle) on FDG SPECT is predictive of improvement in LVEF and heart failure symptoms postoperatively.

Comparison of uptake, oxidation and lipid distribution of 17-iodoheptadecanoic acid, 15-(p-iodophenyl)pentadecanoic acid and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid in normal canine myocardium.

The kinetics of 17-[123I]iodoheptadecanoic acid (IHDA), 15-(p-[125I]iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[131I]iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPPA) were investigated in normal canine myocardium. After simultaneous intravenous injection, myocardial biopsy specimens and samples of arterial blood were taken over 80 min. IHDA showed the highest myocardial uptake (995 +/- 248 dpm/mg.mCi versus pIPPA: 785 +/- 197 dpm/mg.mCi, ns) and the largest size of oxidation (74% +/- 4% versus pIPPA: 65% +/- 5%, p < 0.05). Myocardial activity of IHDA decreased with a half-time value of 11.2 min (pIPPA: 13.2 min). Phospholipids were the main lipid fraction into which IHDA was incorporated, whereas pIPPA was predominantly incorporated into triacylglycerols. DMIPPA myocardial activity remained constant during the assay period and instead of being oxidized, DMIPPA was mainly incorporated into triacylglycerols (55% +/- 12%). The myocardium-to-blood ratios of DMIPPA were greater than 10:1. The ratios at peak for IHDA and pIPPA were 4.1:1 and 3.9:1, respectively (both p < 0.0001 versus DMIPPA). In conclusion, differences have been found in the myocardial uptake, oxidation and lipid distribution of IHDA, pIPPA and DMIPPA. DMIPPA is a promising tracer for fatty acid uptake studies with single-photon emission computerized tomography because of its prolonged retention and high myocardium-to-blood ratios.