Visualization of myocardial phosphoinositide turnover with 1-[1-(11)C]-butyryl-2-palmitoyl-rac-glycerol in rats with myocardial infarction.

Phosphoinositide turnover mediates the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). We tested the hypothesis that phosphoinositide turnover can be visualized by 1-[1 -(11)C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in both infarcted and noninfarcted myocardium after MI in rats. METHODS: Rats received an injection of 11C-DAG 7 d after left coronary artery ligation, and myocardial lipids were extracted from both infarcted and noninfarcted areas of myocardium (n = 3). Metabolites of 11C-DAG were determined by thin-layer chromatography. Quantitative autoradiography of hearts was performed to visualize myocardial phosphoinositide turnover in rats that received an injection of 11C-DAG 1 d (n = 3) and 7 d (n = 5) after MI and 7 d after a sham operation (n = 3). Quantitative autoradiography with 201TlCl was also performed to evaluate myocardial blood flow in rats 7 d after MI (n = 3). Cells occupying the infarcted myocardium were identified by immunohistochemistry. RESULTS: The radioactivity incorporated into the intermediates of phosphoinositide turnover was predominant in both the infarcted (67.1% +/- 5.2% of the total activity) and the noninfarcted (57.4% +/- 3.2%) myocardium. 11C-DAG radioactivity in the infarcted region normalized to that in the noninfarcted region was 1.09 +/- 0.04 in rats 7 d after MI, which was significantly higher than that in rats 1 d after MI (0.38 +/- 0.03, P < 0.001). 201Tl radioactivity in the infarcted region normalized to that in the noninfarcted region was only 0.19 +/- 0.01 7 d after MI. 11C-DAG radioactivity in the noninfarcted region normalized to that in the right ventricular free wall tended to be increased in rats 1 and 7 d after MI compared with the sham-operated rats; the differences, however, were not statistically significant (1.30 +/- 0.15, 1.20 +/- 0.07, and 1.13 +/- 0.02, respectively). Immunohistochemistry revealed that abundant fibroblasts, myofibroblasts, and macrophages occupied the infarcted myocardium 7 d after MI, but the cellularity was low during the first day after MI. CONCLUSION: These data suggest that 11C-DAG may be useful for visualizing regions with activated phosphoinositide turnover after MI. Because wound healing and fibrogenic processes are important factors of ventricular remodeling, 11C-DAG and PET may offer new information benefiting patient management after MI.     

Effect of angiotensin converting enzyme inhibition on myocardial phosphoinositide metabolism visualised with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol in myocardial infarction in the rat

We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left ventricular (LV) remodelling after MI. We therefore hypothesised that the distribution of 11C-DAG after MI may be affected by the inhibition of angiotensin converting enzyme, which is one of the most important factors in the development of LV remodelling after MI. Rats were injected with 11C-DAG after 3 or 10 weeks of treatment with captopril or no treatment following coronary artery ligation, and quantitative autoradiography was performed. Cells occupying the infarcted region were identified by immunohistochemistry. Compared with untreated rats, treatment with captopril for 3 weeks after MI elicited a reduction in the 11C-DAG uptake in the infarcted region (P<0.05) but not in the non-infarcted region, and was associated with a 22% decrease in the heart weight/body weight ratio. The thallium-201 distribution in the infarcted area was similarly low in the rats with and rats without the 3-week captopril treatment after MI. Abundant macrophages and myofibroblasts occupied the infarcted area in both rats with and rats without the captopril treatment for 3 weeks after MI. The 11C-DAG radioactivity in the infarcted region in the untreated rats was lower 10 weeks after MI than 3 weeks after MI (P<0.01). This finding was in agreement with the results of immunohistochemistry demonstrating that the number and size of macrophages and myofibroblasts were remarkably reduced in rats 10 weeks after MI compared with 3 weeks after MI. Captopril treatment for 10 weeks after MI did not decrease the 11C-DAG radioactivity in the infarcted area further. These data suggest that 11C-DAG is useful for visually detecting regions with activated PI metabolism after MI, and that captopril reduces PI metabolism in the infarcted region in the relatively early phase of MI, which might contribute to the attenuation of ventricular remodelling.     

Myocardial oxidative metabolism in remote normal regions in the left ventricles with remodeling after myocardial infarction: effect of beta-adrenoceptor blockers.

In patients with myocardial infarction (MI), an expansion of the remote normal regions of the left ventricle is often observed. However, the characteristics of such regions are not fully understood. Thus, we investigated this issue from the standpoint of myocardial oxidative metabolism using (11)C-acetate PET. METHODS: In 33 patients with recent MI (24 not receiving beta-blockers, 9 receiving beta-blockers) and 12 age-matched normal control subjects, (11)C-acetate dynamic myocardial PET scanning was performed at rest. Time-activity curves of (11)C-acetate in 5-7 regions of interest (ROIs) on the midventricular transaxial image in each subject were generated, and the clearance rate constant (K(mono)) in each ROI was calculated by monoexponential fitting as an index of myocardial oxidative metabolism. The left ventricular (LV) end-diastolic volume index as an index of LV remodeling and the heart rate. pressure product were obtained in all subjects. RESULTS: The LV end-diastolic volume index was significantly larger in patients with MI without beta-blockers than in normal control subjects (101 +/- 22.5 vs. 61.6 +/- 12.8 mL x m(-2); P < 0.001). There was no significant difference in the heart rate x pressure product between the patients with MI without beta-blockers and the normal control subjects (8,229 +/- 1,503 vs. 8,311 +/- 1,311 mm Hg x min(-1)). The K(mono) in remote normal regions was significantly greater in patients with MI without beta-blockers even when compared with the highest K(mono) on the anteroseptal wall of the left ventricle in normal control subjects (0.078 +/- 0.022 vs. 0.065 +/- 0.007 min(-1); P < 0.01). In contrast, the heart rate. pressure product (6,911 +/- 1,135 mm Hg x min(-1)) and the K(mono) (0.054 +/- 0.009 min(-1)) in remote normal regions were significantly less in patients with beta-blockers than in those without beta-blockers (P < 0.001). No significant difference in the LV end-diastolic volume index was found between the MI patients with and without beta-blockers. Multivariate regression analysis showed that beta-blockers significantly and directly decreased the K(mono) in remote normal regions after adjusting the effect of the heart rate x pressure product, although the prime determinant of the K(mono) in such regions was the heart rate x pressure product. CONCLUSION: Myocardial oxidative metabolism in remote normal regions is accelerated in the left ventricles with remodeling after acute MI. Therapy using beta-blockers normalizes the myocardial oxidative metabolism in such regions through the reduction of the heart rate x pressure product and their direct effect on the myocardium.     

TI-201 washout rate in remote normal regions in patients with prior myocardial infarction and left ventricular remodeling

BACKGROUND: Myocardial characteristics of remote normal regions in patients with myocardial infarction (MI) and left ventricular (LV) remodeling have not been fully elucidated. Thus, we investigated this issue from the viewpoint of myocardial Tl-201 dynamics. METHODS AND RESULTS: In 14 patients with prior anterior MI, 10 with inferior MI, and 14 age-matched patients with atypical chest pain served as controls; exercise stress Tl-201 SPECT and cardiac catheterization were performed. Tl-201 washout rate was calculated for 8 myocardial segments, and LV end-diastolic volume index was obtained as a parameter of LV remodeling. LV end-diastolic volume index was greater in anterior MI patients than in control patients; in contrast, no significant difference was observed between inferior MI patients and control patients. The washout rate in remote normal regions was significantly less in anterior MI patients than in the corresponding segments in control patients (39.8% +/- 8.7% vs 48.4% +/- 4.4%, P < .01). There was no significant difference between inferior MI patients and control patients (43.6% +/- 6.9% vs 47.8% +/- 4.5%). CONCLUSIONS: Reduced Tl-201 washout rates in remote normal regions are found in patients with anterior MI and LV remodeling. Subclinical myocardial ischemia during exercise in remote normal regions exists and may be related to the pathologic condition of such LV walls.     

Clinical outcome of patients with previous myocardial infarction and left ventricular dysfunction assessed with myocardial (99m)Tc-MIBI SPECT and (18)F-FDG PET.

Myocardial viability was assessed by (99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT and (18)F-FDG PET to evaluate the prognosis and treatment strategy of patients with myocardial infarction (MI) and left ventricular (LV) dysfunction. METHODS: One hundred twenty-three consecutive patients with previous MI and LV dysfunction (LV ejection fraction [EF], 35% +/- 6% [mean +/- SD]) who underwent (99m)Tc-MIBI SPECT and FDG PET were followed-up for 26 +/- 10 mo (mean +/- SD). Distributions of the 2 radiotracers in myocardial segments were classified into 2 patterns: myocardial perfusion-metabolism mismatch (MM) and match (M). LV EF and LV end-diastolic diameter (EDD) were measured by echocardiography at baseline, 3 mo (Pos1), and 6 mo (Pos2) after revascularization. Cardiac death, acute MI, unstable angina, and late revascularization (>3 mo) experienced by the patients during follow-up were defined as cardiac events. RESULTS: Sixty-seven patients underwent revascularization and 56 patients were treated medically. Of the 72 patients with > or =2 MM segments, 42 underwent revascularization (group A1) and 30 were treated medically (group A2). Of the 51 patients with <2 MM segments, 25 underwent revascularization (group B1) and 26 were treated medically (group B2). The 4 groups had similar baseline characteristics and rest LV EF. After revascularization, EF (mean +/- SD) increased in group A1 from 36% +/- 5% to 44% +/- 8% (P < 0.0001) in Pos1 and to 51% +/- 9% (P < 0.0001) in Pos2. EDD (mean +/- SD) decreased from 62 +/- 8 mm to 56 +/- 5 mm (P < 0.001) in Pos1 and to 55 +/- 5 mm (P < 0.001) in Pos2. However, EF and EDD were unchanged in group B1 (P > 0.05). During the follow-up, 22 patients (17.9%) suffered from cardiac events, including 11 cardiac deaths, 4 acute MI, 6 late coronary artery bypass grafting, and 1 unstable angina pectoris. The cardiac event rate in group A2 (50%) was significantly higher than that of groups A1 (2.4%; chi(2) = 23.08; P < 0.0001), B1 (12%; chi(2) = 8.94; P = 0.003), and B2 (11.5%; chi(2) = 9.45; P = 0.002). CONCLUSION: Assessment of myocardial viability using hybrid (99m)Tc-MIBI SPECT and FDG PET can predict the clinical outcome and is helpful to decision making in the treatment strategy of patients with MI and LV dysfunction. Revascularization can improve the LV function and clinical outcome of patients with >2 viable myocardial segments.     

Summed thickening score by myocardial perfusion imaging: A risk factor of left ventricular remodeling in patients with myocardial infarction

Background

Left ventricular (LV) remodeling has adverse effects on the prognosis of patients with myocardial infarction (MI). The aim of this study is to identify the risk factors of LV remodeling in MI patients by radionuclide myocardial imaging.

Methods and Results

This retrospective study consisted of 92 patients who had a history of definite prior MI on ECG and underwent both resting gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) and positron emission tomography (PET) myocardial metabolism imaging. LV remodeling was defined as > mean + 2SD of LV end-diastolic volume index (LVEDVi) in the normal database. LV enlargement, cardiac dysfunction, wall thickening abnormalities expressed as summed thickening score (STS) were more severe in the old MI patients as compared to those with subacute MI. STS (Odds ratio, 1.296; P = .004) and the proportion of segments with reduced wall thickening in segments with normal perfusion (Odds ratio, 1.110; P = .001) were identified as the independent factors of LV remodeling in subacute and old MI patients in the multivariate binary regression model. Total perfusion deficit (TPD), viable myocardium, scar, and the proportion of segments with reduced wall thickening in segments with decreased perfusion showed strong correlation with LV remodeling in the univariate regression model as well.

Conclusions

LV remodeling in old MI patients is more extensive and severe than that in subacute MI patients. LV wall thickening abnormalities as expressed by STS and the proportion of segments with reduced wall thickening in segments with normal perfusion are the independent risk factors of LV remodeling in MI patients.

     

Decreased myocardial beta-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy.

Cardiac sympathetic function plays an important role in the regulation of left ventricular (LV) function and the pathophysiology of LV dysfunction. (11)C-CGP-12177 ((11)C-CGP) has been used to assess myocardial beta-adrenergic receptor (beta-AR) density in vivo using PET. The aim of this study is to measure myocardial beta-AR density in patients with nonischemic cardiomyopathy and to compare the measurements with various standard parameters of heart failure (HF), particularly with presynaptic function assessed by (123)I- metaiodobenzylguanidine ((123)I-MIBG) imaging. METHODS: (11)C-CGP PET was performed on 16 patients with nonischemic cardiomyopathy and 8 age-matched healthy volunteers using a double injection method. A (11)C-CGP dynamic scan for 75 min was performed after the injection of (11)C-CGP with a high specific activity. After 30 min, (11)C-CGP with a low specific activity was injected. The beta-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, beta-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using (123)I-MIBG kinetics, and neurohormonal parameters. RESULTS: The beta-AR density of patients was significantly lower than that of healthy volunteers (3.80 +/- 0.96 vs. 7.70 +/- 1.92 pmol/mL; P < 0.0001). In the patients, beta-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, beta-AR density correlated significantly with the (123)I-MIBG washout rate (r = -0.68, P < 0.01) and delayed heart-to-mediastinum ratio (H/M ratio) (r = 0.61, P < 0.05). On the other hand, the correlation between beta-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The beta-AR density of patients with severe HF (New York Heart Association functional [NYHA] class III) was significantly lower than that of those with NYHA functional class I or class II HF (3.24 +/- 0.96 vs. 4.24 +/- 0.73 pmol/mL; P < 0.05). CONCLUSION: A reduction in beta-AR density measured by (11)C-CGP PET was observed in patients with nonischemic cardiomyopathy. This downregulation may be due to the increased presynaptic sympathetic tone as assessed by (123)I-MIBG imaging.     

Serial cine-magnetic resonance imaging of left ventricular remodeling after myocardial infarction in rats.

The purpose of the present study was the serial investigation of morphological and functional changes after left coronary artery ligation in the intact rat using cine-magnetic resonance imaging (MRI). MRI studies were performed 4, 8, 12, and 16 weeks after myocardial infarction (MI) with an echocardiogram (ECG)-triggered cine-fast low-angle shot (FLASH)-sequence in a 7-Tesla magnet. MI-size, left ventricular (LV) mass and volumes, cardiac index, ejection fraction (EF), and remote wall and scar thickness of 11 Wistar rats were compared to four sham-operated rats. Stress MRI with dobutamine (10 microl/kg x minute) was performed at 16 weeks. In MI groups (small MI < 30%, N = 5, large MI > 30%, N = 6), there was significant increase of LV mass (small MI + 47.8% increase, large MI + 74.1%) and wall thickness (large MI 1.21 +/- 0.03 to 1.84 +/- 0.07 mm). Scar thickness declined from four to 16 weeks (large MI 0.92 +/- 0.06 to 0.38 +/- 0.02 mm, P < 0.05). End-diastolic volume of both MI groups was significantly elevated but increased further only in animals with large MI from four to 16 weeks (657.1 +/- 38.6 to 869.7 +/- 60.7 microL, P < 0.05). Compared to sham, EF was significantly depressed in MI (large MI 31.5 +/- 2.0%). Wall thickening declined from four to 16 weeks post-MI (large MI 50.9 +/- 9.9 to 28.9 +/- 4.4%, P < 0.05). During stress, sham and MI rats increased wall thickening from 66.5 +/- 8.2 to 111.2 +/- 6.7% and from 30.8 +/- 4.3 to 47.5 +/- 5.8%, respectively (P < 0.05). Hypertrophy was found in all animals with MI throughout the entire period of observation, whereas dilatation after four weeks was only detected in animals with large MI. These morphologic changes were accompanied by an early decline of EF; myocardial function characterized by wall thickening deteriorated later.     

"Doughnut" technetium pyrophosphate myocardial scintigrams. A marker of severe left ventricular dysfunction

The "doughnut" pattern on Tc-99m pyrophosphate (PPi) myocardial scintigraphy is characterized by a border of tracer uptake surrounding a central zone of relatively decreased activity. This pattern is generally associated with large transmural anterior myocardial infarcts (MI) caused by occlusion or critical stenosis of the left anterior descending coronary artery. Such infarcts typically involve a significant portion of the anterior wall and are associated with a complicated clinical course and poor prognosis. In order to evaluate the relationship between the presence of the doughnut pattern and left ventricular (LV) function, radionuclide ventriculography was performed within 15 days after infarction in 58 patients with transmural anterior MI. In patients without previous MI, 15/38 (39.5%) had doughnut scintigrams. These patients demonstrated significant reductions in LV ejection fraction (EF) (28 +/- 10% versus 45 +/- 12%, P less than 0.001) and normalized LV wall motion scores (29 +/- 11% versus 61 +/- 10%, P less than 0.001) when compared with patients with "nondoughnut" scintigrams. Patients with doughnut scintigrams had a significantly greater incidence of severe septal hypokinesis (P less than 0.001) and apical dyskinesis (P less than 0.03). LV end-systolic volumes were also larger in the patients with doughnut scintigrams (73 +/- 32 ml versus 40 +/- 17 mI/M2, P less than 0.005). In contrast, there was no significant difference in LVEF, normalized LV wall motion score, or LV volumes between doughnut and nondoughnut groups in patients with previous MI.     

The potential of contrast-enhanced magnetic resonance imaging for predicting left ventricular remodeling

PURPOSE: To determine whether the myocardial injury size on day 2 measured after gadolinium (Gd)-mesoporphyrin and Gd-diethylenetriamine-pentaacetic acid (DTPA) administration can be used for predicting left ventricular (LV) remodeling 8 weeks later, and to monitor the structural and functional changes in the infarct, peri-infarct rim, and remote myocardium in reperfused infarction using contrast-enhanced and functional magnetic resonance imaging (MRI) MATERIALS AND METHODS: Myocardial infarction (MI) was induced in 27 rats by 1 hour of coronary occlusion/reperfusion. Rats were imaged 2 days and 8 weeks after MI using MRI to determine LV function and size of myocardial injury. All animals received 0.05 mmol/kg Gd-mesoporphyrin 12 hours before the first MRI. A subgroup of 13 rats received 0.3 mmol/kg Gd-DTPA in addition to Gd-mesoporphyrin, and seven rats received 0.05 mmol/kg Gd-mesoporphyrin 12 hours before the second MRI for detection of healed MI. True infarct size (IS) and LV mass were measured postmortem. LV volumes, mass, function, and wall thickness were determined in both imaging sessions. RESULTS: A close correlation was found between contrast-enhanced MRI and postmortem measurements for IS (r = 0.94, P < 0.001 for Gd-mesoporphyrin; r = 0.91, P < 0.001, N = 13 for Gd-DTPA). IS measured on Gd-mesoporphyrin-enhanced images correlated well with end-systolic LV volumes (r = 0.68, P < 0.001) and ejection fraction (r = -0.75, P < 0.001) 8 weeks after MI. Similar correlation with parameters of LV remodeling were found on Gd-DTPA-enhanced MRI. Healed infarcts showed no enhancement on Gd-mesoporphyrin-enhanced MRI. CONCLUSION: Contrast-enhanced MRI can be used as a noninvasive method for determining the initial size of myocardial injury and predicting later LV remodeling. MRI demonstrates the structural and functional changes in infarct, peri-infarct rim, and remote non-infarcted myocardium. The complementary use of functional and contrast-enhanced MRI may provide reliable assessment of therapeutic interventions to reduce IS and LV remodeling.     

Serial MRI evaluation of cardiac structure and function in mice after reperfused myocardial infarction.

This study evaluated the utility of cardiac MRI for assessing the impact of myocardial infarction (MI) on cardiac structure and function in mice following reperfused 1- or 2-hr occlusions of the left anterior descending coronary artery (LAD). When assessed 1 day after MI, the left ventricular ejection fraction (LVEF) had declined by more than half, and remained depressed for the duration of the study. Furthermore, MI initiated dramatic increases in both LV end-systolic volume (LVESV) and end-diastolic volume (LVEDV), with a greater than threefold increase in LVESV and a twofold increase in LVEDV by 4 weeks post-MI. Transmural LV wall thickening (WTh) analysis revealed that noninfarcted myocardium in the remote septal region exhibited an early deficit in contractile function after MI that transiently resolved by day 7, only to be followed by a late phase of dysfunction that became fully manifest by day 28 post-MI. In conclusion, MRI allows the serial assessment of cardiac structure and function after MI in mice, with a resolution adequate to document both regional and temporal changes. The application of these imaging techniques in transgenic and knock-out mice will greatly expedite research aimed at defining the functional roles of individual genes in the pathophysiology of LV remodeling (LVR) after reperfused MI.     

Delayed contrast enhancement and perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET.

Delayed contrast enhancement (DCE) visualized by cardiac MRI (CMR) is a common feature in patients with hypertrophic cardiomyopathy (HCM), presumed to be related to myocardial fibrosis. The pathophysiologic basis of hyperenhancement in this patient group, however, remains unclear as limited histologic comparisons are available. The present study compares the perfusable tissue index (PTI), an alternative marker of myocardial fibrosis obtained by PET, with DCE-CMR in HCM. METHODS: Twenty-one patients with asymmetric septal HCM, 12 chronic myocardial infarction (MI) patients, and 6 age-matched healthy control subjects were studied with DCE-CMR and PET. PET was performed using (15)O-labeled water and carbon monoxide to obtain the PTI. RESULTS: No hyperenhancement was observed in control subjects and the PTI was within normal limits (1.10 +/- 0.07 [mean +/- SD]). In MI patients, the extent of hyperenhancement (25% +/- 16% [mean +/- SD]) was inversely related to the decrease in the PTI (0.94 +/- 0.12; r = -0.65, P < 0.05). Average hyperenhancement in HCM was 14% +/- 12%, predominantly located in the interventricular septum. The PTI in the hypertrophied interventricular septum, however, was not reduced (1.12 +/- 0.13). Furthermore, in contrast to MI patients, there was a modest positive correlation between the extent of DCE and the PTI in HCM (r = 0.45, P < 0.05). CONCLUSION: DCE in the hypertrophied septum of HCM patients is not accompanied by a decline in the PTI, and there is a positive correlation between the extent of DCE and the PTI. These results suggest that hyperenhancement may not be caused solely by fibrotic replacement scarring in this patient group. Other pathologic changes associated with HCM may also cause gadolinium-diethylenetriaminepentaacetic acid hyperenhancement.     

Assessment of systolic thickening with thallium-201 ECG-gated single-photon emission computed tomography: a parameter for local left ventricular function

We measured left ventricular (LV) systolic thickening expressed as a systolic thickening ratio in 28 patients, using 201Tl ECG-gated SPECT. Five normals, 15 patients with prior myocardial infarction, 5 with hypertrophic cardiomyopathy, and 3 with dilated cardiomyopathy were studied. The systolic thickening ratio was calculated as [(end-systolic--end-diastolic pixel counts) divided by end-diastolic pixel counts], using the circumferential profile technique of both end-diastolic and end-systolic short axial images. Functional images of the systolic thickening ratio were also displayed with the "bull's-eye" method. The mean systolic thickening ratio thus calculated were as follows: normals, 0.53 +/- 0.05 (mean +/- 1 s.d.); non-transmural prior myocardial infarction, 0.33 +/- 0.09; transmural prior myocardial infarction, 0.14 +/- 0.05; hypertrophic cardiomyopathy in relatively nonhypertrophied areas, 0.56 +/- 0.11; hypertrophic cardiomyopathy in hypertrophied areas, 0.23 +/- 0.07; and dilated cardiomyopathy, 0.19 +/- 0.02. The systolic thickening ratio analysis by gated thallium SPECT offers a unique approach for assessing LV function.     

Automatic quantification of defect size using normal templates: a comparative clinical study of three commercially available algorithms

Infarct size assessed by myocardial single-photon emission tomography (SPET) imaging is an important prognostic parameter after myocardial infarction (MI). We compared three commercially available automatic quantification algorithms that make use of normal templates for the evaluation of infarct extent and severity in a large population of patients with remote MI. We studied 100 consecutive patients (80 men, mean age 63 +/- 11 years, mean LVEF 47% +/- 15%) with a remote MI who underwent resting technetium-99m tetrofosmin gated SPET study for infarct extent and severity quantification. The quantification algorithms used for comparison were a short-axis algorithm (Cedars-Emory quantitative analysis software, CEqual), a vertical long-axis algorithm (VLAX) and a three-dimensional fitting algorithm (Perfit). Semiquantitative visual infarct extent and severity assessment using a 20-segment model with a 5-point score and the relation of infarct extent and severity with rest LVEF determined by quantitative gated SPET (QGS) were used as standards to compare the different algorithms. Mean infarct extent was similar for visual analysis (30% +/- 21%) and the VLAX algorithm (25% +/- 17%), but CEqual (15% +/- 11%) and Perfit (5% +/- 6%) mean infarct extents were significantly lower compared with visual analysis and the VLAX algorithm. Moreover, infarct extent determined by Perfit was significantly lower than infarct extent determined by CEqual. Correlations between automatic and visual infarct extent and severity evaluations were moderate (r = 0.47, P < 0.0001 to r = 0.62, P < 0.0001) but comparable for all three algorithms. Correlations between LVEF and visual evaluation of infarct extent (r = -0.80, P < 0.0001) and severity (r = -0.82, P < 0.0001) were good but correlations were significantly lower for all three algorithms (r = -0.48, P < 0.0001 to r = -0.65, P < 0.0001). Systematically lower correlations were found in non-anterior infarctions (n = 69) and obese patients (BMI > or = 30 kg/m2, n = 32) compared with anterior infarctions and non-obese patients for all three algorithms. In this large series of post-MI patients, results of infarct extent and severity determination by automatic quantification algorithms that make use of normal templates were not interchangeable and correlated only moderately with semiquantitative visual analysis and LVEF.     

Incremental prognostic value of left ventricular function by myocardial ecg-gated fdg pet imaging in patients with ischemic cardiomyopathy

BACKGROUND: The purpose of this study was to determine the independent value of left ventricular (LV) functional parameters derived from gated fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to predict prognosis in patients with ischemic cardiomyopathy undergoing myocardial viability assessment. METHODS AND RESULTS: We studied 90 consecutive patients with coronary artery disease and low LV ejection fraction (26% +/- 7%) undergoing gated FDG PET to assess myocardial viability for potential revascularization. The primary endpoint for this analysis was the occurrence of cardiac death, myocardial infarction, or worsening heart failure (HF) to New York Heart Association class IV. During follow-up (22 +/- 14 months), 21 patients had an event (17 died, 4 had myocardial infarctions, and 4 had worsening HF). On Cox regression analysis, the event-free survival rate at 2 years was lower for patients with an end-diastolic volume (EDV) of 260 mL or greater (relative risk, 2.7; P = .014), end-systolic volume (ESV) of 200 mL or greater (relative risk, 2.5; P = .021), and LV mass of 143 g or greater (relative risk, 1.6; P = .009). In a risk-adjusted model, EDV (chi 2 = 68, P < .0001) and ESV (chi 2 = 75, P = .035) added a significant amount in the estimation of events over the perfusion-FDG mismatch pattern (chi 2 = 40, P < .001). In a stratified Cox model, patients with PET mismatch, LV ejection fraction lower than 25%, and EDV of 260 mL or greater had the lowest survival rate (P = .006). These patients showed an apparent survival benefit with revascularization but without an improvement in HF symptoms. CONCLUSION: LV functional parameters determined by gated FDG PET have incremental prognostic value over viability information in patients with ischemic cardiomyopathy. Our data suggest that patients with residual viability and advanced cardiac remodeling are at high clinical risk. In these patients the apparent survival benefit of revascularization may not be associated with a measurable improvement in HF symptoms.     

Gated cardiac 13N-NH3 PET for assessment of left ventricular volumes, mass, and ejection fraction: comparison with electrocardiography-gated 18F-FDG PET.

The purpose of this study was to evaluate myocardial electrocardiography (ECG)-gated 13N-ammonia (13N-NH3) PET for the assessment of cardiac end-diastolic volume (EDV), cardiac end-systolic volume (ESV), left ventricular (LV) myocardial mass (LVMM), and LV ejection fraction (LVEF) with gated 18F-FDG PET as a reference method. METHODS: ECG-gated 13N-NH3 and 18F-FDG scans were performed for 27 patients (23 men and 4 women; mean+/-SD age, 55+/-15 y) for the evaluation of myocardial perfusion and viability. For both 13N-NH3 and 18F-FDG studies, a model-based image analysis tool was used to estimate endocardial and epicardial borders of the left ventricle on a set of short-axis images and to calculate values for EDV, ESV, LVEF, and LVMM. RESULTS: The LV volumes determined by 13N-NH3 and 18F-FDG were 108+/-60 mL and 106+/-63 mL for ESV and 175+/-71 mL and 169+/-73 mL for EDV, respectively. The LVEFs determined by 13N-NH3 and 18F-FDG were 42%+/-13% and 41%+/-13%, respectively. The LVMMs determined by 13N-NH3 and 18F-FDG were 179+/-40 g and 183+/-43 g, respectively. All P values were not significant, as determined by paired t tests. A significant correlation was observed between 13N-NH3 imaging and 18F-FDG imaging for the calculation of ESV (r=0.97, SEE=14.1, P<0.0001), EDV (r=0.98, SEE=15.4, P<0.0001), LVEF (r=0.9, SEE=5.6, P<0.0001), and LVMM (r=0.93, SEE=15.5, P<0.0001). CONCLUSION: Model-based analysis of ECG-gated 13N-NH3 PET images is accurate in determining LV volumes, LVMM, and LVEF. Therefore, ECG-gated 13N-NH3 can be used for the simultaneous assessment of myocardial perfusion, LV geometry, and contractile function.     

Prediction of left ventricular remodeling and analysis of infarct resorption in patients with reperfused myocardial infarcts by using contrast-enhanced MR imaging

PURPOSE: To prospectively evaluate the accuracy of clinical and cardiac magnetic resonance (MR) imaging parameters for predicting left ventricular (LV) remodeling by using follow-up imaging as reference standard, and to prospectively evaluate infarct resorption in patients with reperfused first myocardial infarcts. MATERIALS AND METHODS: The study was approved by the institutional ethics committee and all patients gave written informed consent. In 55 patients (48 men, seven women; mean age+/-standard deviation, 56 years+/-13), contrast material-enhanced and cine MR imaging were performed 5 days+/-3 and 8 months+/-3 after myocardial infarction (MI). Microvascular obstruction (MO) and infarct size were estimated at first-pass enhancement (FPE) and delayed enhancement (DE) MR, respectively. Remodeling was defined as an increase in LV end-diastolic volume index of 20% or higher at follow-up. Differences in continuous and categorical data were analyzed by using Student t test and Fischer exact test as appropriate. RESULTS: Patients with remodeling (n=13, 24%) had higher creatine kinase MB (P<.05), more anterior infarcts (P<.05), more often a reduced Thrombolysis in Myocardial Infarction flow (P<.05), larger infarct size at DE MR (P<.001), a greater extent of MO at FPE MR (P<.01), lower ejection fraction (P<.001) and higher LV end-systolic volume index (P<.01). Infarct size at DE MR was a powerful predictor for remodeling (odds ratio: 1.18, P<.001), demonstrating that the risk for remodeling increased 2.8-fold with each 10% increase in infarct size. Infarct size of 24% or more of LV area predicted remodeling with high sensitivity (92%), specificity (93%), and accuracy (93%). Infarct resorption was larger in patients with remodeling (P<.01). CONCLUSION: Infarct size 24% or more of the LV area constitutes an important threshold to predict remodeling. Patients with remodeling develop disproportionate infarct resorption.     

Dipyridamole-induced abnormal Tl-201 lung uptake in patients with normal myocardial perfusion: A marker of increased left ventricular filling pressures

BACKGROUND: The mechanism of dipyridamole-induced abnormal increased T1-201 lung uptake in patients without coronary artery disease is poorly understood. The purpose of this study was to evaluate the relation between dipyridamole-induced abnormal T1-201 lung uptake and left ventricular (LV) diastolic indexes using Doppler, color M-mode and Tissue Doppler modalities at rest, and at dipyridamole stress echocardiograpy (DSE) in patients with normal myocardial perfusion and LV function. METHODS AND RESULTS: 18 consecutive patients (mean age 64 +/- 7 years) with normal myocardial perfusion and increased lung T1-201 uptake on dipyridamole stress-redistribution single photon emission computed tomography (SPECT) were included in our study. These patients were compared with 18 age-matched control patients with normal perfusion and normal T1-201 lung uptake. All patients underwent DSE. A good correlation was found between the T-201 lung uptake, the peak early velocity of mitral inflow (E, r = 0.57) and estimated pulmonary capillary wedge pressure (PCWP = 1.24[E/Ea] + 1.9, r = 0.68). In patients with increased L/H ratio compared to control group, the E and the PCWP were significantly higher at baseline 81 +/- 18 vs 68 +/- 11 (cm/s) and 13 +/- 3 vs 10.2 +/- 2 (mmHg). An additional significant increase of E to 91 +/- 23 (cm/s (P = 0.001)) and PCWP to 14.8 +/- 3 (P = 0.005) after dipyridamole administration was seen; in contrast to a nonsignificant change observed in control group. For the detection of a dipyridamole induced PCWP >12 mmHg, a L/H ratio of >/=50% had a sensitivity of 72% and a specificity of 83%, resulting in a positive and a negative predictive value of 81% and 75%, respectively. CONCLUSIONS: A dipyridamole-induced abnormal T1-201 lung uptake in patients with normal myocardial perfusion and systolic function is predictive of elevated filling pressures at rest and in response to dipyridamole administration, probably reflecting an intrinsic resting diastolic dysfunction and a further abnormal response to vasodilatation.     

Imaging of VEGF receptor in a rat myocardial infarction model using PET.

Myocardial infarction (MI) leads to left ventricular (LV) remodeling, which leads to the activation of growth factors such as vascular endothelial growth factor (VEGF). However, the kinetics of a growth factor's receptor expression, such as VEGF, in the living subject has not yet been described. We have developed a PET tracer (64Cu-DOTA-VEGF121 [DOTA is 1,4,7,10-tetraazadodecane-N,N',N',N'-tetraacetic acid]) to image VEGF receptor (VEGFR) expression after MI in the living subject. METHODS: In Sprague-Dawley rats, MI was induced by ligation of the left coronary artery and confirmed by ultrasound (n = 8). To image and study the kinetics of VEGFRs, 64Cu-DOTA-VEGF121 PET scans were performed before MI induction (baseline) and on days 3, 10, 17, and 24 after MI. Sham-operated animals served as controls (n = 3). RESULTS: Myocardial origin of the 64Cu-DOTA-VEGF121 signal was confirmed by CT coregistration and autoradiography. VEGFR specificity of the 64Cu-DOTA-VEGF121 probe was confirmed by in vivo use of a 64Cu-DOTA-VEGFmutant. Baseline myocardial uptake of 64Cu-DOTA-VEGF121 was minimal (0.30 +/- 0.07 %ID/g [percentage injected dose per gram of tissue]); it increased significantly after MI (day 3, 0.97 +/- 0.05 %ID/g; P < 0.05 vs. baseline) and remained elevated for 2 wk (up to day 17 after MI), after which time it returned to baseline levels. CONCLUSION: We demonstrate the feasibility of imaging VEGFRs in the myocardium. In summary, we imaged and described the kinetics of 64Cu-DOTA-VEGF121 uptake in a rat model of MI. Studies such as the one presented here will likely play a major role when studying pathophysiology and assessing therapies in different animal models of disease and, potentially, in patients.     

Comparison of contrast-enhanced MRI with (18)F-FDG PET/201Tl SPECT in dysfunctional myocardium: relation to early functional outcome after surgical revascularization in chronic ischemic heart disease.

Revascularization of viable myocardial segments has been shown to improve left ventricular (LV) function and long-term prognosis; however, the surgical risk is comparatively higher in patients with a low ejection fraction (EF). We compared contrast-enhanced MRI with (18)F-FDG PET/(201)Tl SPECT for myocardial viability and prediction of early functional outcome in patients with chronic coronary artery disease (CAD). METHODS: Forty-one patients with chronic CAD and LV dysfunction (mean age +/- SD, 66 +/- 10 y; 32 men; mean EF +/- SD, 38% +/- 13%) referred for (18)F-FDG PET, (201)Tl-SPECT and MRI within 2 wk were included. Twenty-nine subjects underwent coronary artery bypass grafting (CABG), and LV function was reassessed by MRI before discharge (17 +/- 7 d after surgery). Two were excluded from outcome analysis (1 death due to sepsis; 1 perioperative myocardial infarction). The extent of viable myocardium by (18)F-FDG PET/(201)Tl SPECT was defined by the metabolism-perfusion mismatch or ischemia, in comparison with the extent of delayed enhancement (DE) on MRI in a 17-segment model. Segmental functional recovery was defined as improvement in the wall motion score of > or =1 on a 4-point scale. EF and LV volume change were used as global functional outcome. RESULTS: Three hundred ninety-four dysfunctional segments were compared, and the extent of DE on MRI correlated negatively with the viability on (18)F-FDG PET. Of 252 dysfunctional segments that were successfully revascularized, the sensitivity, specificity, positive predictive value, and negative predictive value of PET/SPECT were 60.2%, 98.7%, 76.6%, and 96.7% and of MRI were 92.2%, 44.9%, 72.4%, and 78.6% using the cutoff value of 50% DE on MRI, without significant differences in overall accuracies. In 18 subjects who underwent isolated CABG, improvement of EF (> or =5%) and reverse LV remodeling (> or =10% LV size reduction) was best predicted by the no DE on MRI, and patients with substantial nonviable myocardium on (18)F-FDG/SPECT predicted a poor early functional outcome (all P < 0.001). CONCLUSION: Accurate prediction of early functional outcome by PET/SPECT and contrast-enhanced MRI is possible.