Doumit Daou

Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms

OBJECTIVES The aim of this study was to assess the diagnosis of myocarditis in patients presenting with acute myocardial infarction (MI) and normal coronary angiograms. BACKGROUND Most often in these patients, the etiologic diagnosis remains unclear once they are found to have normal coronary arteries. The diagnosis of myocarditis mimicking MI is clinically relevant, because numerous arguments suggest a relation between myocarditis and dilated cardiomyopathy. Myocardial indium-111 (111In)-antimyosin antibody (AMA)/rest thallium-201 (201Tl) imaging allows noninvasive detection of myocarditis. METHODS Forty-five patients admitted to three intensive care units for suspicion of acute MI, with normal coronary angiograms, were investigated. Indium-111-AMA planar images and then a dual-isotope rest AMA/201Tl tomographic study were performed. Six-month echocardiographic follow-up was obtained in 80% of the patients with initial left ventricular (LV) wall motion abnormalities. RESULTS In eight patients, AMA and 201Tl scintigraphy were negative. In two patients, a matched 201Tl defect and focal AMA uptake suggested acute MI (due to prolonged vasospasm or spontaneously reperfused coronary occlusion). In 17 patients, diffuse AMA uptake over the whole LV suggested diffuse myocarditis. In 18 patients, focal AMA uptake with a normal 201Tl scan suggested diffuse but heterogeneous, or focal myocarditis. Complete functional recovery was observed in 81% of the patients with a pattern of myocarditis. CONCLUSIONS Among 45 patients presenting with acute MI and normal coronary angiograms, 38% had diffuse myocarditis and 40% had a scintigraphic pattern of heterogeneous or focal myocarditis. Short-term follow-up showed complete LV functional recovery in 81% of these patients.

Noninvasive Nuclear Imaging Enables the In Vivo Quantification of Striatal Dopamine Receptor Expression and Raclopride Affinity in Mice

The increasing use of genetically engineered mice as animal models of human disease in biomedical research, latest advances in imaging technologies, and development of novel, highly specific radiolabeled biomarkers provide great potential to study receptor expression and gene function in vivo in mice. 11C-raclopride is a widely used PET tracer to measure striatal D2 receptor binding and was used to test the feasibility of the multiple-ligand-concentration receptor assay for D2 receptor quantification. Methods: Mice underwent a total of 4 scans with decreasing specific activities from 141 to 0.4 GBq/μmol, corresponding to 11C-raclopride injected doses of 2.4 to 1,274 nmol/kg, using either a standard bolus injection protocol (n = 12) or a bolus–plus–constant infusion protocol to attain true equilibrium conditions (n = 7). Receptor occupancy was plotted as a function of raclopride dose, and D2 receptor density and raclopride affinity were calculated using linear and nonlinear regression analysis, respectively. In addition, we used ex vivo autoradiography, a more spatially accurate imaging technology, to validate the in vivo PET measurements, and we performed test–retest experiments to determine the reproducibility and reliability of the PET-derived measures. Results: The receptor occupancy curves showed that an injected tracer dose of 4.5 nmol/kg induces approximately 10% receptor occupancy, whereas 1% receptor occupancy will be achieved at tracer doses of approximately 0.45 nmol/kg. Using the bolus injection protocol and nonlinear regression analysis, we determined that the average D2 receptor density was 9.6 ± 1.1 pmol/mL, and the apparent raclopride affinity was 5.0 ± 0.6 pmol/mL. These values agreed well with those obtained at true equilibrium conditions. In contrast, linear Scatchard analysis did not lead to the expected linear relationship because nonsaturable binding was observed at high raclopride concentrations, and thus, it seems to be unsuitable for quantitative 11C-raclopride analysis in mice. Conclusion: Our data showed that the tracer mass, if higher than 4 nmol/kg, can strongly affect binding parameter estimations and must be considered when performing kinetic analysis, specifically in mice. We also demonstrated that the in vivo determination of D2 receptor density and raclopride affinity is feasible in mice using multiple-injection protocols and nonlinear regression analysis.

Nonlimited exercise test combined with high-dose dipyridamole for thallium-201 myocardial single-photon emission computed tomography in coronary artery disease.

Clinical, electrocardiographic, and thallium-201 single-photon emission computed tomography data were evaluated in 397 consecutive patients divided into 3 groups according to coronary hyperemic stimulation: 186 patients (group I; Ex) had maximal symptom-limited exercise ergometric stress testing, 93 patients (group II; Dip) had intravenous dipyridamole (0.7 to 0.8 mg/kg) stress testing, and 118 patients (group III; Dip+Ex) had dipyridamole (0.7 to 0.8 mg/kg) plus nonlimited (i.e., symptom-limited) exercise stress testing, achieving a maximal workload (mean +/- SD) of 102 +/- 37 W. Clinical tolerance was higher in Ex than in Dip groups (p < 0.01), and tended to be higher in Dip+Ex than in Dip groups (p = NS). Image quality--as judged by signal-to-noise ratios--was superior in Ex and Dip+Ex groups when compared with the Dip group (p < 0.01). Chest pain and electrocardiographic positivity were more frequent in the Dip+Ex group than in the Dip group (p < 0.05), despite more extensive coronary artery disease (CAD) in the Dip group; and reversible scintigraphic defects were more frequent in Dip+Ex versus Dip (p < 0.01) and in Ex versus Dip groups (p < 0.05) in patients with established CAD, as well as for the whole group. We conclude that, in patients unable to achieve 85% of their maximal predicted heart rate, the combination of high-dose dipyridamole plus nonlimited exercise stress testing is superior to dipyridamole stress testing alone, and comparable to maximal exercise testing.

Quantitative analysis of hibernating myocardium by dobutamine tissue Doppler echocardiography

D stress echocardiography is a useful modality to detect hibernating myocardium in patients with chronic coronary artery disease.1,2 A quantitative assessment of myocardial wall velocities can be obtained by tissue Doppler echocardiography (TDE) analysis,3–5 a method that can quantify regional myocardial velocities objectively and detect subtle alteration of contractility during stress echo.6–8 In patients with coronary artery disease, TDE has been applied to the study of old or recent infarctions apparently related to a 1-vessel stenosis in patients free from left ventricular dysfunction.5,9 A decrease in myocardial velocity gradients has also been reported during dobutamine challenge on 1-vessel coronary lesions without myocardial infarction.6 Our study addresses a population of patients presenting with left ventricular dysfunction with ejection fraction ,50% related to chronic and severe 3-vessel disease. To image more segments in these patients with multivessel disease, we used an apical TDE approach at rest and under dobutamine. The study was designed to test if the obtained quantitative information could enable detection of viable or nonviable segments in this specific population. • • • Eighty-seven segments with optimal image definition were analyzed at rest and with low-dose dobutamine in 26 patients (20 men, aged 56 6 8 years) with coronary artery disease who had resting regional left ventricular dysfunction without recent myocardial infarction (,3 weeks). Ejection fraction measured with radionuclide ventriculography was 34 6 9% (range 15% to 50%). All patients had coronary angiograms that showed the presence of significant 3-vessel stenosis (.70% diameter stenosis of major epicardial arteries). The contractile reserve and the resting perfusion characteristics of myocardial segments were assessed with the combination of standard dobutamine gray scale echocardiography and rest-reinjection thallium-201 (Tl-201) tomography on a semiquantitative basis. A segment was considered viable if both techniques documented a viability on the region of interest. Eight patients did not undergo revascularization (2 preoperative deaths, 6 patients treated medically). The equipment consisted of a wide-angle, phasedarray, 2-dimensional scanner and a color Doppler flow and tissue imaging system (Acuson 128 XP 10, Acuson Inc., Mountain View, California). Low-dose dobutamine (10 to 20 gamma/kg/min) was infused to detect the viability of severely hypokinetic or akinetic segments. Standard echocardiographic studies were interpreted by 1 experienced investigator who was blinded to all other data. Wall motion was semiquantitated by use of a 6-grade scoring system: hyperkinesia 5 0, normal 5 1, mild hypokinesia 5 2, severe hypokinesia 5 3, akinesia 5 4, and dyskinesia 5 5. A change from grade 3, 4, or 5 to grade 2, 1, or 0 was considered positive for the viability evaluation. A regional enhancement selection box was used to image only the left ventricle before switching to the TDE mode. The velocity scales usually varied between 9 and 13 cm/s. TDE images were digitized on-line and stored on optical disk. The images were transfered to a personal computer for image processing using dedicated software developed in our laboratory.10 Stress and 4-hour rest-reinjection TI-201 singlephoton emssion computed tomography was performed after intravenous administration of 3 and 1.5 mCi of the tracer, respectively, with dose variation according to patient’s body weight. Details from our method have been previously described.11 The TI-201 uptake was scored visually using a 5-point intensity score for each segment.12 A 13-segment ventricular model derived from the 16-segment model was used for the analysis of isotopic and echographic images. The apical portion of the left ventricle, which accounted for the 13th segment as well as the anterior wall, was excluded from our quantitative analysis. The TDE quantitative analysis was blinded to the standard echo interpretation and the rest-reinjection TI-201 single-photon emssion computed tomographic studies. Only apical 4and 2-chamber views obtained at rest and under 10 gamma/kg/min of dobutamine were used for the present quantitative analysis. The velocity measurements were obtained from an algorithm developed in our laboratory and applied to 2-dimensional images (Figures 1 and 2). Once the images were stored on optical disks, they were downloaded to a computer and converted into the appropriate format for image processing with our dedicated software. Calibration of distance was achieved on the 2-dimensional image. The region of interest for analysis of velocities was located in the brightest colored area of each segment in systole. Several lines perpendicular to the left ventricular cavity were traced from endocardium (endo) to epicardium (epi) for lateral and inferior segments. For the septal segments, we discarded the outer layer adjacent to the right ventricle, and the lines were traced from the outer midpart of the wall to the From the Departments of Cardiology and Nuclear Medicine, University Hospital Bicetre, and Department of Imaging Processing, “Ceremade,” Paris IX-Dauphine University, Paris, France. Dr. Larrazet’s address is: L’Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75674 Paris cedex 14, France. E-mail: fabrice.larrazet@imm.fr. Manuscript received September 27, 2000; revised manuscript received and accepted March 19, 2001.

Electrocardiograph-gated single photon emission computed tomography radionuclide angiography presents good interstudy reproducibility for the quantification of global systolic right ventricular function.

BackgroundElectrocardiograph-gated single photon emission computed tomography (SPECT) radionuclide angiography provides accurate measurement of right ventricular ejection fraction and end-diastolic and end-systolic volumes. AimIn this study, we report the interstudy precision and reliability of SPECT radionuclide angiography for the measurement of global systolic right ventricular function using two, three-dimensional volume processing methods (SPECT-QBS, SPECT-35%). These were compared with equilibrium planar radionuclide angiography. MethodsTen patients with chronic coronary artery disease having two SPECT and planar radionuclide angiography acquisitions were included. ResultsFor the right ventricular ejection fraction, end-diastolic volume and end-systolic volume, the interstudy precision and reliability were better with SPECT-35% than with SPECT-QBS. The sample sizes needed to objectify a change in right ventricular volumes or ejection fraction were lower with SPECT-35% than with SPECT-QBS. The interstudy precision and reliability of SPECT-35% and SPECT-QBS for the right ventricle were better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography on the same population. ConclusionSPECT-35% and SPECT-QBS present good interstudy precision and reliability for right ventricular function, with the results favouring the use of SPECT-35%. The results are better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography. They need to be confirmed in a larger population.

Residual area at risk after anterior myocardial infarction: are ST segment changes during coronary angioplasty a reliable indicator? A comparison with technetium 99m-labeled sestamibi single-photon emission computed tomography.

BackgroundThe aim of this study was to assess whether, after anterior myocardial infarction, ST segment changes during percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending coronary artery correlated with the amount of ischemic myocardium in the area at risk, measured with 99mTc-labeled sestamibi single-photon emission computed tomography (SPECT) during ballon inflation.Methods and ResultsQuantitative continuous monitoring of the ST segment was performed during PTCA of the left anterior descending coronary artery in 11 patients, and corresponding SPECT imaging was compared with a rest acquisition performed before PTCA. SPECT was quantified by a bull’s-eye analysis according to main criteria: (1) the planimetered defect size during PTCA as an indicator of the size of the area at risk, (2) the change in the pathologic/normal area count ratio in the area at risk as an index of the severity of ischemia, and (3) the difference between the size of the defect during PTCA and at baseline. ST segment changes were correlated to the variation in pathologic/normal area count ratio (19%±14%; r=0.61; p<0.05) but not to the sizes of the scintigraphic defects.ConclusionST segment changes induced by occlusion of the infarct-related coronary artery during PTCA are related mostly to the severity of ischemia rather than to the size of the area at risk.

The value of a completely automatic ECG gated blood pool SPECT processing method for the estimation of global systolic left ventricular function.

ObjectivesElectrocardiographically gated blood pool SPECT (GBPS) is an interesting method for measuring left ventricular (LV) ejection fraction (LVEF) and volume. Recently, the availability of completely automatic GBPS processing software has been reported. We aimed to evaluate its reliability in measuring global LV systolic function. In addition, using the same population, we compared its reliability to that of three previously reported methods for processing GBPS. MethodsWe studied the performances of the new GBPS system for the evaluation of LVEFs and volumes in 29 patients. The LVEF provided by the planar equilibrium radionuclide angiography (planarLAO) and LV volumes provided by radiological LV contrast angiography (X-rays) were used as ‘gold standards’. ResultsThe new GBPS system failed in one patient. It shows good reproducibility for the measurement of both LVEF and volume. LVEF provided by this system is moderately correlated to planarLAO (r=0.62; P<0.001). The new GBPS constantly overestimates LVEF (P<0.05). Results for LV volumes are moderately correlated to those obtained by X-ray investigation (r=0.7; P<0.001) but are significantly lower (P<0.0001). There is a linear correlation between the average and the paired absolute difference for LV volumes (r=0.52, P=0.0001). ConclusionsThe new, completely automatic, GBPS processing software is an interesting, moderately reliable method for measuring LVEF and volume. The performance of the method is lower than that previously reported for the same population for the other three GBPS processing methods.

Cardiac gated equilibrium radionuclide angiography and multiharmonic Fourier phase analysis: Optimal acquisition parameters in arrhythmogenic right ventricular cardiomyopathy

BackgroundMultiharmonic Fourier phase analysis of radionuclide angiography is a well-established method for the diagnosis of arrhythmogenic right ventricular cardiomyopathy. We sought to determine the optimal acquisition parameters: number of frames per cycle and number of counts per frame, with all other acquisition and processing parameters being fixed.Methods and ResultsRadionuclide angiography with list mode acquisition was performed in 10 normal subjects (pilot group) and 11 patients with arrhythmogenic right ventricular cardiomyopathy (validation group), allowing the reconstruction of electrocardiography-gated constant phase studies with different parameters: 16, 24, and 32 frames per cycle and 200, 400, 600, and 800 kcounts per frame. Three harmonics Fourier phase analysis was applied, and optimal acquisition parameters (defined as those providing best homogeneous phase distribution histogram in the pilot group) were defined as judged by the H3 right ventricular phase SD and Δ 95%. These were 16 frames per cycle and 600 kcounts per frame. Then we verified in the validation group that these optimal acquisition parameters did not induce any significant relative loss of information compared with other acquisition parameters with more temporal resolution (24 and 32 frames per cycle) or more statistics (800 kcounts per frame). This result was realized by the calculation of normalized H3 right ventricular SD, right ventricular Δ 95%, and (SD[left ventricle]-SD[right ventricle]).ConclusionsIn practice, 16 frames per cycle and 600 kcounts per frame are optimal for multiharmonic Fourier phase analysis, with all other acquisition and processing variables being fixed as specified.

Early detection of right ventricular functional abnormalities in patients with complex right premature ventricular contractions.

BackgroundRight ventricular (RV) premature contractions, although generally benign, may represent the first manifestation of arrhythmogenic RV cardiomyopathy. The diagnostic and prognostic value of RV functional abnormalities evidenced by equilibrium radionuclide angiocardiography (ERNA) with multiharmonic Fourier analysis has been validated in patients with severe RV arrhythmias suspected of being affected by arrhythmogenic RV cardiomyopathy. The aim of this study was to assess the prevalence of the same RV functional abnormalities in patients with frequent left bundle branch block pattern premature ventricular contractions (PVCs), without known heart disease, using ERNA as a screening tool. MethodsThe study included 377 consecutive patients (mean age: 40±15 years, males: 58%) presenting with complex PVCs. Cine mode and multiharmonic analysis were used to define global enlargement and areas of dyskinesia of both ventricles. Studies were classified as: normal, right and/or left ventricular abnormalities either localized or diffuse. ResultsERNA was normal in 302 patients (80%) and evidenced RV functional abnormalities in 75 patients (20%). Patients with RV outflow tract PVCs (n=276) were affected to the same extent as patients with right or left axis PVCs. ConclusionIn a specific population with complex left bundle branch block pattern PVCs, RV functional abnormalities were detected by ERNA in 20% of patients. Consequently, ERNA may serve as a screening tool by selecting patients who may require a specific management.

0305: A new turn in SPECT myocardial perfusion imaging: data-driven cardiac gating is now possible with the new generation CZT SPECT Discovery NM 530c

Aim We previously developed a data-driven (DD) respiratory-motion (RM) correction method for conventional SPECT gamma-cameras (REGAT) and adapted it to the new CZT camera (Discovery NM 530c). We recently reported that RM correction with REGAT applied to CZT myocardial perfusion SPECT imaging (MPI) is clinically feasible and impacts substantially myocardial perfusion defects. In this evaluation, we study whether REGAT applied to MPI (Discovery NM 530c) is capable of generating a data-driven (DD) cardiac gating signal allowing the generation of valid global left ventricular (LV) function parameters (EDV: end diastolic volume; ESV: end systolic volume; EF: ejection fraction). Materials and methods Were included 7 patients addressed for stress/rest MPI. All patients had prone stress MPI (2 MBq/Kg 99mTc-Tetrofosmin) and rest MPI 3-hours later (6 MBq/Kg). All acquisitions were made on Discovery NM 530c. Each acquisition was processed with REGAT to generate a dynamic SPECT acquisition study. The latter was processed to generate a DD cardiac gating signal and generate a mean DD cardiac GSPECT study (GSPECT-DD). In parallel, a mean ECG cardiac GSPECT study was generated using the ECG trigger signal provided by traditional ECG monitor (GSPECT-M). The 2 generated cardiac GSPECT studies were reconstructed on Xeleris workstation and processed with Emory Cardiac Toolbox (ECT). LV EDV, ESV and EF were compared between cardiac GSPECT-DD and GSPECT-M. Results Stress LV EVD, ESV, and EF were 91±24mL, 29±13ml, and 68±10% vs 95±23ml, 29±12ml, and 70±11% with GSPECT-DD vs GSPECTM respectively (P:NS). Rest LV EDV, ESV, and EF were 97±21ml, 32±10ml, and 67±6% vs 101±21ml, 31±10ml, and 69±6% with GSPECT-DD vs GSPECT-M respectively (P:NS). Conclusion Data-driven cardiac gating of MPI with Discovery NM 530c processed with REGAT is clinically feasible. It provides LV global systolic function parameters similar to those provided by the traditional clinically used ECG monitor gating.