Effect of verapamil on absolute myocardial blood flow in hypertrophic cardiomyopathy.

Angina, despite angiographically normal coronary arteries, is a common symptom in patients with hypertrophic cardiomyopathy (HC). Verapamil has been shown to ameliorate silent myocardial perfusion defects documented by thallium-201 in patients with HC. The aim of this study was to investigate the effects of verapamil on absolute regional myocardial blood flow and flow reserve, measured by positron emission tomography (PET) in patients with HC. Echocardiography, exercise stress testing, and measurements of myocardial blood flow at rest and after administration of intravenous dipyridamole (0.56 mg/kg) were undertaken in 20 patients with HC at baseline study and 8 +/- 2 weeks after double-blind randomization to either slow-release verapamil 240 mg or placebo once daily. During treatment, resting myocardial blood flow in the interventricular septum was 0.81 +/- 0.23 versus 0.96 +/- 0.42 ml/min/g in the placebo and verapamil group, respectively (p = NS between groups and when compared with respective baseline study); resting myocardial blood flow in the left ventricular free wall was 0.67 +/- 0.17 versus 0.74 +/- 0.45 ml/min/g, respectively (p = NS). After dipyridamole infusion, myocardial blood flow in the interventricular septum was 1.42 +/- 0.52 versus 1.92 +/- 1.23 ml/min/g (p = NS between groups and when compared with respective baseline study); myocardial blood flow in the left ventricular free wall was 1.25 +/- 0.41 versus 1.68 +/- 1.37 ml/min/g, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients.

We investigated the role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early evaluation of response to chemotherapy in metastatic breast cancer patients. Breast cancer patients who received an epirubicin/paclitaxel--containing regimen as first-line treatment for metastatic disease were included in this study. A PET study was performed within 1 week before the start of treatment, at day 8 after the first course, and at the end of the planned program of chemotherapy. Tumor response was determined clinically and radiographically every 2 courses of treatment. Thirteen patients with metastatic breast cancer who were referred for treatment protocols with gemcitabine/epirubicin/paclitaxel or epirubicin/paclitaxel chemotherapy regimens were included in this study. All metastatic sites were easily visualized on the baseline FDG-PET images, obtained 50 to 60 minutes after tracer injection. Nine patients who completed the planned courses of chemotherapy and the FDG-PET studies were available for analysis. In the six patients who achieved a response to treatment, median glucose standard uptake value (SUV) (semiquantitative analysis) was 7.65 (range, 3.4-12.3) at baseline, 5.7 (range, 2.8-7.6) at day 8 after the first course, and 1.2 (range, 0.99-1.3) at the end of the 6 planned courses of chemotherapy. Three patients who obtained a stable disease as best response had no significant decrease in tumor glucose SUV compared to baseline levels. Qualitative visual analysis in the six responding patients showed a decrease in delineation of tumor mass from background activity soon after the first course, while the nonresponding patients had no significant modification from basal levels. Semiquantitative FDG-PET scanning of metastatic breast cancer sites showed a rapid and significant decrease in tumor glucose metabolism soon after the first course of treatment in patients who achieved a response to first-line chemotherapy. On the contrary, no significant decrease was observed in nonresponding patients.

Significance of both negative T waves and stress-induced normalization of the repolarization phase in infarcted patients: a positron-emission-tomography assessment of regulation of myocardial blood flow and viability of myocardium.

BACKGROUND: The clinical correlation of stress-induced normalization of previously negative T waves (NNTW) to regulation of regional myocardial blood flow (MBF) and tissue viability is still being debated. OBJECTIVE: To clarify its meaning. METHODS: We studied 25 patients, who had previously suffered anterior myocardial infarction and for whom negative T waves were recorded on baseline electrocardiographic precordial leads, by means of positron emission tomography. We obtained MBF in the infarcted myocardial regions under resting conditions for all patients, during infusion of dipyridamole (17 patients) and dobutamine (20 patients), using [13N]-ammonia as a flow tracer. RESULTS: During stress tests, 13 patients exhibited NNTW (group 1) whereas the remaining 12 presented persistent negative T waves (group 2). NNTW was observed in 18 stress studies (for 10 and eight patients during administration of dobutamine and dipyridamole, respectively) whereas persistent negative T waves occurred 19 times (for 10 patients during infusion of dobutamine and nine patients during administration of dipyridamole). A complete concordance of the modifications of the repolarization phase was observed for patients who were subjected both to dipyridamole and to dobutamine studies. Furthermore, we assessed viability of myocardium in 20 of 25 patients using [18F]-fluorodeoxyglucose. For the remaining five patients not subjected to metabolic imaging, a coronary reserve of 1.65 was considered a cut-off of viability. Resting MBF for patients in groups 1 and 2 were similar (0.53 +/- 0.20 versus 0.47 +/- 0.17 ml/min per g, respectively, NS) whereas during pharmacological stress, MBF of patients in group 1 was significantly higher than that for patients in group 2 (0.99 +/- 0.41 versus 0.56 +/- 0.26 ml/min per g, respectively, P < 0.0001). Coronary vasodilating capability, expressed as stress/resting MBF ratio, turned out to be 1.88 +/- 0.49 and 1.16 +/- 0.37 for patients in groups 1 and 2, respectively (P < 0.0001). We observed no difference in mean exercise work load (9.6 +/- 2.80 versus 8.46 +/- 2.18 min, NS) and rate- pressure product (24230 +/- 6425 versus 24207 +/- 8146 mmHg beats/ min, NS) at peak for the two categories of patients. All 13 patients in group 1 (100%) had viable myocardium in the anterior infarcted areas whereas only one of 12 patients in group 2 did (9%, P< 0.0001 versus group 1). Finally, a subanalysis for the specific pharmacological agent used was performed and it gave similar results. CONCLUSION: Regardless of the specific stress test able to elicit the electrocardiographic sign, infarcted dysfunctional areas with stress-induced NNTW were demonstrated to have a higher coronary vasodilating capability and a greater probability of viability of myocardium than had persistent negative T wave regions. Therefore, detection of NNTW appears to be a cheap first-line method for the identification both of a better preserved coronary microcirculatory function and of the persistence of viability of myocardium in the infarcted areas.

Evaluation of reconstructed scatter fraction on PET images.

This paper describes a procedure proposed for the quantitative evaluation of the influence of the scattering noise on the reconstructed PET images. Applying the same experimental procedure used to evaluate the Scatter Fraction (SF) on the sinograms obtained measuring line sources within a uniform scattering medium, the method here proposed permits the computation, after reconstruction, of a derived index of the SF i.e. the Reconstructed Scatter Fraction (RSF). This offers the advantage of providing an estimate of the scatter noise directly on the images obtained in the same processing conditions as during the in vivo human studies. Comparative data of SF and RSF are reported as well as the effect of varying the filter function and of the measured attenuation correction on the RSF. The preliminary results obtained show that the values of the reconstructed scatter fraction are closer to the SF ones when this last is computed only in the cylinder region and the RSF is computed on images reconstructed with a ramp filter.

User-friendly image processing software tools: general purpose features and application to the correlation of PET-CT brain images.

An interactive software package, performing some useful general purpose image processing operations and being used as a tool for the problem of the anatomical correlation of PET brain images, is under development. The software is developed as a comprehensive tool with a graphic user-interface allowing the display of the processed images through the use of a variety of colormaps. The implemented routines perform a lot of processing operations on the images: a) Local image processing, i.e. smoothing and sharpening, contours extraction, interactive expansion, shrinking and thresholding of the gray scale, histogram equalization. b) ROI handling, i.e., ROI drawing and computing, transformation of an image to a ROI, ROI editing. c) Additional operators include frequency space image processing such as FFT.

Verification of the integral transformation of the projections technique for scatter correction in positron tomographs.

A scatter correction algorithm, based on the integral transformation of the projections, has been implemented when using the C.N.R. positron tomograph in Pisa. The performance of the method has been evaluated by measurements on ad hoc phantoms. The technique allows a significant average reduction of the reconstructed scatter fraction. The limitations of this approach have also been investigated.

Adrenergically mediated coronary vasoconstriction in patients with syndrome X.

Several studies have shown that coronary vasodilator reserve is impaired in some patients with chest pain and angiographically normal coronary arteries. In a subgroup of these patients, who additionally show ST depression on the electrocardiogram during exercise and are generally labelled as having Syndrome X, the impairment of coronary flow reserve is associated with metabolic and functional signs consistent with an increased sympathetic drive. The aim of the present investigation was to ascertain whether the impairment of coronary vasodilator reserve in patients with Syndrome X is due to adrenergically mediated vasoconstriction of coronary microcirculation. Myocardial blood flow (MBF), at baseline and following intravenous infusion of dipyridamole (0.56 mg/kg over 4 minutes), was measured by means of 13N-ammonia and dynamic positron emission tomography in 10 females (mean age 52 +/- 8 years) with a chest pain history, ST-segment depression during exercise, and angiographically normal coronaries. The first MBF study was performed while the patients were off therapy; a repeat MBF study was performed following 1 week of treatment with the alpha-1 blocker doxazosin (2 mg/day). Off therapy MBF was 1.13 +/- 0.25 ml/min/g at baseline and increased to 2.35 +/- 0.66 ml/min/g following dipyridamole. Coronary vasodilator reserve (dipyridamole/baseline MBF) was 2.18 +/- 0.56. During treatment with doxazosin, baseline MBF was not different from the control value (1.25 +/- 0.50 ml/min/g), while added dipyridamole significantly increased MBF to 3.52 +/- 1.20 ml/min/g (p < 0.01 vs. off therapy). Coronary vasodilator reserve was significantly increased (2.91 +/- 0.92, p < 0.01 vs. control value) by doxazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term treatment with verapamil on left ventricular function and myocardial blood flow in patients with dilated cardiomyopathy without overt heart failure.

Myocardial blood flow (MBF) abnormalities are present in early stage dilated cardiomyopathy (DCM) and have been attributed to coronary microvascular abnormalities. The favorable effects of verapamil on coronary microcirculation might indicate its use in early stage DCM. We assessed the safety of long-term combination therapy of verapamil and enalapril and its effects on both left ventricular function and myocardial perfusion compared with enalapril alone in 18 patients with DCM (15 men, 3 women; mean age, 50+/-9 years) without overt heart failure (NYHA class I-II). At baseline and after 6 months of randomized treatment with either enalapril (10-20 mg) (nine patients, group 1) or enalapril (10-20 mg) and verapamil (120-240 mg) (nine patients, group 2), left ventricular function was assessed at rest, during handgrip, and during bicycle exercise by equilibrium radionuclide angiography. Mean MBF was measured at rest and after dipyridamole by positron emission tomography (PET) and 13N-ammonia as a flow tracer. At baseline, the two groups had reduced left ventricular ejection fraction at rest, which was further impaired during isometric exercise, but increased at peak bicycle exercise. MBF was similarly reduced in the two groups at rest and during dipyridamole. During treatment, no adverse events occurred in either group. After 6 months there was no significant difference in the main study variables either between the two groups or within each group before and after treatment. Long-term combination therapy with verapamil and enalapril is safe in patients with DCM without overt heart failure. Despite no favorable effect on myocardial perfusion, combined treatment prevented deterioration of left ventricular function, similarly to enalapril alone.

Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms.

BACKGROUND: Coronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients. METHODS AND RESULTS: We have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04 +/- 0.22 ml.min-1.g-1; it increased to 1.32 +/- 0.47 ml.min-1.g-1 (p less than 0.01 versus baseline value) during atrial pacing and to 2.52 +/- 0.96 ml.min-1.g-1 (p less than 0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02 +/- 0.33 ml.min-1.g-1 after dipyridamole (range, 2.13-5.46 ml.min-1.g-1), and 14 (33%) patients had a mean flow of 1.48 +/- 0.29 ml.min-1.g-1 (range, 1.06-2.04 ml.min-1.g-1, p less than 0.01 versus the "high-flow group"). CONCLUSIONS: Approximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the "low-flow group" had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients.

28. Accuracy of Qualitative and Semiquantitative Analysis of 18FDG Positron Emission Tomography Scans in the Evaluation of Primary and Metastatic Lesions.

Background: 18FDG PET scans are often interpreted on the basis of visual estimation of regional tracer uptake. Whether semiquantitative analysis may help clinicians in the recognition of neoplastic masses still remains debated.Materials and Methods: 134 patients with 144 dubious lesions on CT scans (89 pulmonary, 16 hepatic, 39 soft tissue) were studied by means of PET and 18(F)fluorodeoxyglucose. PET images were qualitatively interpreted by the consensus of two nuclear physicians. Standardized uptake value (SUV) and SUV lean were quantified in both normal and suspicious tissues. SUVs results in the lesion were also expressed as normalized values for the normal mean value in each organ (SUVs/org) and for the overall mean value in normal tissues (SUVs/norm).Results: All patients underwent cytological and/or hystological evaluation of the lesions: 53/144 (37%) were recognized as negative while 91/144 (63%) as positive for primary or metastatic disease. Qualitative analysis resulted in 75% specificity and 93% sensitivity. SUVs, SUVs lean, SUVs/org and SUVs/norm resulted significantly (p < 0.001) higher in positive than in negative lesions by cytology/histology. ROC curves analysis provided optimal cut-off values of 2.5, 0.8, 2.5 and 3, for SUVs, SUVs lean, SUVs/org and SUVs/norm, respectively. Using these cut-offs, specificity and sensitivity resulted 90 and 94%, 83 and 97%, 88 and 93%, 94 and 93%, respectively.Conclusion: Our data suggest that, in patients with CT scan suspicious lesions, visual analysis of PET scans is affected by a high number of false negative results. Semiquantitative assessment of regional metabolic activity has an incremental value and should be used in PET scan interpretation of dubious lesions.