Difference in myocardial flow reserve between patients with dilated cardiomyopathy and those with dilated phase of hypertrophic cardiomyopathy: evaluation by 15O-water PET.

BACKGROUND: The clinical features of patients with the dilated phase of hypertrophic cardiomyopathy (DHCM) may resemble those of patients with dilated cardiomyopathy (DCM); that is, systolic dysfunction and left ventricular dilatation. Myocardial flow reserve (MFR) is impaired in patients with nonischemic cardiomyopathy, and the reduced MFR may be related to poor prognosis. Several studies report that the mortality rate for patients with DHCM is higher than for DCM, but the difference between these 2 cardiomyopathies is still unclear. The purpose of this study was to assess the MFR of these 2 cardiomyopathies, using (15)O-water positron emission tomography (PET) to elucidate their differences. METHODS AND RESULTS: In total 30 patients were investigated: 23 with DCM (Group A) and 7 with DHCM (Group B). All those who were in a stable condition underwent cardiac catheterization. Myocardial blood flow (MBF) at rest and under ATP infusion was measured by (15)O-water PET, and the MFR was calculated. There were no significant differences in the hemodynamics of the 2 groups. The mean MFR in DHCM was significantly lower than that in DCM (1.49+/-0.31 vs 2.62+/-1.08; p=0.042), whereas MBF at rest did not differ (DCM vs DHCM: 0.66+/-0.20 vs 0.49+/-0.05 ml . min(-1) . g(-1); NS). The MFR in both Group A and B was significantly decreased compared with the normal controls (MFR in normal controls: 5.15+/-1.64, p=0.00015, 0.00013, respectively). CONCLUSIONS: These results suggest that impaired vasodilatation (ie, dysfunction of the microcirculation) is more severe in patients with DHCM than in patients with DCM, even though patients' characteristics and hemodynamics do not differ.

A catheter-based intravascular radiation detector of vulnerable plaques.

UNLABELLED: Detection of vulnerable plaques before rupture is important in preventing acute coronary events such as myocardial infarction. Although therapeutic strategies such as percutaneous transluminal coronary angioplasty appear to prevent coronary occlusion and consequently may lead to improved prognosis in these patients, a method of detecting vulnerable plaques has not been established. A nuclear method that uses an intravascular radiation detector (IVRD) with the plaque-avid tracer (18)F-FDG is one of the most promising methods. The catheter-based IVRD consists of a catheter probe (a scintillator and flexible optic fibers), photomultipliers, a controller, and an automatic pullback unit and personal computer. A phantom study demonstrated that this detector was highly sensitive to (18)F and enabled the detection of (18)F point sources. However, details of the detection system in vivo remain unclear. METHODS: To evaluate vulnerable plaques in vivo, we investigated a canine femoral artery and coronary artery using this detector system. Our goal was to estimate the ability of this device to navigate through these arteries and to detect (18)F point sources fixed on their adventitia. RESULTS: In the study using a canine femoral artery, the IVRD could detect the point sources with good repeatability. In the study using an open-chest canine model, the catheter probe could easily be advanced into the left descending coronary artery, and the IVRD could detect target sources attached externally to the coronary artery (7- to 15-mm intervals) with good resolution. CONCLUSION: This newly developed catheter-based IVRD was able to detect, with good resolution, the slight radioactivity from (18)F point sources attached to the femoral artery and the coronary adventitia. These results show that catheter-based detection of coronary vulnerable plaques may be feasible.

Myocardial metabolism of 123I-BMIPP under low-dose dobutamine infusion: implications for clinical SPECT imaging of ischemic heart disease.

PURPOSE: 123I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of 123I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake. METHODS: Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6). RESULTS: Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48+/-19% vs 66+/-14%, p<0.05) and its subsequent retention (73+/-13% vs 85+/-8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0+/-20.0% to 15.8+/-9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3+/-21.9% to 71.3+/-10.1%, p<0.05). CONCLUSION: These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight into the pathophysiology of stunned myocardium.

Right lateral decubitus position reduces QT dispersion in patients with chronic heart failure.

A greater QT dispersion in patients with chronic heart failure (CHF) appears to be a non-invasive marker of susceptibility to malignant ventricular arrhythmias. We evaluated whether QT dispersion in CHF patients is modified by the patients' recumbent position. In 12 CHF patients, and age and sex-matched 12 normal subjects, a single 12-lead surface ECG was recorded in each postural position [left lateral decubitus position (L), supine position (S), and right lateral decubitus position (R)]. In normal subjects, the QT dispersion was comparable in the three recumbent positions [L: 47+/-15 (SD) ms, S: 40+/-9 ms, R: 38+/-14 ms, P=NS]. In contrast, in CHF patients, QT dispersion was significantly shorter in R than those in L and S (L: 93+/-42 ms*, S: 81+/-29 ms*, R: 63+/-24 ms, *P <.05 vs. R). In conclusion, reclining in R reduces the prolonged QT dispersion in CHF patients.

Expression of MHC-beta and MCT1 in cardiac muscle after exercise training in myocardial-infarcted rats.

To evaluate the hypothesis that increasing the potential for glycolytic metabolism would benefit the functioning of infarcted myocardium, we investigated whether mild exercise training would increase the activities of oxidative enzymes, expression of carbohydrate-related transport proteins (monocarboxylate transporter MCT1 and glucose transporter GLUT4), and myosin heavy chain (MHC) isoforms. Myocardial infarction (MI) was produced by occluding the proximal left coronary artery in rat hearts for 30 min. After the rats performed 6 wk of run training on a treadmill, the wall of the left ventricle was dissected and divided into the anterior wall (AW; infarcted region) and posterior wall (PW; noninfarcted region). MI impaired citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities in the AW (P < 0.01) but not in the noninfarcted PW. No differences in the expression of MCT1 were found in either tissues of AW and PW after MI, whereas exercise training significantly increased the MCT1 expression in all conditions, except AW in the MI rats. Exercise training resulted in an increased expression of GLUT4 protein in the AW in the sham rats and in the PW in the MI rats. The relative amount of MHC-beta was significantly increased in the AW and PW in MI rats compared with sham rats. However, exercise training resulted in a significant increase of MHC-alpha expression in both AW and PW in both sham and MI rats (P < 0.01). These findings suggest that mild exercise training enhanced the potential for glycolytic metabolism and ATPase activity of the myocardium, even in the MI rats, ensuring a beneficial role in the remodeling of the heart.

A catheter-based radiation detector for endovascular detection of atheromatous plaques.

PURPOSE: Although various radiopharmaceuticals have been developed for the detection of atheromas, external imaging techniques have limitations when it comes to the detection of small plaques. In this study, we developed a charged particle-sensitive detector for the endovascular detection of small plaques. METHODS: The device consists of a probe, an automatic pullback unit and a controller. The probe, which consists of a plastic scintillator and flexible optical fibres, is 1.0 mm in diameter. The probe was inserted into a catheter placed on (18)F point sources, and then the radioactivity was measured as the probe was pulled out stepwise. RESULTS: The sensitivity for (18)F was 9.3 cps/kBq, and there was a close linear correlation between the peak counts and source dose until at least 0.8 MBq. Furthermore, this device showed low background counts (<0.1 cps) and a low detection limit (0.21 kBq). To investigate the effect of background radioactivity on the measurement at the point sources, a ball phantom was prepared and five (18)F point sources were set on the ball's surface. Even though 298 MBq of (18)F-fluorodeoxyglucose was injected into the ball, the point sources located every 10 mm on the ball's surface were detectable separately. CONCLUSION: The data gathered suggest that a catheter-based radiation detector in combination with charged particle-emitting radiopharmaceuticals is useful for the endovascular detection of small lesions such as coronary plaques.