Early surgery with aggressive surgical approach to improve 6-month outcomes in patients with active infective endocarditis: contribution of cerebral preoperative magnetic resonance imaging.

OBJECTIVES: We investigated the hypothesis that early surgery for infective endocarditis (IE) attenuates the rate of death or embolic events and does not increase the rate of relapse or postoperative valvular dysfunction (PVD) at 6 months. METHODS: 21 consecutive patients who underwent surgical treatment of IE were prospectively included. We assessed 6-month postoperative clinical outcomes by comparing early surgery (Group E, surgery within 72 h) and conventional treatment (Group C). Nine patients (43%) were assigned to Group E based on a combination of preoperative evaluation parameters, including the findings of cerebral magnetic resonance imaging (MRI), which was performed in all patients with left-sided IE. RESULTS: Six surgical plans (5 advancements and 1 postponement) were modified by routine MRI. Although preoperative echocardiography did not confirm all annular invasions, the rate of periannular infection, which was treated by pericardial annular patch plasty (56%) in patients with native-valve IE, was higher in Group E than C (P = 0.006). Early surgery based on MRI findings resulted in no postoperative embolic events or cerebral bleeding. The 6-month mortality rate was 0% in both groups, although the calculated 6-month IE mortality rate was 49.2 ± 25% and 28.8 ± 18%, respectively. No recurrence of IE or PVD occurred in Group E. The 6-month rate of freedom from composite events was 100% in Group E. CONCLUSIONS: Aggressive treatment (periannular resection and disuse of a prosthetic annuloplasty ring) and optimal antibiotic therapy based on intraoperative microorganisms, even in patients who underwent early surgery, reduced the 6-month relapse and PVD rates.

[An approach to complete the manual for determination of serum pirmenol levels].

In order to complete TDM manual for pirmenol in Sapporo Medical Center NTT East, we developed HPLC method and pretreatment procedure for pirmenol samples obtained from patients. Serum (250 microliters) was alkalinized and pirmenol was extracted into n-hexane, and then the drug was again extracted into an acidic solvent, 0.044 M KH2PO4 (pH 2.6) including 0.5% triethylamine. The aqueous extract was used for quantitative determination of the drug by HPLC. The mobile phase consisted of the above acidic solvent-acetonitrile (5:1, v/v) was delivered at 45 degrees C with a flow rate of 1 ml/min through a 4.6 mm x 25 cm ODS-3, a reversed-phase column. Detection of pirmenol and the internal standard (disopyramide) was achieved at 263 nm. Pirmenol and disopyramide was eluted at 5 and 11 min, respectively. Assay limit (25 ng/ml) and accuracy of the analytical method were satisfactory for TDM of pirmenol. During the HPLC analysis of patient samples, no substances that interfered with pirmenol detection were found. It was shown that 1) hemolysis did not affect pirmenol assay at all, 2) pirmenol was stable in the blood samples for at least 24 h even if they were stood at room temperature, and 3) pirmenol was stable for at least 3 days in frozen serum but there significant decrease was observed in pirmenol concentration after 7 days.

Serial changes in BMIPP uptake in relation to thallium uptake in the rat myocardium after ischaemia.

Several clinical studies have shown that iodine-123 labelled 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) uptake is often lower than the uptake of perfusion tracers in patients with ischaemic heart disease. However, BMIPP accumulation may not decrease during the acute phase of a stunned myocardium in patients with acute coronary syndrome. We evaluated serial changes in BMIPP and perfusion tracer uptake in the myocardium after ischaemia. We performed a 20-min left coronary artery occlusion followed by reperfusion in male Wistar rats. One hour after the reperfusion, echocardiography was performed. Intravenous injection of iodine-125 labelled BMIPP and thallium-201 was performed 1 day (acute group) and 5 days (subacute group) after the operation. To determine the myocardial distribution of 125I-BMIPP and 201Tl, dual-tracer autoradiography was conducted. We identified regions of interest in the anterolateral wall as an area at risk and in the inferoseptum as a remote control area. The anterolateral wall/inferoseptum ratio (A/I ratio) was calculated to compare the distributions of 125I-BMIPP and 201Tl. Coronary occlusion induced hypokinesia in the anterolateral region 1 h after the reperfusion. The A/I ratio of 125I-BMIPP was significantly higher than that of 201Tl in the acute group (1.01 +/- 0.15 vs 0.80 +/- 0.23, P<0.001). On the other hand, there was no significant difference between the A/I ratios of 125I-BMIPP and 201Tl in the subacute group (0.88 +/- 0.18 vs 0.85 +/- 0.18). Two rats showed a significantly lower A/I ratio of 125I-BMIPP than 201Tl in the subacute phase. These data suggest that BMIPP uptake is preserved despite a decrease in perfusion in the acute phase after ischaemia. In the subacute phase, on the other hand, BMIPP uptake is similar to or even lower than thallium uptake. Since BMIPP uptake may change with time after ischaemia, careful interpretation of BMIPP uptake after ischaemia is required in a clinical setting.

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15-labeled water PET.

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.

Increased cycle length variability during ventricular fibrillation: a novel predictor of arrhythmia recurrence.

To evaluate the clinical value of cycle length (CL) variability during ventricular fibrillation (VF), 26 patients who underwent implantable cardioverter defibrillator (ICD) implantation were enrolled. In VF induced for defibrillation testing, mean and SD of VFCL, mean successive differences (MSD) of VFCL, and coefficient of variations of the VFCL (CV(FF)) (SD x 100/mean VFCL) were calculated. During the follow-up period of 20 +/- 2 months, ventricular arrhythmias recurred in 13 patients. MSD and CV(FF) were 31 +/- 3(*) ms and 15.6 +/- 1.3(**) in recurrence group (n = 13), and 17 +/- 2 ms and 9.0 +/-1.1 in non-recurrence group (n = 13) ((*)P <.005, (**)P <.001 vs. nonrecurrence group). Relatively good repeatability of mean VFCL, MSD and CV(FF) in each patient was confirmed by the Bland-Altman method. In VF induced by programmed ventricular stimulation before ICD implantation, MSD and CV(FF) in recurrence group were also increased significantly. Kaplan-Meier estimates revealed that MSD >or= 20 ms and CV(FF) >or= 12 predicted higher arrhythmia recurrence (MSD, P =.039; CV(FF), P =.0069 by the log-rank test). By multivariate analysis, CV(FF) >or= 12 was a significant predictor of recurrent arrhythmic events (P =.019). In conclusion, the CL variability of VF, which was evaluated as MSD and CV(FF), is increased in patients with arrhythmia recurrence. These values may reflect the degree of electrical heterogeneity, and appears to be useful indexes of the future arrhythmic events.

Estimation of myocardial blood flow and myocardial flow reserve by 99mTc-sestamibi imaging: comparison with the results of [15O]H2O PET.

We developed a noninvasive method to quantitatively estimate the myocardial blood flow (MBF) index and flow reserve (MFR) using dynamic and static data obtained with technetium-99m sestamibi, and compared the results with MBF and MFR measured by oxygen-15-labeled water ([(15)O]H(2)O) PET. Twenty patients with coronary artery disease (CAD) and nine normal subjects underwent both (99m)Tc-sestamibi and PET studies within 2 weeks. From the anterior view, dynamic data were acquired for 2 min immediately after the injection of (99m)Tc-sestamibi, and planar static images were also obtained after 5 min at rest and during ATP stress (0.16 mg kg(-1) min(-1) for 5 min) on another day. The area under the time-activity curve on the aortic arch (Aorta ACU), myocardial weight with the SPET image (M), and the myocardial count on the planar image for 1 min (C(m)) were obtained. The MBF index (MBFI) was calculated as follows: MBFI=Cm/Aorta ACU x 100M. MFR was measured by dividing the MBFI at ATP stress by MBFI at rest. The MBFI measured by (99m)Tc-sestamibi was significantly correlated with MBF obtained using [(15)O]H(2)O PET (MBFI=13.174+11.732 x MBF, r=0.821, P<0.001). Furthermore, MFR measured by (99m)Tc-sestamibi was well correlated with that obtained using [(15)O]H(2)O PET, with some underestimation (r=0.845, P<0.001). MFR using (99m)Tc-sestamibi in patients with CAD was significantly lower than that in normal subjects (CAD: 1.484+/-0.256 vs normal: 2.127+/-0.308, P<0.001). These data suggest that the MBFI and MFR can be measured with (99m)Tc-sestamibi. This may be useful for the quantitative assessment of CAD, especially in those patients with diffuse coronary disease.

[The trend of anti-arrhythmic drug development].

New anti-arrhythmic drugs have been developed by the progress of molecular-biological and physiological research on an ion channel and the elucidation of pharmacological effects of traditional anti-arrhythmic drugs. After CAST study, K+ channel blockers instead of Na+ channel blockers were developed and used in anti-arrhythmic treatment. In Sicilian Gambit, it was advocated that the anti-arrhythmic drug selection was based on both pharmacological action of drugs and mechanism of arrhythmias, including electrical remodeling which was mainly studied on atrial fibrillation and structural remodeling such as myocardial fibrosis. Furthermore, the target of anti-arrhythmic treatment will be not only the arrhythmic control with drugs but changing many factors related to the arrhythmic substrates, modulators and triggers of arrhythmias.

Low-dose dobutamine stress gated SPET for identification of viable myocardium: comparison with stress-rest perfusion SPET and PET.

The detection of viable myocardium is important for the prediction of functional recovery after revascularisation. However, a fixed perfusion defect often includes viable myocardium, and perfusion imaging then underestimates myocardial viability. We previously reported that low-dose dobutamine stress gated single-photon emission tomography (SPET) provides similar findings to dobutamine stress echocardiography in the assessment of myocardial viability. The present study investigated whether low-dose dobutamine stress gated SPET is of additional value as compared with stress-rest technetium-99m tetrofosmin SPET for the detection of myocardial viability. Standard stress-rest perfusion SPET, low-dose dobutamine stress gated SPET and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) were studied in 23 patients (mean age 67+/-7.6 years) with previous myocardial infarction. Twenty-one of them were successfully studied with each technique. FDG PET viability (FDG uptake >/=50%) was employed as the gold standard. One-day stress-rest (99m)Tc-tetrofosmin myocardial SPET was performed. After the resting study, gated SPET was acquired following infusion of 7.5 microg kg(-1) min(-1) of dobutamine. Left ventricular wall motion in 16 segments was assessed by cine mode display using a four-point scale. Myocardial viability was considered present when there was improvement by one point. Of a total of 336 segments analysed, 53 had persistent defects on stress-rest perfusion SPET. FDG viability was seen in 16 of 17 dobutamine-responsive segments, but in only 11 of 36 dobutamine non-responsive segments ( P<0.01). Thus, in the segments with persistent defects, viability findings on low-dose dobutamine stress gated SPET were concordant with those on FDG PET in 77% of segments (kappa value =0.55). For the detection of FDG-viable myocardium, the combination of stress-rest perfusion SPET and low-dose dobutamine stress gated SPET achieved a better sensitivity than stress-rest perfusion SPET alone (35/46, 76% vs 19/46, 41.3%, P<0.001), with a similar specificity (25/29, 86% vs 26/29, 90%, P=NS). We conclude that in the identification of viable myocardium, low-dose dobutamine stress gated SPET may provide additional information missed on a routine stress-rest perfusion scan. Dobutamine stress gated SPET may provide new insights into myocardial viability on the basis of ischaemia and contractile reserve.

[Science in atherosclerosis].

Ischemic heart disease and cerebral vascular accident are major cause of death in Japan. Development of these diseases is based on atherosclerosis, which would become evident in the middle-aged. Atherosclerosis is a process of aging, because its progression is closely associated with increase in age. Other factors such as smoking, eating habits and obesity are known to facilitate it. Therefore, it is very important for each one of us to learn the risk factors of atherosclerosis and to prevent it by paying attention to our life style. In this citizen joint symposium, we focused on the strategy for treatment and prevention of atherosclerosis by summarizing its mechanisms and consequences. Participation in the symposium could hopefully stimulate our civil activities against atherosclerosis and help promoting our health care in Hokkaido.