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A time-over-threshold (ToT)-based positron emission tomography (TODPET) scanner was designed and fabricated. The PET scanner consisted of eight block detectors, each of which is composed of a 12×12 array of 2×2×10 mm 3 Pr:LuAG crystals individually coupled with a 12×12 UV-enhanced avalanche photodiode (APD) array. The APDs were individually read out using a custom-designed time-over-threshold application-specific integrated circuit (ASIC) and field-programmable gate array (FPGA) readout system. The PET scanner has an energy resolution of 10% and a time resolution of 4.2 ns. A spatial resolution of 1.17 mm (FWHM) was demonstrated in the initial results.

The breast cancer is one of the most frequent cause of death among female cancer patients. However, when discovered at the early stage, the probability of recovery is very high. Therefore, the development of positron emission mammography (PEM) to detect the breast cancer at the early stage with high efficiency is demanding. As the diameter of the scanner part is small, a scintillator with faster response is required. As the recently developed Pr:LuAG has almost twice as short scintillation decay time than that of Ce:LSO, the Pr:LuAG scintillator was employed in our recently developed PEM system. One camera unit consisted of 20 × 64 scintillator pixels optically coupled with three H8500-03 multi anode photomultipliers. The Pr:LuAG pixel size is 2.1 × 2.1 × 15 mm 3 and the BaSO 4 was used as a reflector. Four planar cameras are placed at both sides. Therefore, eight cameras were installed at both sides of the instrument. The spatial resolution was evaluated to be 1.1 mm using the 22 Na point source. Fluorodeoxyglucose with 18 F hotspot image was also detected using the breast phantom.

In order to detect the breast cancer at the early stage with high efficiency, we intend to develop positron emission mammography (PEM), using Pr:LuAG single crystal as a scintillator of this scanner. PEM has the same mechanism of PET, where two 511 keV annihilation gamma-rays are detected by two gamma cameras at opposite side, and reconstruction of the data shows the position of the cancer with malignancy grades. After cutting and polishing processes for each crystal to a physical dimensions of 2.1 × 2.1 × 15 mm3, Pr:LuAG array covered with BaSO4 reflector was used as a sensor head. The one camera unit consisted of 20 × 64 pixels optically coupled with three H8500-03 multi anode PMTs. Our PEM required four cameras at each side. Finally, eight cameras were installed in both sides of the prototype instrument and the spatial resolution was evaluated using the 18F in the breast phantom.

Changes in the autonomic nervous activity can be induced by various sensory and emotional stimuli. The authors examined whether the power spectral analysis of heart rate variability (HRV) could detect changes in autonomic tone following a lavender aroma treatment or not. Healthy young women (n=10, 23+/-3 years old) underwent continuous electrocardiographic (ECG) monitoring before and after (10, 20, 30 minutes) the lavender fragrance stimuli. HRV was expressed by three indices: low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components (nLF and nHF, respectively) as well as LF/HF ratio. Increases in the parasympathetic tone were observed after the lavender fragrance stimulus as seen as increases in the HF component and decreases in the LF/HF. Additional measurement with positron emission tomography (PET) demonstrated the regional metabolic activation in the orbitofrontal, posterior cingulate gyrus, brainstem, thalamus and cerebellum, as well as the reductions in the pre/post-central gyrus and frontal eye field. These results suggested that lavender aromatic treatment induced not only relaxation but also increased arousal level in these subjects.

Objectives We sought to prospectively compare the prognostic value of cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging with that of heart rate variability (HRV) in patients with mild-to-moderate chronic heart failure (HF). Background Cardiac I-123 MIBG imaging, which reflects cardiac adrenergic nerve activity, provides prognostic information on chronic HF patients. Reduced HRV, indicating derangement in cardiac autonomic control, was also reported to be associated with a poor prognosis in chronic HF patients. Methods At study entry, I-123 MIBG imaging and 24-h Holter monitoring were performed in 65 chronic HF outpatients with a radionuclide left ventricular ejection fraction Results At a mean follow-up of 34 ± 19 months, WR (p Conclusions Cardiac MIBG WR has a higher prognostic value than HRV parameters in patients with chronic HF. The combination of abnormal WR and n-VLFP would be useful to identify chronic HF patients at a higher risk of cardiac events.

In patients with paroxysmal atrial fibrillation (Paf), the identification of the coexistence of sinus node dysfunction (SND) has therapeutic implications. This study sought to prospectively determine whether SND in patients with Paf would be identified by use of atrial early potential (EP), low-amplitude potentials early in signal-averaged P wave.The study population consisted of 149 patients with Paf. Signal-averaged electrocardiography was recorded with the P-wave-triggering technique. The root mean square voltage for the initial 30 MS and the duration of initial low-amplitude signals4 microV of signal-averaged P wave were measured in the vector magnitude. The criteria of EP were defined as "the root mean square voltage for the initial 30 MS3.0 microV and the duration of initial low-amplitude signals4 microV22 MS." SND was diagnosed by use of the conventional 12-lead electrocardiography, 24-hour Holter monitoring, and bedside electrocardiographic monitoring.Thirty-eight of 149 patients with Paf had EP. Eighteen (47%) of 38 patients with Paf and EP had SND, whereas SND was found in only 5 (5%) of the other 111 patients with Paf without EP (P.0001). EP gave a sensitivity of 78% and a specificity of 84% for the detection of SND in patients with Paf.EP would be useful for the identification of SND in patients with Paf.

OBJECTIVESWe sought to prospectively determine whether patients with congestive heart failure (CHF) at risk for paroxysmal atrial fibrillation (PAF) could be identified by clinical and study variables including the P-wave signal-averaged electrocardiogram (P-SAECG).BACKGROUNDAlthough it is important to assess the risk of developing PAF in patients with CHF, it still remains difficult to predict the PAF appearance in patients with CHF clinically.METHODSThe study group consisted of 75 patients in sinus rhythm without a history of PAF, whose left ventricular ejection fraction, as measured by radionuclide angiography, was

Background It is well known that paroxysmal atrial fibrillation (PAF) often precedes the establishment of chronic atrial fibrillation (CAF). However, there have been no definite methods to predict the transition from PAF to CAF. The purpose of this report was to determine prospectively whether P-wave–triggered signal-averaged ECG (P-SAE) is useful for the prediction of the transition to CAF in patients with PAF. Methods and Results One hundred twenty-two consecutive patients with PAF were prospectively followed after P-SAE, echocardiography, and 24-hour Holter monitoring at study entry. The duration (Ad) and root-mean-square voltage for the last 30 ms (LP30) of the filtered P wave were measured in P-SAE. The abnormality of P-SAE for the prediction of transition to CAF was defined as Ad ≥145 ms and LP30 P 2 =8.6, P =.003) and LP30 (χ 2 =5.1, P =.02), although significant differences in the left atrial dimension (40.8±5.3 versus 37.3±5.5 mm, P P Conclusions These results indicate that P-SAE could be useful to identify patients at risk for the transition from PAF to CAF.

The beat-to-beat variation of PR interval, which is thought to be a reflection of autonomic nervous system, is difficult to measure with accuracy because the variation is too subtle. However, R wave amplitude in the P wave triggered SAECG is easily attenuated in comparison to that in the R wave triggered SAECG, which might be due to PR interval fluctuation. To determine whether autonomic neuropathy could be detected by use of SAECG, two types of SAECGs triggered by P and R waves were recorded in 23 diabetics with autonomic neuropathy and 41 age matched controls. The peak voltage of filtered QRS complex was measured in the R wave and P wave triggered SAECGs. Percent attenuation of the filtered QRS voltage was calculated by dividing the difference between the voltages in the R wave and P wave triggered SAECGs by the voltage in R wave triggered SAECG. The percent attenuation of filtered QRS voltage was significantly smaller in diabetics with autonomic neuropathy than controls (4.6% +/- 4.9% vs 16.3% +/- 15.0%; P < 0.001). These results suggest that the degree of attenuation of filtered QRS voltage in the P wave triggered SAECG would be useful for the detection of autonomic neuropathy.

Objectives. This study sought to determine whether patients with sick sinus syndrome could be detected by analyzing the initial portion of the signal-averaged P wave corresponding to the electrical activity of the perinodal atrial myocardial cells.Background. In sick sinus syndrome, pathophysiologic abnormalities have been shown not only in the sinus node, but also in atrial muscle, especially the perinodal portion.Methods. The study included 41 patients with sick sinus syndrome and 140 age-matched control subjects. Eighteen of 41 patients with sick sinus syndrome had paroxysmal atrial fibrillation. Signal-averaged P wave electrocardiograms (ECGs) were recorded through a bandpass filter of 40 to 300 Hz with a P wave-triggering technique. Signals of the orthogonal bipolar leads were combined into a spatial magnitude. The root mean square voltage for the initial 30 ms (EP30) and the duration of initial low amplitude signals 22 ms as atrial early potential gave a sensitivity of 76%, a specificity of 91%, a positive predictive value of 74% and a negative predictive value of 93% for identification of patients with sick sinus syndrome.Conclusions. These results suggest that the long, low amplitude signals early in the filtered P wave on the signal-averaged ECGs are characteristic of sick sinus syndrome. Thus, the atrial early potential could be a useful marker to identify patients with sick sinus syndrome.

In this report, PEM scanner using a Pr:LuAG scintillator crystal will be discussed. We have developed the PEM scanner with planer detectors which can change the angle and the distance depending on the condition of diagnosis. The planer detectors were composed of four units respectively and one unit consisted of a 20 × 64 pixels scintillator array optically coupled with three H8500 multi anode photomultipliers. As a scintillator Pr:LuAG was installed which possesses interesting properties such as a very fast decay time of 20 ns and a good energy resolution of 4.2 %. The Pr:LuAG pixel size was 2.1 mm × 2.1 mm × 15 mm and the BaSO4-type reflector was used for the array assembly. Based on this PEM system we have performed the clinical studies and compared with the images detected by the PET scanner. Because the spatial resolution of PEM is better than PET, advantages of PEM scanner were clearly shown.

A Positron Emission Mammograph (PEM) with a pair of planer detectors dedicated for breast cancer detection is developed under collaborations of Tohoku University, Kobe City Collage of Technology, and Furukawa Co., Ltd. It uses thin crystals made of a scintillator Pr:Lu3A15O12 (Pr:LuAG) of 2.1×2.1×15.0 mm in size combined with H8500 position sensitive Photo multi tubes (PMTs) from Hamamatsu. The PEM system is comprised of two opposing detectors that have 140×200 cm2 field of view (FOV). We present its basic architecture with fundamental performance, such as spatial resolution, time resolution, energy resolution, and data acquisition count rate. The Spatial resolution measured using a 22Na point sauce was found to be 1.1 mm FWHM for image planes parallel to the detector faces. Time resolution was 3.1 ns FWHM. And, energy resolution was 11.6 % FWHM (@511 keV) at the center of detector blocks. Coincident count rate was improved dramatically for optimizing energy windows level and implementation a new offset correction method.

We have developed Time over Threshold (ToT) based Pr:LuAG-APD PET (TODPET) tomograph with a mixed signal front-end. The tomograph consists of 8 block detectors, each of which is composed of a 12 × 12 array of 2 × 2 x 10mm3 Pr:LuAG crystals individually coupled with 12 × 12 UV-enhanced APD arrays. The APDs are individually read out with a custom-designed Time over Threshold ASIC and FPGA readout system. Developed PET tomograph has the energy resolution of 10% and the time resolution of 4.2ns. The 1.76mm spatial resolution (FWHM) is achieved for the first result.

To determine whether the extent of myocardial fibrosis in dilated cardiomyopathy could be estimated noninvasively, signal-averaged electrocardiograms were recorded in 32 patients with dilated cardiomyopathy, followed by left ventricular endomyocardial biopsy. The root mean square voltage for the last 40 msec (V40), the duration of the filtered QRS complex (fQRSd) and the duration of low amplitude signals40 microV (LAS) were obtained by signal-averaged electrocardiography. The extent of fibrosis in all biopsy samples was measured by the point-counting method. The extent of myocardial fibrosis closely correlated with fQRSd (r = 0.623, p0.001), LAS (r = 0.570, p0.001), and V40 (r = -0.355, p0.05). When fibrosis was classified into intercellular and interfascicular types, the extent of intercellular fibrosis more closely correlated with fQRSd (r = 0.695, p0.0001), LAS (r = 0.640, p0.0001), and V40 (r = -0.533, p0.005). These results suggest that signal-averaged electrocardiograms might be useful for estimation of the extent of myocardial fibrosis, especially intercellular fibrosis in patients with dilated cardiomyopathy.

Objectives. The purpose of this study was to elucidate whether the effectiveness of long-term beta-blocker therapy could be predicted before this therapy is started. Background. Long-term beta-blocker therapy has recently been reported to provide a favorable effect in treatment of congestive heart failure due to dilated cardiomyopathy. Methods. Several measurements including histologie variables before administration of metoprolo'. were retrospectively compared among 18 good responders (showing improvement of at least one New York Heart Association functional class or an increase in ejection fraction ≥0.10 12 months after drug administration) and 12 poor responders without such improvement. Results. Although there were no significant differences between the two groups in age, gender, functional class, heart rate, blood pressure, pulmonary capillary wedge pressure, cardiac index, left ventricular end-diastolic dimension and ejection fraction, percent fibrosis estimated by the point-counting method in endomyocardial biopsy specimens was significantly lower in good than in poor responders (7.6 ± 5.7 vs. 14.2 ± 9.7%, p < 0.05). Moreover, when the types of fibrosis were classified as interfascicular and intercellular by the dominance of counted points, there were 13 cases of interfascicular fibrosis and 5 cases of intercellular fibrosis in good responders and 1 case of interfascicular fibrosis and 11 cases of intercellular fibrosis in poor responders (p < 0.001, sensitivity 72%, specificity 91%, predictive accuracy 80%). These results suggest that improvement with long-term beta-blocker therapy may be more likely to occur in patients with less myocardial fibrosis, with interfascicular fibrosis the dominant type. Conclusions. The extent and type of fibrosis may be important factors in the prediction of the effectiveness of long-term betablocker therapy for dilated cardiomyopathy.

Nowadays, the neural receptor study has been reported in many research papers. Human studies related with neural receptors have made progress by the technological improvement of positron emission tomography (PET) and development of various radiopharmaceuticals that can specifically bind to neuroreceptors. A previous study by Koepp et al. revealed, in 1998, that the release of neuronal dopamine had been increased in human brain during performing a "goal-directed task" (video game). Given an idea from this previous study, we hypothesized that the release of histamine, another neurotransmitter in the brain, might change under the influence of physiological factors such as stress and circadian rhythm. The purpose of our present study was to evaluate the change of brain histamine release induced by stress and circadian rhythm in the healthy human subjects by using [11C]doxepin and PET method.

To clarify the relationship between clotting and lytic activities of intracardiac thrombi, and to elucidate whether this could be used to evaluate the embolic risk the ratio of indium-111 radioactivity accumulated on thrombi to that in the blood pool using dual-tracer technique %IE as a parameter of the clotting activity, and D-dimer, which is a fibrin specific degradation product, as a parameter of lytic activity were measured in 37 patients with intracardiac thrombi. Fifteen of the 37 patients had past histories of arterial embolization. The values of D-dimer correlated significantly with those of %IE (r = 0.758, p less than 0.01), e.g., the higher the values of D-dimer the higher the values of %IE. 37 patients were divided into 2 groups using the regression line for the D-dimer and %IE domains. Eleven patients above the regression line had thrombosis in excess of fibrinolysis but the remaining 26 patients under the regression line had fibrinolysis in excess of thrombosis. The incidence of past embolic episodes was 82% (9/11) in patients with thrombosis in excess of fibrinolysis but 23% (6/26) in patients with fibrinolysis in excess of thrombosis. These results demonstrated that intracardiac thrombi were under the dynamic process between the clotting and the lytic activities and moreover patients with intracardiac thrombi and thrombosis in excess of fibrinolysis had a substantial risk of arterial embolization.

The incidence of breast cancer is in the first place as a cause of death among Japanese women. The breast cancer is a type of cancer which can be cured relatively easily when detected early. However, it is now clear that the detection of breast cancer is difficult without imaging modalities such as X-ray mammography and/or ultrasonic echography. These imaging devices are useful, however, morphological information only are not enough for differentiating cancer from other benign diseases. Positron emission tomography (PET) for whole-body diagnosis can give us functional information regarding the degree of malignancy. But still there remain various problems such as limited spatial resolution and motion artifacts due to respiratory movement, as well as an issue of the high costs. To compensate these weak points, we have started development of the positron emission mammography (PEM) dedicated for the local diagnosis of the breast tissue.

To clarify whether the formation of thrombi could be induced by atrial fibrillation itself or by factors predisposing to atrial fibrillation such as mitral stenosis, plasma D-dimer levels (cross-linked fibrin degradation products) were measured in 73 patients with chronic atrial fibrillation (Group 1) and 21 patients without atrial fibrillation (Group 2). In Group 1, 49 of the 73 patients had factors predisposing to atrial fibrillation such as valvular heart disease, and the remaining 24 had lone atrial fibrillation. In Group 2, 16 patients had organic heart disease and the remaining 5 had a chest pain syndrome.The plasma D-dimer level was significantly higher in Group 1 (150 ± 19 ng/ml) than in Group 2 (61 ± 3 ng/ml) (p < 0.01. mean ± standard error of the mean). In both groups, there were no significant differences in plasma D-dimer level between patients with and without organic heart disease (146 ± 18 versus 156 ± 46 ng/ml in Group 1; 61 ± 4 versus 59 ± 10 ng/ml in Group 2).These findings indicate that atrial fibrillation itself may be more important than factors predisposing to atrial fibrillation in the development of intracardiovascular clotting.

We sought to prospectively compare the prognostic value of cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging with that of heart rate variability (HRV) in patients with mild-to-moderate chronic heart failure (HF).Cardiac I-123 MIBG imaging, which reflects cardiac adrenergic nerve activity, provides prognostic information on chronic HF patients. Reduced HRV, indicating derangement in cardiac autonomic control, was also reported to be associated with a poor prognosis in chronic HF patients.At study entry, I-123 MIBG imaging and 24-h Holter monitoring were performed in 65 chronic HF outpatients with a radionuclide left ventricular ejection fraction40%. The cardiac MIBG heart to mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. The time and frequency domain parameters of HRV were calculated from 24-h Holter recordings.At a mean follow-up of 34 +/- 19 months, WR (p0.0001), H/M on the delayed image (p = 0.01), and normalized very-low-frequency power (n-VLFP) (p = 0.047) showed a significant association with the cardiac events (sudden death in 3 and hospitalization for worsening chronic HF in 10 patients) on univariate analysis. Multivariate analysis revealed that WR was the only independent predictor of cardiac events, although the predictive accuracy for the combination of abnormal WR and n-VLFP significantly increased, compared with that for abnormal WR (82% vs. 66%, p0.05).Cardiac MIBG WR has a higher prognostic value than HRV parameters in patients with chronic HF. The combination of abnormal WR and n-VLFP would be useful to identify chronic HF patients at a higher risk of cardiac events.

OBJECTIVE—To determine whether cardiac iodine-123 metaiodobenzylguanidine (123I MIBG) imaging is useful in predicting the prognosis of patients with chronic heart failure. DESIGN—Cardiac 123I MIBG imaging was done on entry to the study. The cardiac MIBG washout rate was calculated from anterior chest view images obtained 20 and 200 minutes after injection of the isotope. Study patients were divided into two groups with washout rates above and below 27% (the mean value + 2 SD obtained in 20 normal subjects), and were then followed up. SETTING—Tertiary referral centre. PATIENTS—79 patients with chronic heart failure in whom the left ventricular ejection fraction was less than 40%. RESULTS—There were 37 patients in group 1 (washout rate of ⩾ 27%) and 42 in group 2 (

Aims This study sought to investigate whether the spatial dispersion of signal-averaged P wave duration would be increased in patients with paroxysmal atrial fibrillation, by use of precordial mapping of the P wave signal-averaged ECG. Methods and Results The P wave signal-averaged ECG was recorded by the P wave-triggering method from 16 precordial leads in 55 patients with paroxysmal atrial fibrillation and 57 control subjects. As an index of the dispersion of signal-averaged P wave duration, we obtained the difference between the maximum and minimum in 16 recording sites. The dispersion was significantly greater in the patients with paroxysmal atrial fibrillation than the controls (26·6±9·5 vs 14·8±6·7ms, P

Objective—To determine whether the effectiveness of long term β blocker treatment for idiopathic dilated cardiomyopathy can be predicted by signal averaged electrocardiography (ECG). Patients—31 patients with dilated cardiomyopathy and without bundle branch block were included in a retrospective study and 16 in a prospective study. Methods—A signal averaged ECG was recorded before β blocker treatment, and three variables were measured from the vector magnitude: QRS duration, root mean square voltage for the last 40 ms (RMS40), and duration of the terminal low amplitude signals ( 20 µV, LAS40

To clarify how the long-term β-blocker (β) therapy for the patients (pts) with dilated cardiomyopathy (DCM) improves the rate of freedom from cardiac death (RFCD), 57 DCM pts with β (metoprolol; 40–60 mg/day)(G-l, followup; 6–120 M) and 72 DCM pts without β (G-2, follow-up; 6–102 M) were followed up. The survival was confirmed by annual interview. The cause of death and the preterminal condition of the pts were obtained from family members, medical personnel or medical recordings. The RFCO was analyzed with Kaplan-Meier life table method. At entry, there were no significant differences in age, sex, blood pressure, heart rate, left ventricular end-diastolic dimension (64.0 ± 6.0 vs 63.5 ± 6.8 mm) and ejection fraction (40.7 ± 9.1 vs 42.3 ± 8.3%) measured by echocardiography, and the severity of ventricular arrhythmia by 24 hours Holter monitoring (according to the Lawn's grade) between G-l and G-2. During the follow-up period, non-cardiac death occurred in 2 pts in G-1 and in 3 pts in G-2. The annual RFCD were calculated as shown below; 1Y 2Y 3Y 4Y 5Y 6Y 7Y G-1 1.0 * 1.0 # 0.98 * 0.98 # 0.98 # 0.98 # 0.87 * G-1 0.91 0.86 0.84 0.84 0.72 0.62 0.62 * p l 0.05 # P l 0.01 vs G-2 The number of death from heart failure did not show significant difference between G-1 (3 of 57 pts) and G-2 (4 of 72 pts). On the other hand, sudden death has occurred more often in G-2 (10 of 72 pts) than in G-1 (1 of 57 pts) (p l 0.05), resulting in that the RFCD was significantly better in G-l than in G-2. These results indicate that the long-term β-blocker therapy for DCM might improve the rate of freedom from cardiac death due to prevention of sudden death rather than of death from heart failure.

A 49-year-old woman was seen because of exertional dyspnea. Two-dimensional echocardiography revealed the presence of a large mass in the left atrium. An urgent operation was performed because the tumor suddenly stuck in the mitral orifice. The lesion, which occupied the entire left atrium, was resected during cardiopulmonary bypass. Histologic analysis revealed malignant hemangiopericytoma.

Aminophylline (Am) a potent adenosine receptor blocker, may increase transmural blood flow in the ischemic myocardium by preventing the maldistribution of coronary flow, although this agent is known to elevate myocardial oxygen consumption. To determine whether aminophylline does have this action, symptom-limited ramp-fashioned treadmill stress testing, combined with gas exchange analysis, was performed in 20 patients with coronary heart disease. In the first stress testing, Am (7 mg/kg) was administered over a 20-min period just before exercise. The second stress testing, the control study, was carried out without Am. There were no significant differences in basal heart rate, systolic blood pressure, rate-pressure product or oxygen consumption (VO2) before exercise, in the two studies with without Am. After the administration of Am, heart rate increased (72 ± 13 to 80 ± 16 bpm; mean ± SD, P < 0.05), as did rate-pressure product (96 ± 28 to 108 ± 33 mmHg × bpm × 100, P < 0.05), although the systolic blood pressure and VO2 did not show significant changes. During exercise, Am effected a significant increase in exercise duration (8.9 ± 2.6 versus 10.4 ± 2.8 min, P < 0.01). The rate-pressure product recorded at peak exercise was also significantly higher after Am (212 ± 56 versus 251 ± 74 mmHg × bpm × 100, P < 0.05). However, there was no significant difference in ST segment change in ECG at the end-point of exercise between the two study groups, with and without Am. Moreover, exercise maximal VO2 (20.5 ±5.1 versus 21.6 ± 6.5 ml/min) and anaerobic threshold (14.8 ± 2.7 versus 14.8 ± 2.8 ml/min) were not significantly different in the two study groups. These findings indicate that administration of Am to patients with coronary artery disease does not induce deterioration, but rather improves exercise capacity.

To clarify the characteristics of the frequency content of atrial signal-averaged electrocardiograms (ECGs) during sinus rhythm in patients with paroxysmal atrial fibrillation, P wave-triggered signal-averaged ECGs were recorded in 28 patients with and 34 control patients without paroxysmal atrial fibrillation. Fast Fourier transform analysis was performed on the 100-ms segment starting 75 ms before the end of the P wave. An area ratio (AR50) was calculated by dividing the area under the spectrum curve between 20 and 50 Hz, multiplied by 100, by the area between 0 and 20 Hz. Magnitude ratios (MR20, MR30, MR40 and MR50) were calculated by dividing the magnitude at 20, 30, 40 and 50 Hz, respectively, multiplied by 100, by the maximal magnitude of the entire signal. AR50 was significantly greater in patients with than without paroxysmal atrial fibrillation (62.3 +/- 34.2 vs. 42.4 +/- 18.4). MR20 and MR30 were also significantly greater in patients with than without paroxysmal atrial fibrillation (MR20 76.1 +/- 15.2 vs. 60 +/- 20.2; MR30 41 +/- 18.8 vs. 26.6 +/- 14.4), although no significant differences in MR40 or MR50 were observed between the two patient groups. The difference in MR30 between groups remained significant even after taking into account the presence of organic heart disease. It is concluded that, irrespective of the presence of organic heart disease, the terminal portion of the P wave contained significantly more components in the 20- to 50-Hz range, especially around 30 Hz, in patients with than in patients without paroxysmal atrial fibrillation. These results suggest that frequency analysis could characterize atrial signal-averaged ECGs of patients at risk for paroxysmal atrial fibrillation.

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.

To determine whether patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm, the signal-averaged electrocardiogram triggered by P waves was recorded in 42 patients with paroxysmal atrial fibrillation (Paf group) and in 50 control patients. The root mean square voltages (LP10, LP20, and LP30) for the last 10, 20, and 30 msec and the duration (Ad) of filtered (40-300 Hz) P wave of the spatial magnitude were measured. LP10 and LP20 were significantly lower in the Paf than in the control group (LP10, 1.92 +/- 0.58 versus 2.49 +/- 0.78 microV, p less than 0.001; LP20, 2.47 +/- 0.78 versus 3.46 +/- 1.20 microV, p less than 0.0001), although no significant difference in LP30 was found between groups. Ad was also significantly longer in the Paf than in the control group (137.0 +/- 14.3 versus 118.6 +/- 11.3 msec, p less than 0.001). These differences between the Paf and control groups remained significant even after dividing by the presence or absence of organic heart diseases. The criteria of "LP20 = 3.5 microV or less" and "Ad greater than 120 msec" as defining "atrial late potential" gave a sensitivity of 91% and a specificity of 76%. These findings suggest that patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm by using the P wave-triggered signal-averaged electrocardiogram.

In sick sinus syndrome (SSS), pathophysiological abnormalities have been shown not only in the sinus node but also in the atrial muscle, especially of the perinodal portion. To investigate whether the electrophysiological abnormalities of atrial muscle in SSS would induce the characteristic P wavepattern, especially in the initial portion of the P wave, we studied 37 patients with SSS and 67 age-comparable control patients. using the P wave-triggered signal-averaged electrocardiography. Sixteen of 37 SSS patients had paroxysmal atrial fibrillation (Paf). Signal-averaged electrocardiograms were recorded with a band-pass filter of 40–300 Hz and signals of 200 beats or more were averaged with the P wave-triggering technique. The P wave complexes of the three bipolar leads were combined into a spatial magnitude, and then the root mean square voltage for the initial 30 ms (EP30) and the last 20 m (LP20) of filtered P wave were measured. The duration (Ad) and root mean square voltage (RMS) of the total filtered P wave were also measured. Results SSS with Paf SSS without Pat Control EP30 (μV) 2.55 ± 1.17 * 2.16 ± 0.98 * 3.93 ± 1.23 LP20 (μV) 1.98 ± 0.40 # † 2.79 ± 1.04 3.35 ± 1.76 Ad (ms) 145.8 ± 16.1 * † 131.2 ± 14.1 $ 123.7 ± 11.7 RMS (μV) 6.20 ± 0.41 5.82 ± 0.82 6.20 ± 1.47 * p l 0.0001 # P l 0.005 $ p l 0.05 vs. Control † p l 0.01 vs SSS Without Pat The amplitude of initial portion of filtered P wave was significantly lower and the duration was longer in SSS patients with/without Paf than the controls, while there was no significant difference in the amplitude of the terminal portion between SSS patients without Paf and controls. The criteria of “EP30 ≤ 3.0 μV and Ad g 130 m” as defining “atrial early potential” gave a sensitivity of 76%, a specificity of 83% and a predictive accuracy of 81% for detection of patients with SSS. These results indicate that the low amplitude signals in the initial portion of filtered P wave were characteristic of SSS, so that the recognition of atrial early potential might be promising to identify patients with SSS.