Shigeyuki Watanabe

Macrophage Metalloelastase Accelerates the Progression of Atherosclerosis in Transgenic Rabbits

Background— Macrophage metalloelastase (matrix metalloproteinase [MMP]-12) is upregulated in atherosclerotic lesions and aneurysm; thus, increased MMP-12 activity may play an important role in the pathogenesis of atherosclerosis. However, the pathological roles of MMP-12 in the initiation and progression of atherosclerosis have not been defined. Methods and Results— We compared the susceptibility of MMP-12 transgenic (Tg) rabbits to cholesterol-rich diet–induced atherosclerosis with that of non-Tg littermate rabbits. The rabbits were maintained at either relatively lower levels of hypercholesterolemia for shorter periods or higher levels of hypercholesterolemia for longer periods through a diet containing different amounts of cholesterol. We found no significant difference in the aortic atherosclerotic lesion size or quality between Tg and non-Tg rabbits at lower hypercholesterolemia. At higher hypercholesterolemia for longer periods, however, Tg rabbits developed more extensive atherosclerosis in the aortas and coronary arteries than did non-Tg rabbits. Histological examinations revealed that atherosclerotic lesions of Tg rabbits contained prominent macrophage infiltration associated with marked disruption of the elastic lamina in the tunica media with occasional formation of aneurysm-like lesions. Furthermore, increased expression of MMP-12 derived from macrophages was associated with elevated expression of MMP-3, suggesting that MMP-12 may play a pivotal role in the cascade activation of other MMPs, thereby exacerbating extracellular matrix degradation during the progression of atherosclerosis. Conclusions— Overexpression of MMP-12 causes accelerated atherosclerosis in Tg rabbits. These results suggest that macrophage-derived MMP-12 participates in the progression of atherosclerosis.

Effect of age on carotid arterial intima-media thickness in childhood.

To investigate relationships between carotid arterial intima-media thickness (IMT) and age in childhood, we performed high-resolution carotid arterial ultrasonography in 60 healthy children (27 boys, 33 girls; age range, 5–14 years) determined by screening to have no dyslipidemia or hypertension. No plaque formation was found, and irregularity of IMT (root mean square roughness of IMT) did not correlate with age. Mean IMT increased in a linear manner with age [IMT in millimeters = (0.009 × age in years) + 0.35] (r = 0.39, P = 0.002). This correlation remained significant after adjustment for gender, parental smoking, systolic and diastolic blood pressure, body mass index, and serum concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. None of these known cardiovascular disease risk factors in adults had a significant relationship with age-adjusted IMT in children. While circumferential wall stress and diastolic blood pressure were not correlated with age, mean IMT and lumen diameter showed significant positive relationships with circulating blood volume, which was calculated as the function of height and weight. These data suggested that age-dependent physiologic thickening of arterial walls begins in childhood.

Association of Sleep-Disordered Breathing and Ventricular Arrhythmias in Patients Without Heart Failure

The prevalence and characteristics of sleep-disordered breathing (SDB) in patients with ventricular arrhythmias, such as premature ventricular complexes and ventricular tachycardia, are unknown. Therefore, this study was conducted to evaluate the prevalence of SDB in patients with severe ventricular arrhythmias and normal left ventricular (LV) function. Thirty-five patients (63% men, mean age 57.4 +/- 13.8 years) underwent a sleep study. All patients had ventricular tachycardia or frequent premature ventricular complexes (>or=300/hour) and had been referred to the cardiology department for medication, catheter ablation therapy, or the implantation of a cardioverter-defibrillator. Patients with heart failure with LV ejection fractions <50% were excluded; in the remaining patients, the mean LV ejection fraction was 63.9 +/- 8.0%. Twenty-one patients (60%) had SDB with apnea-hypopnea indexes >or=5/hour, and the average apnea-hypopnea index was 22.7 +/- 17.9/hour. Twelve patients (34%) had moderate to severe SDB, with an average apnea-hypopnea index of 33.6 +/- 16.6/hour. Central dominant sleep apnea was evident in 3 patients with SDB. The average age and body mass index were significantly higher in patients with SDB than in those without SDB (age 62.0 +/- 12.8 vs 50.6 +/- 12.7 years, body mass index 26.3 +/- 4.0 vs 21.2 +/- 2.0 kg/m2). In conclusion, this study found a high prevalence of SDB in patients with ventricular arrhythmias and normal LV function.

The correlation of irregularities in carotid arterial intima-media thickness with coronary artery disease

Abstract. Noninvasive ultrasonographic assessment of carotid artery intima-media thickness (IMT) can improve risk stratification for coronary artery disease (CAD) in certain patients. Several measurements have been used to evaluate carotid atherosclerosis by ultrasonography. Although it has been reported that angiographic arterial irregularities correlate with pathologic changes of atherosclerosis and the occurrence of cardiovascular events, only a few studies have assessed carotid arterial wall irregularity by ultrasonography. The purpose of this study was to evaluate the irregularity of IMT quantitatively, and its association with the presence or absence of CAD. The correlation of maximum and mean IMT values, and IMT irregularity with the presence or absence of CAD, was investigated in 90 patients who had undergone coronary angiography. IMT was measured by manual tracking of the far wall of the common carotid arteries, carotid bulbs, and internal carotid arteries. The IMT irregularity was defined as the root mean square (RMS) difference between each IMT and averaged IMT. Multiple logistic regression analysis, after adjustment for coronary risk factors, indicated that the RMS difference was a more accurate predictor of CAD than were the mean or maximum IMT values. These results indicate that the evaluation of IMT irregularity by ultrasonography is a useful predictor for the presence of coronary atherosclerosis.

Mechanical Dyssynchrony Assessed by Speckle Tracking Imaging as a Reliable Predictor of Acute and Chronic Response to Cardiac Resynchronization Therapy

Speckle tracking echocardiography (STE) has the potential to detect the heterogeneous initiation of active myocardial contraction, which is the primary cause of left ventricular (LV) systolic dysfunction in patients with mechanical dyssynchrony. This study was designed to assess the ability to predict response to cardiac resynchronization therapy (CRT) of STE-derived dyssynchrony parameters in comparison with invasive hemodynamic assessments. Thirty patients referred for CRT were studied. The time difference of first peak (Td-(first peak)) and the maximum peak (Td-(max peak)) on the radial strain-time curves of the earliest and the latest segments were measured as the dyssynchrony parameter. Peak positive dP/dt (dP/dt(max)) was measured as the indicator of global LV systolic performance. CRT responders were defined as patients with LV end-systolic volume reduction greater than 15% at 3 months after CRT. CRT increased the dP/dt(max) compared with the baseline study (P < .001). Percent changes in the dP/dt(max) (dP/dt(max)) were significantly correlated with Td-(first peak) (R = 0.743, P < .001), but weakly correlated with Td-(max peak) (R = 0.390, P = .03). Twenty patients (66%) were identified as chronic CRT responders. Receiver operating characteristics analysis revealed that Td-(first peak) shared a similar ability with dP/dt(max) to detect chronic responders (Td-(first peak) >167.0 ms, area under the curve [AUC] 0.945; dP/dt(max) >16.2%, AUC 0.934) compared with Td-(max peak) (>194.5 ms, AUC 0.820). STE-derived Td-(first peak) showed a reliable ability to predict the acute and chronic response to CRT as well as dP/dt(max).

The wake of a large vortex is associated with intraventricular filling delay in impaired left ventricles with a pseudonormalized transmitral flow pattern.

Although an intraventricular filling delay has been observed in patients with a psuedonormalized transmitral flow pattern, little is known about the underlying hydrodynamic nature of this phenomenon. Methods: To examine those hydrodynamics, we studied every echocardiographic frame showing ventricular inflow (80 Hz) in the apical long‐axis view and M‐mode image using contrast echocardiography in 29 patients with a psuedonormalized pattern and in 26 normal controls. The velocity of the filling flow front (Vp), the ratio of Vp to E, and the mean radius of the vortices associated with the filling flow were measured. Results: In both groups, vortices were observed at the ridge of the mitral valve during acceleration of the E‐wave. The mean radius of the vortices was greater in the pseudonormalized filling group than that in the control group (8 ± 2 vs 3 ± 1 mm, P < 0.0001). Vp was smaller in the pseudonormalized group than in the control group (36 ± 6 vs 47 ± 6 cm/sec, P = 0.0008). Vp/E was <1 and smaller in the pseudonormalized group than that in the control group (0.46 ± 0.13 vs 0.59 ± 0.07, P = 0.014) and negatively correlated with the mean radius of the vortices (r = 0.54, P < 0.0001). Conclusions: Contrast echocardiography identified uniform flow characteristics with blood in the filling flow front moving in well‐developed vortices and resulting in a left ventricular filling delay in the impaired left ventricle in spite of an increased early transmitral flow velocity.

Deposition at low substrate temperatures of high-quality TiO2 films by radical beam-assisted evaporation.

We deposited high-quality TiO2 films by an oxygen-radical beam-assisted evaporation (RBE) method at a lower substrate temperature (Ts) than that for a TiO2 film deposited by conventional thermal evaporation (TE) with neutral-oxygen gas. The films were then evaluated in terms of refractive index, shift of wavelength of a peak in the reflection curve, and absorption coefficient. The TiO2 films deposited by RBE at Ts < 473 K showed higher refractive indices, were more compact, and had lower absorption coefficients than the film deposited by TE at Ts = 473 K.

Actual conditions of implantable defibrillation therapy over 5 years in Japan

The aim of this study was to describe the recent conditions associated with implantable defibrillation therapy for individual underlying heart diseases.

Combined approach with Doppler echocardiography and B-type natriuretic peptide to stratify prognosis of patients with decompensated systolic heart failure

BACKGROUND Based on the importance of left ventricular (LV) diastolic function in stratification of the cardiac prognosis in patients with systolic heart failure (SHF), we attempted to identify the prognostic impact of Doppler echocardiographic examinations and plasma B-type natriuretic peptide (BNP) concentration. METHODS Of 73 patients admitted with decompensated SHF (ejection fraction <45%), 58 were included. Among these, 21 patients had ischemic heart disease and 27 non-ischemic dilated cardiomyopathy. In all patients, Doppler echocardiographic examinations and measurements of the plasma B-type natriuretic peptide concentration were simultaneously performed before discharge. Patients were followed up for 36 months after discharge. Primary end point for the follow-up was readmission for acute decompensated heart failure or cardiac death. RESULTS During the mean follow-up period of 28±12 months, 16 patients (27.6%) were readmitted with decompensated heart failure. Based on the stepwise multivariate Cox regression analysis, mitral E/A ratio (chi-square=6.5, relative risk=1.7, p=0.01) and BNP (chi-square=3.9, relative risk=1.7, p=0.04) were identified as independent predictors of primary endpoints. Based on ROC analysis, the optimal cutoff point of E/A was 1.05 (AUC=0.836, p=0.002) and that of plasma BNP concentration was ≥254.5 pg/ml (AUC=0.768, p=0.002). In high-risk patients with E/A ≥1, event-free survival rates were significantly lower in patients with BNP <254.5 pg/ml (p<0.001). CONCLUSIONS The complementary assessment of Doppler transmitral flow and plasma BNP concentration may be reliable in identifying the prognosis of patients with SHF.

Electrical Space-Time Abnormalities of Ventricular Depolarization in Patients with Brugada Syndrome and Patients with Complete Right-Bundle Branch Blocks Studied by Magnetocardiography

Background: Both ventricular depolarization abnormalities (QRS complex) and repolarization ones (ST/T) are still controversial in literature. The objective of this study was to clarify the space‐time variations that occur in patients carriers of Brugada syndrome using Magnetocardiography and also compare them with cases of complete right‐bundle branch block (CRBBB) and individuals without any dromotropic disorder (control group).