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Background and purpose Many clinical trials have shown that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can significantly reduce coronary artery disease in both primary and secondary prevention. A recent study showed that aggressive lipid-lowering therapy with strong statins could achieve coronary artery plaque regression, as evaluated with gray-scale intravascular ultrasound (IVUS). However, it is unknown whether coronary plaque regression and stabilization are reinforced when eicosapentaenoic acid (EPA) is used with a strong statin. Methods and subjects We aim to assess patients with stable angina or acute coronary syndrome who had undergone successful percutaneous coronary intervention (PCI) with integrated backscatter IVUS (IB-IVUS) guidance. They will be randomly allocated to receive pitavastatin (4 mg), or pitavastatin (4 mg) plus EPA (1800 mg), and prospectively followed for 6–8 months. Results The primary endpoint will be changes in tissue characteristics in coronary plaques, evaluated by IB-IVUS, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels, and inflammatory markers. The safety profile will also be evaluated. Conclusions The combination therapy of EPA and pitavastatin for regression of coronary plaque evaluated by IB-IVUS (CHERRY) study will be the first multicenter study using IB-IVUS to investigate the effects of combination therapy with pitavastatin and EPA on coronary plaque volume and tissue characteristics.

Background There is a residual risk of coronary heart disease (CHD) despite intensive statin therapy for secondary prevention. The aim of this study was to investigate whether coronary plaque regression and stabilization are reinforced by the addition of eicosapentaenoic acid (EPA) to high-dose pitavastatin (PTV). Methods We enrolled 193 CHD patients who underwent percutaneous coronary intervention (PCI) in six hospitals. Patients were randomly allocated to the PTV group (PTV 4 mg/day, n = 96) or PTV/EPA group (PTV 4 mg/day and EPA 1800 mg/day, n = 97), and prospectively followed for 6–8 months. Coronary plaque volume and composition in nonstenting lesions were analyzed by integrated backscatter intravascular ultrasound (IB-IVUS). Results The PTV/EPA group showed a greater reduction in total atheroma volume compared to PTV group. IB-IVUS analyses revealed that lipid volume was significantly decreased during follow-up period in only PTV/EPA group. The efficacy of additional EPA therapy on lipid volume reduction was significantly higher in stable angina pectoris (SAP) patients compared to acute coronary syndrome patients. EPA/AA ratio was significantly improved in PTV/EPA group compared to PTV group. There was no significant difference in the incidence of major adverse cardiovascular events and side effects. Conclusions Combination EPA/PTV therapy significantly reduced coronary plaque volume compared to PTV therapy alone. Plaque stabilization was also reinforced by EPA/PTV therapy in particular SAP patients. The addition of EPA is a promising option to reduce residual CHD risk under intensive statin therapy.

SummaryUsing our “echo-dynamography”, blood flow structure and flow dynamics during ventricular systole were investigated in 10 normal volunteers. The velocity vector distribution demonstrated blood flow during ejection was laminar along the ventricular septum. The characteristic flow structure was observed in each cardiac phases, early, mid- and late systole and was generated depending on the wall dynamic events such as peristaltic squeezing, hinge-like movement of the mitral ring plane, bellows action of the ventricle and dimensional changes in the funnel shape of the basal part of the ventricle, which were disclosed macroscopically by using the new technology of high speed scanning echo-tomography and microscopically by the strain rate distribution measured by phase tracking method.The pump function was reflected on the changes in the flow structure represented by the flow axis line distribution and the acceleration along the flow axis line. The acceleration of the ejection had three modes, “A”, “B” and “C”, and generated by the wall dynamic events. “A” appeared from the apical to the outflow area along the main flow axis line, “B” along the anterior mitral leaflet and the branched flow axis line, and “C” generated by the high speed vortex behind the mitral valve. The magnitude of the acceleration was estimated quantitatively from the velocity gradient along the flow axis line. Macroscopic and microscopic asynchrony in the myocardial contraction and extension appeared systematically in the local part of the ventricular wall, which was helpful for making the flow structure and for performing the smooth pump function.

Background Although the deformability of the left ventricular (LV) wall appears to be important in maintaining effective cardiac performance, this has not been debated by anyone, probably owing to the difficulties of the investigation. Objectives This study applies a new technology to demonstrate how the LV wall deforms so as to adjust for optimum cardiac performance. Subjects and methods Ten healthy volunteers were the subjects. Using echo-dynamography, an analysis at the “microscopic” (muscle fiber) level was done by measuring the myocardial axial strain rate (aSR), while the “macroscopic” (muscle layer) level contraction-relaxation/extension (C-R/E) properties of the LV wall were analyzed using high frame rate 2D echocardiography. Results Deformability of the LV was classified into three types depending on the non-uniformity of both the C-R/E properties and the aSR distribution. “Basic” deformation (macroscopic): The apical posterior wall (PW) thickness change was concentric and monophasic, whereas it was eccentric and biphasic in the basal part. This deformation was large in the PW, but small in the interventricular septum (IVS). The elongation of the mitral ring diameter and the downward movement of its posterior part were shown to be concomitant with the anterior extrusion of the PW. “Combined” deformation (macroscopic and microscopic): This was observed when the basic deformation was coupled with the spatial aSR distribution. Three patterns were observed: (a) peristaltic; (b) bellows-like; and (c) pouch-like. “Integrated” deformation: This was the time serial aSR distribution coupled with the combined deformation, illustrating the rotary pump-like function. The deformability of the LV assigned to the apical part the control of pressure and to the basal part, flow volume. The IVS and the PW exhibited independent behavior. Conclusions The non-uniformity of both the aSR distribution and the macroscopic C-R/E property were the basic determinants of LV deformation. The apical and basal deformability was shared in LV mechanical function.

ObjectivesUsing newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction–extension (C–E) property, which has an important relationship to LV function.MethodsStrain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821μm in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30–50 years).ResultsThe time course of the SR distribution disclosed the characteristic C–E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function.The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions.ConclusionThe newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C–E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV.

Summary Background The existence as well as the exact genesis of left ventricular suction during rapid filling phase have been controversial. In the present study, we aimed at resolution of this problem using noninvasive and sophisticated ultrasonic methods. The clinical meaning was also documented. Methods Ten healthy male volunteers were examined by 2D echocardiography and echo-dynamography which enables us to obtain detailed instantaneous data of blood flow and wall motion simultaneously from the wide range of the left ventricle. The correlation of blood flow and wall motion was also studied. Results Rapid ventricular filling was divided into 2 phases which had different physiology. The early half (early rapid filling: ERF) showed the effect which was alike drawing a piston. This was proved by the shape of the velocity of inflow and the basal muscle contraction which actively assisted extension of the relaxed apical and central parts of the left ventricle, giving the negative pressure which causes the ventricular suction. The later half (late rapid filling: LRF) showed the turning of the fundamental flow and the squeezed basal part just like the sphincter in addition to the expansion of the apical and central portions of the left ventricle, and all of these cooperatively augmented the suction effect. Conclusion Ventricular suction does exist to help ventricular filling. Simultaneous appearance of the contraction in the basal part and the relaxation or extension in the apical part during the post-ejection transitional period was made to occur the suction in the LV. And it can be said that the suction appeared in the late stage of systole as the one of the serial systolic phenomena.

SummaryUsing echo-dynamography, systolic blood flow structure in the ascending aorta and aortic arch was investigated in 10 healthy volunteers. The blood flow structure was analyzed based on the two-dimensional (2D) and 1D velocity vector distributions, changing acceleration of flow direction (CAFD), vorticity distribution, and Doppler pressure distribution. To justify the results obtained in humans, in vitro experiments were done using straight and curved tube models of 20mm diameter.The distribution of the CAFD showed a spiral staircase pattern along the flow axis line. In addition, the changes in the velocity profile in the short-axis direction, 2D distribution of the vorticity, and velocity vector distribution on the aortic cross-section plane, all confirmed the presence of systolic twisted spiral flow rotating clockwise toward the peripheral part of the ascending aorta.The rotation cycle of this spiral flow correlated inversely with the maximum velocity of the aortic flow, so that this cycle was shorter in early systole and longer in late systole. The model experiments showed similar results.The spiral flow seemed to be produced by several factors: (i) anterior shift of the direction of ejected blood flow due to the anterior displacement of the projection of the aorta; (ii) accelerated high pressure flow ejected antero-upward; (iii) inertia resistance at the peripheral boundary of the sinus of Valsalva; and (iv) reflection caused by the concave spherical structure of the inner surface of the basal part of the aorta.Because the main spiral flow axis line nearly coincided with the center line of the aorta, it is concluded that the occurrence of the spiral flow plays an important role in maintaining the blood flow direction passing through the cylindrical curved aortic arch and thus in keeping the most effective ejection as well as in dispersing the shear stress in the aortic wall.