Search

Abstract Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. Clinical trial registration NCT02918305 (http://www.clinicaltrials.gov).

From the correlation between the blood flow dynamics and wall dynamics in the left ventriocle (LV) analyzed using echo-dynamography, the ejection mechanisms and role of the intra-ventricular vortex in the LV were elucidated in detail during the pre-ejection transitional period (pre-ETP), the very short period preceding LV ejection. The study included 10 healthy volunteers. Flow structure was analyzed using echo-dynamography, and LV wall dynamics were measured using both high-frame-rate two-dimensional echocardiography and a phase difference tracking method we developed. A large accelerated vortex occurred at the central basal area of the LV during this period. The main flow axis velocity line of the LV showed a linearly increasing pattern. The slope of the velocity pattern reflected the deformity of the flow route induced by LV contraction during the pre-ETP. The centrifugal force of the vortex at its junction with the main outflow created a stepwise increase of about 50% of the ejection velocity. Ejection of blood from the LV was accomplished by the extruding action of the ventricular wall and the centrifugal force of the accelerated vortex during this period. During ejection, acceralated outflow was considered to create a spiral flow in the aorta with help from the spherical structure of the Valsalva sinus.

Complicated aortic arch plaques (CAP) and their progression are important for recurrent ischemic stroke (IS) and its prognosis. We investigated the effects and clinical benefits of rosuvastatin therapy on this pathophysiology. The purpose of this study was to investigate whether rosuvastatin prevention of aortic arch plaque progression improved the prognosis of IS patients.Ninety-seven consecutive acute cerebral embolism patients were retrospectively surveyed. All had transesophageal echocardiography (TEE) to assess the presence or absence of CAP, defined as aortic wall thickness ≥4 mm or plaque ulceration. Patients received conventional antithrombotic therapy as clinically indicated. All patients with CAP were recommended to receive 5 mg rosuvastatin/day, administered by their attending physicians; not all physicians followed this recommendation. Six-month follow-up TEEs were performed in patients with CAP who received rosuvastatin. Major adverse cerebrovascular events (MACEs) comprised recurrent IS and death.CAP was detected in 39 patients (40%), and MACEs in 15. Multivariate regression analysis showed that patients with CAP not taking rosuvastatin was an independent risk factor for MACEs (odds ratio = 18.044; 95% confidential interval = 2.089-155.846, p 0.01). When patients were divided into three groups: those with CAP taking rosuvastatin, those with CAP not taking rosuvastatin, and those without CAP, Kaplan-Meier analysis demonstrated that patients with CAP not taking rosuvastatin had significantly more MACEs than those in the other two groups (long-rank test; χRosuvastatin therapy prevented aortic arch plaque progression in IS patients with CAP, and may also have long-term clinical benefits.

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.

The effect of rosuvastatin was investigated on complicated aortic arch plaque (CAP) morphology and lipid profiles in acute cerebral embolism (CE) patients with normal low-density lipoprotein-cholesterol (LDL-c) levels. Transesophageal echocardiography (TEE) studies were performed in 56 consecutive CE patients with LDL-c less than 140 mg/dL who were not taking lipid-lowering agents at baseline. CAP observed by TEE was defined as the presence of greater than 4-mm diameter, ulcerated, or mobile aortic plaque. Patients were divided into those with CAP versus without CAP (group A, n=24, age 69±8 years) and without CAP (group B, n=32, age 62±10 years). Of the 24 group A patients, 18 received 5 mg/d of rosuvastatin for 6 months and had follow-up TEE studies. In Group A, the baseline values of high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A-1 (ApoA-1) were significantly lower than in Group B (44±15 versus 55±15 mg/dL, P=.0059; 103±19 versus 137±25 mg/dL, P=.0006, respectively) and age and serum high-sensitivity C-reactive protein concentration were significantly higher (69±8 vs. 62±10 years, P=.0080; 2.34±3.05 vs. 0.67±1.00 mg/dL, P=.0054, respectively). By multivariate logistic regression analysis, ApoA-1 was shown to be an independent predictor of CAP (odds ratio=.894, 95% confidence intervals .800-.996, P=.0483). In the 18 group A patients receiving rosuvastatin for 6 months, aortic arch plaque diameter and serum LDL-c were significantly decreased (5.8±2.2 to 5.1±2.1 mm, P=.0377; 110±23 to 81±23 mg/dL, P=.0008, respectively), whereas serum HDL-c and ApoA-1 concentrations were significantly increased (42±8 to 52±9 mg/dL, P=.0002; 109±22 to 135±15 mg/dL, P=.0002, respectively). Plaques were morphologically improved in 11 patients, unchanged in 6, and worsened in 1. These data suggest that rosuvastatin improves plaque morphology concomitant with improving lipid profiles in CE patients with normal LDL-c levels.

Albuminuria is an established risk factor for mortality and cardiovascular events in the general population. Albuminuria might be a marker of the various pathophysiologic changes, such as diffuse vascular injury and systemic inflammation, that arise in patients with chronic heart failure (CHF). However, the relation between albuminuria and CHF has not yet been fully elucidated. Therefore, the purpose of the present study was to assess the prevalence and prognostic significance of albuminuria in patients with CHF secondary to ischemic or idiopathic dilated cardiomyopathy. Of the 712 patients with CHF, 311 had normoalbuminuria, 304 had microalbuminuria, and 97 had macroalbuminuria. The patients with albuminuria had more cardiovascular co-morbidity and worse renal function than those with normoalbuminuria. A total of 152 cardiac events occurred during the follow-up period. Kaplan-Meier analysis demonstrated that patients with albuminuria had a greater incidence of cardiac events than those without albuminuria. Furthermore, albuminuria was significantly associated with an increased risk of cardiac events, even after adjustment for other prognostic variables. In conclusion, albuminuria is a powerful and independent predictor of adverse prognosis in patients with CHF and could be useful for risk stratification of patients with CHF.

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.

To evaluate left atrial appendage (LAA) dysfunction using left atrial pulse-wave tissue Doppler imaging (PW-TDI) in acute cerebral embolism (ACE) patients with sinus rhythm (SR), transthoracic (TTE) and transesophageal echocardiograhy (TEE) were performed in 60 consecutive patients with SR without obvious left ventricular dysfunction within 2 weeks after ACE. Two groups were identified: LAA dysfunction [LAA emptying peak flow velocity (LAA-eV)

Background Elevated aortic stiffness determined by transesophageal echocardiography (TEE), and presence of complicated aortic plaque provide prognostic information about cerebrovascular disease risk. Recently, pulse-wave tissue Doppler imaging (PW-TDI) has offered a new technique for assessing aortic wall stiffness. Methods The following aortic long-axis view TEE measurements were carried out in 103 consecutive acute ischemic stroke patients and 72 controls (stroke-free patients requiring TEE for conditions such as atrial fibrillation and valvular heart disease): (a) PW-TDI motion velocities measured as expansion peak velocity during systole (Vs) and contraction peak velocity during diastole (Vd); (b) aortic arch stiffness parameter β (Aoβ), defined as β = ln (systolic blood pressure/diastolic blood pressure)/([Dmax − Dmin]/Dmin), where ln is the natural logarithm, Dmax is maximum aortic lumen diameter, and Dmin is minimum aortic lumen diameter. The PW-TDI of Vs and Vd was compared with conventional vessel parameters brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI, calculated from blood pressure and PWV). Results Comparing acute ischemic stroke patients versus controls, Vs and Vd were significantly decreased (3.3 ± 1.6 vs. 3.9 ± 2.0 cm/sec, P

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.

The interaction between local myocardial motion and blood flow dynamics should be assessed to evaluate left ventricular pump function.The contour map of the absolute value of blood flow velocity in the left ventricle (LV) was drawn. The ridgeline of the contour was defined as the "flow axis line". LV wall motion was assessed by the tracing endocardial border in consecutive B-mode images and by myocardial tissue velocity distribution obtained by the optical flow method.The location of the main flow axis line was affected by the local myocardial movement in the short axis direction. The flow axis line method is superior to the previous investigations on two-dimensional blood flow analysis because it considered three-dimensional blood flow.The flow axis line represents not only intracardiac blood flow structure but also its interaction with the cardiac wall motion.

Circulatory maintenance with a left ventricular assist device (LVAD) alone during cardiac arrest until heart transplantation has been evaluated. To assess the effect on the autonomic nervous system, the sympathetic neurogram was analyzed by power spectrum and coherence function. LVAD were inserted between the left atrium and the descending aorta in seven adult mongrel dogs and ventricular fibrillation was induced electrically. Renal sympathetic nerve activity (RSNA) was detected by bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were calculated. Under the condition of circulatory maintenance with only LVAD, coherence at the cardiac rhythm frequency was decreased, and coherence at the LVAD pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed during maintenance of the circulation with only LVAD contributed to the sympathetic neurogram.

The case of a 57-year-old man, who had a brother suddenly died at 62 years of age, admitted to other hospital with palpitation. Because his Holter ECG showed non-sustained ventricular tachycardia, and ultrasound cardiography showed left ventricular hypertrophy with normal cardiac function, he was introduced to our hospital for further cardiac examination of hypertrophic cardiomyopathy. Although his coronary angiography showed no organic stenosis, and his magnetic resonance imaging demonstrated asymmetrical septal hypertrophy and delayed enhancement on inferolateral wall of left ventricle compatible with hypertrophic cardiomyopathy, his biopsied tissue from cardiac muscle revealed cardiac Fabry disease. He received enzyme replacement therapy after implantation of implantable cardioverter defibrillator (ICD) for primary prevention. After 7 months from implantation, he had an appropriate ICD therapy for sustained ventricular tachycardia. Primary prevention of ICD implantation for patients with Fabry disease has not been established, while some cases of cardiac Fabry disease show fatal ventricular tachyarrhythmia in their lives. Primary prevention of ICD could be a considerable therapeutic option in some patients with cardiac Fabry disease, especially who demonstrated a family history of sudden death or ventricular tachyarrhythmias.

A 69-year-old man with effort angina was admitted to our institution. Echocardiography showed poor left ventricular systolic function with akinesis of the anterior wall and severe hypokinesis of the inferior wall. We performed coronary angiography, which revealed two diseased vessels including chronic total occlusion in the left anterior descending artery and severe stenosis in the right coronary artery (RCA). In addition, aortography revealed aortoiliac occlusive disease known as Leriche syndrome. As the patient's symptom was stable, we first planned to perform endovascular therapy (EVT) for Leriche syndrome to make a route for intra-aortic balloon pumping. We prepared a bi-directional approach from bi-femoral arteries and a left brachial artery. The guidewire was passed through the occlusive area using the retrograde approach. The self-expanding stents were deployed by a kissing technique. At one week after EVT, a 6Fr sheath was inserted from the right radial artery and an intra-aortic balloon pump was successfully inserted through the right femoral artery for percutaneous coronary intervention (PCI) to the RCA. Two drug-eluting stents were successfully deployed to RCA after using an atherectomy device (rotablator). We reported the case as a successfully performed PCI to the RCA after EVT for Leriche syndrome.

YAMBE, T., NITTA, S., CHIBA, S., SAIJOH, Y., NAGANUMA, S., AKIHO, H., KAKINUMA, Y., IZUTSU, K., KIKUCHI, Y., NAGANUMA, T., SUGAWARA, S., TANAKA, M., MEGURO, T., SASAKI, H., MITSUOKA, M., TERASAWA, Y., NITTA, K., KATAHIRA, Y., OHTOMO, T., ENDOH, N., TAKEDA, H., SONOBE, T., TAKAHASHI, K., MIURA, M., SATO, N. and MOHRI, H. Silent Obstruction of the Coronary Stenosis between Diagnostic Angiography and Later Percutaneous Transluminal Coronary Angioplasty without Myocardial Infarction. Tohoku J. Exp. Med., 1991, 163 (3), 167-174 - Among 204 patients with severe coronary artery senosis amenable to percutaneous transluminal coronary angioplasty (PTCA), 5 (2.5%) developed new silent total coronary occlusion of the vessel to be dilated without any chest symptom during the period between diagnostic coronary angiography and repeat coronary angiography at the time of the operation. We evaluated the clinical and angiographical characteristics of the patients with silent obstruction of the coronary artery in a short time, compared with the patients with unstable angina pectoris, who is considered to be suffering from acute myocardial infarction with severe chest symptom. None of the clinical variables studied showed a significant difference between the two groups. Among the angiographic variables, the degree of collateral was higher and impaired coronary perfusion distal to the lesion was more frequently found in unstable angina group. These results suggest that unstable angina is in a later stage of the ischemic heart disease compared with the time of the diagnostic angiography in patients with silent obstruction. Silent obstruction of high degree coronary stenosis is presumably due to the development of collateral circulation.