Kazushi Urasawa

A new approach for evaluation of left ventricular diastolic function: Spatial and temporal analysis of left ventricular filling flow propagation by color M-mode doppler echocardiography

OBJECTIVES To evaluate left ventricular diastolic function and differentiate the pseudonormalized transmitral flow pattern from the normal pattern, the propagation of left ventricular early filling flow was assessed quantitatively using color M-mode Doppler echocardiography. BACKGROUND Because the propagation of left ventricular early filling flow is disturbed in the left ventricle with impaired relaxation, quantification of such alterations should provide useful indexes for the evaluation of left ventricular diastolic function. METHODS Study subjects were classified into three groups according to the ratio of early to late transmitral flow velocity (E/A ratio) and left ventricular ejection fraction: 29 subjects with an ejection fraction > or = 60% (control group); 34 with an ejection fraction < 60% and E/A ratio < 1 (group I); and 25 with ejection fraction < 60% and E/A ratio > or = 1 (group II). The propagation of peak early filling flow was visualized by changing the first aliasing limit of the color Doppler signals. The rate of propagation of peak early filling flow velocity was defined as the distance/time ratio between two sampling points: the point of the maximal velocity around the mitral orifice and the point in the mid-left ventricle at which the velocity decreased to 70% of its initial value. High fidelity manometer-tipped measurement was performed in 40 randomly selected subjects. RESULTS The rate of propagation decreased in groups I and II compared with that in the control group (33.8 +/- 13.8 [mean +/- SD] and 30.0 +/- 8.6 vs. 74.3 +/- 17.4 cm/s, p < 0.001, respectively) and correlated inversely with the time constant of left ventricular isovolumetric relaxation and the minimal first derivative of left ventricular pressure (peak negative dP/dt) (r = 0.82 and r = 0.72, respectively). CONCLUSIONS Spatial and temporal analysis of filling flow propagation by color M-mode Doppler echocardiography was free of pseudonormalization and correlated well with the invasive variables of left ventricular relaxation.

Intracoronary Delivery of Adenovirus Encoding Adenylyl Cyclase VI Increases Left Ventricular Function and cAMP-Generating Capacity

BackgroundWe tested the hypothesis that the intracoronary injection of a recombinant adenovirus encoding adenylyl cyclase type VI (ACVI) would increase cardiac function in pigs. Methods and ResultsLeft ventricular (LV) dP/dt and cardiac output in response to isoproterenol and NKH477 stimulation were assessed in normal pigs before and 12 days after the intracoronary delivery of histamine followed by the intracoronary delivery of an adenovirus encoding lacZ (control) or ACVI (1.4×1012 vp). Animals that had received ACVI gene transfer showed increases in peak LV dP/dt (average increase of 1267±807 mm Hg/s;P =0.0002) and cardiac output (average increase of 39±20 mL · kg−1 · min−1;P <0.0001); control animals showed no changes. Increased LV dP/dt was evident 6 days after gene transfer and persisted for at least 57 days. Basal heart rate, blood pressure, and LV dP/dt were unchanged, despite changes in cardiac responsiveness to catecholamine stimulation. Twenty-three hour ECG recordings showed no change in mean heart rate or ectopic beats and no arrhythmias. LV homogenates from animals receiving ACVI gene transfer showed increased ACVI protein content (P =0.0007) and stimulated cAMP production (P =0.0006), confirming transgene expression and function; basal LV AC activity was unchanged. Increased cAMP-generating capacity persisted for at least 18 weeks (P <0.0002). ConclusionsIntracoronary injection of a recombinant adenovirus encoding AC provides enduring increases in cardiac function.

Endovascular Treatment for Infrainguinal Vessels in Patients With Critical Limb Ischemia OLIVE Registry, a Prospective, Multicenter Study in Japan With 12-Month Follow-up

Background—Recent technical advances have made endovascular treatment (EVT) an alternative first-line treatment for critical limb ischemia. Methods and Results—A prospective multicenter study was conducted to evaluate the clinical outcomes of 314 Japanese critical limb ischemia patients (mean age, 73±10 years) with infrainguinal arterial lesions who underwent EVT. Patients were enrolled from December 2009 to July 2011 and were followed-up for 12 months. The primary end point was amputation-free survival (AFS) at 12 months. Secondary end points were anatomic, clinical, and hemodynamic measures, including 12-month freedom from major adverse limb events. The 12-month AFS rate was 74%, with body mass index <18.5 (hazard ratio [HR], 2.22; P=0.008), heart failure (HR, 1.73; P=0.04), and wound infection (HR, 1.89; P=0.03) associated with a poor prognosis for AFS. The 12-month major adverse limb event-free rate was 88%, with hemodialysis (HR, 1.98; P=0.005), heart failure (HR, 1.69; P=0.02), and Rutherford classification 6 (HR, 2.25; P=0.002) associated with a poor prognosis for major adverse limb events. The median time for wound healing was 97 days, with body mass index <18.5 (HR, 0.54; P=0.03) and wound infection (HR, 0.60; P=0.04) being significant risk factors for unhealed wounds after EVT. At 12 months, 34% had undergone reintervention (bypass surgery, 2.6%; repeat EVT, 31.7%), and 73% were major adverse event–free. Conclusions—The high reintervention rate notwithstanding, EVT was an effective treatment for Japanese critical limb ischemia patients with infrainguinal disease, with satisfactory AFS and major adverse limb event-free rates. The results of this study will be helpful for the future evaluation of critical limb ischemia therapy. Clinical Trial Registration—URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000002830.

Chronic effects of enalapril and amlodipine on cardiac remodeling in cardiomyopathic hamster hearts.

This study examined the effects of long-term treatments with the angiotensin-converting enzyme inhibitor, enalapril, and the calcium antagonist, amlodipine, on the morphologic changes, progressive left ventricular dysfunction, and gene expression of the ryanodine receptor (RyR) and phospholamban (PLN) in dilated cardiomyopathy. From the ages of 5 through 20 weeks, dilated cardiomyopathic hamsters, BIO53.58 (BIO), and control hamsters, F1b, orally received either enalapril or amlodipine. Cardiac function was assessed by echocardiography. At the age of 20 weeks, the collagen volume fractions were analyzed by the stereologic method. RyR and PLN messenger RNAs (mRNAs) were examined by Northern blot in the amlodipine group. In BIO, the reduction of left ventricular percentage of fractional shortening was attenuated in the enalapril group (p < 0.05) and amlodipine group (p < 0.001), and the increase in the collagen volume fraction and the loss of myocytes were suppressed in the amlodipine group compared with the untreated group. RyR mRNA level decreased in BIO (p < 0.01) compared with F1b, but PLN mRNA level was unchanged. RyR and PLN mRNA levels were unaffected by the treatment with amlodipine. Enalapril and amlodipine prevent progressive remodeling and reduce cardiac dysfunction in BIO. Amlodipine prevents fibrosis and cell death without modifying RyR and PLN mRNA levels in BIO.

Coronary Disease Morphology and Distribution Determined by Quantitative Angiography and Intravascular Ultrasound

Although previous studies have demonstrated that even quantitative coronary angiography (QCA) can not provide accurate disease morphology, there has not been a systematic comparison of disease morphology determined by QCA and intravascular ultrasound (IVUS), particularly in Japanese patients. Therefore, the present study prospectively examined patients in a multicenter cooperative study. A total of 491 coronary sites from 562 patients (446 men, 116 women; mean age, 64+/-11 years) who underwent coronary interventions were enrolled. The target lesions (>50% diameter stenosis) were evaluated pre-operatively by both QCA and IVUS operating at 30-40 MHz and the percent area stenosis, eccentricity index (EI) and lesion length were determined. The minimal (min) and maximal (max) distances from the center of the stenotic lesion to the outline of the vessel wall were measured, and the EI was calculated by the formula: [(max - min)/max]. By QCA, lesion length was determined by measuring the distance between the proximal and distal shoulders of the lesion. When the lesions were observed by IVUS with a motorized pull-back system, the length was calculated by multiplying the time for observation of the disease and 0.5 or 1 mm/s. Although the severity of the stenosis determined by QCA (86+/-10%, mean +/- SD) did not differ from that by IVUS (83+/-13%), there was no correlation between them (r=0.32, y=0.25x+65) and the correlation did not improve when lesions with remodeling, enlargement (n=176) or shrinkage (n=79) were omitted from the calculation. The EIs by QCA and IVUS were 0.51+/-0.26 and 0.52+/-0.22, respectively (NS), and there was no correlation between them (r=0.30, y=0.36x+33). However, when the lesions with remodeling were excluded, the correlation greatly improved (r=0.80, y=0.84x+10.6, p<0.05). Lesion length determined by QCA (12.4+/-6.1 mm) was significantly shorter than that by IVUS (16.3+/-8.9 mm, p<0.01). These results demonstrate that coronary angiography significantly misinterprets disease morphology in terms of severity, eccentricity and length, in part because of vessel remodeling that can be accurately determined only by IVUS.

Final 3-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Either Biodegradable Polymer or Durable Polymer: NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial

Background—There is a paucity of data reporting the clinical outcomes of biodegradable polymer biolimus-eluting stent (BP-BES) compared with durable polymer everolimus-eluting stent (DP-EES) beyond 1 year after stent implantation when the polymer is fully degraded. Methods and Results—The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BP-BES with DP-EES in patients scheduled for percutaneous coronary intervention using drug-eluting stent (DES) without any exclusion criteria among 98 participating centers in Japan. The trial was designed to evaluate noninferiority of BP-BES relative to DP-EES in terms of any target-lesion revascularization at 1 year and death or myocardial infarction at 3 years. Between May and October 2011, 3235 patients were randomly assigned to receive either BP-BES (1617 patients) or DP-EES (1618 patients). Complete 3-year follow-up was achieved in 97.6% of patients. At 3 years, the primary safety end point of death or myocardial infarction occurred in 159 patients (9.9%) in the BP-BES group and in 166 patients (10.3%) in the DP-EES group, demonstrating noninferiority of BP-BES relative to DP-EES (P noninferiority<0.0001 and P superiority=0.7). Cumulative incidence of target-lesion revascularization was not significantly different between the 2 groups (7.4% versus 7.1%; P=0.8). By a landmark analysis at 1 year, the cumulative incidences of death or myocardial infarction and target-lesion revascularization were also not significantly different between the 2 groups (4.6% versus 5.2%; P=0.46 and 3.3% versus 2.7%; P=0.39, respectively). Conclusions—Safety and efficacy outcomes of BP-BES were non inferior to those of DP-EES 3 years after stent implantation. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01303640.

Successful Covering of a Hepatic Artery Aneurysm with a Coronary Stent Graft

In a 54-year-old woman with liver cirrhosis who underwent orthotopic liver transplantation, the postoperative course was complicated by aneurysm formation in the hepatic artery. Abdominal ultrasonography showed a daily increase in the size of the aneurysm in spite of careful management including strict rest and continuous intravenous infusion of antihypertensive agents. Since the patient’s poor systemic status was a major obstruction to operative resection, transcatheter therapy was thought more preferable. We evaluated the lesion with intravascular ultrasonography as an adjunct to angiography and a dissection with a flap was well visualized. The aneurysm was covered with a commercially available stent-graft, designed for treatment of the coronary artery. This is a rare case in which a Jostent was implanted into the hepatic artery after liver transplantation.

Three-dimensional reconstruction of computed tomographic images of anomalous origin of the left main coronary artery from the pulmonary trunk in an adult

We present a 49-year-old female case of anomalous origin of the left main coronary artery from the pulmonary trunk. Multidetector computed tomography was performed, and 3-dimensional reconstruction of computed tomographic images found that the left main coronary artery originated from left sinus of the pulmonary trunk and the right coronary artery from the right coronary cusp of the aorta. We speculate that this patients long life may be due to the dominant right coronary artery and rich collateral from the right coronary artery to the left coronary artery.

Alteration of extracellular matrix in dilated cardiomyopathic hamster heart.

The purpose of this study was to characterize the collagen in hereditary dilated cardiomyopathic hamster hearts, and to examine the participation of the collagen in the occurrence and progression of cardiomyopathy.BIO 53.58 hamsters (5, 10, 20 weeks old) were used as the model of dilated cardiomyopathy. Flb hamsters were used as controls. The collagen content was almost constant at any age in the Flb hamsters, but increased with age in BIO 53.58 hamsters. Type III collagen increased significantly in BIO 53.58 hamsters at 10 weeks. The acetic acid solubility of collagen decreased in BIO 53.58 hamsters as the fibrosis progressed, but was unchanged in controls. Reducible crosslinks showed a tendency to decrease progressively in BIO 53.58 hamsters. There were no differences between Flb and BIO 53.58 hamsters at 5 weeks, but its expression in BIO 53.58 hamsters at 10 and 20 weeks of age increased compared to Flb controls.These findings indicate that in the early phase of cardiomyopathy the extracellular matrix of the myocardium is rich in type III collagen. In the later phase, the matrix resembles that of hard tissues, whose collagen is mainly of type I collagen and is insoluble. These data suggest that the increased collagen synthesis may impair the cardiac function in the development of cardiomyopathy.

Fibromuscular dysplasia involving coronary arteries--a case report.

The authors report a young patient with fibromuscular dysplasia involving multivessels including coronary arteries. If young patients have chest pain on effort, fibromuscular dysplasia of coronary arteries must be considered. As fibromuscular dysplasia is a chronic progressive disease and some cases progress rapidly in a few months, careful follow-up and comprehensive medical management may be necessary in such patients.