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AIM We investigated whether cardio-ankle vascular index (CAVI), an arterial stiffness marker, independently predicts future cardiovascular events in subjects with metabolic disorders. METHODS 1562 outpatients underwent CAVI between April 2004 and March 2006 at Toho University, Sakura Medical Center in Chiba, Japan. Patients who already had cardiovascular events at baseline, patients with low ankle brachial index (＜0.9), and patients with atrial fibrillation were excluded. After exclusion, 1080 subjects with metabolic disorders including diabetes mellitus, hypertension and dyslipidemia were screened and followed prospectively. RESULTS Eventually, 1003 subjects (92.9% of 1,080 subjects) followed until March 2012 (follow-up duration 6.7±1.6 years) were analyzed. During the observation period, 90 subjects had new-onset myocardial infarction or angina pectoris confirmed by angiography. All subjects were stratified into quartiles by baseline CAVI (Q1: CAVI ≤8.27, Q2: CAVI 8.28-9.19, Q3: CAVI 9.20-10.08, Q4: CAVI ≥10.09). Age, male ratio and future cardiovascular events increased as CAVI quartile became higher. In Cox proportional hazards regression analysis, the factors independently associated with higher risk of future cardiovascular events were every 1.0 increment of CAVI [hazard ratio (HR) 1.126, p= 0.039], male gender (HR 2.276, p=0.001), smoking (HR 1.846, p=0.007), diabetes mellitus (HR 1.702,p=0.020), and hypertension (HR 1.682, p=0.023). CONCLUSION In individuals with metabolic disorders, CAVI was a predictor of future cardiovascular events, independent of traditional coronary risk factors. CAVI is a potentially valuable tool to identify persons likely to benefit from more intensive therapeutic approaches.

Objective To investigate the relationship between Parkinson's disease (PD) and the cardio-ankle vascular stiffness index (CAVI), a novel non-invasive measurement of vascular stiffness. Methods A total of 63 PD subjects who underwent CAVI measurement were enrolled, including 30 men and 33 women 69.1±7.5 years of age (range: 46-79 years). Sixty-three non-PD subjects (30 men, 33 women, mean age: 68.7±7.6 years [range: 43-79 years]) served as controls. Comparisons between the control and PD subjects were made using Fisher's protected least significant difference, the Bonferroni-Dunn test, Scheffe's test and the unpaired t-test. Results 1) The average CAVI values were as follows: control, 9.3±0.9; PD, 9.0±1.0 (p=0.049). The differences in the CAVI values between the groups and the index values (normative data provided internally in the VaSera system) were as follows: control, 0.4±0.8; PD, 0.03±0.9 (p=0.011). The CAVI values of the PD patients were significantly smaller than those of the control subjects. 2) Among the control subjects, the CAVI values in the subjects with atherosclerotic risk factors (hypertension, dyslipidemia and/or diabetes) were significantly higher than those observed in the subjects without risk factors. In contrast, among the PD patients, the CAVI values in the subjects with atherosclerotic risk factors were equivalent to those observed in the subjects without risk factors. 3) Among the PD patients, the CAVI values did not change with the motor stage. Conclusion The results of the present study show that, compared with control subjects, PD patients exhibit normal CAVI values despite having mild but significant atherosclerotic risk factors, e.g., hypertension and diabetes. These findings suggest that PD patients are less vulnerable to systemic atherosclerosis than their risk factors may suggest.

The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. Arterial stiffness is closely related to afterload, and elevated afterload aggravates heart failure. We hypothesized that CAVI is a potential marker of afterload in patients with heart failure. Thirty patients who were admitted because of acute heart failure were identified retrospectively from a review of clinical records. Plasma brain natriuretic peptide (BNP) levels, CAVI, cardiothoracic ratio (CTR), and echocardiographic parameters obtained during acute and chronic phases of heart failure were analyzed. Left ventricular ejection fraction (LVEF) increased significantly and CTR, BNP and CAVI decreased significantly after treatment of heart failure. A significant negative correlation was observed between the change in CAVI and change in LVEF in all subjects (r = -0.3272, P < 0.05). To examine the relationship between CAVI and LVEF, we divided the patients into two subgroups (∆CAVI < -0.5; CAVI decrease group, ∆CAVI ≥ -0.5; CAVI non-decrease group). CAVI was significantly improved after heart failure treatment only in the CAVI decrease group. LVEF decreased significantly in both groups, but the P value was smaller in the CAVI decrease group than in the CAVI non-decrease group. The change in LVEF correlated significantly with the change in CAVI in the CAVI decrease group (r = -0.4201, P < 0.05), whereas no significant correlation was found in the CAVI non-decrease group. CAVI correlates inversely with LVEF after heart failure treatment. Our results suggest that CAVI might partially reflect the afterload in patients with heart failure.

Background The distribution of frequency power (DFP) within the QRS complex (QRS) is unclear. This study aimed to investigate the DFP within the QRS in ischemic cardiomyopathy (ICM) with lethal ventricular arrhythmias (L-VA). A computer simulation was performed to explore the mechanism of abnormal frequency power. Methods The study included 31 ICM patients with and without L-VA (n = 10 and 21, respectively). We applied the continuous wavelet transform to measure the time-frequency power within the QRS. Integrated time-frequency power (ITFP) was measured within the frequency range of 5–300 Hz. The simulation model consisted of two-dimensional myocardial tissues intermingled with fibroblasts. We examined the relation between frequency power calculated from the simulated QRS and the fibroblast-to-myocyte ratio (r) of the model. Results The frequency powers significantly increased from 180 to 300 Hz and from 5 to 15 Hz, and also decreased from 45 to 80 Hz in patients with ICM and L-VA compared with the normal individuals. They increased from 110 Hz to 250 Hz in ICM alone. In the simulation, the high-frequency power increased when the ratio (r) were 2.0–2.5. Functional reentry was initiated if the ratio (r) increased to 2.0. Conclusions Abnormal higher-frequency power (180–300 Hz) may provide arrhythmogenic signals in ICM with L-VA that may be associated with the fibrous tissue proliferation.

Myocardial tissue fluid flow (MTFF) directly represents the oxygen supply to the cardiomyocytes. Therefore, imaging of MTFF is carried out by fluorescence cardioscopy (FC).Sixty-six patients with coronary artery disease underwent FC using fluorescein as an indicator of MTFF because this dye exhibits fluorescence in tissue fluid but not in the blood. Three mL of 10% fluorescein was injected intravenously and fluorescence images of the left ventricular endocardial surface were obtained by FC at 30 seconds and 1, 3 and 6 minutes later to evaluate the MTFF.The CF images were classified as follows: diffuse with high intensity indicating normal MTFF; diffuse but with low intensity indicating decreased MTFF, no fluorescence indicating absent MTFF, and patchy fluorescence indicating patchy preservation of MTFF. MTFF was normal in all 18 patients with chest pain syndrome, patchy fluorescence was decreased or absent in 16 of 20 patients with angina and/or old myocardial infarction due to organic coronary artery disease, and was patchy in 21 of 28 patients with vasospastic angina. Ten of these 20 patients underwent coronary stenting with successful angiographic results in all. However, MTFF disturbance frequently remained.FC is clinically feasible for evaluation of MTFF disturbance, for evaluation of even emergency coronary interventions, and for guidance of transendocardial angiogenic and myogenic therapies in patients with coronary artery disease.

経胸壁ドプラ心エコー法による冠動脈の描出が可能となり，冠血流速波形の解析から冠循環の評価が行われるようになってきた．冠動脈遠位部は検出率が高く，その血流評価に対する多数の報告がなされているのに対して，冠動脈近位部を評価した報告は少ない．今回我々は，経胸壁ドプラ心エコー法により，冠動脈近位部狭窄の診断が可能であった不安定狭心症の2症例を経験したので報告する．症例1：79歳，男性．胸痛を主訴に入院．発作時の心電図では II ，III，aVF，V3‐6のST低下を認めた．経胸壁心エコー検査では，左室壁運動が心尖部で若干低下していたが左室駆出率は正常であった．大動脈弁レベルの短軸像で冠動脈近位部を直接描出したところ，左前下行枝近位部に加速血流を認め拡張期最高血流速度は104cm/秒と高速であった．冠動脈造影の結果，分節6に99%狭窄を認め，経胸壁心エコー検査で認められた狭窄部と一致していた．狭窄部にステントを留置し良好な拡張に成功した．術後の経胸壁心エコー検査では，冠動脈内の加速血流は消失し拡張期最高血流速度は40cm/秒と正常化した．症例2：59歳，男性．胸痛を主訴に入院．発作時の心電図で II ，III，aVFの陰性T波を認めた．経胸壁心エコー検査では，左室壁運動異常は認めなかった．大動脈弁レベルの短軸像で冠動脈近位部を直接描出したところ，右冠動脈近位部に加速血流を認め拡張期最高血流速度は108cm/秒と高速血流であった．冠動脈造影の結果，分節1に99%狭窄を認め，経胸壁心エコー検査で認められた狭窄部と一致していた．狭窄部にステントを留置し良好な拡張に成功した．術後の経胸壁心エコー検査では，冠動脈内の加速血流は消失し拡張期最高血流速度は26cm/秒と正常化した．非ST上昇型の不安定狭心症において，経胸壁ドプラ心エコー法により冠動脈近位部の狭窄病変を直接描出することが可能であった．本法は，冠動脈近位部狭窄の有無を心臓カテーテル検査前に予測する上で有用な検査法と考えられた．

大動脈四尖弁は大動脈二尖弁と同様に大動脈弁機能不全の原因疾患となる先天性弁膜症である. 発生頻度は大動脈二尖弁より少なく稀な疾患である. 今回, 超音波検査により術前に大動脈弁四尖弁と診断し得た2症例を経験したので報告する. 症例1 : 63歳, 男性, ペースメーカー植込み術を受けている. 労作時呼吸困難を自覚するようになり入院した. 心エコー検査の結果, 重度の大動脈弁逆流を認め, 左冠尖と無冠尖の間に副尖を有する大動脈四尖弁であった. 手術で四尖が確認され大動脈弁置換術 (SJM 23 mm) を施行した. 組織像では軽度の線維増生と粘液変性が認められた. 症例2 : 58歳, 女性, 高血圧と気管支喘息のため近医で加療を受けていた. 労作時呼吸困難を自覚するようになり入院した. 心エコー検査の結果, 重度の大動脈弁逆流と大動脈弁狭窄の所見を認めたが, 大動脈弁形態は不明であった. 経食道心エコー検査を施行し, 左冠尖と右冠尖の間に副尖を有する大動脈四尖弁と判明した. 手術で四尖が確認され大動脈弁置換術 (SJM 17 mm) を施行した. 組織像では高度の線維増生と石灰化が認められた. 心エコー検査で大動脈弁膜症の原因を検索する際には大動脈四尖弁の可能性も考慮に入れ慎重に観察する必要がある.

The mechanism of the antithrombotic effects of heparin and the synthetic antithrombin agent argatroban was evaluated in a dog model. Thrombus formation following balloon injury was evaluated by angioscopy in the right iliac arteries of 20 dogs to serve as a control. After the evaluation of the growth of thrombus on the control side, heparin (200 U/kg) or argatroban (0.2 mg/kg) was infused intravenously, and the distal site of the contralateral left iliac artery was injured in the same manner. At 30 to 120 min before the final examination, the proximal site of the left iliac artery also was injured. After antithrombotic drug infusion, the percent angioscopic stenosis at the distal site was much lower (P0.0001) than that of the control site (mean stenosis index: 0.67 in heparin vs. 3.8 in control, and 0.25 in argatroban vs. 4.3 in control); however, thrombus formation was observed at the proximal site. With local delivery of a low dose of either antithrombotic drug (n=10), an antithrombotic effect was maintained until 4 h after the infusion. A very weak fluorescence of FITC-heparin was detected at the injured artery 2 h after infusion. In a shunt experiment involving 5 dogs, carotid arteries were injured and incubated in oxygenated Krebs--Henseleit solution before auto grafting into the femoral artery. At 2 h after the grafting, no thrombus was formed in the grafted vessels incubated for 4 h, but was formed in those incubated for 10 min. These results indicate that the relatively long antithrombotic effect of these drugs may be due to a local drug effect at the injured artery, as well as the recovery of the anti-thrombogenicity of the injured artery.

Aim To evaluate progression of arteriosclerosis using cardio-ankle vascular index(CAVI) and carotid duplex ultrasonography(DUS) in young and adolescent patients considered to be at risk of cardiovascular disease. Methods We evaluated the progression of arteriosclerosis using CAVI and carotid DUS in 240 young and adolescent patients. Dyslipidemia(DL), hypertension(HT), and diabetes mellitus(DM) were major cardiovascular risk factors. Patients were divided to 4 groups according to number of risk factors. Results In terms of risk factors, CAVI and CAVI difference(CAVI-D) were elevated only in the HT group(p=0.0290, p=0.0243 vs. no risk respectively). CAVI-D was positively associated with diastolic blood pressure(DBP). Mean IMT was positively associated with LDL-C or systolic blood pressure, and negatively with HDL-C. Plaque score was associated with LDL-C or DBP. In patients with the 3 risk factors, CAVI, CAVI-D and mean intima-media thickness(IMT) were significantly higher than in those without risk(p=0.0009, p=0.0042 and p=0.0151 respectively), and CAVI and CAVID were higher than in those with 1 risk(p=0.0204 and p=0.0231). Carotid plaque develops from around 30 years of age in Japan. Despite numbers of risk factors, there were no differences in CAVI, CAVI-D, mean IMT or plaque score between smoker and non-smoker groups. Conclusion In conclusion, an increase in the number of risk factors also results in progression of arteriosclerosis in young and adolescent patients. HT was the most important risk factor for arteriosclerosis in these patients.

A model to assess thrombus formation following vascular injury was evaluated using various interventional systems. The model consisted of a 'stretchable' shunt box that served as an arteriovenous shunt between the carotid artery and jugular vein in dogs. Arterial homografts obtained from both carotid and femoral arteries were mounted between two plastic connectors attached to either side of the shunt box. The opposing walls of the shunt box were then stretched apart to achieve the original length of the arteries. The arterial side of the box was connected to the ipsilateral carotid artery and the venous side was connected to the contralateral jugular vein. Haemostasis valves were placed at the exit ports on the venous side of the shunt box. These were used as an access to the various interventional catheters into the lumens of the homografts. Interventions were performed prior to initiating blood flow. After the interventions, 111indium-labelled platelets were injected on the arterial side of the shunt box and arterial blood flow initiated across the shunt. After one hour of circulation through the shunt box, the blood flow was interrupted, and the homografts were perfusion-fixed with glutaraldehyde and segments removed for radioactive counts and processed for histology. This shunt box was then used to compare platelet adhesion and thrombus formation after balloon angioplasty (BA) to direct laser (LA) and laser-thermal angioplasty (LTA). A total of 28 arteries were used from seven dogs. In each experiment, one homograft was used as control, and three other homografts were treated with either BA, LA or LTA. Following the interventions, 111indium-labelled platelets were injected and circulated for one hour using the dog's native circulation. Labelled platelet counts for BA (19102+/-4869/cm2; mean +/- SE) were significantly greater than LA (7038+/-980/cm2), thermal LTA (5189+/-1961/cm2), and control (1575+/-541/cm2), respectively (p0.05, ANOVA). Histology examination showed few platelets at LA, LTA and control sites whereas extensive platelet adhesion was noted at BA treated sites. The model provided a means to conduct simultaneous comparison of several interventions under similar conditions. In this case thermal treatment of the arterial homografts had the least amount of platelet adhesion.

Acute reocclusion after successful angioplasty is a severe complication. The preventive effects of heparin, the synthetic antithrombin, argtroban, and the defibrinogenating agent batroxobin on reocclusion after balloon angioplasty of thrombotic occlusions were evaluated in canine iliac arteries. After the 2-hour-old thrombus was evaluated by angiography and angioscopy, percutaneous transcatheter angioplasty (PTA) was performed on the thrombotic stenosis. We used one of the three agents, heparin (100 U/kg), the antithrombin argatroban (0.3 mg/kg), or the defibrinogenating agent batroxobin (0.3 U/kg). Then angioscopy and angiography were performed before, just after, and 2 hours after PTA. After PTA, angiography revealed a marked reduction in percent stenosis in all groups (from 88 ± 8% to 24 ± 4% in the heparin group, from 79 ± 7% to 26 + 11% in the argatroban group and from 89 ± 12% to 32 ± 7% in the batroxobin group). At 2 hours after PTA, angiography demonstrated a greater reduction in percent stenosis with argatroban (from 26 ± 11% to 9 ± 3%) and batroxobin (from 32 ± 7% to 10 ± 8%), and maintenance of percent stenosis reduced by PTA with heparin (from 24 ± 5% to 28 ± 9%) when compared with the significant reversal of percent obstruction in the control side. Angioscopic visualization also demonstrated a similar trend. These results show that these antithrombotic drugs have a preventive effect on reocclusion after balloon angioplasty for thrombotic obstruction.

Since the treatment of thrombotic disease by antithrombotic drugs may be associated with bleeding complications, a local delivery technique for administration of the drug may be useful. The efficacy of low-dose local delivery of an antithrombotic drug on thrombosis was investigated in 73 dogs. The antithrombotic drug (heparin, 25U/kg, antithrombin: argatroban, 0.05mg/kg, or defibrinogenating agent: batroxobin, 0.05U/kg) was infused locally to a 1-h-old thrombus, and no drug was given in controls. The effect of the local delivery on the thrombus was evaluated. Low- and high-dose systemic drug delivery was also evaluated. The mean reduction in thrombotic coronary stenosis observed by angiography was 30.3% with argatroban, 22% with heparin, and 20.8% with batroxobin (P < 0.005 vs controls). Systemic delivery of low-dose heparin or argatroban did not induce any change in thrombus size. With high-dose systemic drug delivery (heparin 250 U/kg, argatroban 0.5 mg/kg), the mean reduction of thrombotic stenosis was 15.2% with heparin and 32.8% with argatroban (P < 0.005 vs controls). In iliac arterial thrombosis, after local delivery of the drugs, the mean reduction of thrombotic stenosis observed by angiography was 24.4% in the argatroban group, and 19.2% in the heparin group (P < 0.05 vs controls, respectively). With high-dose systemic heparin delivery, the mean reduction of the thrombotic stenosis was 13.2% (P < 0.01 vs control). Angioscopy also demonstrated a similar trend. The high-dose drug delivery reduced systemic coagulability. Thus, local delivery of an antithrombotic agent can reduce the thrombus size in the coronary and iliac arteries without having any significant influence on coagulability.

To examine whether angiogenesis and myocardial salvage occur, 30 micrograms basic fibroblast growth factor (bFGF) and 3 mg heparin sulfate (HS) were injected through the right atrium into the pericardial cavity by a thin needle-tipped catheter in a canine model of acute myocardial infarction. One month later infarcted weight/left ventricle weight was 24% +/- 5.2%, 25% +/- 4.0%, 18% +/- 2.4%, and 10% +/- 1.8% (mean + SE) in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Vascular number in the infarcted area of the outer layer was 13 +/- 3.3, 20 +/- 2.2, 47 +/- 8.3, and 136 +/- 26.3/200 x 200 microns2 in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Thus the vascular number was the largest in the bFGF plus HS group. The vascular number was larger in the subepicardial than in the subendocardial infarcted areas. Vessels directed from the epicardium toward the subepicardial infarcted area were also observed. The transcatheter intrapericardial injection of bFGF plus HS caused angiogenesis and myocardial salvage. This method might bring about a selective therapeutic and preventive modality of myocardial infarction irrespective of coronary anatomy and contraindications for coronary interventions and surgery.

It is not known whether the individual lesions that constitute tandem lesions of the coronary artery are developmentally or rheologically related. Luminal changes and their rheological significance were examined by percutaneous angioscopy in 44 tandem lesions of 21 patients with ischemic heart disease. Angioscopically, individual narrowing of angiographically documented tandem lesions appeared only as a tangentially expressed prominent portion of an atherosclerotic spiral fold. The directions of the fold were counterclockwise in the proximal to middle segments and clockwise in the distal segment of the right coronary artery, clockwise in the proximal to middle segments and counterclockwise in the distal segment of the left anterior descending artery, and counterclockwise in the proximal to middle segments of the left circumflex artery. The bloodstream always ran along the spiral folds in the tandem lesions. The results suggest that angiographically documented tandem coronary lesions are merely a tangential expression of atherosclerotic spiral folds and that they may act to prevent blood turbulence by generating a spiral laminal flow.

Ablation of the AV junction is an accepted technique for the management of selected supraventricular tachyarrhythmias. Radiofrequency ablation appears to be safe and effective for AV junction ablation in most patients, but the need for firm tissue contact may make it less effective for ventricular tachycardia and certain ectopic/atrial tachycardias. Laser energy can also be delivered through a catheter, and thus it may be an attractive alternative energy source for ablation. A new laser-electrode catheter was developed for modification of conduction through the AV node as a model for ablation of an arrhythmia substrate. A window for delivery of continuous-wave Nd:YAG laser energy was placed between the two electrodes of a bipolar electrode catheter. In vitro studies using a matrix of power versus time were performed to determine the energy that would create lesions of the appropriate size in vivo. Using this information, advanced AV block was successfully created in 16 of 17 dogs (94%) with the laser-electrode catheter. Advanced AV block was successfully created in all four dogs in the chronic study, and it persisted for 1-24 weeks of follow-up until sacrifice of the animals. Histologic examination demonstrated discrete thermal damage at the AV junction with no instances of septal perforation in the acute studies or progressive necrosis in chronically maintained dogs. Advanced AV block may be produced consistently and safely in dogs using a combined laser-electrode catheter.

We investigated the relationship between stroke and cardio-ankle vascular stiffness index (CAVI), a novel noninvasive measure of vascular stiffness.Eighty-five patients with cerebrovascular disease who underwent CAVI were enrolled in the current study. They were 63 men and 22 women with a mean age of 70.0 ± 10.8 years. They were divided into 4 groups according to neurologic abnormalities and magnetic resonance imaging (MRI) findings: 12 with transient ischemic attack (TIA), 26 with white matter ischemic lesions (WMLs), 17 with large artery atherosclerosis, and 30 with small vessel occlusion. Eight hundred fifty-four healthy patients (487 men and 367 women; mean age 65.1 ± 9.4 years) served as controls. The results were stratified by gender and age and statistically analyzed using the Fisher, Bonferroni-Dunn, and Scheffe tests.The average of CAVI was as follows: control males 60 to 69 years of age, 9.05 ± 0.82 (as a representative value); TIA, 9.3 ± 1.5; WML, 10.3 ± 1.3; large artery atherosclerosis, 10.2 ± 1.2; and small vessel occlusion, 10.0 ± 1.6, respectively. The difference in CAVI between each group and age- and gender-matched controls was 0.492 for TIA (no statistical significance); WML, 0.733 (P.001, and P = .002 Scheffe); large artery atherosclerosis, 0.838 (P.001, and P = .005 Scheffe); and small vessel occlusion, 1.034 (P.001), respectively. Linear regression analysis of CAVI and plaque score revealed a significant relationship in patients with ischemic cerebrovascular disease (P.05).Compared with healthy control subjects, CAVI is statistically greater in patients with ischemic cerebrovascular diseases, particularly with WML, large artery atherosclerosis, and small vessel occlusion, but not in patients with TIA. CAVI had a clear relationship with carotid ultrasound plaque score. It appears that CAVI is a simple and noninvasive test for indicating atherosclerosis in patients with stroke.

Background Recently, arterial stiffness parameter called cardio-ankle vascular index (CAVI) has been developed. In the current study, using coronary angiographic (CAG) findings, the usefulness of CAVI as a marker of the severity of coronary atherosclerosis was compared with that of carotid atherosclerosis parameters obtained from high-resolution B-mode ultrasonography. Method and Result A total of 109 participants who underwent CAG were enrolled in the current study. They were divided into 4 groups according to the number of stenotic vessels on CAG; no lesion (0VD), 1-vessel (1VD), 2-vessel (2VD) and 3-vessel (3VD) groups. CAVI was significantly higher in 1VD group compared with the 0VD group (p

HMG-CoA reductase inhibitors (statins) have recently been reported to improve cardiac function, and decrease the incidence of heart failure (HF) in hyperlipidemic patients. However, evidence for statin treatment in patients with HF remains a subject of debate. Thus, a study was initiated to examine the effects of pitavastatin on cardiac function evaluated by echocardiographic findings and plasma brain natriuretic peptide (BNP) levels in patients with HF. Twenty-three patients with HF were treated with pitavastatin 1-2 mg/day in addition to standard therapy for 7.5 +/- 3.8 months. Left ventricular end-diastolic dimension (LVDd) and left ventricular end-systolic dimension (LVDs) were determined by echocardiography. Left ventricular ejection fraction (LVEF) was calculated using Teichholz's formula. Serum lipid and plasma BNP levels were also measured. During the follow-up period, LVEF was increased from 42 +/- 11 to 48 +/- 13% (P = 0.002). LVDs was reduced from 43 +/- 10 to 40 +/- 10 mm (P < 0.001), while there was no change in LVDd. E/A (n = 10) and deceleration time (n = 7), obtained in some patients, did not change significantly (0.89 +/- 0.33 to 0.77 +/- 0.17%, and 215 +/- 46 to 227 +/- 72 msec, respectively). In addition, the plasma BNP level was moderately, but significantly decreased from 94 +/- 78 to 70 +/- 56 pg/mL (P = 0.005). In subgroup analysis, LVEF was improved in both patients with ischemic and nonischemic HF. There was no significant correlation between the percent change in serum total cholesterol and the percent change in LVEF by pitavastatin treatment. Serum total cholesterol, LDL-cholesterol, and triglycerides decreased by 21%, 30%, and 15%, respectively, and HDL-cholesterol increased by 12%. Pitavastatin improved cardiac function in patients with HF, which generally worsens with time. The results suggest that pitavastatin may be beneficial for treatment of HF.

It is well known that the nonionic contrast media cmrently used are safer than ionic high-osmolar contrast media (1). However, contrast media-related cardiovascular adverse effects are still observed, especially in high-risk patients following their injection into left ventricle and coronary arteries (2,3). Iomeprol 400 (400 mgI/mL) (Iomeron; Bracco SpA, Milan, Italy; Eisai, Tokyo, Japan), which has been recentily developed, has some advantages such as 30-50 mg/mL higher iodine content and a lower osmolality of 750 mosm/kg • H20 than existing nonionic monomeric contrast media (4,5). Consequently, we can expect iomeprol 400 to have a better image and reduction of osmolality-related adverse effects such as patient discomfort and untoward hemodynamic and ECG changes. It is also noteworthy tha~ the use of iomeprol 400 is imperative and of clinical value, especially for the obese and broad-chested patients during cine cardioangiography. In this study, to determine the patient tolerance, safety, and usefulness of iomeprol 400 in cardioangiography, we compared the patient discomfort and hemodynamic and ECG effects of iomeprol 400 with those of iomeprol 350 (350 mgI/mL) during left ventriculography (LVG) and coronary angiography using a crossover design.

To pinpoint the link between plaque characteristics and acute coronary syndromes, we performed a 12-month prospective follow-up study in 157 patients with stable angina pectoris in whom regular coronary plaques were observed by percutaneous coronary angioscopy. Acute coronary syndromes occurred more frequently in patients with yellow plaque than in those with white plaques (11 of 39 vs 4 of 118; p = 0.00021). Moreover, the syndromes occurred more frequently in patients with glistening yellow plaques than in those with nonglistening yellow plaques (9 of 13 vs 2 of 26; p = 0.00026). Thrombus arising from the ruptured identical plaques was confirmed by angioscopy as the culprit lesion of the syndromes. The results indicate that acute coronary syndromes occur frequently and in a short time in patients with glistening yellow plaques and that angioscopy but not angiography is feasible for prediction of the syndromes.

The antithrombotic effect of three different types of antithrombotic agents (antithrombin:argatroban, heparin, defibrinogenating agent: batroxobin) were evaluated in canine coronary and iliac arteries. An occlusive thrombus was produced by balloon injury. One of the three agents was infused intravenously at 1 hour after thrombus formation (heparin 250 U/kg, argatroban 0.5 mg/kg, batroxobin 0.5 U/kg) and the effect of thrombus size reduction was evaluated. On the contralateral side of the iliac artery, the preventive effect of these agents on thrombus formation was evaluated after balloon injury. In the iliac artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 69% to 32% in the argatroban group, and from 64% to 51% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography demonstrated the same trend. The percent area stenosis with thrombus at 60 minutes following balloon injury was 0.75% in the argatroban group, 18.9% in the heparin group (P < 0.05 vs argatroban), and 12.9% in the batroxobin group. Thrombus size at the treated site was smaller than that at the control site in all three groups (P < 0.05 vs control). In the coronary artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 84% to 53% in the argatroban group, and from 86% to 68% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography also demonstrated the same trend. The activated partial thromboplastin time (APTT) was prolonged to 189% of the control value with argatroban and to 1253% of the value with heparin (P < 0.0001). Fibrinogen was markedly reduced with batroxobin. These results showed that both the antithrombin agent and the defibrinogenating agent have a preventive effect on thrombus formation and the effect on thrombus size reduction, without marked prolongation of the APTT.

Recent advances in fiberoptic technology enables us to observe the cardiac chambers percutaneously in various categories of heart disease. We applied cardioscopy in 4 patients with HCM. Two of them presented excessive or good left ventricular function and no history of congestive heart failure (CHF). The other two patients showed reduced left ventricular function with a history of CHF. Cardioscopy was successfully performed in all patients. In patients with excessive or good left ventricular function, the color of the endocardial surface was light brown mixed with white. The trabeculae were significantly thick and contracted vigorously. In patients with reduced left ventricular function, the color was whiter, and the thickness and contraction of the trabeculae were reduced obviously. Myocardial biopsy revealed that interstitial fibrosis was prominent in the latters. These results indicate that (1) cardioscopy is safe and useful for evaluation of the internal surface of the ventricle in patients with HCM, and (2) cardioscopic characteristics of the ventricle are closely related to histopathological features.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

UNLABELLED The vasoreactivity and thrombogenicity of laser-thermal angioplasty were examined and compared with those of balloon angioplasty in an atherosclerotic rabbit iliac artery. Eight rabbits underwent laser-thermal angioplasty with a 1.7-mm hot-tip probe activated at 7 W with a probe temperature of 126 +/- 19 degrees C in one iliac artery. The other iliac artery was treated with balloon angioplasty using a 2.0-mm balloon. Angiographic luminal diameter increased from 0.19 +/- 0.15 to 1.54 +/- 0.35 mm by laser and from 0.29 +/- 0.22 to 1.84 +/- 0.20 mm by balloon (P less than 0.0001, respectively). However, it decreased to 1.34 +/- 0.42 for laser and 0.45 +/- 0.39 for balloon 60 minutes later (P less than 0.0001 vs immediately post). Both iliac arteries were visualized using angioscopy, which revealed thrombotic obstruction of 91% stenosis in the ballooned artery and 8% stenosis in the lased artery. Vasoreactivity of treated vessels was also investigated. Segments 3-mm long were obtained from either treated artery or control artery and examined for noradrenaline (10 -7 M) contraction. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Developed tension was 0.13 +/- 0.21 g for laser thermal and 2.33 +/- 0.4 g for its control (P less than 0.0001), and 0.15 +/- 0.16 g for balloon dilatation and 2.12 +/- 0.43 g for its control (P less than 0.0001). Neither acetylcholine at 10 -6 M or papaverine at 10 -4 M induced relaxation of treated segments. Histology showed slight thermal injury at thermally-treated sites without thrombus, and intimal and medial dissection with thrombus formation at balloon dilated site. IN CONCLUSION (1) neither a laser-thermal recanalized or a balloon dilated obstructed artery is vasoreactive to constrictive or relaxant agents; and (2) laser-thermal angioplasty results in less thrombogenicity than balloon angioplasty under moderate probe temperature.

Coronary collateral vessels reduce damage to ischemic myocardium after coronary obstruction. Factors that stimulate collateral formation are expected to have ameliorating effects on myocardial infarction. In a canine experimental myocardial infarct model, intracoronary injection of basic fibroblast growth factor (bFGF) improved cardiac systolic function and reduced infarct size. Treatment with bFGF increased the number of arterioles and capillaries in the infarct. Thus, the angiogenic action of bFGF might lead to a reduction in infarct size. The application of bFGF might bring about a therapeutic modality for the salvage of infarcted myocardium.

The morphology and function of the cardiac chambers have been evaluated clinically using cineventriculography, computed tomography, magnetic resonance imaging, and endomyocardial biopsy. Excluding the invasive technique of biopsy where tissue is actually removed, these other non-invasive techniques reveal only indirect evidence of endocardial and subendocardial pathology and, therefore, allow the potential for misdiagnosis from insufficient data. Fiberoptic examinations, as recently demonstrated in coronary, pulmonary, and peripheral vessels, allow direct observation of pathology otherwise unobtainable. Recently, similar techniques have been applied to examine the cardiac chambers of dogs and the right heart of humans. In this study, we examine the feasibility and safety of percutaneous fiberoptic cardioscopy of the left ventricle in patients with myocarditis.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The feasibility of percutaneous transluminal cardioscopy of the left ventricle was examined in 35 patients with or without various heart diseases. A guiding balloon catheter (7 or 9 French) was introduced through the right femoral artery into the left ventricle. The balloon was inflated, and a fiberscope (1.6 or 4.3 French) was advanced to the distal tip of the catheter. The balloon was then manipulated against the portion of the ventricle targeted for examination, and heparinized saline (10 U/ml) at body temperature was infused through the catheter at 5 ml/sec for 3 to 6 sec. The images were recorded on videotape and 16 mm cinefilm. In 4 patients without demonstrable heart disease, the endocardial surface of the left ventricle was brown and the trabeculae became prominent during systole. The chordae connected to the mitral leaflets were white. In 3 of 5 patients with dilated cardiomyopathy, the endocardium was light yellow with thin trabeculae which barely contracted during systole. The endocardium was red or reddish-brown in 3 patients with acute myocarditis. In patients with rheumatic mitral stenosis white patches were scattered on the endocardial surface. In 7 of 8 patients the akinetic or dyskinetic segments representing prior infarctions were white. No complications other than transient ventricular arrhythmias were noted. We conclude that percutaneous fiberscopic imaging with a guiding balloon catheter is feasible and safe, and yields highly detailed images of the endocardium.

Percutaneous transluminal coronary angioplasty has been proposed as definitive therapy for coronary recanalization of occluded coronary arteries in patients with acute myocardial infarction (AMI). The effects of transluminal angioplasty (TA) on experimental occlusive canine arterial thrombi that closely simulated the clinical condition was examined by a fiberoptic method. Experimental arterial thrombosis was produced by endothelial denudation and induction of luminal stenosis. Eighteen dogs that showed total occlusion of the iliac artery with thrombi were evaluated. Seven dogs (group A) with 6-hour-old thrombi received 20,000 IU/kg intravenous urokinase (UK) but did not show recanalization. TA was performed with a Gruentzig or Simpson-Robert balloon catheter and its effect was evaluated by a vascular fibroscope. Eight dogs (group B) with 6-hour-old thrombi underwent primary TA. After TA, less than 50% luminal obstruction with residual thrombi was visualized in five dogs (71%) of group A and four dogs (50%) of group B. Residual thrombi showed a doughnut-like or globular type shape and consisted of dense fibrin networks and compact platelet aggregates. All dogs in group B received 20,000 IU/kg intravenous UK after TA, but most of them showed progression of thrombus size despite UK infusion. In conclusion, the results suggest (1) that TA is effective in recanalization of an occluded artery with aged thrombus that is resistant to thrombolytic therapy and (2) that vascular fiberscope is a useful method for evaluation of the effects of TA on occlusive arterial thrombus.

In this study we reevaluated whether the sole cause of mitral valve prolapse (MVP) and aortic valve prolapse (AVP) is myxomatous degeneration. Forty-two surgical cases of prolapsed valves with mitral and/or aortic regurgitation were reviewed (AVP in nine, MVP in 27, and combined AVP and MVP [CVP] in six). On microscopic examination, myxomatous degeneration was observed in 20 patients, including six with AVP, 13 with MVP, and one with CVP. In the other 22 patients, including three with AVP, 14 with MVP, and five with CVP, microscopic examination revealed fibrosis with vascularization and scattered infiltration of inflammatory round cells caused by postinflammatory changes with or without chronic inflammation. We coined the term "postinflammatory valve prolapse" (PIVP) to describe these valves. Both postinflammatory and myxomatous degeneration were observed in seven patients with floppy mitral valves attributable to PIVP. Rupture of chordae tendineae was present in six patients with myxomatous mitral valve and three with PIVP. Seven patients with PIVP had a history of rheumatic fever. The results suggest that valvular prolapse is produced not only by myxomatous degeneration but also by postinflammatory changes, including those caused by rheumatic fever.

Percutaneous transluminal coronary angioscopy was performed during routine coronary angiography in seven patients and during PTCA in one patient with ischemic heart disease. A flexible fiberscope with an external diameter of 1.4 mm was introduced through an 8F or 9F guiding catheter used for PTCA into the coronary arteries. Warmed saline solution (15 to 20 ml) was injected through the guiding catheter into the coronary arteries for replacement of blood. Twenty-one of the 31 coronary segments were visualized and photographed on color cinefilms. The lumen of the atherosclerotic segment showed narrowing with smooth surface or with spiral folds. PTCA caused dilatation of the stenosed segment with scattered thin thrombi. These findings indicate the usefulness of angioscopy to observe luminal changes in the coronary arteries of patients with ischemic heart disease.

The thrombolytic effects of urokinase (UK) and preventive effects of batroxobin, heparin, and aspirin on the recurrence of thrombosis in the coronary artery were studied in 118 anesthetized dogs with severe endothelial denudation and luminal stenosis of the coronary artery. Occlusive thrombi developed in 68 (58%) preparations (dogs), accompanied by a decrease of coronary blood flow and pressure, an electrocardiographic ST elevation, and epicardial cyanosis. An intravenous infusion of 20,000 IU/kg of UK reopened the occluded coronary artery in all 32 preparations with 1-h-old thrombi, in 6 (86%) of 7 preparations with 2-h-old thrombi, and in 5 (83%) of 6 preparations with 3-h-old thrombi. However, recanalization was not observed in preparations with thrombi more than 4-h-old. Occlusion recurred within 6 h after recanalization in 2 (18%) of 18 preparations pretreated with batroxobin (1-2 BU/kg) (p less than .005 vs. control UK group), in 1 (14%) of 7 preparations administered a continuous infusion of 30 U/kg per h of heparin (p less than .05 vs. control UK group), in 4 (57%) of 7 preparations pretreated with 2 mg/kg of aspirin, and in 7 (64%) of 11 preparations not pretreated (control UK group). Complete prevention was observed only in the group administered 2 BU/kg of batroxobin. Histologically, these thrombi closely simulated clinical arterial thrombi. Myocardial hemorrhage and contraction band necrosis were observed in the reperfused hearts. In conclusion, experimental canine coronary thrombi more than 4-h-old were resistant to thrombolytic therapy, and batroxobin and heparin were effective in the prevention of coronary reocclusion.

房室伝導障害例においてヒス束電位図による電気生理学的所見と刺激伝導系の組織学的所見との相関を調べるため, 各種房室伝導障害23例, 対照13例の計36例を対象として以下の成績を得た。1) 正常のヒス束電位図を示した13例中1例のみがHis束分岐部に著明な変化を示したが, 他の12例には特に変化はみられず, 無病正診率は92.3% (12/13) であった。2) 1度房室ブロック7例中2例にH-Vブロックに相当する病変を呈し, 有病正診率は28.5%であった。以下2度房室ブロックでは33.3% (1/3) , 3度房室ブロックでは84.6% (11/13) で高度のブロック程, 高い相関を得た。3) 以上ヒス東電位図と組織病変との対比の結果, 綜合正診率は72.7% (26/36) であった。

We performed a pathological study of experimental canine myocardial infarction (MI) induced by coronary thrombosis which was made by endothelial denudation and induction of luminal stenosis in 20 dogs (Group I). Another model of experimental MI by coronary ligation was also evaluated in Groups II and HI. Thirteen dogs of Group I and 7 of Group II underwent persistent coronary occlusion for 6-8 h (Group IA and Group IIA), and 7 of Group I and 7 of Group II underwent coronary reper-fusion with intravenous urokinase (UK) (20,000 IU/kg) in Group IB for 5 h following temporary coronary occlusion for 3 h (Groups IB and IIB). The remaining 5 dogs underwent coronary reperfusion for 5 h following intravenous 20,000 IU/kg UK after 3 h ligation. Microscopically, myocardial hemorrhage was present in 6 (86%) Group IB, 4 (31 %) Group IA and in no Group IIA dogs (p

The applicability of fiberoptic angioscopy with a guiding balloon catheter to observe the cardiac chambers, valves and the great vessels was examined in anesthetized dogs. A No. 11 French guiding balloon catheter (balloon diameter 50 French) was introduced through either the right jugular vein or the right femoral vein into the right heart, and then a fiberscope (4.3 French in diameter) was introduced through the catheter into the right heart in 10 dogs. The balloon was inflated with air and gently pushed against the luminal surface, warm saline was infused through the catheter to displace the blood, and the luminal surfaces were photographed on 16 mm color cinefilms. Pulmonary angioscopy was also performed in these dogs. Similarly, the guiding catheter and fibercope were introduced through the right common carotid artery into the left ventricle for observation of the luminal changes in the other 10 dogs. The luminal surfaces of the superior vena cava, right atrium, right ventricle, and pulmonary artery could be observed in all dogs. The trabeculae of the left ventricle, contracting and relaxing synchronously with the cardiac beat, could also be observed in all dogs. However, observations of the tricuspid valve, aortic valve, papillary muscle, and chordae were successful in only some dogs. Postmortem examinations revealed no obvious endocardial or intimal damage. The results indicate the applicability and safety of angioscopy guided by a balloon catheter for observations of the luminal changes in the cardiac chambers and great vessels.

Angiography and angioscopy were used to examine arterial luminal changes induced by experimental vasospasm. The right common carotid artery of the dog was perfused with Krebs-Henseleit solution at a constant pressure, 3,4-diaminopyridine (DAP), a selective potassium channel blocker was applied on the adventitia, and the luminal changes were observed with angiography and angioscopy. Angiographically vasospasm (defined as a reduction in the internal diameter to less than 50% of the control value) was always induced by the topical application of 5 X 10(-1) mol/L DAP. The internal diameter decreased to 25% +/- 7% (mean +/- standard error, n = 6) 15 minutes after the application. The vasospasms propagated 2.7 +/- 0.6 and 1.1 +/- 0.3 cm downstream and upstream, respectively. Angioscopy showed that the lumen narrowed gradually and concentrically. Perfusion of the artery during vasospasm for 15 minutes with a backflow of blood from the contralateral artery resulted in thrombosis at the spastic segment. The results indicate that carotid vasospasm can be constantly induced by DAP, thrombosis occurs in the spastic artery, and angioscopy is useful for serial observation of the luminal changes induced by vasospasm.

Effects of prazosin, dobutamine, isoproterenol and SGB-1534, a new alpha-blockade, on congestive heart failure (CHF) in dogs were investigated. The model was made by protease injection into the left ventricular free wall, saline loading, and dextran and methoxamine infusions. By this maneuver, left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular end-diastolic pressure (LVEDP) were markedly increased, aortic blood flow (AoBF) was decreased, and systemic blood pressure was unchanged. In this model, the intravenous administration of prazosin (0.1 approximately 10.0 micrograms/kg, i.v.) increased AoBF and decreased LAP in a dose-dependent manner. The improvement of the CHF by prazosin was considered to result from its vasodilating action. SGB-1534 (0.1 approximately 10.0 micrograms/kg, i.v.) improved the CHF mainly through its vasodilating and positive inotropic actions, which is because SGB-1534 decreased SVR and increased Vmax. The magnitudes of vasodilation by SGB-1534 was greater than those by prazosin. These data indicate that SGB-1534 is useful in the treatment of CHF. Both dobutamine (5 approximately 100 micrograms/kg, i.v.) and isoproterenol (0.001 approximately 0.1 micrograms/kg, i.v.) improved the CHF through their vasodilating and positive inotropic actions in the canine CHF. The ratio of positive inotropism/vasodilation was greater for dobutamine than isoproterenol. The vasoconstriction by the large dose of dobutamine might participate in this difference between dobutamine and isoproterenol.

The effects of TMB-8, an inhibitor of Ca2+ release from the intracellular store site, on impaired left ventricular relaxation caused by global ischemia were examined in 45 anesthetized dogs. In the non-ischemic group, the intracoronary infusion of 100 micrograms/min TMB-8 suppressed the decrease in T, an index of left ventricular relaxation, by increasing the atrial pacing rate. In the ischemic group, the intracoronary infusion of 30 and 100 micrograms/min TMB-8 suppressed the increases of T and left ventricular end-diastolic pressure caused by ischemia and increase of pacing rate. The results indicate that TMB-8 suppresses the ability of relaxation in non-ischemic myocardium and prevents the impairment of left ventricular relaxation induced by left ventricular global ischemia.

Coronary arteries isolated from cadavers autopsied within 7 hours after death were perfused with canine arterial blood, and the processes of thrombus formation at the segments stenosed with atheroma and the thrombolytic effects of urokinase were investigated by angioscopy. Ten minutes of blood perfusion caused thin mural thrombi localized at the stenotic or nonstenotic segments. During 30 minutes of blood perfusion, the thin mural thrombi of the outlet or inlet of the segment grew into a doughnut-shaped thrombus. Also, the thin mural thrombi in the stenotic segment grew into a streamer-like thrombus and drifted downstream. These thrombi grew in size with increasing perfusion time and finally obstructed the stenotic segment. Globular thrombi close to the outlet also were formed in a few preparations. Unlike the thrombi at the stenotic segment, the mural thrombi in the nonstenotic segments did not grow into massive thrombi. The thrombi were reduced in size within 10 minutes of perfusion with 320 U/ml or more of urokinase. During thrombolysis, sandstorm-like dispersion of the blood cells occurred, small fragments detached from the mother thrombus and flew downstream, or the fibrin core of the thrombus was exposed. The results indicate the usefulness of angioscopy for the dynamic and serial investigations of thrombosis and thrombolysis.

To gain insight into mechanisms underlying phasic coronary vasospasm in patients with variant angina pectoris, we studied whether phasic contractions could be induced in isolated canine and human coronary arteries by agents which block potassium channels. Phasic contractions of canine coronary arteries were always induced by 3,4-diaminopyridine (10(-2) M) and less frequently by 4-aminopyridine (10(-2) M). These agents also caused phasic contractions in human, swine and monkey coronary arteries and in canine basilar, carotid, renal and femoral arteries. The cycle length of phasic coronary contractions ranged from 30 sec to 1 hour, and the developed tension was 2.5 times greater than for potassium contractions. The contractions continued for more than 11 hours. Morphologically, perinuclear vacuolization, a characteristic change of vasospasm, appeared in the coronary smooth muscles. The phasic contractions were not eliminated by tetrodotoxin, atropine, phentolamine or yohimbine, but they were eliminated by nicorandil which activates potassium channels and nifedipine which blocks slow calcium channels. The results indicate that potassium channel blockers can induce phasic arterial contractions.

To evaluate pathologic features of myocardial infarction of the right ventricle (MI-RV), we analyzed 106 autopsy cases with transmural myocardial infarction (MI) (fresh in 46 cases and healed in 60). Anterior MI was observed in 47, posterior MI in 54 and lateral in 5. There were 13 cases (12%) with MI-RV (anterior in 1 case and posterior in 12), which included 10 cases with fresh MI and 3 with healed MI. All cases with MI-RV had associated transmural interventricular septal infarction. Of the 13 cases with MI-RV, 9 (69%) had right ventricular dilatation (RVD) and 2 had right ventricular hypertrophy. Extensive MI-RV (more than 1/3 of the right ventricle) was observed in 8 (89%) of those with RVD. Of 93 cases of MI without MI-RV, 14 (16%) had RVD. The incidence of RVD was greater in cases with MI-RV than in those without (p less than 0.005). All 12 cases with posterior MI-RV had significant (greater than or equal to 75%) narrowing of the right coronary artery (RCA), and 19 cases (87%) of those with posterior MI without MI-RV, had similar lesions. In conclusion, the incidence of RVD and significant narrowing of RCA was greater in cases with posterior MI-RV than in those with posterior MI.