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Kazuhiro Shimizu,1 Tomoyuki Yamamoto,2,3 Mao Takahashi,1 Shuji Sato,1 Hirofumi Noike,1 Kohji Shirai2 1Department of Internal Medicine, 2Department of Vascular Function, Toho University Sakura Medical Center, Chiba, 3Biological Information Analysis Section, Fukuda Denshi Co., Ltd, Tokyo, Japan Purpose: The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI).Subjects and methods: The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey–Kramer test was used for post hoc comparisons.Results: In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (–1.4±0.7 vs –1.4±0.9, –1.1±0.7 vs –1.4±1.0, –0.8±0.7 vs –1.2±1.0, and –0.5±0.7 vs –1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes (normal controls vs CAD; –3±7 vs –10±11, –3±5 vs –10±11, –3±6 vs –13±10, and –1±6 vs –11±10 mmHg, respectively). ΔDiastolic BP in the normal controls was significantly higher than in the CAD patients at 5 and 10 minutes (normal controls vs CAD; –8±6 vs –4±4 and –9±4 vs –6±5 mmHg, respectively). Conclusion: After NTG administration, the stiffness of the arteries from the origin of the aorta to the ankle as measured by CAVI decreased in both the normal controls and CAD patients, indicating that the response of arterial smooth muscle cells to nitric oxide is preserved even in CAD patients under medication. Keywords: arterial stiffness, cardio-ankle vascular index, nitroglycerin, nitric oxide, stiffness parameter

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.

Masayo Suzuki,1 Mao Takahashi,1 Takuo Iizuka,1 Hitoshi Terada,2 Hirohumi Noike,1 Kohji Shirai3 1Cardiovascular Center, Internal Medicine, 2Department of Radiology, 3Department of Vascular Function, Sakura Hospital, Medical Center, Toho University, Sakura City, Chiba Prefecture, Japan Background: Familial hypercholesterolemia (FH) is associated with premature coronary arterial disease. We aimed to determine the incidence of coronary artery stenosis (CAS) in asymptomatic FH patients using coronary computed tomography angiography (CCTA). To investigate the association between CAS and atherosclerosis of carotid arteries, we performed ultrasonography to measure the mean intima-media thickness (IMT), maximum IMT, and plaque score. We also aimed to examine the significance of the cardio-ankle vascular index (CAVI) and its association with the incidence of CAS in asymptomatic FH patients. Patients and methods: We enrolled consecutively, 31 FH patients without symptoms of coronary artery disease. Based on the CCTA findings, we divided the patients into two groups, those with and without CAS, and compared various parameters and risk factors of the two groups. Results: Of 31 FH patients, seven patients (22.6%) had CAS. The proportion of male patients and mean low-density lipoprotein-cholesterol level were higher in patients with CAS than in those without CAS (P22.6% of the asymptomatic FH patients. Patients with CAS tended to have enhanced levels of carotid plaque markers, but no increase was noted in CAVI. FH patients should be continuously monitored using CCTA and ultrasonography. Keywords: CAVI, coronary artery stenosis, heterozygous familial hypercholesterolemia, CCTA, ultrasound evaluation of the carotid artery

Background Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. Methods and results In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. Conclusions Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

AIM To investigate the effect of smoking and smoking cessation on cardio-ankle vascular index (CAVI). METHODS The subjects were 82 smokers (77 men, 64+/-10 years) and 20 non-smokers (18 men, 61+/-7 years). CAVI was measured every 3 months and CAVI severity was classified into 3 levels. Decreased, unchanged, and increased CAVI severity levels were coded as "improvement," "no change," and "exacerbation," respectively. Smoking status was coded as "success" for complete abstinence, "partial success" for a reduced number of cigarettes, and "failure" for an unchanging number of cigarettes. RESULTS Compared with non-smokers, smokers showed a higher CAVI (p

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.

To evaluate the stabilizing effects of an antilipemic agent, bezafibrate, on coronary plaques, we carried out a prospective angioscopic and angiographic open trial. From April 1997 to December 1998, 24 patients underwent coronary angioscopy of plaques in non-targeted vessels during coronary interventions and then again 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrate (14 patients, 21 plaques) groups. Oral administration of bezafibrate (400 mg/day) was started immediately after the intervention and was continued for 6 months. The vulnerability score was determined based on the angioscopic characteristics of plaques and compared before and 6 months later. Six months later, the vulnerability score was reduced (from 1.6 to 0.8; P

A sensitive immunoassay system using a specific monoclonal antibody against lipoprotein lipase (LPL) recently demonstrated the presence of an LPL mass in preheparin serum. We reported that a preheparin serum LPL mass (pre-LPL mass) reflected the level of functioning LPL activity in the whole body and could be deeply involved in the progression of coronary atherosclerosis of stable organic angina pectoris. We examined the relation between the pre-LPL mass and acute myocardial infarction (AMI). We studied 44 males with AMI (AMI group) and 16 males with a normal coronary artery (NCA group), and measured the pre-LPL mass by enzyme-linked immunosorbent assay. Coronary risk factors including the pre-LPL mass were compared between the two groups and multiple regression analysis was performed for AMI. There were no significant differences in the lipid data, but the pre-LPL mass level was significantly low in the AMI group (52 +/- 16 vs 41 +/- 14 ng/ml, p = 0.01), and a low pre-LPL mass concentration was observed in the small sized LDL group and/or the Midband positive group. Multiple regression analysis revealed that a low pre-LPL mass and hypertriglyceridemia were independent risk factors for AMI (t value = 2.1, 2.4). The result indicates that a low pre-LPL mass may be an important risk factor for AMI and stable organic angina pectoris.

Background Since long-term administrations of anti-hyperlipidemic agents result in reduction in % stenosis or increase in minimum lumen diameter (MLD) of stenotic coronary segments, it is generally believed that anti-hyperlipidemic agents stabilize vulnerable coronary plaques. However, recent pathologic and angioscopic studies revealed that vulnerability of coronary plaques is not related to severity of stenosis and the rims rather than top of the plaques disrupt, and therefore, angiography is not adequate for evaluation of vulnerability.Angioscopy enables macroscopic pathological evaluation of the coronary plaques. Therefore, we carried out a prospective angioscopic open trial for evaluation of the stabilizing effects of bezafibrate on coronary plaques.Methods From April, 1997 to December, 1998, 24 patients underwent coronary angioscopy of the plaques in the non-targeted vessels during coronary interventions and 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrat (14 patients, 21 plaques) groups. Oral administration of bezafibrate (Bezatol SR, 400mg/day) was started immediately after the interventions and was continued for 6 months. The vulnerability score was determined based on angioscopic characteristics of plaques and it was compared before and 6 months later.Results Six months later, vulnerability score was reduced (from 1.6 to 0.8;p < 0.05) in bezafibrate group and unchanged (from 1.4 to 1.3; NS) in control group. In bezafibrate group, the changes in vulnerability score was not correlated with those in % stenosis or MLD. Conclusion The results indicate that bezafibrate can stabilize coronary plaques.

We report a case of dilated cardiomyopathy with hyperthyroidism. A 28-year-old man was admitted because of congestive heart failure and atrial fibrillation, and was newly diagnosed as having hyperthyroidism. Despite administration of antithyroid medication, he developed recurrent congestive heart failure. An echocardiogram revealed a moderately dilated left ventricle with diffuse hypokinesis. Though his thyroid function normalized, the patient's cardiac dysfunction did not improve. Beta-blocker therapy was begun with subsequent improvement in clinical symptoms. This suggests that beta-blocker treatment may be effective in patients with atrial fibrillation associated with cardiomyopathy and hyperthyroidism.

Emergency coronary angiography of a 53-year-old man with acute coronary syndrome revealed stenosis in right coronary artery. During angioplasty, the ECG change showed three kind of ST deviation, namely inferior ST elevation with precordial ST depression, inferior ST elevation with precordial ST elevation, and inferior ST depression with precordial ST elevation. The present case shows that the ST deviation of the inferior ischemia with right ventricular ischemia takes various patterns. This phenomenon is decided by degree of right main coronary and right side branch blood flow.

Aim: The aim of this study was to clarify the relationship between CAVI and serum cystatin C levels to understand the role of arterial stiffness in the presence of renal insufficiency.Methods: We enrolled 206 consecutive patients with cardiovascular risk factors and/or coronary artery disease (CAD) in the study. Serum cystatin C, estimated glomerular filtration rate (eGFR), and plasma levels of von Willebrand factor (vWF) and plasminogen activator inhibitor (PAI-1) were measured. CAVI was determined as an index of arterial stiffness.Results: For all patients, the mean serum cystatin C level was 0.81±0.21 mg/L and mean eGFR was 65.8±15.5 mL/min per 1.73 m2. In univariate analysis, CAVI levels significantly correlated with cystatin C levels (r=0.414, p

急性前壁梗塞発症6時間以内にECG記録し得た85例を増高T波(type A, n=12), ST上昇(type B, n=21)およびドーム型,平坦型ST上昇(type C, n=52)の3 typeに分類し比較検討した。(1)3ヵ月以上前より狭心症の既往を有する割合はtype Aでは25%を占め,type B (33%)およびC (50%)に比し少ない傾向を示した。(2)type Aは梗塞発症より1.6時間とtype B (2.4時間)およびtype C (2.6時間)に比し早期ECGに認められ,それぞれの時間におけるCPK値は112IU/l, 347IU/lおよび522IU/lとtype Aはtype Bおよびtype Cに比し低値を示した。また最大CPK値はそれぞれ2,729IU/l, 1,986IU/lおよび2,152IU/lと有意差はなかった。梗塞発症より最大CPKを示すまでの時間は,type Aは12.6時間とtype B (17.6時間)およびC (18.0時間)に比しより短いことが示された。(3)type Aの死亡率は41.7%とtype B (19.0%)およびC (30.8%)に比し高率を占めた。一方,生存例のCCU滞在日数は,type Aは3.8日でtype B (5.1日)およびtype C (7.2日)に比し短いことからその早期予後は良好と解された。(4)慢性期冠動脈造影所見上,type Aは梗塞責任冠動脈の完全閉塞を認めず,type Bでは55%, type Cでは全例に完全閉塞を認めた。以上の結果より増高T波は,急性心筋梗塞発症早期心電図に認められ,狭心症の既往なく突発する傾向を示した。また最大CPKまでの時間は短く,生存例は良好な経過をとり,その冠動脈造影上,全例完全閉塞がないことより内科的初期治療による梗塞責任冠動脈の早期再疎通の結果と思われた。さらに狭心症の既往歴が少ないこと,梗塞発症時の症状が強いこと,および慢性期の冠動脈造影上側副血行路が不良であることから推測すると,増高T波を示す一要因として梗塞発症前の虚血程度が軽微である可能性が示唆された。

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

急性心筋梗塞に対する急性期治療の進歩は目覚ましいものがある。しかし,急性期心室性不整脈の発生頻度はいまだ高率で,とくにsecondary VTなどのポンプ失調に伴う不整脈の予後は不良とされている。今回われわれは急性心筋梗塞130例のうち,発症24時間以内にLown分類2以下の心室性不整脈を呈した88例をA群,Lown分類3以上の心室性不整脈を呈した42例をB群とし,その臨床像,予後につき比較検討した。平均年齢はA群64.3歳,B群66.7歳,性別はA群男性69例,女性19例,B群男性26例,女性16例であった。CCU入室中の完全房室ブロック合併はA群9%, B群26.2%,ショック合併はA群10.2%, B群64.3%,入院時Forrester 3以上のポンプ失調合併はA群4.5%, B群19.1%とそれぞれB群はA群に比し有意に高率を示した。入院中のcardiac eventの発生頻度は心不全がA群6.8%, B群30.9%,重度不整脈がA群19.3%, B群52.4%,死亡がA群5.7%, B群57.1%とそれぞれB群はA群に比し有意に高率を示した。入院中死亡のA群5例,B群24例の死因についてはA群で心不全・心破裂が80%を占めるのに比し,B群ではVT・Vfが21%を占めた。また,入院中死亡29例中,入院時Killip 4以上のポンプ失調合併は75.9%と高率であった。一方,A群71例,B群15例の最長3年での長期予後では,cardiac event (AMI, UAP, heart failure, death)の発生頻度に両群間に差異はなかった。Kaplan-Meier法を用いた生存曲線では,退院直前の生存率はA群94.3%, B群42.8%とB群はA群に比し有意に低率であった。しかし,退院後では両群間に差異はなかった。以上より,急性期重度不整脈は急性期死亡と関連があり,そのほとんどはポンプ失調に伴うもので急性期重度不整脈とポンプ失調は相互に悪影響し,予後不良の要因と思われた。

The present study investigated the clinical significance of preheparin serum lipoprotein lipase (LPL) mass in coronary vasospasm by examining its relationship with the acetylcholine-induced coronary artery response in patients without angiographically demonstrable atherosclerotic coronary artery disease (CAD). The subjects were 39 men who had suspected CAD and who underwent coronary angiography. Coronary vasospasm was defined as a marked luminal narrowing or total occlusion provoked by the intracoronary administration of acetylcholine. Preheparin LPL mass was lower (p

We report a 63-year-old woman, with a partial type of common atrioventricular canal and mitral stenosis, who was hospitalized because of dyspnea on exertion. Two-dimensional echocardiogram showed an ostium primum atrial septal defect with two well-formed AV valves located at the same level. However, both anterior and posterior mitral leaflets were markedly thickened with a thickened subvalvular apparatus, and the commisures were fused. Echocardiographic measurements demonstrated a mitral valve area of 1.48 cm2 with mild mitral regurgitation. Cardiac catheterization demonstrated mild pulmonary artery hypertension with a large left to right shunt (72%) at the atrial level. The combination of the partial type of common atrioventricular canal and mitral stenosis is rare; only one similar case has been reported previously in the literature.(Internal Medicine 34: 441-145, 1995)

Background Factor Xa inhibitor is a key drug in the coagulation cascade. Parenteral anticoagulation using low molecular weight heparin or fondaparinux is the recommended form of treatment for most patients presenting with venous thrombosis. Following the acute phase, edoxaban is recommended. We present a case of extensive deep vein thrombosis treated using fondaparinux and edoxaban. Case presentation A 63-year-old man with redness, pain, and swelling of the left leg lasting for more than 1 month was referred to our hospital. Ultrasonography revealed a thrombus in the left femoral vein. Computed tomographic angiography revealed clots in the distal right pulmonary artery. Thus, the anticoagulant treatment was initiated with subcutaneous injections of fondaparinux (7.5 mg) for 5 consecutive days, followed by once daily oral administration of edoxaban (60 mg). After 3 months of treatment, a regression of thrombotic clots was shown. Three months later, the remaining clots disappeared, leaving only mural thrombi; no bleeding complications were observed during the treatment period. Conclusion The anticoagulant treatment with subcutaneous fondaparinux and subsequently with oral edoxaban was effective for treating extensive deep vein thrombosis. Electronic supplementary material The online version of this article (doi:10.1186/s12959-016-0089-x) contains supplementary material, which is available to authorized users.