Elevated concentrations of pentraxin 3 are associated with coronary plaque vulnerability.

Inflammation is a critical contributing factor to the development and progression of atherosclerosis. Pentraxin 3 (PTX3) is produced abundantly in atherosclerotic lesions while C-reactive protein (CRP) is mainly produced in the liver. In this study, we investigated whether plasma levels of PTX3 might be a sensitive marker both for the severity of coronary artery disease and vulnerable plaques. Next, we determined whether assays for inflammatory molecules can be used to monitor the therapeutic effects of telmisartan on stabilization of vulnerable atherosclerotic plaques. We measured PTX3 concentrations in the peripheral and coronary sinus plasma of 40 patients with angina pectoris (AP) and 20 control subjects. Next, in 28 patients with AP, we determined the correlation between levels of inflammatory molecules and the computed tomography (CT) density of plaques as a quantitative index of plaque vulnerability. There was no significant difference in peripheral plasma PTX3 concentrations between patients with AP and control subjects, while coronary sinus plasma PTX3 concentrations were significantly higher in AP patients than control subjects. The concentrations of PTX3 in coronary sinus and peripheral plasma correlated with Gensini scores as an index of severity of coronary atherosclerosis. Interestingly, there was a significantly negative correlation between plasma PTX3 concentrations and CT density (r=-0.67, p<0.01). On the other hand, CT density did not correlate with the peripheral plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) or high-sensitivity CRP (hsCRP). Furthermore, telmisartan treatment for 6 months decreased plasma concentrations of PTX3 but not those of MCP-1 or hsCRP in 12 patients with essential hypertension. Multivariate regression analysis revealed that changes in PTX3 levels were independent of blood pressure changes. PTX3 is likely more specific than hsCRP as an indicator of coronary plaque vulnerability that could lead to plaque rupture.


Comparison of chronic-stage histopathological findings among 3 coronary stents implanted in the same patient.

A 73-year-old woman suffering from anterior thoracic pain on exertion presented to our hospital. We performed coronary angiography and noted three stenotic legions in each coronary artery. For each angiographic finding, we implanted a bare metal stent (BMS), sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) into the right coronary artery, left anterior descending and left circumflex coronary arteries, respectively. Nine months later, she died of lung disease, and we could compare the histopathological findings among the three coronary stents. In the drug-eluting stents, very thin intima, infiltration of inflammatory cells, and fibrin deposition were observed, while thick intima and no inflammatory findings were observed in the BMS. Fibrin deposition was more marked in the PES than in the SES. This report shows marked differences in the subsequent pathological course among three stents in the same patient.


Ventricular tachycardia in cardiac sarcoidosis controlled by radiofrequency catheter ablation.

We report a case of a 78-year-old woman with cardiac sarcoidosis with a history of syncope and palpitation. Further assessment with echocardiography, gadolinium-enhanced cardiovascular magnetic resonance (CMR) and histology led to a diagnosis of cardiac sarcoidosis. As the patient suffered from ventricular tachycardia (VT) despite active corticosteroid therapy, an implantable cardioverter-defibrillator (ICD) was positioned. She was also administered a beta blocker, but an electrical storm appeared every several days requiring ICD therapy. The drug-refractory VT was finally controlled with a catheter ablation session, during which we could detect the VT focus in the right ventricular outflow tract next to the aneurysm by using an electroanatomic mapping system (CARTO). Referring to echocardiographic and CMR images proved very useful in detecting the aneurysm using the CARTO system.


Serial imaging changes during treatment of Takayasu arteritis with pulmonary artery stenosis.

Most cases of chronic stenosis or occlusive lesions of the pulmonary arteries are attributed to thromboembolism, and pulmonary arteritis is extremely rare as the primary cause of these entities. We report a case of pulmonary stenosis and occlusion caused by Takayasu arteritis. The patient was a 54-year-old woman who presented with dyspnea. Total occlusion of the left pulmonary artery and significant stenosis of the right pulmonary artery caused by Takayasu arteritis were confirmed by various imaging modalities including pulmonary angiography, (18)fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging and real-time three-dimensional transesophageal echocardiography. After 6 weeks of steroid therapy, follow-up imaging studies showed that the stenotic lesion had resolved.


Acute hemodynamic effects of adaptive servo ventilation in patients with pulmonary hypertension.


A synthetic prostacycline agonist, ONO-1301, ameliorates ventricular remodeling after acute myocardial infarction via up-regulation of HGF in rat.


Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia.

The aim of the present study was to evaluate the factors that modulate the protective action of statins on cardiorenal function, regardless of the lipid-lowering effect. To treat abnormal serum lipid profiles, low-dose pitavastatin (1.0 mg/day) was administered to 65 hyperlipidemic patients. The exclusion criteria included left ventricular ejection fraction <40% and apparent renal disease. Age- and gender-matched patients with hyperlipidemia (n = 40) served as the controls. After 12 to 16 weeks of pitavastatin treatment, pitavastatin had decreased low-density lipoprotein cholesterol (from 143.5 ± 31.4 to 98.2 ± 19.4 mg/dl, p <0.01), triglycerides (from 157.7 ± 57.2 to 140.5 ± 60.7 mg/dl, p <0.01), E/e' (from 10.8 ± 6.2 to 9.0 ± 4.5, p <0.05), a parameter of left ventricular diastolic function, and albuminuria (from 47.6 ± 55.9 to 28.5 ± 40.0 mg/g creatinine, p <0.01). Furthermore, pitavastatin decreased serum transforming growth factor-1 (from 709 ± 242 to 550 ± 299 pg/ml, p <0.01), urinary 8-hydroxy-2'-deoxyguanosine (from 6.6 ± 4.1 to 5.0 ± 3.1 g/g creatinine, p <0.01), an oxidative stress marker, and increased urinary nitrate and nitrite (from 22.5 ± 14.6 to 29.4 ± 27.6 nmol/g creatinine, p <0.05). No such changes were observed in the controls. Multiple regression analysis in the pitavastatin group revealed the effect of pitavastatin on cardiorenal function was associated with suppression of oxidative stress, but not on low-density lipoprotein cholesterol reduction. In conclusion, pitavastatin decreases E/e' and albuminuria, which is associated with suppression of oxidative stress.


Observation of short-term atorvastatin-induced changes in coronary arterial plaque properties using integrated backscatter intravascular ultrasound in a patient.


Validation of longitudinal peak systolic strain by speckle tracking echocardiography with visual assessment and myocardial perfusion SPECT in patients with regional asynergy.

Automated function imaging (AFI) is a recently developed method of calculating the longitudinal peak systolic strains (LS) of the regional left ventricular (LV) wall using speckle tracking echocardiography and displaying them on a single bull's-eye map. The feasibility of AFI in patients with regional LV wall motion abnormalities caused by myocardial infarction (MI) was evaluated by comparison with visual assessment and myocardial perfusion single-photon emission computed tomography (SPECT). Segmental LS was measured by AFI in 60 patients with MI (67 ± 11 years) and 58 controls (71 ± 9 years). Wall thickening (WT) was measured by SPECT in 20 patients with MI. There was a strong positive linear relationship between the wall motion score index by expert visual assessment and global LS. The receiver-operating characteristic analysis revealed the best cutoff value of 11% < LS to identify hypokinetic segments. The overall accuracy of wall motion scoring by LS in the 2,006 segments was 96.8% (κ = 0.90) compared with visual assessment. The correlation coefficient between LS and WT was R² = 0.65 in the 340 segments. Assessment of LV regional asynergy by AFI showed good agreement with visual and SPECT assessments. AFI is clinically useful for quantitative assessment of LV regional wall motion abnormalities.


繰り返す心不全と維持透析導入から離脱しえた腎動脈狭窄症の一例

繰り返す心不全と維持透析導入から離脱しえた腎動脈狭窄症の一例


Bosentan ameliorated exercise-induced pulmonary arterial hypertension complicated with systemic sclerosis.

Pulmonary arterial hypertension (PAH) is a frequent complication in patients with systemic sclerosis. Bosentan is used in patients with symptomatic PAH; however, it has not been established whether or not bosentan ameliorates the progression of PAH in patients with no PAH-related symptoms. We present a case of systemic sclerosis with no PAH-related symptoms in which bosentan ameliorated exercise-induced PAH evaluated by 6-minute walk stress echocardiography, brachial flow-mediated dilation, and skin temperature of hands and feet. The results suggest that administration of bosentan in patients with early-stage PAH ameliorates pulmonary arterial vasodilatation through improvement of endothelial function.


Images in cardiovascular medicine. Cardiac magnetic resonance imaging and 2-dimensional speckle tracking echocardiography in secondary cardiac amyloidosis.


Congenital ventricular aneurysm as an unexpected complication of monomorphic premature ventricular contractions.

Congenital ventricular diverticulum (CVD) in adults is a rare cardiac malformation, which includes fibrous type congenital ventricular aneurysm (CVA). CVA is often clinically asymptomatic and shows no abnormality in the electrocardiogram or chest X-ray. However, some cases of sudden death resulting from ventricular tachycardia, cardiac embolism or ventricular rupture have been reported. Therefore, physicians should perform further cardiac imaging studies to detect a CVA if ventricular arrhythmia originating from the left ventricle is observed. Here, we report two successfully followed cases of CVA which were diagnosed from premature ventricular contractions.


Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury.

Activation of the renin-angiotensin system exacerbates atrial remodeling, leading to atrial fibrillation and thrombosis, especially in a condition with decreased NO bioavailability. Recently, it has been reported that statins reduce the incidence of atrial fibrillation through attenuation of atrial remodeling; however, the mechanisms have not been completely elucidated. Therefore, we aimed to clarify the beneficial effect of statin on atrial remodeling in condition with reduced NO bioavailability. Endothelial NO synthase(-/-) mice were sham operated or infused with angiotensin II (Ang II) via an osmotic minipump for 2 weeks, and Ang II-infused mice were divided into 3 treatment groups: pitavastatin, Tempol (a free radical scavenger), or vehicle. Echocardiography and electrocardiography showed that Ang II infusion caused left atrial enlargement and a high incidence of atrial fibrillation, whereas pitavastatin and Tempol prevented these abnormalities. In histological analysis, Ang II-induced atrial interstitial fibrosis, perivascular fibrosis, and cardiomyocyte hypertrophy were all attenuated by pitavastatin and Tempol. Immunohistochemical staining showed that Ang II downregulated thrombomodulin and tissue factor pathway inhibitor and upregulated tissue factor and plasminogen activator inhibitor 1 in the left atrium and that pitavastatin and Tempol corrected the thrombogenic condition. Moreover, pitavastatin and Tempol reduced Ang II-induced atrial superoxide production and atrial transforming growth factor-beta1 expression and Smad 2/3 phosphorylation. Atrial rac1-GTPase activity, known to activate NADPH oxidase, was attenuated by pitavastatin but not by Tempol. In conclusion, pitavastatin exerts endothelial NO synthase-independent protective actions against Ang II-induced atrial remodeling and atrial fibrillation with enhanced thrombogenicity through suppression of oxidant injury.


Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.

AIM: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment. RESULTS: Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels. CONCLUSION: Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.

Journal of Atherosclerosis and Thrombosis


Diagnostic utility of cardiac magnetic resonance for detection of cardiac involvement in female carriers of Duchenne muscular dystrophy.


Synthetic prostacycline agonist, ONO-1301, ameliorates left ventricular dysfunction and cardiac fibrosis in cardiomyopathic hamsters.

Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood flow and increased collagen synthesis. Administration of growth factors was reported to attenuate left ventricular (LV) remodeling and dysfunction in animal models of dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor and vascular endothelial growth factor from various cell types and ameliorate ischemia-induced LV dysfunction in mice and pigs. We evaluated therapeutic efficacy of ONO-1301 in the Syrian hamster (TO-2), a model of genetically determined dilated cardiomyopathy. Either vehicle or a slow releasing form of ONO-1301 (ONO-1301-PLGA, 10mg/kg/3 weeks) was administered subcutaneously every 3 weeks to TO-2 hamsters from 24 to 32 weeks of age (n=12 for each group). Age-matched F1B hamsters were used as a control. Plasma concentration of HGF was elevated in ONO-1301-PLGA group (p<0.05). Echocardiographic study demonstrated that LV fractional shortening was significantly improved in the ONO-1301-PLGA group (25+/-4%, p<0.01) compared with that in the vehicle group (19+/-2%). Cardiac fibrosis was significantly reduced by ONO-1301-PLGA (p<0.05) as determined by Azan-Mallory staining. Capillary density of left ventricle was markedly reduced in TO-2 hamsters. ONO-1301-PLGA significantly increased capillary density in TO-2 group (p<0.05). ONO-1301 improved LV dysfunction and reduced cardiac fibrosis in the hamster model of dilated cardiomyopathy. ONO-1301 might hold a therapeutic potential in the treatment of dilated cardiomyopathy.


Clinical Utility of Single Beat E/e' Obtained by Simultaneous Recording of Flow and Tissue Doppler Velocities in Atrial Fibrillation with Preserved Systolic Function.

We evaluated the usefulness of the ratio of the early diastolic transmitral flow velocity (E) to the mitral annular velocity (e') calculated from simultaneously recorded E and e' in atrial fibrillation (AF). The ratio of the E to the e' (E/e') has been reported as a useful index even in AF patients. However, E and e' were measured during different beats in the previous studies. Fifty-six AF patients with preserved systolic function (mean age 66 +/- 11 years) underwent routine echocardiographic study. The E/e' was calculated from the E and e' simultaneously recorded by the dual Doppler echocardiography. A single-beat E/e' was calculated from simultaneously recorded E and e' when the preceding RR interval/pre-preceding RR interval = 1. Brain natriuretic peptide (BNP) levels were also examined. Twenty-one patients underwent simultaneous pulmonary artery catheterization. The single-beat lateral E/e' correlated with pulmonary capillary wedge pressure (PCWP) (r = 0.74, p < 0.001). The single-beat lateral E/e' of >or=11 could predict elevated PCWP (>or=15 mm Hg) with a sensitivity of 90% and a specificity of 90%. The single-beat lateral E/e' also correlated well with the log BNP concentration. The single-beat lateral E/e' of >or=9.2 predicted a plasma BNP level of >or=200 pg/ml with 88% sensitivity and 84% specificity. The single-beat lateral E/e' correlated with plasma BNP level and PCWP in AF patients with preserved systolic function. In addition, the single-beat lateral E/e' (>or=11) was a good predictor of elevated PCWP (>or=15 mm Hg). Dual Doppler echocardiography offers an advantage of providing the single-beat lateral E/e' correctly even in AF patients, for the evaluation of left ventricular diastolic function.


Telmisartan Decreases Plasma Levels of Asymmetrical Dimethyl-L-Arginine and Improves Lipid and Glucose Metabolism and Vascular Function

Telmisartan is an angiotensin II receptor blocker (ARB) and also an activator of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We investigated whether telmisartan improves vascular endothelial function in patients with essential hypertension with the production of endothelial nitric oxide synthase (eNOS) through PPAR-gamma.Telmisartan was administered to 15 patients with essential hypertension. To assess vascular function, asymmetric dimethylarginine (ADMA), an eNOS inhibitor synthesized by endothelial cells, and the pulse-wave velocity (PWV) were measured. The serum levels of lipid, glucose, and glycohemoglobin (HbA1c) were also evaluated before and after treatment. Telmisartan therapy significantly decreased the blood pressure and total- and LDL-cholesterol levels. HbA1c was also significantly improved but not in fasting plasma glucose. The serum levels of ADMA were significantly decreased (0.48 +/- 0.08 to 0.42 +/- 0.05 nmol/mL; P = 0.01). PWV values were significantly decreased by telmisartan from 1,822.5 +/- 352.3 to 1,661.5 +/- 299.8 cm/second (P = 0.04*). Telmisartan decreased PWV presumably via the activation of PPAR-gamma, suggesting that this agent improves vascular endothelial function via its pleiotropic effects, a mechanism that is different from its hypotensive effects.


Platypnea-orthodeoxia syndrome associated with patent foramen ovale and aortic ectasia.

A 59-year-old man was admitted for dyspnea on exertion and edema. The patient did not have any pulmonary diseases that could cause dyspnea. Transesophageal echocardiography on the tilting bed with contrast infusion revealed a right-to-left shunt through the patent foramen ovale. Therefore, he was diagosed as platypnea-orthodeoxia syndrome due to the patent foramen ovale. Surgical closure was done and all of his symptoms had improved.


A case of neurogenic myocardial stunning presenting transient left ventricular mid-portion ballooning simulating atypical takotsubo cardiomyopathy.

A 57-year-old female patient, who was initially suspected to have subarachnoid hemorrhage, was admitted to our hospital. She experienced severe dyspnea and chest pain owing to pneumonia on the fourth admission day. Electrocardiography showed ST-segment elevation in leads V(2) through V(5), and echocardiography revealed hypokinetic left ventricular wall motion. No stenosis was found in the coronary arteries by urgent coronary angiography. However, left ventriculography revealed that the basal and apical areas were hyperkinetic and the mid portion was akinetic. After a month, left ventricular wall motion was improved and coronary artery spasm provocation tests were negative. Although the clinical course of this patient was similar to that of neurogenic myocardial stunning, the shape of her left ventricle was not typical.


Effect of azelnidipine on autonomic nerve activity in essential hypertension

本態性高血圧症におけるアゼルニジピンの自律神経活動に及ぼす影響についての検討


心肥大を合併する本態性高血圧患者におけるアゼルニジピンによる抗動脈効果作用および心肥大抑制作用の検討


Calcineurin-NFAT pathway-dependent cardiac remodeling in mice deficient for GC-A, a receptor for atrial and brain natriuretic peptides.

Although disruption of guanylyl cyclase (GC) A, a natriuretic peptide receptor, induces cardiac hypertrophy and fibrosis, the molecular mechanism underlying these effects are not well understood. In this study, we examined the role of calcineurin, a calcium-dependent phosphatase, in cardiac remodeling in GCA-knockout (GCA-KO) mice. At 14 weeks of age, calcineurin activity, nuclear translocation of nuclear factor of activated T cells c3 (NFATc3), and modulatory calcineurin-interacting protein 1 (MCIP1) gene expressions were increased in the hearts of GCA-KO mice compared with wild-type (WT) mice. Blockade of calcineurin activation by FK506 (6 mg/kg body weight administered subcutaneously once a day from 10 to 14 weeks of age) significantly decreased the heart-to-body weight ratio, cardiomyocyte size, and collagen volume fraction in GCA-KO mice, whereas FK506 did not affect these parameters in WT mice. Overexpression of atrial and brain natriuretic peptides, collagen, and fibronectin mRNAs in GCA-KO mice was also attenuated by FK506. Electrophoretic mobility shift assays demonstrated that GATA4 DNA-binding activity was increased in GCA-KO mice, and this increase was inhibited by calcineurin blockade. In neonatal cultured cardiac myocytes, inhibition of GCA by HS142-1 (100 microg/mL) increased basal and phenylephrine (10(-6) mol/L)-stimulated calcineurin activity, nuclear translocation of NFATc3, and MCIP1 mRNA expression. In contrast, activation of GCA by atrial natriuretic peptide (10(-6) mol/L) inhibited phenylephrine (10(-6) mol/L)-stimulated nuclear translocation of NFATc3. These results suggest that activation of cardiac GCA by locally secreted natriuretic peptides protects the heart from excessive cardiac remodeling by inhibiting the calcineurin-NFAT pathway.


C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction

We assessed the hypothesis that in vivo administration of C-type natriuretic peptide (CNP) might attenuate cardiac remodeling after myocardial infarction (MI) through its antifibrotic and antihypertrophic action. Recently, we have shown that CNP has more potent antifibrotic and antihypertrophic effects than atrial natriuretic peptide (ANP) in cultured cardiac fibroblasts and cardiomyocytes. Experimental MI was induced by coronary ligation in male Sprague-Dawley rats; CNP at 0.1 mug/kg/min (n = 34) or vehicle (n = 35) was intravenously infused by osmotic mini-pump starting four days after MI. Sham-operated rats (n = 34) served as controls. After two weeks of infusion, the effects of CNP on cardiac remodeling were evaluated by echocardiograpic, hemodynamic, histopathologic, and gene analysis. C-type natriuretic peptide markedly attenuated the left ventricular (LV) enlargement caused by MI (LV end-diastolic dimension, sham: 6.7 +/- 0.1 mm; MI+vehicle; 8.3 +/- 0.1 mm; MI+CNP: 7.7 +/- 0.1 mm, p < 0.01) without affecting arterial pressure. Moreover, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt(max), dP/dt(min), and cardiac output in CNP-treated MI rats compared with vehicle-treated MI rats. Importantly, CNP infusion markedly attenuated an increase in morphometrical collagen volume fraction in the noninfarct region (sham: 3.1 +/- 0.2%; MI+vehicle: 5.7 +/- 0.5%; MI+CNP: 3.9 +/- 0.3%, p < 0.01). In addition, CNP significantly reduced an increase in cross-sectional area of the cardiomyocytes. These effects of CNP were accompanied by suppression of MI-induced increases in collagen I, collagen III, ANP, and beta-myosin heavy chain messenger ribonucleic acid levels in the noninfarct region. These data suggest that CNP may be useful as a novel antiremodeling agent.

Journal of the American College of Cardiology


Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy: interference between CNP and endothelin-1 signaling pathways.

C-type natriuretic peptide (CNP) is known to play a role in the local regulation of vascular tone. We recently found that CNP is also produced by cardiac ventricular cells. However, its local effect on myocyte hypertrophy remains to be elucidated. The present study investigated the effects of CNP on cultured cardiac myocyte hypertrophy and the interaction between CNP and endothelin-1 (ET-1) signaling pathways. CNP attenuated basal and ET-1-augumented protein synthesis, atrial natriuretic peptide secretion, hypertrophy-related gene expression, GATA-4 and MEF-2 DNA binding activities, Ca(2+)/calmodulin-dependent kinase II activity, and ERK phosphorylation. CNP also inhibited ET-1-induced increase in intracellular Ca(2+) concentration. These effects of CNP were mimicked by a cGMP analog, 8-bromo cGMP. However, the inhibitory effects of CNP on the hypertrophic response of myocytes were significantly diminished at high concentrations of ET-1. Although CNP increased intracellular cGMP levels in myocytes, ET-1 suppressed CNP-induced cellular cGMP accumulation. A protein kinase C activator and Ca(2+) ionophore mimicked this suppressive effect of ET-1. We further examined the effect of CNP on the paracrine action of ET-1 secreted from cardiac nonmyocytes. CNP and 8-bromo cGMP significantly inhibited ET-1 secretion from nonmyocytes. Although nonmyocyte-conditioned medium increased the protein synthesis in myocytes through endogenous ET-1 action, this increase was significantly attenuated by pretreatment of nonmyocytes with CNP and 8-bromo cGMP. These findings demonstrate that CNP inhibits ET-1-induced cardiac myocyte hypertrophy via a cGMP-dependent mechanism, and conversely, ET-1 inhibits CNP signaling by a protein kinase C- and Ca(2+)-dependent mechanism, suggesting mutual interference between CNP and ET-1 signaling pathways.


Elevated concentration of soluble vascular endothelial cadherin is associated with coronary atherosclerosis.

Vascular endothelial (VE)-cadherin, a Ca(2+)-dependent cell adhesion molecule, is expressed in atherosclerotic lesions by endothelial cells and is associated with neovascularization, although the relationship between circulating VE-cadherin and coronary artery disease has not been studied. The plasma concentration of VE-cadherin was measured in peripheral blood (femoral artery) and the coronary sinus of 24 patients with acute myocardial infarction (AMI), 26 with stable angina pectoris (AP), 18 with old myocardial infarction (OMI), and 30 control subjects (Control) who had no coronary artery stenosis on angiography. For the patients with AMI, blood samples were obtained in the acute (day 1) and chronic (day 21) phases. The plasma concentration of VE-cadherin was measured by enzyme-linked immunosorbent assay. The correlation between the plasma VE-cadherin concentration and the Gensini score was also determined as an index of the severity of coronary atherosclerosis. The plasma concentrations of VE-cadherin (ng/ml) in both the peripheral and coronary sinus blood were higher in patients with AMI, AP, and OMI than in the control subjects, and were similar in the 3 groups with coronary artery disease (femoral artery: AMI 5.1+/-2.5, AP 4.7+/-2.4, OMI 4.5+/-3.3, Control 2.6+/-2.3; coronary sinus: AMI 5.6+/-2.6, AP 5.0+/-2.3, OMI 5.0+/-2.9, Control 2.4+/-2.1, respectively). Plasma VE-cadherin concentrations were higher in the coronary sinus than peripheral blood samples in patients with AMI (p<0.01), AP (p<0.01), and OMI (p<0.05). The plasma VE-cadherin concentration was the same in the acute and chronic phases in patients with AMI. In the 3 groups of patients with coronary disease, both the peripheral plasma VE-cadherin concentration and the coronary sinus concentration correlated with the Gensini score (r=0.32, p<0.01 and r=0.42, p<0.001, respectively). Multiple regression analysis revealed that the plasma VE-cadherin concentration predicted the Gensini score independently of sex, age, hypertension, diabetes mellitus, smoking, and the lipid profiles. Increased secretion of VE-cadherin from the epicardial arteries is associated with the degree of coronary atherosclerosis, indicating the presence of atherosclerosis rather than disease activity.


Increased soluble platelet/endothelial cell adhesion molecule-1 in the early stages of acute coronary syndromes.

Specific molecules including inflammatory cell adhesion molecules mediate attachment of blood leukocyte and platelets to the endothelium and mononuclear cell migration into the arterial intima. However, the clinical significance of soluble cell adhesion molecules very early in the course of acute coronary syndrome is not known. We assayed platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), intercellular adhesion molecule-1 (ICAM-1, CD54), and P-selectin (CD62P) in plasma obtained from 20 patients within 3 h after the onset of acute myocardial infarction (AMI); 16 patients with unstable angina pectoris; 20 patients with stable angina pectoris, and 28 controls. Blood samples were obtained on hospital admission and again 1 week after onset of AMI and unstable angina, and on admission in patients with stable angina and controls. Plasma PECAM-1 concentration (ng/ml) on admission was higher in patients with AMI (25.6+/-4.7) and unstable angina (24.7+/-4.4) than in stable angina (20.5+/-4.4) and control (18.8+/-3.8) groups. In both AMI and unstable angina, plasma PECAM-1 had decreased significantly by 1 week (AMI, 20.8+/-4.0; unstable angina, 21.0+/-4.1). Plasma ICAM-1 concentration (ng/ml) on admission was higher in patients with AMI (254+/-70), unstable angina (264+/-78), and stable angina (245+/-68) than in controls (201+/-56), but did not differ between the three coronary syndromes. Plasma P-selectin concentration did not differ between the four groups, including controls. Therefore, soluble PECAM-1 concentration may be a sensitive markers providing early diagnostic aid in acute coronary syndromes.


Relation of age and sex to atrial electrophysiological properties in patients with no history of atrial fibrillation.

Although atrial fibrillation is a common arrhythmia, especially in elderly men, little is known about age related changes in atrial electrophysiological properties or gender differences. The aim of this study was to analyze the effects of aging on vulnerability to atrial fibrillation and assessed gender differences in those age related changes. An electrophysiological study was performed on 73 patients with no history of atrial fibrillation, structural heart disease, or conditions with potential effects on cardiac hemodynamic or electrophysiological function, including 25 women (mean age 49 +/- 18 years; range 12-84 years). The following atrial excitability parameters were assessed: spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation (A2/A1 x 100), effective refractory period, wavelength index (effective refractory period/A2), and inducibility of atrial fibrillation. There were no significant differences in percent maximum atrial fragmentation (143 +/- 28 vs 142 +/- 35%), effective refractory period (241 +/- 39 vs 238 +/- 50 ms), wavelength index (2.9 +/- 0.8 vs 3.1 +/- 0.9), induction of atrial fibrillation (10 [21%] vs 7 [28%]), or age (50 +/- 17 vs 49 +/- 20 years) between men and women. Age was not statistically different between those patients with and without induction of atrial fibrillation in men (48 +/- 14 vs 50 +/- 18 years) and women (48 +/- 18 vs 49 +/- 21 years). Percent maximum atrial fragmentation and effective refractory period were directly correlated with age in men (r = 0.35, P = 0.01; r = 0.46, P < 0.001, respectively) and women (r = 0.42, P = 0.04; r = 0.45, P = 0.02, respectively), though wavelength index did not correlate with age in men (r = -0.04) or women (r = -0.04) with no history of atrial fibrillation. Considering these findings, the authors conclude that the mechanism triggering atrial fibrillation may be different between older and younger patients with atrial fibrillation, because younger patients who have no marked substrate for atrial fibrillation may need many trigger beats to induce atrial fibrillation.


Relation between circulating soluble Fas ligand and subsequent ventricular remodelling following myocardial infarction


Effects of angiotensin II receptor antagonists on [(123)I]metaiodobenzylguanidine myocardial imaging findings and neurohumoral factors in chronic heart failure

Previous studies have not investigated the ef-ficacy of angiotensin II (AII) receptor antagonists against cardiac sympathetic overactivity in patients with chronic heart failure (CHF) using [(123)I]metaiodobenzylguanidine (MIBG) myocardial imaging. We studied 34 CHF patients with fractional shortening of the left ventricular (LV) diameter <==25% or LV ejection fraction <==45% in echocardiograms. An AII receptor antagonist (losartan or candesartan) was administered. Before and 6 months after the administration, MIBG myocardial imaging and echocardiography were performed, and neurohumoral factors were investigated. MIBG imaging revealed that the antagonist did not significantly change the heart-to-mediastinum ratio. However, the washout rate fell significantly (from 32.6% +/- 7.6% to 28.2% +/- 7.5%; P < 0.001). No significant changes occurred in LV diameter, fractional shortening, or LV ejection fraction. Circulating atrial (ANP) and brain natriuretic peptides (BNP), and aldosterone fell significantly. Changes in the MIBG washout rate correlated positively with changes in BNP ( r = 0.35, P < 0.05). In 19 patients also being treated with angiotensin-converting enzyme (ACE) inhibitors, the MIBG washout rate also fell significantly with AII antagonists, as did BNP and aldosterone. The decreased MIBG washout and BNP in patients with CHF induced by the AII receptor antagonists suggests the efficacy of these agents in modifying cardiac sympathetic function and neurohumoral factors, even with ACE inhibition. Combination therapy with AII receptor antagonists and ACE inhibitors appears effective for CHF.


Serum hepatocyte growth factor predicts ventricular remodeling following myocardial infarction

Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) stimulate endothelial cell proliferation and induce angiogenesis, but the timing and significance of their release in patients with acute myocardial infarction (AMI) are unknown in relation to future left ventricular remodeling. Venous blood samples were obtained at admission and up to 3 weeks later in 40 patients with AMI and in 40 age- and sex-matched control subjects. Blood samples were also taken from the coronary sinus (CS) in 20 patients on day 7 following AMI. Left ventricular end-diastolic volume in the subacute (1 week) and chronic (3 months) phases was assessed by left ventriculography to identify the remodeling group (n=15), which was defined as an increase in left ventricular end-diastolic volume index > or =5 ml/m(2) relative to the baseline value. Serum HGF and VEGF concentrations were higher in newly admitted patients with AMI than in the controls (HGF, 0.33 +/-0.09 vs 0.24+/-0.08 ng/ml, p<0.01; VEGF, 92.2+/-43.1 vs 67.2+/-29.8 pg/ml, p<0.01), peaking on day 7 (HGF, 0.41+/-0.12; VEGF, 161.7+/-76.9), and gradually decreasing between days 14 and 21. The HGF concentration in the CS did not differ from the concentration in the periphery, but the VEGF concentration was significantly more abundant in the CS than in the peripheral sample on day 7 (p<0.05). The serum HGF concentration on day 7 was higher in the remodeling group than in the nonremodeling group (0.47 +/-0.13 vs 0.36+/-0.09 ng/ml, p<0.01), but there was no difference between the groups on admission, day 14 and day 21. The serum VEGF concentration did not differ between the remodeling and nonremodeling groups at any time. Thus, the serum HGF concentration on day 7 after AMI is mostly from noncardiac sources and predicts left ventricular remodeling.


Plasma concentrations of fibrinolytic factors in the subacute phase of myocardial infarction predict recurrent myocardial infarction or sudden cardiac death

The prognostic value of plasma concentrations of tissue type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein has been reported in patients with coronary artery disease. However, the association between cardiac events and these factors during the acute and subacute phases of myocardial infarction (MI) is unknown. The purpose of this study was to determine whether elevated plasma concentrations of t-PA, PAI-1, and C-reactive protein in patients with MI are associated with future recurrent MI or sudden cardiac death. We studied 106 consecutive patients who survived a confirmed first MI between 1993 and 1998 in our hospital. The control group consisted of 50 patients who had no significant coronary artery stenosis. Blood samples were obtained at the time of admission for acute MI and on the 28th day after admission. Patients were followed for a mean of 50 months after these measurements. The primary end points were sudden cardiac death and fatal or nonfatal acute MI. Of the 92 patients who were available for follow-up, 10 had cardiac events. Both the plasma t-PA and PAI-1 concentrations were elevated on day 1 of acute MI compared to the control group and decreased by day 28, but remained higher than those in the controls. Plasma C-reactive protein concentration was also elevated on day 1 and decreased by day 28. Using a stepwise variable choice model of Cox proportional hazards analysis including these fibrinolytic factors and C-reactive protein, only the t-PA concentration in the subacute phase was a significant predictor of cardiac events (relative risk per S.D. 3.20, P<0.01). We further found that independent of other risk factors, an elevated t-PA concentration was predictive of cardiac events. This study reveals that a rise in endogenous t-PA concentration during the subacute phase of MI could predict recurrent MI or sudden cardiac death.


Mitral inflow and mitral annular motion velocities in patients with mitral annular calcification: evaluation by pulsed Doppler echocardiography and pulsed Doppler tissue imaging

We evaluated the relationship between the mitral inflow velocities by pulsed Doppler echocardiography and mitral annular motion velocities by pulsed Doppler tissue imaging in patients with mitral annular calcification. Fifty-three patients with mitral annular calcification were divided into two groups: severe mitral annular calcification (n=15, mitral annular calcification bigger than or equal 5mm in width) and mild mitral annular calcification (n=38, mitral annular calcification <5mm in width). In addition, 20 patients with hypertensive heart disease (HHD group) and mild left ventricular hypertrophy but no mitral annular calcification and 30 normal individuals (normal group) were studied. The early diastolic mitral inflow velocity (E) was higher in the severe mitral annular calcification group (0.75+/-0.26 m/s) than in the HHD and normal groups (mild mitral annular calcification, 0.65+/-0.21; HHD, 0.57+/-0.24; normal, 0.55+/-0.15m/s), and the late diastolic mitral inflow velocity (A) was higher in the severe mitral annular calcification group (1.24+/-0.23 m/s) than in the other three groups (mild mitral annular calcification, 0.96+/-0.20; HHD, 0.84+/-0.23; normal, 0.75+/-0.13 m/s). In contrast, the early and late diastolic annular velocities (Ea, Aa) were lower in the severe mitral annular calcification group (Ea: 5.7+/-2.2; Aa: 11.9+/-4.4 cm/s) than in the other three groups (Ea: mild mitral annular calcification, 8.3+/-2.5; HHD, 7.7+/-2.2; normal, 9.0+/-1.8 cm/s; Aa: mild mitral annular calcification, 14.2+/-4.1; HHD, 14.3+/-2.8; normal, 14.2+/-2.1cm/s). Mitral valve area was smaller in the severe mitral annular calcification group (2.6+/-1.0 cm(2)) than in the other three groups (mild mitral annular calcification, 3.1+/-0.7; HHD, 4.1+/-0.7; normal, 4.2+/-0.9 cm(2)). In the mitral annular calcification and normal groups, the A correlated inversely with mitral valve area (r=-0.67, P<0.01) and directly with severity of mitral annular calcification (r=0.65, P<0.01), and the Ea correlated inversely with left ventricular wall thickness (r=-0.37, P<0.01) and severity of mitral annular calcification (r=-0.45, P<0.01). Patients with severe mitral annular calcification have higher mitral inflow velocities due to mitral annular restriction and lower mitral annular velocities caused by decreased mitral annular motion and abnormal left ventricular relaxation.


A case of thyrotoxicosis with pancytopenia

We report a 49-year-old man with primary hyperthyroidism who presented with pancytopenia. The patient presented with leg edema, sinus tachycardia, cardiomegaly, and pleural effusions, all from congestive heart failure. Laboratory data showed pancytopenia and primary hyperthyroidism; echocardiogram showed diffuse hyperkinesis of the left ventricular wall and right ventricular overloading. The bone marrow was moderately hypercellular and compatible with arrested hematopoiesis. Pancytopenia and heart failure improved after administration of methimazole and diuretics. However, high levels of thyroid hormone recurred with pancytopenia 4 months after admission. Therefore, subtotal thyroidectomy was performed, and the levels of thyroid hormones and peripheral blood cell counts have remained normal. Pancytopenia may be caused by hyperthyroidism.


Clinical Significance of Coronary Flow Reserve in Hypertrophied Heart: Comparison With Doppler Index, Hemodynamics and Plasma Natriuretic Peptide Concentrations

肥大心における冠血流予備能の意義:ドップラー心エコー図指標，心内圧および血漿ナトリウム利尿ペプチド濃度との対比検討．

The relationship was investigated between coronary flow reserve and Doppler echocardiographic parameters, hemodynamic parameters and plasma natriuretic peptide concentrations in the hypertrophied heart. The subjects were 19 patients with hypertrophied heart due to various etiologies and no significant coronary artery stenosis. All patients were in sinus rhythm. The left ventricular wall thickness, the E/A ratio in transmitral flow velocity pattern and the Doppler index were determined by Doppler echocardiography, and the plasma atrial and brain natriuretic peptide concentrations were measured. At cardiac catheterization, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure were measured, and the coronary flow reserve was obtained by injecting intracoronary adenosine triphosphate into the left anterior descending artery using a Doppler guidewire. Coronary flow reserve in the patients was significantly lower than in 11 normal control subjects (2.50 +/- 0.76 vs 3.90 +/- 0.64, p < 0.001). There were no significant correlations between coronary flow reserve and the left ventricular wall thickness or the E/A ratio. The mean value of the Doppler index in the patients was 0.48 +/- 0.10 and there was a significant negative correlation between coronary flow reserve and the Doppler index (r = -0.73, p < 0.001). The correlation between coronary flow reserve and left ventricular end-diastolic pressure was not significant, but there was a significant negative correlation between coronary flow reserve and pulmonary capillary wedge pressure (r = -0.64, p < 0.01). There were significant negative correlations between coronary flow reserve and atrial (r = -0.62, p < 0.01), or brain natriuretic peptide concentrations (r = -0.56, p < 0.05). Coronary flow reserve may reflect overall cardiac performance evaluated by the Doppler index and plasma natriuretic peptide concentrations in the hypertrophied heart, and the measurement of coronary flow reserve may be useful for evaluating disease severity in patients with hypertrophied heart.


Plasma and platelet plasminogen activator inhibitor-1 in patients with acute myocardial infarction

Several studies have demonstrated an increased level of plasma plasminogen activator inhibitor-1 (PAI-1) in patients with coronary artery disease (CAD). However, the concentration of PAI-1 in platelets, which accounts for more than 90% of the blood PAI-1, is unknown in these patients. The present study evaluated the concentrations of PAI-1 and several fibrinolytic factors in the plasma and platelets of patients with CAD and the serial changes in patients with acute myocardial infarction (AMI). All 72 subjects had coronary angiography and were divided into 3 groups: CAD(-) group without coronary artery stenosis or myocardial ischemia (n=20), CAD(+) group with either stable angina pectoris (n=18) or old myocardial infarction (n=12) with coronary artery stenosis, and the AMI group admitted within 24h of symptom onset who underwent successful percutaneous transluminal coronary angioplasty (n=22). The concentrations of plasma PAI-1, tissue plasminogen activator (t-PA), and t-PA x PAI-1 complex were similar in the CAD(-) and CAD(+) groups, but were greater on day 1 in the AMI group compared with the 2 CAD groups. There were no significant differences between the 3 groups in the plasma concentrations of thrombin antithrombin III complex (TAT), alpha2-plasmin inhibitor-plasmin complex (PIC), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF-4). The platelet PAI-1 concentrations did not differ between the CAD(-) and CAD(+) groups, but was greater on day 1 in the AMI group compared to the CAD groups. The platelet beta-TG and PF-4 were similar between the 3 groups. In the AMI group, both the plasma and platelet PAI-1 concentrations were greater on day 1, but the plasma PAI-1 rapidly decreased by day 5 and remained low on day 28 compared with day 1. The platelet PAI-1 concentration gradually decreased by day 5 and was further decreased by day 28. The serial changes of the plasma t-PA and t-PA PAI-1 complex during the course of AMI were similar to those of the plasma PAI-1. A positive correlation was found between the plasma and platelet PAI-1 in all 72 patients, but not in the AMI group alone. These results suggest that the PAI-1 that has accumulated in platelets at the onset of AMI might be released in large amounts into the plasma, resulting in an increase in thrombus formation.


Pulmonary venous flow velocity patterns in sinus rhythm and atrial fibrillation : the difference between the right and left pulmonary veins


Serial changes in serum VEGF and HGF in patients with acute myocardial infarction

The time course of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) release in patients with acute myocardial infarction (AMI) is unknown. Blood samples were obtained at the time of admission and 3, 7, 14 and 21 days later in 32 patients with AMI and 30 control patients. Serum VEGF and HGF, as well as C-reactive protein (CRP) and amyloid A protein (SAA), were determined. Both serum VEGF and HGF levels on admission in patients with AMI were higher than control values and peaked on day 7. VEGF levels in patients with preinfarction angina were higher than in patients with no preinfarction angina, whereas the HGF level did not differ. Both CRP and SAA levels peaked on day 3, and the CRP level on day 3 correlate with both VEGF and HGF levels on day 7. We hypothesized that the serum VEGF level is associated with preinfarction ischemia and the increase in VEGF and HGF on day 7 of AMI may represent a response to acute inflammation.


Role of circulating vascular endothelial growth factor and hepatocyte growth factor in patients with coronary artery disease

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are thought to stimulate endothelial cell proliferation and induce angiogenesis in vivo. However. the precise mechanism responsible for VEGF and HGF release in patients with coronary artery disease is still unknown. We studied serum concentrations of VEGF and HGF in 20 patients with acute myocardial infarction (AMI), 20 patients with stable angina pectoris (AP) who had reversible perfusion defects on stress myocardial scintigraphy, and 16 patients with old myocardial infarction (OMI) who had no reversible defects on stress myocardial scintigraphy. The control group consisted of 20 patients with atypical chest pain who had angiographically normal coronary arteries. Serum VEGF and HGF concentrations were measured by enzyme-linked immunosorbent assay. Both the serum VEGF and HGF concentrations in the early stage of myocardial infarction in the patients with AMI were higher than those in the patients with AP and with OMI, and control patients. The VEGF concentration in the patients with AP was higher than in the patients with OMI, whereas the HGF concentration did not differ in the patients with AP and OMI. The VEGF concentration in AMI patients who had had preinfarction angina on admission was higher than that of patients who had had no preinfarction angina, whereas the HGF concentration did not differ between the two groups of patients. These results suggest that the serum VEGF concentration may reflect myocardial ischemia to a greater degree than the serum HGF concentration.


Fibrinolytic factors, serum lipid and C-reactive protein predicting cardiac events in Japanese patients with coronary atherosclerotic lesions

Although disturbances of the fibrinolytic system and serum lipid, and the presence of inflammation, may be risk factors for coronary artery disease (CAD), few reports have investigated these relationships in Japanese patients. Data on 106 patients (79 men and 27 women, mean age 62.3 years) with atherosclerotic lesions on the coronary angiogram were evaluated prospectively to identify whether the factors were useful in predicting the risk of coronary events during a follow-up of 50+/-4 months. Of the 106 patients who were followed, 11 patients had coronary events (4 acute myocardial infarction and 7 unstable angina pectoris). In univariate Cox analyses, a high level of tissue-plasminogen activator (t-PA), apolipoprotein CII, C-reactive protein (CRP), and a low level of high-density lipoprotein-cholesterol (HDL-C) was each associated with a significant increase in the risk of future cardiac events. The stepwise model of Cox proportional hazards analysis selected only a high level of t-PA and CRP as predictors of cardiac events. Controlling for any risk factor did not lower the relation between t-PA and the risk of cardiac events, whereas the relative risk of cardiac events in CRP was not significant when controlled for HDL-C. Thus, in prospective data obtained from a cohort of Japanese patients with coronary atherosclerotic lesions, the elevation of t-PA was an independent predictor of subsequent cardiac events. The prognostic role of CRP in cardiac events was related to a low level of HDL-C.


経胸壁心エコー法による左心耳血流の検出:経食道法との比較検討．

経胸壁心エコー法による左心耳血流の検出:経食道法との比較検討．

Journal of Clinical and Experimental Medicine


Relationship between flow dynamics in the left atrium and hemostatic abnormalities in patients with nonvalvular atrial fibrillation

To investigate the relationship between left atrial (LA) flow dynamics and hemostatic markers in nonvalvular atrial fibrillation (AF), 45 patients with nonvalvular AF who had not received anticoagulants were evaluated by transesophageal echocardiography. We determined the LA appendage flow and the presence of LA spontaneous echo contrast (SEC) or thrombus. We measured plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 in peripheral blood as hemostatic markers. The patients were divided into a low-velocity group (n = 19; sum of peak emptying and filling LA appendage flow velocities < 40 cm/s) and a high-velocity group (n = 26; > or = 40 cm/s). The maximum LA diameter was significantly greater and the LA expansion fraction was significantly smaller in the low-velocity group than in the high-velocity group. LA SEC or thrombus was observed in 11 patients (58%) in the low-velocity group, but not in any patients in the high-velocity group (p < 0.001). The plasma levels of TAT, fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 were significantly higher in the low-velocity group than in the high-velocity group. The plasma levels of TAT, fibrinopeptide A, beta-thromboglobulin, and platelet factor 4 were significantly higher in 8 patients without LA SEC or thrombus in the low-velocity group than in 26 patients in the high-velocity group. Patients with nonvalvular AF accompanied by an enlarged and dysfunctioning LA and a decreased LA appendage flow velocity had increased intravascular coagulation-fibrinolysis activity and platelet activation. These abnormalities may be closely related to the thrombogenetic state in patients with nonvalvular AF.


Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n = 7), hypertension (n = 2), and atrial fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, (1) left ventricular ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/- 14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to 272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure.


急性心筋梗塞におけるplasminogen activator inhibitor-1(PAI-1) と梗塞サイズとの関係．


Right heart flow dynamics after tricuspid valve annuloplasty. Characteristics and time course

To evaluate the effect of tricuspid annuloplasty (TAP) on right heart flow dynamics, we analyzed tricuspid inflow velocity pattern, jugular venous pulse and color Doppler flow signal of tricuspid regurgitation (TR) before and after surgery in 16 patients who underwent TAP (TAP group). Cardiac rhythm was atrial fibrillation in all patients. Twelve patients with lone atrial fibrillation served as controls (AF group). Patients in the TAP group were studied before and serially after surgery with a mean follow-up period of 2.7 years. TAP was performed according to the modified De Vega technique in all patients. In a comparison of the most recent data in the TAP group and the data in the AF group, the maximum tricuspid inflow velocity was significantly increased, and both the deceleration time of the tricuspid inflow velocity wave and the y-h interval of the jugular venous pulse were significantly prolonged in the TAP group compared to the AF group. Immediately after surgery, in the TAP group, the area of the TR jet was markedly decreased, and the deceleration time of the tricuspid inflow velocity wave was significantly prolonged compared to those before surgery. The area of the TR jet was dramatically decreased and remained small during the follow-up period. Thus, TAP may produce mild tricuspid stenosis but may also confer sustained preventive effects against TR.


Echocardiographic assessment of right atrial function in patients with myocardial infarction with reference to obstructive lesions of the coronary arteries


Tricuspid inflow and regurgitant flow dynamics after mitral valve replacement: Differences relating to surgical repair of the tricuspid valve

Changes in tricuspid inflow and regurgitant flow dynamics were evaluated in patients with functional tricuspid regurgitation (TR) who underwent mitral valve replacement (MVR) with and without tricuspid annuloplasty (TAP). In a group of 30 patients, all with atrial fibrillation, 15 underwent TAP performed according to the modified De Vega technique; the remaining 15 did not undergo TAP. Patients were studied before and serially after surgery, using pulsed and color Doppler echocardiography. The mean follow up was 4.7 years in the TAP group and 5.1 years in the non-TAP group. In the TAP group, immediately after surgery, the area of the TR jet decreased markedly, and the deceleration time of the tricuspid inflow velocity wave was significantly prolonged compared with that before surgery. By contrast, in the non-TAP group, both the area of the TR jet and deceleration time of tricuspid inflow velocity were virtually unchanged. The area of the TR jet remained small for a long period in the TAP group, but in non-TAP patients was increased in four cases over seven years, with two patients developing right-sided heart failure. Recent data showed the area of the TR jet to be significantly smaller, with maximum tricuspid inflow velocity significantly increased, and deceleration time of the tricuspid inflow velocity wave significantly prolonged in the TAP group compared with the non-TAP group. In patients with functional tricuspid regurgitation undergoing MVR, concomitant TAP may cause mild tricuspid stenosis, but produces sustained preventive effects against TR. Careful follow up is needed in patients who have not undergone TAP, as TR is not markedly decreased and may even be exacerbated. Aggressive TAP is recommended in patients showing dilatation of the tricuspid annulus, even if TR is mild.


妊娠の循環動態:左室収縮時間および色素希釈法による心拍出量についての検討．

妊娠の循環動態:左室収縮時間および色素希釈法による心拍出量についての検討．

Japanese Journal of National Medical Services


虚血性心疾患の診断におけるタリウム負荷心筋SPECTの有用性の検討．

虚血性心疾患の診断におけるタリウム負荷心筋SPECTの有用性の検討．


Elevated Concentration of Interferon-Inducible Protein of 10kd (IP-10) is Associated with Coronary Atherosclerosis.


Predictors of Local Hypercoagulability after Sirolimus-Eluting Stent Implantation: Implication for Correlates of Late Stent Thrombosis.


Elevated Concentration of Pentraxin 3 is Associated with Coronary Plaque Vulnerability.


Ghrelin Attenuates Myocardial Ischemia/Reperfusion Injury via the Extracellular Signal-Regulated Kinase 1/2 and Phosphatidylinositol.


Long-Term Local Inflammatory Response after Coronary Artery Stenting with Drug-Eluting Stent.


Left Atrial Volume does not reflect Brain Natriuretic Peptide Levels in Patients with Atrial Fibrillation.


Importance of Left Atrial Function for the Pseudonormalization of Transmitral Flow Velocity Pattern in Patients with Hypertrophic Cardiomyopathy.


E/e' as a Predictor of the Cardiac Response to Increment of Preload in Patients with Atrial Fibrillation.


Long-term endothelial dysfunction after coronary artery stenting with drug-eluting stent associated with local inflammatory response.


Local hypercoagulability and endothelial dysfunction after sirolimus-eluting stent implantation: implication for late stent thrombosis.


Elevated concentration of Pentraxin 3 is associated with coronary plaque vulnerability.


Long-term local inflammatory response after coronary artery stenting with drug-eluting stent.


C-type natriuretic peptide ameliorates the progression of experimental autommune myocarditis.


Assessment of Left Atrial Ejection Force in Patients with Hypertensive Heart Disease.

Journal of the American Society of Echocardiography


Importance of Left Atrial Function in Cardiac Response to Increment of Preload in Patients with Old Myocardial Infarction: Assessment by Automated Left Atrial Volume Tracking Method.


Beat-To-Beat Variation of Mitral Annular Velocities in Atrial Fibrillation.


The Mitral L-Wave Predicts the Cardiac Response to Preload Increment in Atrial Fibrillation.


Usefulness of Tei Index in Atrial Fibrillation: Assessment by Dual Doppler Echocardiography.


Multicenter Trial for the Validation of Automated Function Imaging in Patients with Local Left Ventricular Asynergy (VANILLA Study).


Role of Left Atrial Function for Pseudonormalization of Transmitral Flow Velocity Pattern in Patients with Hypertrophic Cardiomyopathy.


Assessment of the cardiac response to increment of preload in patients with atrial fibrillation using dual pulsed Doppler echocardiography.


Measurement of left atrial volume curve by advanced 2D tissue tracking technique: validation by contrast multidetector computed tomography.


Relationship Between the Ratio of Peak Early Diastolic Transmitral Flow and Mitral Annular Velocities and the Plasma B-Type Natriuretic Peptide (BNP) Concentration in Patients with Atrial Fibrillation: Assessment by Simultaneous Recording of Transmitral Flow and Mitral Annular Velocity.

Journal of the American College of Cardiology


Effect of aging on left atrial myocardial strain evaluated by 2D tissue tracking during lower body positive pressure.


Differentiation of left atrial dysfunction by changes in transmitral flow velocities during lower body positive pressure.


Ghrelin Protects Myocardium Against Ischemia/Reperfusion Injury via Inhibiting Myocardial Apoptosis.


Preload Stress Echocardiography for the Assessment of Heart Failure With Preserved Ejection Fraction