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Background: An association between atrial high-rate episode (AHRE) and stroke has been reported, although data for the Asian population are limited. This study aimed to investigate the role of AHRE in ischemic and major bleeding events in patients who underwent a cardiac implantable electronic device (CIED) procedure., Methods and results: This single-center historical cohort study included 710 patients (age: 78±11 years, 374 women) who underwent a CIED-related procedure between October 2009 and September 2019 at Shimane Prefectural Central Hospital (median follow-up period: 4.5 [2.5, 7] years, 3439 person-years). Based on the maximum AHRE burden, patients were divided into: (1) <6 min; (2) ≥6 min to 24-h; and (3) ≥24-h groups. The cumulative incidence of ischemic (ischemic stroke, systemic embolism, and transient ischemic attack) and major bleeding (≥3 Bleeding Academic Research Consortium bleeding criteria) events after the procedure were compared. Uni- and multivariate analyses were performed to identify factors associated with these events. The incidence of both events increased with the rising AHRE burden, being significantly higher in the ≥24-h group than in the <6 min group. Multivariate analysis found age ≥85 years to be the only independent factor associated with both events., Conclusions: Longer AHRE duration is associated with a high number of major bleeding and ischemic events. Monitoring these bleeding risks is mandatory when clinicians are considering anticoagulation therapy for such patients.

Background: Cadmium-zinc-telluride (CZT) cameras have improved the evaluation of patients with chest pain. However, inferior/inferolateral attenuation artifacts similar to those seen with conventional Anger cameras persist. We added prone acquisitions and CT attenuation correction (CTAC) to the standard supine image acquisition and analyzed the resulting examinations., Methods and Results: Seventy-two patients referred for invasive coronary angiography (CAG), and who also underwent rest/stress myocardial perfusion imaging (MPI) on a CZT camera in the supine and prone positions plus CTAC imaging, to examine known or suspected CAD between April 2013 and March 2014 were included. A sixteen-slice CT scan acquired on a SPECT/CT scanner between rest and stress imaging provided data for iterative reconstruction. Sensitivity, specificity, accuracy, and positive and negative likelihood ratios (LRs) were calculated to compare MPI with CAG on a per-patient basis. Per-patient sensitivity, specificity, and accuracy of supine images to predict coronary abnormalities on CAG were 35% [95% confidence interval (CI) 19-52], 86% (95% CI 80-92), and 74% (95% CI 66-82); those of prone imaging were 65% (95% CI 45-81), 82% (95% CI 76-87), and 78% (95% CI 68-85); and those of CTAC were 59% (95% CI 41-71), 93% (95% CI 87-97), and 85% (95% CI 76-91), respectively., Conclusions: Prone acquisition and CTAC images improve the ability to assess the inferior/inferolateral area.

A 76-year-old woman was hospitalized repeatedly due to unexplained heart failure. On admission, she had hypertensive acute heart failure. Her symptoms disappeared promptly after the initial treatment; however, her systolic blood pressure remained at over 160 mmHg despite her taking three antihypertensive drugs. Closer examination revealed hemodynamically significant right renal artery stenosis and a lack of left kidney function. We performed percutaneous transluminal renal angioplasty using CO2 angiography in combination with iodinated contrast agents. The patient's renal function and blood pressure improved, however, CO2 gas-induced mild ischemic colitis occurred. We discuss the possibility of the use of combined iodinated contrast angiography and CO2 angiography to avoid contrast-induced nephropathy and the complications peculiar to CO2 angiography.

Objective The recognition of clinical symptoms is critical to developing an effective therapeutic strategy for aortic valve stenosis (AS). Although AS is common, little is known about the factors influencing the natural history of AS patients who are 80 years of age older in advanced aging societies. We investigated the natural history and indications for valve procedures in AS patients of 80 years of age or older. Methods The medical records of 108 consecutive AS patients (moderate grade or higher) who are 80 years of age or older (mean age, 84.2±3.9 years; female, 65 patients) were reviewed to investigate their symptoms, the development of congestive heart failure, the incidence of referral for aortic valve replacement and death. The median duration of follow-up was 9 months (interquartile range, 2 to 25 months). Results The probability of remaining free of events (valve replacement and death) was 29±13% in all patients. There was no significant difference in the aortic valve area of the symptomatic and asymptomatic patients (0.85±0.28 cm(2) vs. 0.88±0.25 cm(2), p=0.59). The aortic valve (AV) velocity and AV area index were predictors of subsequent cardiac events (p<0.05). Conclusion The severity of AS was the only factor to affect the prognosis of AS patients who were 80 years old of age or older. It is necessary to frequently monitor the subjective symptoms of such patients and to objectively measure the AV area.

Coronary artery fistulas are rare and the feeding artery is ectatic and tortuous. It is not well-known whether coronary artery ectasia (CAE) is a risk factor of acute coronary syndrome (ACS) in the puerperal periods. A 40-year-old woman with a coronary artery fistula and an ectatic right coronary artery (RCA) had delivered twins. A month later, she had chest pain and coronary angiography revealed thrombogenesis in the RCA. She had no risk factors of cardiovascular disease or thrombogenesis. We should recognize that CAE is a risk factor for ACS in women in the perinatal and puerperal periods.

Myxoma is a common benign cardiac tumor that may rarely cause an acute myocardial infarction. A 77-year-old woman was admitted to our hospital with chest pain. Electrocardiography showed an ST elevation in leads V3-6. Transthoracic echocardiography revealed an ovoid mass with fragmentation in the left atrium and hypokinesia of the left ventricular apex. Coronary angiography indicated the presence of a coronary embolism that was suspected to be from the left atrial mass. The mass was removed by emergency surgical resection to avoid a further systemic embolism and was diagnosed pathologically as a myxoma. The patient was discharged after 13 days with no complications.

Myocardial calcification is rare. An 88-year-old man who had previously been diagnosed with apical hypertrophic cardiomyopathy exhibited left ventricular asynergy on echocardiography before undergoing cholecystectomy. Computed tomography revealed severe calcification in the apical region of the left ventricular myocardium, although the coronary arteries were intact and the hemodynamics on right heart catheterization were normal. The cause of the left ventricular asynergy appeared to be myocardial calcification, thought to be the result of rheumatic fever based on the patient's past history. Stress echocardiography showed a latent risk for the development of heart failure due to the distensibility of the calcified left ventricular myocardium.

Objectives: The Japanese guidelines for hypertension management recommend reducing salt intake to <6 g/day for hypertensive patients. However, it is not currently known whether hypertensive patients' awareness of the recommended reduced salt diet correlates with their actual intake. Therefore, the purpose of this study was to investigate the relationship between actual salt intake of Japanese hypertensive patients and their awareness of the recommended guidelines for reduced dietary salt intake., Methods: In total, 236 outpatients (146 males and 90 females) with a mean age 69.7 ± 12.5 years were included in this study. Daily dietary salt intake was estimated using sodium and creatinine concentrations detected in spot urine samples. The patients filled out a questionnaire regarding their awareness of recommended salt restriction for hypertension management. The questionnaire distinguished the patients' awareness of recommended salt restriction in four levels (low, moderate, high and very high)., Results: The mean estimated salt intake was 9.72 ± 2.43 g/day. Patients' awareness regarding salt intake in all levels provided in the questionnaire did not correlate with actual salt intake (p = 0.731)., Conclusion: Our results demonstrated that Japanese hypertensive outpatients consumed higher levels of salt than the target value recommended by Japanese guidelines. There was no correlation between actual salt intake and patients' awareness of the recommended reduction in salt. These results suggest that monitoring salt intake and informing patients of their actual salt intake are necessary for effective hypertension management.

Streptococcus pneumoniae is the most common cause of community-acquired bacterial meningitis in adults. Pneumococcal endocarditis coexisting with meningitis is rare, especially in healthy individuals. A 66-year-old woman was admitted with pneumococcal bacteremia, meningitis, and arthritis. She was in good condition before admission. Because of typical presentation of bacterial meningitis characteristics and normal echocardiographic findings, the patient was administered antibiotics for meningitis and arthritis. On hospitalization day 59, she developed a fever, and echocardiography showed severe aortic regurgitation, perforation, and vegetation of the aortic valve. She was diagnosed with pneumococcal endocarditis and underwent aortic valve replacement surgery. In general, invasive pneumococcal infections occur in debilitated middle-aged men with predisposing factors such as chronic alcoholism, chronic obstructive pulmonary disease, and immunosuppressive conditions. In this case, regardless of the appropriate treatment and no risk of invasive pneumococcal infections, infective endocarditis occurred. < Learning objective: This case suggested that invasive pneumococcal infections progressing to infective endocarditis can occur in healthy individuals and underscore the importance of careful observation in patients with pneumococcal meningitis, in particular, in the case of blood culture positive patients.>.

Background: Left atrial volumes (LAVs) have been suggested to represent long-term exposure to elevated pressures. This study examined the recurrence of heart failure (HF) based on LAV in patients initially diagnosed with congestive HF (CHF)., Methods: This study comprised 77 patients (age, 75 ± 8 years) with well-documented, clinically defined HF, and complete two-dimensional echocardiographic examinations. The echocardiographic examinations were performed on admission and after medical treatment (90 ± 43 days after initial examination). Patients with atrial fibrillation, flail mitral valve, or mitral valve replacement were excluded from this study., Results: The initial left ventricular ejection fraction (LVEF) was 44 ± 17% and the indexed LAV (LAVI) was 61 ± 22 mL/m(2) . After medical treatment, a decreased LAVI was observed in 38 patients and an increased LAVI (LA remodeling) was observed in 39 patients. With median follow-up periods of 454 days, compared to patients with decreased LAVI, patients with LA remodeling had a significantly higher incidence of CHF recurrence (P = 0.008). Patients with LA remodeling had a CHF-free survival rate of 36 ± 13% vs. 81 ± 9% (those without LA remodeling). A multivariate analysis indicated that, follow-up LV end-systolic volume (P = 0.04), LVEF (P = 0.005) and LAVI (P = 0.04) independently predicted CHF recurrence., Conclusions: Patients initially diagnosed with CHF follow divergent courses based on their LAV. LA remodeling after medical treatment can be useful for predicting CHF recurrence during follow-up., (© 2013, Wiley Periodicals, Inc.)

Left ventricular (LV) myxomas are rare. We present a case of a LV myxoma arising from the interventricular septum of the LV outflow tract in a 76-year-old woman. General examination of the patient did not reveal any abnormality except for a grade 3/6 systolic murmur in the left parasternal area. Transthoracic echocardiography revealed a round pedunculated mass (size, 23 mm × 11 mm × 10 mm) at the interventricular septum with a broad pedicle. The mass was successfully removed and was pathologically confirmed to be a myxoma. < Learning objective: This is the rare case of left ventricular (LV) myxoma arising from LV outflow tract, which was pathologically confirmed.>.

Background: Carbamazepine (CBZ), which is widely used in management of epilepsy or neuropathic pain, causes fatal severe cutaneous adverse reactions (SCARs). CBZ-induced SCARs are known to occur in strong association with human leukocyte antigen (HLA)-A*31:01 in Japanese and European populations. HLA genotyping is currently used to detect human HLA-A*31:01., Objective: To establish a simple and rapid screening assay specific for HLA-A*31:01, the loop-mediated isothermal amplification (LAMP) method was employed on a sample Japanese population., Methods: A set of LAMP primers targeting exon 2 of HLA-A*31:01 were designed. Thirty-two clinical samples including the representative HLA-A allele in Japan were used to assess the specificity of LAMP primers in the detection of HLA-A*31:01., Results: The HLA-A*31:01-specific LAMP assay showed consistency with polymerase chain reaction reverse sequence-specific oligonucleotide probe (PCR-rSSO) and polymerase chain reaction-sequence based typing (PCR-SBT) results., Conclusion: High sensitivity and specificity of the HLA-A*31:01 LAMP assay was confirmed. Considering its convenience, the assay can be widely used to screen patients at high genetic risk of CBZ-induced SCARs., (Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Giant cell arteritis (GCA) is an autoimmune disease characterized by granulomatous inflammation in the wall of medium-sized and large-sized arteries, and it usually occurs in patients over 50 years of age.(1)) Symptoms are nonspecific, and include fatigue, fever, and headache.(2)) It is occasionally combined with aortic complications, and ruptures resulting in death. These complications occur as late events, usually several years after diagnosis and often after other symptoms have subsided.(3)) Physicians should therefore be alert for complications of the large arteries in GCA. Here we present a case of GCA combined with ascending aortic dissection and rupture 3 weeks after diagnosis.

A 70-year-old man was admitted because of syncope and dyspnea. Two months before admission, exertional dyspnea occurred with syncope. Ventricular tachycardia with a monomorphic left bundle-branch block configuration was detected. An echocardiographic examination showed severe dilatation and diffuse, severe hypokinesis of the right ventricle, with thrombus formation in the right ventricular apex. Based on the clinical picture, the patient was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC). This case emphasizes the need for early identification of RV abnormalities in patients with ARVC to determine appropriate therapy.

Background: Recent reports revealed the presence of acquired von Willebrand syndrome type 2A in patients with aortic valve stenosis (AS). von Willebrand factor (vWF) has been shown to play a vital role in platelet adhesion. Therefore, we measured the platelet retention rates, which reflect platelet adhesion, in patients with severe AS., Methods: In addition to echocardiography, routine blood screening tests were performed and the platelet retention rates were measured using collagen-coated bead columns in 21 patients with severe AS and in 21 control subjects., Results: Patients with severe AS showed the maximum aortic valve pressure gradients of 110.9±22.7 mmHg, and effective orifice areas of 0.59±0.20 cm2. The results of routine blood tests in patients with severe AS were comparable to those of control subjects; however, the platelet retention rates in the AS patients (7.3±5.0%) were significantly lower than those in control subjects (30.5±11.8%, p<0.001). A significant negative correlation was observed between maximum aortic valve pressure gradients and platelet retention rates (r = -0.81, p<0.001). In 8 patients with severe AS, the platelet retention rates increased from 5.8±3.6% to 16.0±2.4% after aortic valve replacement (p<0.001)., Conclusion: These findings suggest that impairment of platelet retention rate is seen in almost all patients with severe AS. Clinicians should be aware of the possibilities of vWF-mediated platelet dysfunction and bleeding tendency in patients with severe AS., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

This paper aims to describe the usefulness of transthoracic echocardiography in the follow-up of recurrent nonbacterial thrombotic endocarditis (NBTE) associated with neoplastic conditions. A 60-year-old woman with advanced uterine cancer developed recurrent areas of aseptic vegetation on the mitral valve along with cerebral, renal and splenic embolisms. Echocardiographic assessments revealed vegetation and thrombotic events on three occasions. In this case, transthoracic echocardiography was effective in following the decreased frequency of attachment of the NBTE vegetation to the mitral valve and reductions in the size of the area of vegetation following treatment with unfractionated heparin infusion, hysterectomy and chemotherapy.

Long QT syndrome (LQTS) is a hereditary ion channelopathy resulting in prolonged cardiac repolarization and abnormal prolongation of the QT interval on the electrocardiogram (ECG). The patients are likely to develop ventricular arrhythmias and sudden cardiac death. Molecular biology and basic electrophysiology studies revealed an approach to the management of patients with LQTS, which includes genotype-based risk stratification. A 16-year-old-woman with QT prolongation on ECG had frequent syncopal episodes and an attack of ventricular tachycardia followed by ventricular fibrillation. The SCN5A mutation (intravene sequence 4-1 c/t) in addition to the KCNH2 mutation (Arg56Gln) was identified. Her mother and older sister were also diagnosed as having LQTS, but had only a single mutation ( KCNH2 ). Her older sister had an episode of syncope, but her mother did not. Genetic analysis sometimes reveals 2 or more mutations in LQTS patients with clinical phenotypes of the Romano-Ward syndrome. Compound mutations in different LQTS-related genes are likely to modify clinical characteristics. In addition, comprehensive screening of LQTS-related genes might be needed when facing family members with different clinical manifestations. < Learning objective: Molecular biology and basic electrophysiology studies revealed an approach to the management of patients with LQTS, which includes genotype-based risk stratification. We described a case of LQTS having compound mutations of KCNH2 and SCN5A who had frequent syncopal episodes and an attack of ventricular fibrillation. The mutations of 2 different genes were associated with a severe phenotype of LQTS. Comprehensive screening of LQTS-related genes might be needed for estimating the severity of LQTS.>.

Background: Although rare, bloodstream infections caused by Aeromonas tend to be very severe and progress rapidly., Case Report: We report a case of an 81-year-old man with fetal septicemia and endotoxin shock caused by Aeromonas hydrophila. The patient had dilated cardiomyopathy, paroxysmal atrial fibrillation, interstitial pneumonitis and renal dysfunction was admitted to our hospital with chest pain and dyspnea. Transthoracic echocardiography demonstrated impaired left ventricular wall motion and severe mitral regurgitation due to tethering. Cardiac catheterization revealed severe stenotic lesions in the left anterior descending artery and the right coronary artery. Surgery for coronary artery bypass grafts and mitral annuloplasty were performed. However, 2 days after surgery, he suddenly developed a high-grade fever and his hemodynamics deteriorated rapidly. His blood cultures revealed gram-negative Bacillus and the endotoxin concentration in the blood was elevated. Despite intensive support efforts, the patient died 1 day after the sudden change. His blood culture revealed A. hydrophila., Conclusions: Whenever Aeromonas is found in a patient's bloodstream, clinicians should start appropriate and intensive treatment immediately.

Background: Takayasu arteritis and ulcerative colitis are immune-mediated inflammatory diseases; genetic factors are assumed to play an important role in the pathogenesis of these 2 diseases. However, the coexistence of these 2 diseases has rarely been reported., Case Report: In this report, we present a rare case of a 29-year-old man with a 4 years history of ulcerative colitis who developed Takayasu arteritis. He was found to carry the following human leukocyte antigens (HLA): A11, A24, B52, B62, DR4, and DR9., Conclusions: We present a case report and review of the pertinent literature on serological analysis of HLA haplotype of the patients who exhibit both these diseases. In patients with both Takayasu arteritis and ulcerative colitis, high frequency of HLA-A24, B52, and DR 2 is observed. The pathological relevance of HLA-A24, B52, and DR2 to concomitant Takayasu arteritis and ulcerative colitis requires further investigation.

Background: Activation of inducible nitric oxide synthase (iNOS) has been reported in congestive heart failure (CHF) conditions. However, it is unknown whether activation of iNOS affects prognosis of CHF patients. We prospectively studied the influence of activation of iNOS in the forearm on the outcome of CHF patients., Methods and Results: Forearm blood flow (FBF) responses to 3 doses of acetylcholine (ACh) and nitroglycerin (NTG), and 4 doses of a selective iNOS inhibitor (aminoguanidine: Amn) and a nonselective NOS inhibitor (L-NMMA) were examined using plethysmography in 68 patients with CHF from idiopathic dilated cardiomyopathy. Plasma brain natriuretic peptide (BNP) and tumor necrosis factor-alpha (TNF-alpha) were also measured in all patients. During the mean follow-up period of 3.8 years, 25 patients were hospitalized for worsening heart failure and 9 of these patients died. Patients with adverse events had a diminished vasodilator response to ACh (P < .001) compared to patients without adverse events. Amn significantly decreased FBF (P < .001) in patients with adverse events, but not in patients without adverse events. FBF responses to NTG and L-NMMA were not significantly different between the 2 groups. When grouped by maximum FBF responses to each drug above and below the median value, multivariate Cox proportional hazards model analyses for cardiac event showed a significance in the FBF response to Amn (adjusted hazard ratio 5.89, P < .001). FBF responses to maximum dose of Amn significantly correlated with BNP and TNF-alpha levels (both P < .001)., Conclusions: CHF patients with vascular iNOS activation, as demonstrated by a greater vasoconstrictor response to Amn, had poor outcomes. Activation of iNOS in peripheral vessels, associated with proinflammatory cytokines in accordance to the severity of heart failure, is a marker for, or contributes to, adverse events in patients with CHF.

Long-term administration of nicorandil has been shown to improve outcomes through cardioprotective effects in patients with coronary artery disease. To identify the mechanisms responsible for these effects, this study examined the impact of long-term nicorandil administration on endothelial function, systemic inflammatory markers, and oxidative stress in patients with cardiovascular risk factors. Fifty-three patients were assigned to receive either nicorandil therapy (15 mg/day; n = 26) (nicorandil group) or usual care (n = 27) (nonnicorandil group). All study participants underwent flow-mediated vasodilatation (FMD) of the brachial artery 1 month before treatment, just before treatment, and at 3, 6, and 12 months following treatment. At identical time points, serum levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL) and high-sensitivity C-reactive protein (hs-CRP) were collected. Compared with the nonnicorandil group, the nicorandil group demonstrated significantly increased FMD at 12 months, a finding not replicated for endothelium-independent vasodilatation with nitroglycerine. Analysis of biochemical markers revealed significantly reduced MAD-LDL levels in the nicorandil group at 12 months, as compared to slightly increased MAD-LDL levels in the nonnicorandil group. Significant reductions in hs-CRP levels were also noted at 6 and 12 months in the nicorandil group, while no change was found in the nonnicorandil group. Results demonstrated that long-term nicorandil therapy is associated with gradual improvements in endothelial function. Our findings also suggest that nicorandil treatment may result in cardiovascular protection through pleiotropic effects including reductions in oxidative injury and systemic inflammation.

There are few reports of cardiac involvement in patients with Kugelberg-Welander disease. We report a case of a 51-year-old man with Kugelberg-Welander disease who presented with syncope. His electrocardiogram showed complete right bundle branch block and transient complete atrioventricular block without escape rhythm. He was successfully treated with emergency temporary pacing followed by permanent pacemaker implantation. In this report, we review the relevant literature and argue that patients with Kugelberg-Welander disease should be evaluated regularly for cardiac disease.

1. Previous clinical studies with prostaglandin I(2) (PGI(2)) analogue beraprost sodium suggested the potential effects on protection of cardiovascular events in patients with peripheral artery disease. Although the mechanism is not well known, experimental studies have shown protective effects of endothelial cells. This study was designed to examine the effects of beraprost sodium on vascular endothelial function in the forearm of patients with coronary artery disease. 2. Beraprost sodium (120 microg/day) was orally administered to 14 coronary artery disease patients for 4 weeks and then stopped for 4 weeks. Eleven control patients did not receive beraprost sodium treatment. Reactive hyperemia was induced in the forearm, endothelium-dependent vasodilatation was assessed by plethysmography, and urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) was measured at baseline, 4 weeks and 8 weeks. 3. Both groups had similar reactive hyperemic responses at baseline. In the control group, reactive hyperemic response and urinary 8-iso-PGF(2alpha) remained unchanged for 8 weeks. In the beraprost group, maximum forearm blood flow increased significantly (P = 0.01) after 4 weeks of treatment and returned to baseline at 8 weeks. Duration of hyperemia increased significantly (P = 0.003) after 4 weeks, and remained greater than baseline at 8 weeks (P = 0.02). Urinary 8-iso-PGF(2alpha) decreased significantly (P = 0.03) after 4 weeks, and tended to be lower at 8 weeks (P = 0.07). Changes in reactive hyperemia correlated weakly but significantly with changes in 8-iso-PGF(2alpha) (P < 0.001). 4. Beraprost sodium decreased oxidative stress and improved forearm endothelium-dependent vasodilatation in coronary artery disease patients. The favorable effects on vascular endothelium could potentially lead to a decrease in vascular events.

Background: Peripheral vascular endothelial dysfunction is an independent predictor of cardiovascular events, and can be assessed noninvasively by measuring reactive hyperemia, either by vascular ultrasound measurement of flow-mediated vasodilatation or, less commonly, by measurement of blood flow using plethysmography. In the present study reactive hyperemia was measured using plethysmography in healthy subjects with multiple cardiovascular risk factors., Methods and Results: Reactive hyperemia was measured following 5-min occlusion of the upper arm in 449 healthy subjects (302 men, 147 women, age range 20-70 years) with (n=352) and without (n=97) risk factors such as smoking, hypertension, diabetes mellitus, hypercholesterolemia, obesity, family history of cardiovascular disease, and menopause. Maximum blood flow and minimum vascular resistance in reactive hyperemia did not differ between subjects with and without risk factors regardless of gender. Duration of reactive hyperemia, however, was significantly shorter in subjects with risk factors. Age-adjusted mean value of duration of reactive hyperemia was significantly smaller in men with a smoking habit, diabetes mellitus, hypercholesterolemia or obesity, and in women with smoking habit, hypertension, diabetes mellitus or obesity. The number of risk factors significantly correlated with the duration of reactive hyperemia in both men (r=-0.56, p<0.001) and women (r=-0.62, p<0.001), suggesting that endothelial dysfunction increases with the number of risk conditions clustering in a single individual., Conclusions: Duration of reactive hyperemia reflects cardiovascular risk factors and decreases with the number of risk conditions. These findings suggest that the duration of reactive hyperemia measured with plethysmography is potentially useful for assessing endothelial dysfunction.

Recent studies have demonstrated that proinflammatory cytokines induce large amounts of nitric oxide (NO) and that the amount increases in patients with congestive heart failure (CHF). There are, however, few reports regarding the relationships between NO production, cytokines and the severity of heart failure, so the plasma concentrations of nitrite and nitrate (NOx), tumor necrosis factor-alpha (TNF-alpha) and brain natriuretic peptide (BNP) were measured in 43 patients with CHF caused by dilated cardiomyopathy and 26 age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using plethysmography during infusions of acetylcholine and nitroglycerin and after the administration of the NO synthesis inhibitor L-NMMA (N(G)-monomethyl-L-arginine). Plasma concentrations of both NOx and TNF-alpha were significantly higher in the patient group than in the control group (p<0.001) and correlated closely with BNP concentrations (p<0.001). There was a positive relationship between NOx and TNF-alpha concentrations (r=0.80, p<0.001). Administration of L-NMMA significantly reduced FBF in both groups, and the percent change in FBF from baseline correlated significantly with TNF-alpha concentrations (r=0.63, p<0.001). The FBF response to acetylcholine was depressed in the patient group and correlated inversely with TNF-alpha concentrations. The FBF response to nitroglycerin did not correlate with TNF-alpha concentrations. The findings indicate that the concentrations of NO and TNF-alpha in patients with CHF increase in proportion to the severity of heart failure, and that TNF-alpha plays a role in the enhanced systemic and local production of NO.

Exercise capacity is often reduced in patients with atrial fibrillation (AF), but very few studies have focused on changes in endothelial function as a potential mechanism for the exercise limitation. The present study used using venous occlusion plethysmography to investigate whether nitric oxide (NO)-mediated vasodilatation is attenuated during exercise in patients with AF by measuring forearm blood flow (FBF) in 10 patients at rest and immediately after 2 levels of rhythmic handgrip exercise, before and after inhibition of NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA, 100 micromol). The measurements were repeated 1 day after restoration of sinus rhythm by cardioversion. FBF responses to graded doses of acetylcholine (ACh) were also observed before and after cardioversion. Heart rate decreased after cardioversion, but blood pressure did not change. FBF at rest was not affected by cardioversion, but at the highest level of exercise it increased from 28.4+/-2.3 ml x min(-1) x dl(-1) before to 39.4+/-3.2 ml x min(-1) x dl(-1) after cardioversion (p<0.05). L-NMMA significantly decreased FBF at rest (p<0.01) and depressed the increase in FBF response to exercise after (p<0.01), but not before cardioversion. The FBF response to ACh was also accelerated significantly after cardioversion. The present results provide new evidence that NO bioavailability is depressed at rest and during exercise in patients with AF.

Background and Purpose: Assessment of left atrial appendage (LAA) function with transesophageal echocardiography is useful for detecting patients at high risk for thromboembolism as a result of atrial fibrillation (AF). A recent study reported that the atrium is the main source of brain natriuretic polypeptide (BNP) in AF patients without overt heart failure. The purpose of this study was to assess a possible relationship between LAA function and plasma BNP levels in nonvalvular AF., Methods: Thirty-four consecutive patients with chronic nonvalvular AF (age, 69+/-9 years) underwent transesophageal echocardiography and plasma BNP measurement. Thirteen patients with a history of thromboembolism or echocardiographic evidence of thrombus (E + group) were compared with 21 AF patients without complications (E- group)., Results: The E+ group patients demonstrated greater impairment of LAA velocity and higher plasma BNP levels than the E- group patients (LAA velocity: 12+/-6 versus 31+/-17 cm/s, P<0.05; plasma BNP: 126+/-53 versus 86+/-45 ng/L, P<0.05). Overall analysis of the continuous variables with multiple logistic regression analysis revealed that BNP was a significant predictor of thromboembolism. There was a weak but significant negative correlation between plasma BNP levels and LAA flow velocity (r=0.38, P<0.05). No intergroup difference in plasma atrial natriuretic polypeptide levels was found., Conclusions: The present data suggest the usefulness of measuring plasma BNP levels, which may reflect augmented atrial secretion of BNP from the impaired atrial myocardium, in detecting patients at high risk for thromboembolic complications in nonvalvular AF.

1. The aim of the present study was to determine whether the vasorelaxant effect of atrial natriuretic peptide (ANP) is, in part, endothelium dependent in humans. 2. We used veno-occlusive plethysmography to measure forearm blood flow (FBF) during intra-arterial infusions of ANP (4, 8, 16, 32 pmol/min per dL forearm tissue volume) before and after the inhibition of nitric oxide (NO) synthesis by N(G)-monomethyl-L-arginine (L-NMMA; 100 micromol) in seven normal healthy subjects. 3. Atrial natriuretic peptide caused a dose-dependent increase in FBF both before and after L-NMMA and significantly reduced the plasma concentration of angiotensin (Ang) II. Administration of L-NMMA significantly diminished the increase in FBF in response to ANP infusion (P < 0.05). 4. These results suggest that the forearm vasodilative response to ANP is modulated, in part, by an endothelium-derived NO-mediated mechanism associated with a decrease in AngII caused by ANP.

Objectives: The functional activation of inducible nitric oxide synthase (iNOS) was evaluated as a source of nitric oxide (NO) in the forearm of patients with heart failure., Background: Although endogenous NO is normally produced by constitutive NO synthase (cNOS) in patients with congestive heart failure (CHF), expression of iNOS provides an additional source of NO. However, there are no in vivo studies showing functional activation of iNOS in humans., Methods: A nonselective NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), and a selective inhibitor of iNOS, aminoguanidine, were administered intra-arterially in graded doses into the brachial arteries of 13 patients with CHF and 10 normal control subjects. Forearm blood flow (FBF) was measured simultaneously in the infused and noninfused arms by plethysmography. Arterial and venous plasma concentrations of nitrite/nitrate (NOx) were measured at baseline and at the highest dose of each drug., Results: L-NMMA significantly reduced the FBF ratio between the infused and noninfused arms in both the control and patient groups (35 +/- 12% and 34 +/- 10%, respectively; both p < 0.001). Aminoguanidine at the same concentration significantly reduced the ratio in the patient group (15 +/- 9%, p < 0.01), with no change in the control group. The arterial NOx concentration was not affected by either drug; however, venous NOx concentrations were significantly decreased in both the control and patient groups by L-NMMA (18 +/- 5% and 18 +/- 17%, respectively; both p < 0.05) and in the patient group only by aminoguanidine (7 +/- 6%, p < 0.05)., Conclusions: These findings suggest that NO production in the forearms of patients with CHF is induced partly by iNOS activation, whereas in normal subjects, it can be ascribed to cNOS activation.

Background: Although there have been many studies on the effects of atrial fibrillation (AF) on cardiac function, few studies have been done on its effects on endothelial function. The present study was designed to examine the effects of AF on endothelial function in human subjects., Methods and Results: Changes in forearm blood flow (FBF) induced by acetylcholine and nitroglycerin were measured by using plethysmography in 14 patients with lone AF, 13 patients with AF and underlying heart disease, and 12 normal control subjects. In the patients, these measurements were repeated after cardioversion. Although baseline FBF was the same in the 3 groups, acetylcholine-induced increases in FBF were significantly smaller in both patient groups than in the control group, and FBF increases were particularly depressed in AF patients with underlying heart disease. After restoration of sinus rhythm by cardioversion, FBF response to the highest dose of acetylcholine increased by 46% in patients with lone AF (n = 10) and by 90% in AF patients with underlying heart disease (n = 11). Nitroglycerin-induced vasodilatation was the same in all 3 groups and was not affected by cardioversion., Conclusions: These findings suggest that endothelium-dependent vasodilatation is impaired by AF and improves after sinus rhythm is restored.

Objectives: We examined whether a relationship exists between the vasoconstrictive response to endogenous nitric oxide (NO) synthesis inhibition and the severity of heart failure in patients with congestive heart failure (CHF)., Background: Controversy exists as to whether the vasoconstrictive response to NO synthesis inhibition in patients with CHF is comparable to that in normal subjects or is enhanced., Methods: Forearm blood flow (FBF) and calculated forearm vascular conductance (FVC) were obtained using plethysmography before and after administration of the NO synthesis inhibitor L-NMMA (NG-monomethyl-L-arginine) in 40 patients with CHF due to dilated cardiomyopathy and in 16 normal control subjects. Basal plasma B-type natriuretic peptide (BNP) and nitric oxide concentrations were measured in all subjects., Results: Plasma BNP and nitrite/nitrate (NOx) levels in the patients group were significantly greater and baseline FBF was significantly less. Administration of L-NMMA significantly decreased FBF and FVC in both groups. The percent changes in FBF (%FBF) and FVC (%FVC) from the baseline after L-NMMA correlated significantly with plasma BNP level (%FBF: r = 0.72; %FVC: r = 0.76; both p < 0.001). Percent changes in both FBF and FVC were greater in patients with BNP > or = 100 pg/ml than in normal subjects; however, in patients with BNP < 100 pg/ml they were comparable to those in normal subjects., Conclusions: Vasoconstrictive response to L-NMMA in patients with CHF was preserved or enhanced in proportion to the basal plasma BNP level, indicating a close relationship between the contribution of endogenous NO to basal vasomotor tone and the severity of heart failure.

We report a case in which 2-dimensional echocardiography established the diagnosis of a left ventricular subepicardial aneurysm that was followed by rupture and sudden death before surgery. Two-dimensional echocardiography is of great help in detecting this rare complication after myocardial infarction. Urgent surgical treatment is warranted for this condition.

Recent in vitro experiments have shown that amrinone enhances the release of nitric oxide (NO) from the endothelium and induces NO mediated vasodilatation. This in vivo study examined whether amrinone causes vasodilatation mediated by endothelium-derived NO, and whether this effect is attenuated in patients with endothelial dysfunction. Eight patients with congestive heart failure and 10 age- and sex-matched healthy volunteers were studied. Forearm blood flow (FBF) was measured before and during infusion of drugs of acetylcholine, amrinone, and nitroglycerin in incremental doses. After the completion of these measurements, 100 micromol of N(G)-monomethyl-L-arginine (L-NMMA) was infused intraarterially. Thereafter, FBF measurement in response to incremental doses of amrinone was repeated. Infusion of incremental doses of amrinone caused a comparable increase in amrinone plasma concentration in both groups. Baseline FBF was 3.2+/-0.79 ml/min/100 ml in controls vs. 2.91+/-0.79 ml/min/100 ml in patients (p = 0.43). In both groups, FBF increased in response to acetylcholine, amrinone, and nitroglycerin. During infusion of the highest dose of nitroglycerin, FBF was not different between the two groups (p = 0.51); however, FBF during infusion of the highest doses of acetylcholine and amrinone was significantly less in patients than in controls: 9.75+/-2.69 vs. 24.87+/-8.65 ml/min/100 ml (p < 0.001) and 3.79+/-1.21 vs. 7.15+/-2.06 ml/min/100 ml (p < 0.001), respectively. L-NMMA significantly depressed the increase in FBF in response to amrinone in controls, but not in patients. In conclusion, the selective PDE III inhibitor, amrinone, has endothelium-derived NO-mediated vasodilating effects in addition to direct effects. This property may be impaired in patients with endothelial dysfunction.

Recently, the mechanism of longevity in females was proposed to be associated with female hormones. This study examined the effect of aging and sex on vascular endothelial function, and the relationship between female hormone level and endothelial function by ischemic reactive hyperemic response in the forearm using plethysmography. The study population consisted of 246 healthy subjects aged from 20 to 76 years (119 males, 127 females) and 20 healthy females aged 85 years and older (85 to 103 years; mean age 94 years) without distinct cardiovascular disease, hypertension, diabetes mellitus, renal disease, liver dysfunction or anemia. Levels of the female hormones, estradiol and estriol, were measured in females aged more than 85 years. The duration of reactive hyperemia decreased with aging, but the difference between males and females was not significant at any age. In females, the duration was markedly decreased from 110 +/- 36 sec in the fifties to 81 +/- 29 sec in the sixties or older (p < 0.05). Excess flow also showed similar changes to the duration of reactive hyperemia. The duration of reactive hyperemia and excess flow in females aged 85 years and older were similar to those in the fifties, but was significantly longer than those in females 60 years or older. The concentrations of estradiol (44.9 +/- 27.1 pg/ml) and estriol (22.1 +/- 13.4 pg/ml) in females aged 85 years were higher than in the sixties. There was a positive correlation between the duration of reactive hyperemia and the concentration of estradiol (r = 0.56, p < 0.01) or estriol (r = 0.57, p < 0.01). In summary, vascular endothelial function was impaired gradually with aging, but preservation of the function in healthy, very old females was closely associated with levels of female hormone.

The hemostatic effects of microcrystalline partially deacetylated chitin hydrochloride (DAC-HCl) were compared with those of cotton and collagen hydrochloride (collagen-HCl). The DAC-HCl had excellent physical properties as a hemostatic agent such as its ability to absorb and retain blood. In canine blood it induced the release of substances involved in the process of platelet activation, such as beta-thromboglobulin and platelet factor 4, and it also had excellent hemoagglutinative properties. Moreover, in a hemostatic study on bleeding from cancellous bone in canines it exhibited a hemostatic effect comparable to that exhibited by collagen-HCl. Because it also has an intrinsic promotive effect on wound healing, chitin hydrochloride is considered to be a promising hemostatic material., (Copyright 2000 John Wiley & Sons, Inc.)

Amrinone, which is used for the treatment of acute congestive heart failure, has vasodilatory and positive inotropic effects through the increment of intracellular cyclic adenosine monophosphate. Recent in vitro investigations have shown that amrinone has an endothelium-dependent vasodilatory effect. The present study examined whether amrinone shows this endothelium-dependent vasodilatory effect in human peripheral vessels. Forearm blood flow during intra-arterial infusion of graded doses (12.5, 25, 50, 100, 200 micrograms/min) of amrinone was measured using plethysmography in 10 healthy subjects without organic vascular disease before and after nitric oxide synthase blocking with NG-monomethyl-L-arginine (L-NMMA, 400 mumol). The graded dose of amrinone produced progressive increases in amrinone plasma concentrations, and a dose over 100 micrograms/min caused amrinone plasma concentrations of more than 1.0 microgram/ml. The increase in forearm blood flow in response to amrinone was significantly depressed after L-NMMA doses of less than 100 micrograms/min, but the increase in forearm blood flow during infusion of higher doses (100, 200 micrograms/min) was not affected by L-NMMA. These results suggest that endothelial-derived nitric oxide may partially contribute to amrinone-induced vasodilation in humans. Thus, the vasodilatory effect of amrinone might be impaired in patients with endothelial dysfunction.