Myocardial injury in patients with chronic hepatitis C infection.

BACKGROUND & AIMS: The existence of a direct pathogenic link between hepatitis C virus (HCV) infection and myocardial injury has not been confirmed. We investigated the association between myocardial conditions and HCV in patients with HCV-related chronic hepatitis using thallium-201 myocardial scintigraphy. METHODS: In 217 consecutive cases of chronic HCV infection without overt heart disease, we performed electrocardiography (ECG), echocardiography, serum tests on myocardial injury and thallium-201 myocardial scintigraphy. Myocardial injury was confirmed by severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. SS was followed prior to and after interferon (IFN) therapy in 200 patients with chronic hepatitis C. RESULTS: An abnormal ECG was found in 9% of the patients with chronic hepatitis C. Abnormal SS was found in 87% of the chronic hepatitis C patients. Independent factors related to higher pretreatment SS were histology activity index score, serum HCV RNA titer, and indocyanine green disappearance rate. After IFN therapy, SS was improved in patients with sustained virologic response. Among relapsers, SS improved at the initial disappearance of HCV RNA, but it worsened with the reappearance of HCV RNA. SS in non-viral responders did not change with IFN therapy. CONCLUSIONS: Myocardial perfusion defects were found in 87% of the patients with chronic hepatitis C and improved with viral eradication with IFN therapy.

The pitfall of coagulase-negative staphylococci: a case of Staphylococcus lugdunensis endocarditis.

We report a case of a 60-year-old woman. She was transferred from a local hospital to our cardiovascular medicine department with a diagnosis of infectious endocarditis due to Staphylococcus lugdunensis. Transthoracic echocardiograph confirmed the presence of large vegetations on the native aortic and mitral valve, and subsequent severe regurgitation due to the aortic and mitral valve destruction. Emergent operation was performed and patient's life was barely rescued. However, S. lugdunensis belongs to coagulase-negative staphylococci, which are generally regarded as relatively avirulent bacterium, the endocarditis caused by S. lugdunensis can be invasive and often resembles endocarditis due to Staphylococcus aureus. Therefore, whenever this organism is found in patients with endocarditis, early surgical treatment of the infected valve should be considered.

Activation of inducible NOS in peripheral vessels and outcomes in heart failure patients.

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.

Hepatitis C virus infection as a risk factor for increased aortic stiffness and cardiovascular events in dialysis patients.

BACKGROUND: Although links have been found between microorganisms and cardiovascular diseases, the role of hepatitis C virus (HCV) infection in the pathogenesis of arteriosclerosis and cardiovascular events is unclear. The primary objective of this research was to examine whether HCV infection is associated with increased aortic stiffness and cardiovascular events in chronic hemodialysis patients. SUBJECTS AND METHODS: A prospective cohort study was conducted in 94 dialysis outpatients from October 2002 to October 2004. Measurements included carotid-femoral pulse wave velocity (PWV), echocardiographic parameters, serum HCV-RNA (positive in 17 patients), and several items of biochemical data. Multiple logistic regression and the Cox proportional hazard model were used to assess independent determinants of high aortic PWV (> or =10.0 m/sec, mean) and cardiovascular events (including cerebral and peripheral vascular events), adjusting for several risk factors and duration of dialysis. RESULTS: The HCV-positive group had higher aortic PWV and lower serum cholesterol levels. Multivariate analysis indicated mean blood pressure, hemoglobin A1c and HCV viremia to be independent determinants of high PWV. During the follow-up period, 13 patients suffered from cardiovascular events. Prevalence of the diseases at baseline, pulse pressure, left ventricular mass index, HCV viremia and aortic PWV were associated with cardiovascular events. The Kaplan-Meier analysis indicated a significant difference in event-free rates between HCV-positive and HCV-negative patients. CONCLUSION: HCV infection is closely associated with increased aortic stiffness and cardiovascular event in dialysis patients.

Effects of long-term nicorandil administration on endothelial function, inflammation, and oxidative stress in patients without coronary artery disease.

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.

Transient elevation of serum tumor markers in a patient with hypothyroidism.

We report a case of a 66-year-old woman admitted to our hospital for examination and treatment of uterine and rectal prolapse, pleural and pericardial effusion, and ascites. On further examination, she was diagnosed with hypothyroidism. Test results showed markedly elevated concentrations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125). We consequently performed multiple imaging studies, none of which detected a malignancy. Hormonal replacement therapy with levothyroxine was started, and the pleural and pericardial effusion and ascites gradually abated. Concentrations of serum CEA and CA125 also decreased gradually after therapy with levothyroxine. These findings indicate that in patients with hypothyroidism, elevated CEA and CA125 levels do not necessarily indicate malignancy. Conversely, in any patient with elevated serum CEA and/or CA125, hypothyroidism should be considered in the differential diagnosis.

Cardiac involvement in Kugelberg-Welander disease: a case report and review.

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.

Effects of oral beraprost sodium, a prostaglandin I2 analogue, on endothelium dependent vasodilatation in the forearm of patients with coronary artery 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.

Short duration of reactive hyperemia in the forearm of subjects with multiple cardiovascular risk factors.

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.

Vascular involvement in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

A 26-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) was admitted to our hospital for further cardiovascular examination. A muscle biopsy demonstrated strongly succinate dehydrogenase-reactive blood vessels. Pulse wave contour analysis revealed that both capacitive and oscillatory compliance were markedly reduced in this patient compared with 45 normal age-matched control subjects. Hepatocyte growth factor was remarkably elevated in this patient over that of 10 normal control subjects. These findings suggest that a MELAS patient has not only pathologic but also functional vascular involvement. If so, patients with MELAS need systemic vascular assessment.

Increased nitric oxide in proportion to the severity of heart failure in patients with dilated cardiomyopathy: close correlation of tumor necrosis factor-alpha with systemic and local production of nitric oxide.

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.