Successful revascularization to right coronary artery by percutaneous coronary intervention after endovascular therapy for leriche syndrome.

A 69-year-old man with effort angina was admitted to our institution. Echocardiography showed poor left ventricular systolic function with akinesis of the anterior wall and severe hypokinesis of the inferior wall. We performed coronary angiography, which revealed two diseased vessels including chronic total occlusion in the left anterior descending artery and severe stenosis in the right coronary artery (RCA). In addition, aortography revealed aortoiliac occlusive disease known as Leriche syndrome. As the patient's symptom was stable, we first planned to perform endovascular therapy (EVT) for Leriche syndrome to make a route for intra-aortic balloon pumping. We prepared a bi-directional approach from bi-femoral arteries and a left brachial artery. The guidewire was passed through the occlusive area using the retrograde approach. The self-expanding stents were deployed by a kissing technique. At one week after EVT, a 6Fr sheath was inserted from the right radial artery and an intra-aortic balloon pump was successfully inserted through the right femoral artery for percutaneous coronary intervention (PCI) to the RCA. Two drug-eluting stents were successfully deployed to RCA after using an atherectomy device (rotablator). We reported the case as a successfully performed PCI to the RCA after EVT for Leriche syndrome.

High serum level of pentosidine, an advanced glycation end product (AGE), is a risk factor of patients with heart failure.

BACKGROUND: Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling, causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure. METHODS AND RESULTS: Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with end points of cardiac death or rehospitalization. Serum concentration of pentosidine was significantly higher in New York Heart Association (NYHA) Class III/IV patients than in NYHA class I/II patients (P < .0001). Serum pentosidine was also higher in patients with cardiac events than in event-free patients (P < .001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume, and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = .002). The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold). CONCLUSIONS: Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure. Patients were divided into 4 groups based on the serum pentosidine levels.

Cardiac sympathetic denervation and ongoing myocardial damage for prognosis in early stages of heart failure.

BACKGROUND: Iodine-123-metaiodobenzylguanidine ((123)I-MIBG) can assess cardiac sympathetic nervous function. Heart-type fatty acid binding protein (H-FABP) has been used as a marker of ongoing myocardial damage. The prognostic value of combination (123)I-MIBG imaging and H-FABP in heart failure is unknown. METHODS AND RESULTS: We prospectively enrolled consecutive 104 patients with heart failure in whom we quantified (123)I-MIBG scintigraphy, simultaneously measured serum H-FABP and plasma brain natriuretic peptide (BNP) levels, and analyzed clinical outcomes. The multivariate Cox regression analysis revealed that augmented H-FABP level and decreased heart to mediastinum ratio of (123)I-MIBG at 240 minutes (delayed H/M ratio), but not BNP, were the independent predictors for cardiac events. The cutoff values for H-FABP and delayed H/M ratio were determined from the receiver operating characteristic curves as 5.2 ng/mL for H-FABP and 1.73 for delayed H/M ratio. The cardiac event rate was markedly higher in patients with both H-FABP and delayed H/M ratio of (123)I-MIBG was abnormal. Conversely, no cardiac events occurred in patients with both H-FABP level and delayed H/M ratio were normal. CONCLUSION: H-FABP adds independent prognostic information to delayed H/M ratio of (123)I-MIBG imaging, and the combination of these approaches may improve the accuracy of prognostic determination in heart failure.

Hyperuricemia associated with high cardiac event rates in the elderly with chronic heart failure.

OBJECTIVES: Congestive heart failure (CHF) is the major cause of death and hospitalization in the elderly population. Simple markers that can be measured anywhere at low cost are necessary to identify patients at high risk. Recent studies have reported that hyperuricemia is a prognostic marker for CHF. However, it is not yet known whether serum levels of uric acid may provide prognostic information in the elderly population. Therefore, this study tried to identify the clinical characteristics of elderly CHF patients (+/-70 years) in our institution and to evaluate whether uric acid levels can effectively estimate the prognosis for elderly CHF patients. METHODS AND RESULTS: Uric acid levels were analyzed in 247 CHF patients, and patients were followed up for 451 +/- 235 days (mean +/- SD). Elderly CHF patients aged > or =70 years (123 patients) had higher rate of hypertension, lower current smoking rate and higher uric acid levels than those aged < 70 years (124 patients). There were 72 cardiac events including cardiac deaths and readmissions for worsening CHF. Multivariate analysis with the Cox proportional hazard model showed that uric acid was the only independent predictor of cardiac events (hazard ratio 1.544, 95% confidence interval 1.215-2.582, p < 0.0001) in the elderly with CHF. The highest quartile of uric acid level was associated with the highest risk of cardiac events (a 4.45-fold compared to the lowest quartile). Kaplan-Meier analysis revealed that uric acid levels effectively risk stratified elderly CHF patients for cardiac events. CONCLUSIONS: These findings suggest that measurement of uric acid levels in elderly CHF patients may add valuable prognostic information to predict cardiac events.

Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure.

UNLABELLED: Iodine-123-metaiodobenzylguanidine (123I-MIBG) has been used to assess the integrity and function of the cardiac sympathetic nervous system in patients with heart failure. Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured, and H-FABP has been recently used as a novel marker for the diagnosis of ongoing myocardial damage. OBJECTIVE: The aim of the present study was to compare cardiac sympathetic nervous activity assessed by 123I-MIBG imaging with serum levels of H-FABP in patients with heart failure. METHODS: Fifty patients with chronic heart failure were studied. 123I-MIBG imaging was carried out at 30 min (early) and 240 min (delayed) after the tracer injection. We measured serum levels of H-FABP using a sandwich enzyme linked immunosorbent assay. RESULTS: Heart to mediastinum (H/M) ratios of 123I-MIBG decreased and washout rate increased with higher New York Heart Association (NYHA) functional class. H-FABP, norepinephrine and brain natriuretic peptide (BNP) levels increased as the severity of NYHA class advanced. Delayed H/M ratio was significantly correlated with H-FABP (r = -0.296, p = 0.029) and BNP (r = -0.335, p = 0.0213). Myocardial washout rate of 123I-MIBG was also correlated with H-FABP (r = 0.469, p < 0.001), norepinephrine (r = 0.433, p = 0.005), and BNP (r = 0.465, p = 0.001). CONCLUSIONS: These data suggest that cardiac sympathetic nervous activation was associated with ongoing cardiomyocyte damage characterized by an elevated serum level of H-FABP in patients with heart failure. 123I-MIBG imaging is an appropriate approach to evaluate non-invasively not only cardiac sympathetic nervous activity, but also latent ongoing myocardial damage in the failing heart.

Cystatin C, a novel measure of renal function, is an independent predictor of cardiac events in patients with heart failure.

BACKGROUND: Cystatin C, a novel endogenous marker of glomerular filtration rate, has been reported as more sensitive to detect renal insufficiency than creatinine. The purpose of the present study was to examine the clinical significance of serum cystatin C level in patients with mild to moderate heart failure. METHODS AND RESULTS: Serum levels of cystatin C were measured by an enzyme immunoassay in 140 patients with heart failure and 64 control subjects without heart failure. Patients were prospectively followed during a median follow-up period of 480 days, with the end points of cardiac death and progressive heart failure requiring rehospitalization. Serum levels of cystatin C were higher in patients with heart failure than in control subjects (1.14 +/- 0.60 ng/mL versus 0.72 +/- 0.14 ng/mL, P < .001). The Cox multivariate proportional hazard analysis revealed that a change of 1 standard deviation (SD) in cystatin C level was the one of independent predictor for cardiac events (hazard ratio, 1.94; 95% confidence interval, 1.29-6.64; P < .01). The cardiac event rate was markedly higher in patients with elevated cystatin C level (> or =1.0 ng/mL) than in those with normal level (< or =1.0 ng/mL) (38.7% versus 10.3%, P < 0.001). Furthermore in patients with normal creatinine levels (n = 91), the cardiac event rate was similarly higher in patients with elevated cystatin C than in those with normal levels (29.2% versus 7.5%, P = .002). CONCLUSION: Elevation of serum cystatin C, a new marker of renal function, provides promising prognostic information for clinical outcome in patients with mild to moderate heart failure.

Serum heart-type fatty acid binding protein predicts cardiac events in elderly patients with chronic heart failure.

BACKGROUND AND OBJECTIVES: Heart-type fatty acid binding protein (H-FABP) is released into the circulation from the damaged myocardium of patients with severe chronic heart failure. Chronic heart failure is the most frequent cause of death and disability in the elderly. However, there are no data for the prognostic value of H-FABP in the elderly population. This study investigated whether H-FABP can effectively predict the prognosis in elderly patients (> or = 70 years) with chronic heart failure. METHODS: Serum H-FABP levels were measured in 90 chronic heart failure patients > or =70 years old (mean age 77 +/- 4 years, range 70-92 years), and patients were followed-up for 421 +/- 326 days. RESULTS: There were 35 cardiac events (38.9%) including cardiac deaths and readmissions for worsening chronic heart failure. Multivariate analysis with the Cox proportional hazard model showed that H-FABP was the only independent predictor of cardiac events (chi2 = 6.640, p = 0.0100). Kaplan-Meier analysis revealed that H-FABP effectively risk stratified elderly patients with chronic heart failure for cardiac events. CONCLUSIONS: These findings suggest that H-FABP is a reliable marker for prognosis in elderly patients with chronic heart failure.

Combination of heart-type fatty acid binding protein and brain natriuretic peptide can reliably risk stratify patients hospitalized for chronic heart failure.

BACKGROUND: The aim of the present study was to prospectively study whether a combination of markers for myocardial cell injury and left ventricular overload at admission can reliably risk stratify patients hospitalized for chronic heart failure (CHF). METHODS AND RESULTS: Serum concentrations of heart-type fatty acid binding protein (H-FABP) and plasma concentrations of brain natriuretic peptide (BNP) were measured at admission in 186 consecutive patients hospitalized for CHF. During a mean follow-up period of 534+/-350 days, there were 44 cardiac events, including 16 cardiac deaths and 28 readmissions for worsening heart failure. Normal upper limits for H-FABP and BNP values were determined from the receiver operating characteristic curves (4.3 ng/ml for H-FABP and 200 pg/ml for BNP). A stepwise Cox regression analysis demonstrated that high H-FABP (hazard ratio 5.416, p = 0.0002) and high BNP (hazard ratio 2.411, p = 0.0463) were independent predictors of cardiac events. High concentrations of both H-FABP and BNP at admission were associated with the highest incidence of cardiac mortality and cardiac events. Kaplan-Meier analysis also showed that the combination of H-FABP and BNP concentrations could reliably stratify patients for cardiac events. CONCLUSION: Combined measurement of H-FABP and BNP concentrations at admission may be a highly reliable evaluation for risk stratifying patients hospitalized for CHF.

Adenovirus-mediated overexpression of diacylglycerol kinase-zeta inhibits endothelin-1-induced cardiomyocyte hypertrophy.

BACKGROUND: Diacylglycerol (DAG) is a lipid second messenger that transiently accumulates in cells stimulated by endothelin-1 (ET-1) and other Galphaq protein-coupled receptor agonists. Diacylglycerol kinase (DGK) is thought to be an enzyme that controls the cellular levels of DAG by converting it to phosphatidic acid; however, the functional role of DGK has not been examined in cardiomyocytes. Because DGK inactivates DAG, a strong activator of protein kinase C (PKC), we hypothesized that DGK inhibited ET-1-induced activation of a DAG-PKC signaling cascade and subsequent cardiomyocyte hypertrophy. METHODS AND RESULTS: Real-time reverse transcription-polymerase chain reaction demonstrated a significant increase of DGK-zeta mRNA by ET-1 in cardiomyocytes. To determine the functional role of DGK-zeta, we overexpressed DGK-zeta in cardiomyocytes using a recombinant adenovirus encoding rat DGK-zeta (Ad-DGKzeta). ET-1-induced translocation of PKC-epsilon was blocked by Ad-DGKzeta (P<0.01). Ad-DGKzeta also inhibited ET-1-induced activation of extracellular signal-regulated kinase (P<0.01). Luciferase reporter assay revealed that ET-1-mediated increase of activator protein-1 (AP1) DNA-binding activity was significantly inhibited by DGK-zeta (P<0.01). In cardiomyocytes transfected with DGK-zeta, ET-1 failed to cause gene induction of atrial natriuretic factor, increases in [3H]-leucine uptake, and increases in cardiomyocyte surface area. CONCLUSIONS: We demonstrated for the first time that DGK-zeta blocked ET-1-induced activation of the PKC-epsilon-ERK-AP1 signaling pathway, atrial natriuretic factor gene induction, and resultant cardiomyocyte hypertrophy. DGK-zeta might act as a negative regulator of hypertrophic program in response to ET-1, possibly by controlling cellular DAG levels.

Presence of intermittent J waves in multiple leads in relation to episode of atrial and ventricular fibrillation.

Brugada syndrome is characterized by J wave and ST-segment elevation of right precordial leads and causes idiopathic ventricular fibrillation. We experienced a patient of Brugada syndrome with prominent J wave and ST-segment elevation not only in V(1) to V(3) but also in many leads. He suffered spontaneous ventricular fibrillation and resuscitated by direct current. He has no structural heart disease.

Antimicrobial resistance of Neisseria gonorrhoeae in Japan, 1993-2002: continuous increasing of ciprofloxacin-resistant isolates.

Susceptibility testing was conducted on 1357 isolates of Neisseria gonorrhoeae isolated from 1993 through 2002 in Japan to assess the antimicrobial resistance. Selected isolates were characterised by auxotype and analysis was done for mutations within the quinolone resistance-determining region (QRDR) in the gyrA and parC genes, which confer fluoroquinolone resistance to the organism. Isolates with ciprofloxacin resistance increased significantly from 6.6% (1993-1994) to 73.5% (2002). The proportion of plasmid-mediated penicillin-resistant isolates (PPNG) decreased significantly from 7.9% (1993-1994) to 0.9% (2002). The percentage of chromosomal-mediated resistance to penicillin decreased from 27.4% in 2000 to 12.0% in 2001 but increased to 28.9% in 2002. The proportion of isolates with any type of resistance to tetracycline decreased from 24.7% in 2000 to 13.9% in 2001 and then increased to 22.3% in 2002. The proportion of prototrophic isolates significantly decreased from 84.4% in 1992-1993 to 7.7% in 2001, while that of the proline-requiring isolates significantly increased from 4.4% in 1992-1993 and 80.8% in 1998. The proline-requiring isolates were less susceptible to ciprofloxacin than the prototrophic or arginine-requiring isolates. Of 87 isolates resistant to ciprofloxacin, 2 (2.3%) contained five amino acid substitutions within the GyrA and ParC proteins, 76 (87.4%) contained three or four amino acid substitutions and 9 (10.3%) contained one or two amino acid substitutions.

Long-term treatment with angiotensin II type 1 receptor antagonist, CV-11974, restores beta-catenin mRNA expression in volume-overloaded rabbit hearts.

This study aimed to search genes altered in expression after long-term treatment with the angiotensin II type 1 receptor (AT1) antagonist, CV-11974, in volume-overloaded hearts. Arteriovenous shunt was made between the common carotid artery and jugular vein in Japanese White rabbits. Shunt-operated rabbits were randomly treated with CV-11974 or vehicle for 6 weeks, starting 6 weeks after surgery. As controls, sham-operated rabbits were given vehicle. Total RNA was prepared from each left ventricular myocardium. Using differential display, we screened one cDNA encoding human beta-catenin, in which the expression was upregulated after CV-11974 administration in shunt rabbit hearts. Beta-catenin is a molecule that exists in the intercalated disks and also works in cytoplasm as a major component of Wnt signaling. We then examined mRNA expressions of beta-catenin and connexin43 by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The mRNA expressions of beta-catenin and connexin43 were markedly depressed in shunt-operated animals given vehicle compared with sham-operated animals (P < 0.01). These results suggest that downregulation of beta-catenin and connexin43 expression might be involved in the process of ventricular remodeling by volume overload. The RT-PCR also demonstrated that beta-catenin mRNA expression was significantly higher in shunt rabbits treated with CV-11974 than in those given vehicle (P < 0.05). These data suggest that volume overload may downregulate beta-catenin expression by an AT1 receptor-mediated pathway.