Clinical utility of the BIWACO score for patients with atrial fibrillation after percutaneous coronary intervention.

No predictive clinical risk scores for net adverse clinical events (NACE) have been developed for patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). We evaluated NACE to develop clinically applicable risk-stratification scores in the Bleeding and thrombotic risk evaluation In patients With Atrial fibrillation under COronary intervention (BIWACO) study, a multicenter survey which has enrolled a total of 7837 patients. We also investigated the current status and time trends for the use of antithrombotic drugs. A total of 188 AF patients who had received PCI were examined. At discharge, 65% of patients were prescribed a triple therapy (TT), 6% were prescribed a dual therapy, the remaining 29% of patients received dual-antiplatelet therapy. After 4 years, the fraction of patients continuing TT decreased by 15%, whereas oral anticoagulant alone was only 2% of patients. NACE developed in 20% of patients, resulting in death in 5% of the patients, and the remaining 13% experienced bleeding events. We developed risk scores for NACE comprising the five strongest predictive items, which we designated BIWACO scores. The area under the curve was 0.774 for NACE. Our study explored the differences in treatment practices and guideline recommendations for antithrombotic therapy. We concluded that our BIWACO score is useful for predicting clinical outcomes in AF-patients after PCI.

Transcardiac increase in tumor necrosis factor-alpha and left ventricular end-diastolic volume in patients with dilated cardiomyopathy.

BACKGROUND: It remains unclear whether tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are secreted from the failing heart and whether there is a relationship between the transcardiac gradients of these cytokines and left ventricular (LV) remodeling. AIMS: This study evaluated the relationship between transcardiac gradients of cytokines and LV volume and function in congestive heart failure patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We measured the plasma levels of TNF-alpha and IL-6 in the aortic root (Ao) and the coronary sinus (CS) in 60 patients with DCM. There was no difference in plasma IL-6 between the Ao and the CS. However, the plasma TNF-alpha level was significantly higher in the CS than that in the Ao. There was a significant correlation between the transcardiac gradient of plasma TNF-alpha and the LV end-diastolic volume index (LVEDVI) and LV ejection fraction. According to stepwise multivariate analyses, the transcardiac increase of TNF-alpha showed an independent and significantly positive relationship with a large LVEDVI. CONCLUSIONS: These results indicate that the elevated plasma TNF-alpha is partly derived from the failing heart in patients with DCM and that TNF-alpha plays a potential role in structural LV remodeling in patients with DCM.

Endogenous bradykinin suppresses myocardial fibrosis through the cardiac-generated endothelin system under chronic angiotensin-converting enzyme inhibition in heart failure.

In congestive heart failure, angiotensin-converting enzyme inhibitors (ACEIs) may prevent cardiac fibrosis via interaction with both angiotensin II and endothelin-1, which enhance myocardial collagen synthesis. However, whether endogenous bradykinin with an ACEI modifies the cardiac collagen architecture, affecting the endothelin system, has not yet been fully elucidated. We evaluated the changes in circulating hormonal factors, myocardial fibrosis and cardiac gene expression closely linked with heart failure, using an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg/day, n = 6), with an ACEI, enalapril (1 mg/kg/day), in dogs with tachycardia-induced congestive heart failure (270 p.p.m., 22 days) and compared the effects with enalapril alone (n = 6). Although there were no differences observed in blood pressure, plasma renin activity, aldosterone and endothelin-1 levels, combined FR173657 significantly increased the cardiac expression of preproendothelin- 1 mRNA (P < 0.05) and collagen type I and type III mRNA (P < 0.05), and cardiac collagen deposits (P < 0.05), and decreased eNOS gene expression (P < 0.05) in the left ventricle compared with the ACEI-treated group. Furthermore, there was a significant negative correlation between the expression of preproendothelin- 1 and eNOS mRNA levels (r = -0.708, P < 0.001). In conclusion, bradykinin may prevent cardiac fibrosis in part via suppression of the local endothelin system in the failing heart through the enhancement of nitric oxide production under chronic angiotensin-converting enzyme inhibition.

The factors contributing to whether or not hypertensive patients bring their home blood pressure record to the outpatient clinic.

OBJECTIVE: We investigated the factors contributing to whether or not hypertensive patients brought their home blood pressure records to the outpatient clinic. METHOD: We studied 325 hypertensive patients [169 men (66.3+/-11.4 years old) and 156 women (68.1+/-11.2 years old)] who had received medical treatment for hypertension in our outpatient clinic from June to August 2006. RESULTS: Of the 325 patients studied, 206 (63.4%, 101 men, 105 women) brought their home blood pressure records to our outpatient clinic. Logistic analysis showed age [odds ratio (OR) =0.95; 95% confidence interval (CI): 0.93-0.98; p=0.0002], systolic blood pressure in outpatient clinic (OR=1.02; 95% CI: 1.00-1.04; p=0.0488) and the number of medicines prescribed (OR=1.94; 95% CI: 1.37-2.75; p=0.0002) were independent factors contributing to whether or not hypertensive patients bring along their home blood pressure records to the outpatient clinic. CONCLUSION: The contributing factors determining whether the patients bring their home blood pressure records to the outpatient clinic were: younger age, higher systolic blood pressure in the outpatient clinic, and a higher number of antihypertensive drugs. In conclusion, our results suggest that physicians should further motivate older patients, with well-controlled blood pressure in the outpatient clinic, to bring their home blood pressure records to the outpatient clinic.

Perforated mitral valve aneurysm associated with Libman-Sacks endocarditis.

The perforation of a mitral valve aneurysm is a rare disease which induces acute mitral regurgitation and is usually induced by infective endocarditis; however, in this case report, acute heart failure was caused by a perforated mitral valve aneurysm that was speculated to be due to Libman-Sacks endocarditis with systemic lupus erythematosis and secondary anti-phospholipid syndrome. Mitral valve plasty was performed and thereafter heart failure improved.

Contribution of vascular NAD(P)H oxidase to endothelial dysfunction in heart failure and the therapeutic effects of HMG-CoA reductase inhibitor.

BACKGROUND: The vascular NAD(P)H oxidase-derived superoxide anion (O(2)-) plays a crucial role in the pathological progression of hypertension and atherosclerosis, and HMG-CoA reductase inhibitors (statins) have vascular antioxidant effects. However, it is unclear whether the vascular NAD(P)H oxidase is involved in the endothelial dysfunction of congestive heart failure (CHF) and whether HMG-CoA reductase inhibitors (statins) exert their vasoprotective effects in CHF. The present study examined both the involvement of vascular NAD(P)H oxidase in endothelial dysfunction in dogs with tachycardia-induced CHF and the therapeutic effect of a statin (pitavastatin). METHODS AND RESULTS: Femoral blood flow (FBF) responses to acetylcholine was significantly impaired in the CHF group, but were improved by pitavastatin. Vascular O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression were significantly elevated in CHF compared with the normal group. The elevated O(2)-production in the CHF group was suppressed by the NAD(P)H oxidase inhibitor, apocynin, to the normal level. In contrast, neither the gene expression nor the activity of endothelial nitric oxide synthase (eNOS) differed significantly between the normal and CHF groups. However, pitavastatin significantly suppressed O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression and increased eNOS expression and activity compared with the CHF group. CONCLUSIONS: The activated vascular NAD(P)H oxidase contributes to endothelial dysfunction in CHF, which was partly improved by pitavastatin via its inhibition of NAD(P)H oxidase.

Endothelin stimulates an endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine, in experimental heart failure.

Congestive heart failure (CHF) is characterized by increased peripheral vascular resistance. Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor, is present at increased concentrations in the plasma and contributes to the regulation of vascular tone in CHF. An endothelium-derived relaxing factor, nitric oxide (NO), also regulates vascular tone, but endothelium-dependent NO-mediated vasodilation is blunted in CHF. An endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), which inhibits NO production and endothelium-dependent relaxation, is present at increased levels in the plasma and plays a role in impaired endothelial function in CHF. However, at present, the relationship between ET-1 and impaired vascular relaxation in CHF is not well known. We hypothesized that ET-1 inhibits NO-mediated vasodilation via increased ADMA production in CHF, and that an endothelin receptor antagonist can prevent this increase in plasma ADMA levels. In the present study, we first examined whether circulating ADMA levels were increased in a dog model of CHF induced by 3 weeks of rapid ventricular pacing (n=5; 270 beats/min) compared with normal dogs (n=5). After 3 weeks of pacing, cardiac output had decreased significantly (1.56+/-0.16 compared with 2.93+/-0.25 litres/min; P<0.01) and systemic vascular resistance had increased (4653+/-374 compared with 3227+/-396 dyn.s.cm(-5); P<0.01) in dogs with CHF compared with normal dogs. Plasma levels of both ET-1 (4.95+/-0.83 compared with 2.12+/-0.39 pg/ml; P<0.05) and ADMA (3.27+/-0.49 compared with 1.91+/-0.25 nmol/ml; P<0.05) were significantly increased in CHF dogs. A significant positive correlation was observed between plasma ET-1 and ADMA levels (r=0.72, P<0.05). Secondly, we chronically administered an ET(A) receptor antagonist, TA-0201 (0.3 mg/kg; n=5), to paced CHF dogs. Drug administration started on day 8 of pacing and continued throughout the experiment. TA-0201 significantly increased cardiac output (2.58+/-0.24 litres/min; P<0.01) and suppressed the increases in plasma ADMA levels and systemic vascular resistance (2.36+/-0.30 nmol/ml and 2423+/-188 dyn.s.cm(-5) respectively; P<0.05 for each) compared with CHF dogs without TA-0201 treatment. In conclusion, ET-1 contributes to the regulation of vascular tone due, in part, to increased levels of an endogenous NO synthase inhibitor in CHF, and an ET(A) receptor antagonist can prevent the inhibition of NO production and the increased peripheral vascular resistance observed in CHF.

Transcardiac gradient of aldosterone before and after spironolactone in patients with congestive heart failure.

To evaluate the transcardiac extraction of aldosterone before and after spironolactone administration to patients with congestive heart failure, we measured the plasma aldosterone in the aortic root and the coronary sinus in eight congestive heart failure patients with dilated cardiomyopathy. The plasma aldosterone level was significantly lower in the coronary sinus than in the aortic root before spironolactone administration (87.5 +/- 16 versus 62.2 +/- 11 pg/ml, p = 0.01). After chronic treatment with spironolactone, there was no significant difference in the aldosterone level between the aortic root and the coronary sinus (151 +/- 49 versus 148 +/- 48 pg/ml), and the transcardiac gradient of aldosterone (aortic root to coronary sinus) was significantly decreased (25.3 +/- 7.3 versus 3.1 +/- 4.5 pg/ml, p = 0.046). These results indicate that plasma aldosterone is extracted through the heart in congestive heart failure patients with dilated cardiomyopathy, and that spironolactone inhibits the transcardiac extraction of aldosterone in congestive heart failure patients. This suggests that spironolactone blocks the effects of aldosterone on the failing heart in congestive heart failure patients with dilated cardiomyopathy.

Chronic administration of phosphodiesterase type 5 inhibitor suppresses renal production of endothelin-1 in dogs with congestive heart failure.

Endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) play important roles in the regulation of body fluid balance in congestive heart failure (CHF). Renal production of ET-1 increases in CHF and it is a significant independent predictor of sodium excretion. ANP inhibits the ET system through cGMP, a second messenger of ANP. However, in severe CHF, plasma cGMP levels reached a plateau despite the activation of ANP secretion. Thus, ANP does not seem to sufficiently oppose exaggerated ET-1 actions in severe CHF, partially due to the accelerated degradation of cGMP, through phosphodiesterase type 5 (PDE5). We examined the chronic effects of a PDE5 inhibitor, T-1032 (1 mg/kg per day, n=5), on renal function and renal production of ET-1 in dogs with CHF induced by rapid ventricular pacing (270 beats/min). Vehicle dogs were given a placebo (n=5) and normal dogs (n=5) served as normal controls without pacing. In this experimentally produced CHF, plasma levels of ET-1, ANP and cGMP were elevated and renal production of cGMP was increased compared with the normal group, associated with increases in renal expression of preproET-1 mRNA and the number of ET-1-positive cells in glomeruli. In the T-1032 group, systemic and renal production of cGMP were further increased compared with the vehicle group despite no significant difference in plasma ANP levels between the two groups. Subsequently, the agent significantly improved urine flow rate, sodium excretion rate and glomerular filtration rate (GFR) associated with reductions in renal expression of preproET-1 mRNA and the number of ET-1-positive cells compared with the vehicle group. Moreover, there was a significant negative correlation between the number of ET-1-positive cells and GFR (r=-0.802 and P<0.001 respectively). Our results indicate that chronic PDE5 inhibition ameliorates the antagonistic relationship between renal ANP and ET-1 through the cGMP pathway, subsequently preventing renal dysfunction during the progression of CHF.