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An abstract of the study "A Low Dose of Carperitide, an Atrial Natriuretic Peptide, Improves Left Ventricular Diastolic Dysfunction Validated Using Tissue Doppler Imaging in Patients With Idiopathic Dilated Cardiomyopathy," by M. Kato et al. is presented.

Abstract: Mammalian target of rapamycin (mTOR) inhibitors display antiproliferative effects with less nephrotoxicity than calcineurin inhibitors. However, clinical use of mTOR inhibitors can be associated with a series of adverse events. We experienced cases of aphthous stomatitis associated with everolimus (EVL) in four Japanese heart transplant recipients treated at the target trough EVL blood level after a switch from mycophenolate mofetil between April and December 2007. All four patients developed aphthous stomatitis; three required reduction of the exposure and one, EVL discontinuation due to stomatitis as well as other side effects. All patients recovered from stomatitis after reduction or withdrawal of EVL. Thus, we considered that EVL-related stomatitis might occur commonly among the Japanese population. The proper dosage, effects, and frequency of the side effects of mTOR inhibitors may vary by ethnic population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate regional and global left ventricular (LV) function and LV wall thickness (LVVVT) in patients with hypertrophic cardiomyopathy (HCM). Design and setting: Observational study at the National Cardiovascular Centre and Nagoya University Hospital in Japan. Participants: Thirty-six patients with HCM and 16 patients with hypertensive LV hypertrophy (LVH). Main outcome measures: Conventional echocardiography and strain rate (SR) imaging derived from tissue Doppler imaging were performed. Systolic strain (ϵ[subsys]) peak systolic SR (SR[subsys), peak early diastolic SR (SR[subdia]) and LW\/T were obtained from eight LV segments. LV pressure was simultaneously recorded with a high-fidelity microma nometer. Results: The regional ϵ[subsys] and SR[subsys] were correlated with LV\i\/T in patients with HCM (r = 0.50, p<0.001 and r = 0.63, p<0.001, respectively) but not in patients with hypertensive LVH. The standard deviations of LVV\/T, ϵ[subsys] and SR[subsys] obtained from the eight LV segments of each subject were greater for patients with HCM than for patients with hypertensive LVH. The standard deviation of LVWT was correlated with those of ϵ[subsys] and SR[subsys] (r = 0.55, p<0.001 and r = 0.56, p<0.001, respectively). The standard deviations of LVVVT, ϵ[subsys] and SR[subsys] were correlated with tau )r = 0.35, p<0.05; r = 0.47, p<0.00l; and r = 0.39, p<0.005, respectively). Conclusions: Heterogeneity of regional LV systolic function detected by SR imaging is in part attributable to heterogeneity of LVH and may be linked to impaired global LV relaxation in HCM. [ABSTRACT FROM AUTHOR]

Background: Recent reports have demonstrated that use of a left ventricular assist system (LVAS) can initiate recovery of cardiac function, and subsequent weaning from the LVAS has attracted considerable interest. In this study we investigated reliable predictors of LVAS weaning. Methods: Eighty-two patients underwent LVAS implantation between April 1994 and July 2006 at our institution. Cardiac function was restored in 8 patients, who were weaned from LVAS after a mean of 5 months (Group R). Thirty-three patients remained on LVAS support for >1 year (Group N) because natural heart function did not show adequate improvement. We retrospectively evaluated the differences between these two groups. Group R was younger, and had a shorter duration of heart failure than Group N (23.4 vs 36.7 years and 13.3 vs 56.1 months, p < 0.01, respectively). Pathologic findings showed that the interstitial fibrosis score was lower in Group R (p < 0.01). Three months after LVAS insertion, B-type natriuretic peptide (BNP) and fractional shortening (FS) were more favorable (66.6 ± 46 vs 264.5 ± 170 pg/ml, p < 0.01, and 23 ± 17.1 vs 12 ± 9.1%, p < 0.05, respectively) in Group R. Furthermore, Group R received a higher dose of β-blocker (15.4 ± 8.4 vs 5.8 ± 3.9 mg, p < 0.05). Conclusions: Younger age, shorter history of heart failure, and less interstitial fibrosis were effective predictors of weaning from LVAS. Restoration of natural heart function was more rapid and more persistent in candidates for LVAS explantation, and presence of β-blocker played a prominent role in improving cardiac function after LVAS implantation. [Copyright &y& Elsevier]

Background: Volatile agents can mimic ischaemic preconditioning leading to a decrease in myocardial infarct size. The present study investigated if a 15 min sevoflurane administration before cardiopulmonary bypass (CPB) has a cardioprotective effect in patients undergoing coronary surgery.Methods: Seventy-two patients were randomized in two centres. The intervention group (S) received 1 MAC sevoflurane administrated via the ventilator for 15 min followed by a 15 min washout before CPB, the control group did not. The primary outcome was the postoperative troponin Ic peak. A biopsy of the atrium was taken during canulation for enzyme dosages. Results are expressed as mean (SD).Results: Neither troponin Ic nor tissular enzyme measurement exhibited any difference between the groups: peak of troponin Ic was 4.4 (5.6) in S group vs 5.2 (6.6) ng ml(-1) in control group (ns). Intratissular ecto-5'-nucleotidase activity was 7.1 (4.3) vs 8.5 (11.9), protein kinase C activity was 27.1 (15.7) vs 29.2 (28.7), tyrosine kinase activity was 101 (54.1) vs 98.5 (63.3), and P38 MAPKinase activity was 131.1 (76.1) vs 127.1 (86.8) nmol mg protein(-1) min(-1) in S group and control group, respectively (ns). However there were fewer patients with low postoperative cardiac index in S group (11% in S vs 35% in control group, P < 0.05) when considering the per protocol population. In S group, 25% of patients required an inotropic support during the postoperative period, vs 36% of patients in control group (ns).Conclusions: This study did not show a significant preconditioning signal after 15 min of sevoflurane administration. The 15 min duration might be too short or the concentration of sevoflurane too low to induce cardioprotection detected by troponin I levels. [ABSTRACT FROM AUTHOR]

As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks −1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms −1789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects. [ABSTRACT FROM AUTHOR]

Objective: To determine whether concentrations of heart-type fatty acid binding protein (H-FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM). Patients: 92 consecutive patients with DCM were enrolled and followed up for four years. Main outcome measures: Serum concentrations of H-FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate. Results: 23 patients died of cardiac causes, received a left ventricular assist device or underwent heart transplantation during the four-year follow up. Univariate analyses showed that New York Heart Association functional class, heart rate, ejection fraction, serum H-FABP and plasma BNP were significant variables. According to multivariate analysis, serum H-FABP and plasma BNP concentrations were independent predictors of critical cardiac events. Cardiac troponin T before hospital discharge was not a predictor. The area under the receiver operating characteristic curve for death from critical cardiac events was similar between H-FABP and BNP. Patients with an H-FABP concentration at or above the median (⩾ 5.4 ng/ml) had a significantly lower survival rate than those below the median, according to analysis by log rank test (p < 0.0001). When combined with BNP concentration at or above the median (⩾ 138 pg/ml), H-FABP below the median predicted the worst prognosis among the combinations. Conclusions: The concentration of serum H-FABP before discharge from hospital may be an independent predictor for critical cardiac events in DCM. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms of UDP-glucuronosyltransferases (UGTs) are involved in individual and ethnic differences in drug metabolism. To reveal co-occurrence of the UGT1A polymorphisms, we first analyzed haplotype structures of the entire UGT1A gene complex using the polymorphisms from 196 Japanese subjects. Based on strong linkage disequilibrium between UGT1A8 and 1A10, among 1A9, 1A7, and 1A6, and between 1A3 and 1A1, the complex was divided into five blocks, Block 8/10, Block 9/6, Block 4, Block 3/1, and Block C, and the haplotypes for each block were subsequently determined/inferred. Second, using pyrosequencing or direct sequencing, additional 105 subjects were genotyped for 41 functionally tagged polymorphisms. The data from 301 subjects confirmed the robustness of block partitioning, but several linkages among the haplotypes with functional changes were found across the blocks. Thus, important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.The Pharmacogenomics Journal (2006) 6, 63–75. doi:10.1038/sj.tpj.6500335; published online 29 November 2005 [ABSTRACT FROM AUTHOR]

Genetic variations in cardiac ion channels have been implicated not only as the causes of inherited arrhythmic syndromes, but also as genetic risk factors for some acquired arrhythmias. To elucidate the potential roles of genetic polymorphisms of the α subunit of the voltage-gated sodium channel type V ( SCN5A) in cardiac rhythm disturbance, the entire SCN5A coding exons and their flanking introns were sequenced in 166 Japanese arrhythmic patients and 232 healthy controls. We detected 69 genetic variations, including 54 novel ones. Out of the 12 novel nonsynonymous single nucleotide polymorphisms (SNPs), p.Leu1988Arg was found at a frequency of 0.015. The other 11 SNPs were rare (0.001), with 6 found in arrhythmic patients and 5 in healthy controls. The frequency of a novel intronic SNP, c.703+130G>A, was significantly higher in the patients than in the controls, suggesting this SNP is associated with an unknown risk factor for arrhythmia. Following linkage disequilibrium analysis, the haplotype structure of SCN5A was inferred using high-frequency SNPs. The frequency of the haplotype harbouring both p.Leu1988Arg and the common SNP p.His558Arg (haplotype GG) was significantly lower in the patients than in the controls. This finding suggests that this haplotype (GG) might have been positively selected in the controls because of its protective effect against arrhythmias. This study provides fundamental information necessary to elucidate the effect of genetic variations in SCN5A on channel function and cardiac rhythm in Japanese, and probably in the Asian population. [ABSTRACT FROM AUTHOR]

We examined the effects of cilostazol on impaired coronary arterial responses in patients with vasospastic angina (VSA). Thirty patients who were diagnosed with VSA based on an acetylcholine provocation test and 10 subjects with normal coronary arteries were enrolled. The patients were divided into the following 3 groups: no antiplatelet agent treatment group, aspirin treatment, or cilostazol treatment groups. Coronary flow reserve (CFR), coronary flow volume at maximum hyperemia, and epicardial coronary artery diameter after administration of N(G)-monomethyl-L-arginine (L-NMMA) were examined using a Doppler flow wire before and 6 months after the start of this study. CFR, coronary flow volume at maximum hyperemia, and diameter changes by L-NMMA were significantly increased in the cilostazol treatment group compared with the other 2 groups. In conclusion, cilostazol increased CFR and flow-dependent coronary dilation; these changes were attributable to nitric oxide. Cilostazol may improve coronary vascular endothelial dysfunction and coronary hemodynamics in patients with VSA. [ABSTRACT FROM AUTHOR]

Evaluates the cardiac levels of nitric oxide (NO) in patients with mild-to-severe chronic heart failure. Measurement of plasma metabolites of NO in samples of blood from the great cardiac vein and aortic artery; Clinical characteristics of study group; Plasma nitrate plus nitrite concentration and lactate extraction ratio.

Platelet activation is observed in patients with atrial fibrillation (AF). P-selectin, which is expressed on platelet activation, plays an important role in the formation of thromboemobli. Because adenosine is known to attenuate platelet activation, we evaluated adenosine levels and 2 indicators of platelet activation, i.e., expression of P-selectin on platelets and plasma levels of beta-thromboglobulin, in 28 patients with AF (20 men and 8 women, age range 64+/-2 years) with sex- and age-matched (+/-2 years) subjects with sinus rhythm. The incidence of risk factors for stroke except for coronary heart disease and in echocardiographic parameters did not differ between the 2 groups. Plasma adenosine levels were lower (p <0.05) in patients with AF than in controls (mean [interquartile range] 13.4 [19.3-9.3] vs 19.1 [30.8-11.9] nmol/L). The expression of P-selectin on platelets (6.8% [13.6-3.4] vs 4.0% [8.8-1.8]) and plasma levels of beta-thromboglobulin were higher (p <0.05) in patients with AF. Flow cytometric analysis revealed that an antagonist of adenosine receptors, 8-sulfophenyltheophylline, increased the expression of P-selectin on platelets in a dose-dependent manner in the in vitro study. These results suggest that decreased plasma levels of adenosine were associated with platelet activation in patients with AF. Substitution of adenosine may provide a strategy for preventing platelet activation in these patients. [ABSTRACT FROM AUTHOR]

We examined whether angina pectoris (AP) occurring shortly before the onset of acute myocardial infarction (AMI) can render the right ventricle and the conducting tissue resistant to ischemia in 75 patients with an inferior wall AMI. Each patient had total occlusion in the proximal right coronary artery and underwent successful coronary angioplasty < or =24 hours from the onset. We divided patients into 2 groups based on presence or absence of antecedent AP < or =24 hours before the system onset: group 1 (absent) = 57 patients; group 2 (present) = 18 patients. Collateral circulation was more frequently observed in group 2 than in group 1 (group 1 vs 2, 28% vs 61%, p <0.01). Elevation in ST segment > or =1 mm in lead V4R, hemodynamic right ventricular dysfunction, and frequency of high-degree heart block were more frequent in group 1 than in group 2 (75% vs 44%, 79% vs 39%, 53% vs 11%, p <0.05, respectively). Multivariate analysis demonstrated that antecedent AP is the only factor related to these complications. Thus, episodes of AP occurring shortly before onset may restrain development of ischemic damage of the right ventricle and conducting tissue, and are associated with better clinical and functional outcomes among patients with an inferior wall AMI. [ABSTRACT FROM AUTHOR]

The concentration of nitrate plus nitrite, metabolic end products of nitric oxide, in serum prepared from systemic venous blood was significantly (p <0.001) decreased in both heavy (14.5 +/- 1.3 micromol/L) and moderate (17.6 +/- 2.3 micromol/L) smokers relative to that in nonsmokers (22.6 +/- 0.4 micromol/L). [ABSTRACT FROM AUTHOR]

An abstract of the article "International comparison of clinical use of inotrope and vasodilator therapy for acute decompensated heart failure," by H. Yokoyama and colleagues is presented.

An abstract of the article "Intermittent phosphodiesterase type-3 inhibition reduces inflammatory change, restores cardiac remodeling and prevents progression of Heart Failure due to depletion of nitric oxide synthesis," by S. Sanada and colleagues is presented.

An abstract of the article "Value of strain and strain rate imaging in predicting adverse outcomes in patients with chronic pulmonary arterial hypertension," by H. Utsonomiya and colleagues is presented.