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After a percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD), in-stent neoatherosclerosis may pose a risk of in-stent restenosis (ISR). To clarify whether non-fasting hypertriglyceridemia contributes to ISR, we examined the relationship between non-fasting hypertriglyceridemia (i.e., triglyceride (TG) level ≥ 200 mg/dL) and ISR after stenting with a bare metal stent (BMS) post-primary PCI in patients with CAD by means of a single-site retrospective analysis. A total of 1,039 patients with CAD were enrolled, and 86 patients (112 lesions) were evaluated for BMS-ISR 3-6 months post-primary PCI. The percentage of patients with non-fasting hypertriglyceridemia was significantly higher in the ISR (+) group than in the ISR (-) group (P < 0.009). The follow-up period and number of patients in the ISR (+) group were significantly smaller than those in the ISR (-) group (P < 0.001). There were no significant between-group differences in the other baseline patient characteristics before the primary PCI or at the time of the follow-up coronary angiography. However, at the follow-up period, the ISR (+) group had significantly lower diastolic blood pressure and high-density lipoprotein cholesterol levels (P = 0.015) and significantly higher TG levels (P = 0.012) than the ISR (-) group. A multiple logistic regression analysis demonstrated that non-fasting hypertriglyceridemia and a follow-up period of ≥ 6 months were independent risk factors for ISR after primary PCI in patients with BMS implantation for stenotic CAD (P = 0.006), with an adjusted odds ratio of 8.232 (1.201-56.410) and 0.006 (95% confidence interval < 0.001-0.045), respectively. Non-fasting hypertriglyceridemia may be an additional independent risk factor for BMS-ISR after primary PCI in patients with CAD.

After a percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD), in-stent neoatherosclerosis may pose a risk of in-stent restenosis (ISR). To clarify whether non-fasting hypertriglyceridemia contributes to ISR, we examined the relationship between non-fasting hypertriglyceridemia (i.e., triglyceride (TG) level ≥ 200 mg/dL) and ISR after stenting with a bare metal stent (BMS) post-primary PCI in patients with CAD by means of a single-site retrospective analysis. A total of 1,039 patients with CAD were enrolled, and 86 patients (112 lesions) were evaluated for BMS-ISR 3-6 months post-primary PCI. The percentage of patients with non-fasting hypertriglyceridemia was significantly higher in the ISR (+) group than in the ISR (-) group (P0.009). The follow-up period and number of patients in the ISR (+) group were significantly smaller than those in the ISR (-) group (P0.001). There were no significant between-group differences in the other baseline patient characteristics before the primary PCI or at the time of the follow-up coronary angiography. However, at the follow-up period, the ISR (+) group had significantly lower diastolic blood pressure and high-density lipoprotein cholesterol levels (P = 0.015) and significantly higher TG levels (P = 0.012) than the ISR (-) group. A multiple logistic regression analysis demonstrated that non-fasting hypertriglyceridemia and a follow-up period of ≥ 6 months were independent risk factors for ISR after primary PCI in patients with BMS implantation for stenotic CAD (P = 0.006), with an adjusted odds ratio of 8.232 (1.201-56.410) and 0.006 (95% confidence interval0.001-0.045), respectively. Non-fasting hypertriglyceridemia may be an additional independent risk factor for BMS-ISR after primary PCI in patients with CAD.

The purposes of this study were: (1) to confirm the prevalence of sleep-disordered breathing (SDB) in Japanese children using nocturnal pulse oximetry (NPOx) as a screening tool and (2) to examine what kind of parameters are suitable for the evaluation of SDB in children. We conducted a study of 99 children between 4 and 15-year-old and obtained their demographic characteristics and the presence of SDB-related symptoms by questionnaire from their parents. In our study, 36% had been Down syndrome (DS), 25% had cardiovascular disease and 34% had dental/oral abnormality. As SDB-related symptoms, snoring (35%), awake disturbance (48%), arousal (41%) and nocturia (19%) were reported. We analyzed each parameter based on the previous reported data of children and temporary defined normal range as follows; 3%ODI 89% and McGill oximetry score = 1. In non-DS group, each parameter showed abnormal value especially in younger group (abnormality; 61–94%), but the abnormality was decreased during the growth (abnormality; 11–63%). Interestingly, in DS group the value of each parameter was kept on abnormal during the growth (abnormality; 55–100%). We investigated the correlation between McGill oximetry score and ODI or SpO2 nadir. There was a significant positive correlation between McGill oximetry score and 3% or 4% ODI. Moreover, there was a significant negative correlation between McGill oximetry score and SpO2 nadir. Based on NPOx screening, prevalence of SDB was high; however, it was decreased during the growth in non-DS group. Each parameter might be useful for SDB screening in children.

The present study investigated serial changes in the three-dimensional (3D) aspect of the jailed side-branch (SB) ostium. We evaluated 32 patients who underwent examination with optical coherence tomography (OCT) both at baseline and at follow-up. After reconstruction of the 3D images, we classified the configuration of overhanging struts at the SB orifice into three groups according to the 3D aspect of the jailing configuration. The number of compartments divided by the stent strut was counted. The side-branch flow area (SBFA), i.e., the area of the SB ostium except for jailing struts, was measured by cut-plane analysis. Forty-eight SBs of 25 patients were analyzed. Thirteen SBs were classified as the No-jail type (N-type), 19 as the Simple-jail type (S-type; no longitudinal link at the carina), and 16 as the Complex-jail type (C-type; had a link at the carina). In the N-type, the SBFA was significantly increased at follow-up (P = 0.018). In the C-type, the SBFA was significantly decreased at follow-up (P = 0.002). Percent reduction of SBFA in the C-type group was significantly greater than that in the N-type or S-type groups (S-type vs. C-type P = 0.002, N-type vs. C-type P

Background Coronary computed tomography angiography (CCTA) not only provides information regarding luminal stenoses but also allows for visualization of mural atheromatous changes (coronary plaques). Objective We sought to elucidate whether plaques seen on CCTA enable prediction of 2-year outcomes in patients with suspected and known coronary artery disease (CAD). Methods Of 3015 patients who underwent CCTA, the images and 2-year clinical courses of 2802 patients were independently analyzed. The primary endpoint was the composite of all-cause death and acute coronary syndrome. Results During the 2-year observation period, 49 (1.7%) patients developed the primary outcome. The 2-year rates of the primary outcome in the normal (n = 515, no mural lesions), calcium (n = 654, calcified lesion alone), and plaque groups (n = 1633, presence of noncalcified or partially calcified plaques) were 0.2%, 2.0%, and 2.1%, respectively (P = 0.0028). Adverse plaque features such as low attenuation, positive remodeling, spotty calcification, and the napkin-ring sign (low-attenuation core with a higher-attenuation rim) were assessed by an independent core laboratory. Stepwise multivariate Cox proportional hazard analysis showed that a plaque with two or more characteristics (adjusted hazard ratio, 1.98; 95% confidence interval, 1.09–3.60; P = 0.0254), age of ≥67 years (mean), statin treatment after CCTA, and obstructive stenosis remained independent predictors of the primary outcome. Conclusions Plaque imaging in CCTA has predictive value for the 2-year outcome and is a useful identifier for high-risk patients among those with known and suspected CAD.

Background Inflammation and oxidative stress play a crucial role in the pathogenesis of cardiac sarcoidosis (SAR). We investigated whether urinary (U) 8-hydroxy-2′-deoxyguanosine (8-OHdG)—an oxidative DNA damage marker—was related to SAR inflammatory activity. Methods U-8-OHdG levels were measured in 31 SAR patients, classified as active (n=17) or non-active (n=14) based on 18 F-fluorodeoxyglucose positron emission tomography–computed tomography ( 18 F-FDG-PET/CT), 28 dilated cardiomyopathy (DCM) patients, and 30 controls. In active SAR patients, U-8-OHdG levels were reexamined and compared with 18 F-FDG-PET/CT results at 6months after corticosteroid treatment to assess therapeutic response. Results Immunohistochemical examination of left ventricle (LV) autopsy samples from SAR patients revealed positive 8-OHdG staining in cardiomyocyte nuclei from LV sections showing 18 F-FDG accumulation on PET/CT, while serum 8-OHdG levels were significantly higher in the coronary sinus than in the aortic root only in active SAR patients. U-8-OHdG levels in SAR patients were higher than those in controls, and significantly higher in active SAR patients than in non-active SAR and DCM patients. U-8-OHdG was a powerful predictor of active SAR in receiver operating characteristic curve analysis (AUC, 0.98; 95% CI, 0.94–1.02; optimal cutoff value, 13.1ng/mg creatinine), with a sensitivity of 88.2% and a specificity of 92.9%. U-8-OHdG levels in responders significantly decreased at 6months after corticosteroid treatment initiation, in proportion with the decrease in the focal cardiac uptake of 18 F-FDG. Conclusions U-8-OHdG is a potentially clinically useful biomarker for evaluating inflammatory activity and monitoring the effectiveness of corticosteroid therapy in SAR patients.

BackgroundSublingual nitroglycerin capsules or spray is routinely used to treat anginal attacks and to maximally dilate the epicardial coronary arteries during coronary angiography. These dilated coronary vessels have an advantage, but increased heart rates were disadvantageous for coronary computed tomography angiography (CTA).PurposeThe influence of applying nitroglycerin was analyzed regarding the coronary diameter, coronary luminal attenuation, evaluable number of coronary segments, heart rate (HR), HR variability, the optimal reconstruction phase, and image scoring of CTA in the same patients using a 64-slice dual-source CT.Methods and subjectsFifty-two patients with atypical chest pain underwent coronary CTA before and after the administration of sublingual nitroglycerin without heart rate control. The coronary diameter and luminal attenuation were measured on short-axial images in each coronary segment. The coronary vasodilation ratios (VRs) were calculated from the coronary diameters at the same location before and after the use of nitroglycerin. The local institutional review board approved this study and written informed consent was obtained from all the patients.ResultsNo significant differences were noted in the HR variability or optimal reconstruction phase, despite an increase in HR after the use of nitroglycerin. Nitroglycerin significantly enlarged the coronary artery diameter, and VRs of each coronary segment ranged from 7.54% to 22.26%. As compared with baseline coronary diameter, VRs of minor segments (16.91%) were significantly larger than those of major segments (11.35%), and the magnitude of VR correlated with the baseline coronary diameter (r=−0.48, p

Background The aim of this study is to evaluate the accuracy of a newly developed quantitative method using 64-multislice computed tomography angiography (CTA) to detect coronary in-stent restenosis (ISR). Methods and results CTA was performed in 45 patients who underwent stent implantation (79 lesions) and the accuracy to diagnose ISR was evaluated by comparing with invasive coronary angiography (ICA). CTA was evaluated both visually and quantitatively using a new stent restenosis index (SRI) utilizing CT densities at proximal and distal artery lumen from the stented region and the correction value depending on the stent diameter. ICA showed 11 ISR (14%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for visual evaluation were 78%, 75%, 35%, 95%, and 76%, respectively. On the other hand, the quantitative evaluation using SRI represents 82%, 93%, 64%, 97%, and 91%, respectively. Conclusions Evaluation of ISR using SRI is superior to the visual estimation of CTA.

Objective: Recently, we reported that low-dose landiolol (1.5 µg·kg-1·min-1), an ultra-short-acting β-blocker, safely decreased the heart rate (HR) in patients with acute decompensated heart failure (ADHF) and sinus tachycardia, thereby improving cardiac function. We investigated whether low-dose landiolol effectively decreased the HR in ADHF patients with rapid atrial fibrillation (AF). Methods: We enrolled 23 ADHF patients with rapid AF (HR ≥120 beats·min-1 and New York Heart Association class III-IV) and systolic heart failure (SHF: n = 12) or diastolic heart failure (DHF: n = 11) who received conventional therapy with diuretics, vasodilators, and/or low-dose inotropes. They were administered continuous intravenous infusion of low-dose landiolol (1.0-2.0 µg·kg-1·min-1), and their electrocardiograms and blood pressures were monitored for 24 h thereafter. Results: Two hours after starting landiolol, the HR was reduced significantly (22%), without a reduction in blood pressure, and remained constant thereafter. The HR reduction 2 h after landiolol administration was significantly greater in the DHF group than in the SHF group. No incidence of hypotension was recorded. Conclusions: Digitalis or amiodarone is currently recommended for HR control in ADHF patients with rapid AF. Our results showed that continuous infusion of low-dose landiolol may also be useful as first-line therapy in these patients.

Real-time three-dimensional transthoracic echocardiography (3DTTE) has been developed and provides detailed 3D information, noninvasively. However, the accuracy and usefulness of 3DTTE in the evaluation of aortic root geometry are still not clear. 2DTTE and 3DTTE were performed in 161 patients with various cardiac diseases. Multidetector computed tomography (MDCT) was performed in 35 of the 161 patients. The diameters and areas of the aortic annulus were evaluated by these three methods and compared. To evaluate the shape of the aortic annuli, eccentricity index (EI) (1 − minimum diameter/long-axis diameter) were calculated. Maximum dimensions of the aortic annulus measured by MDCT were significantly larger than those by 3DTTE and 2DTTE. The aortic annular areas measured by MDCT and 3DTTE were significantly larger than areas by 2DTTE. A good correlation (r = 0.85) was observed between the areas obtained by 3DTTE and MDCT; however, the correlation between the values by 2DTTE and MDCT was rough (r = 0.44). EI values in 46 % of the patients were greater than 0.1, i.e., the aortic annulus was elliptical. The images obtained by 3DTTE provided accurate values of the aortic annular area, which were equal to the values measured by MDCT. 3DTTE is a useful method to evaluate the aortic annular geometry.

The purpose of this study was to evaluate the image quality (IQ) of dual-source CT (DSCT) versus single-source CT (SSCT). A total of 100 patients underwent 64-section CT coronary angiography (50 DSCT, 50 SSCT). Three observers evaluated the IQ of each coronary segment using a four-point scale (1, excellent; 2, good; 3, fair; 4, no assessment). The IQ of DSCT coronary angiography was compared with SSCT coronary angiography on a per-patient, per-vessel, and per-segment basis using the chi-squared test. The DSCT image quality score (IQS) was significantly lower on a per-patient basis and per-vessel basis for all vessels and on a per-segment basis for some segments (1, 2, 4PD, 4AV, 7, 9, 11, 12, 13) compared with SSCT. The DSCT IQS was significantly lower for certain segments (2, 4PD, 11, 13) with high heart rates (≥70 beats/min). The DSCT IQS was significantly lower for certain segments (1, 2, 3, 4PD, 4AV, 7, 8, 9, 10, 12, 13) with low heart rates (

Previously, we demonstrated in vivo that the nature of the alterations in sarcoplasmic reticulum (SR) function and SR Ca2+ regulatory proteins depends both on the type of mechanical overload imposed and on the duration of the heart disorder. The purpose of the present study was to determine in vitro whether an extrinsic mechanical overload (in the form of high ambient pressure) would cause an up-regulation of ryanodine receptor (RyR) and Ca2+-ATPase, as we previously reported mildly pressure-overloaded, hypertrophied rat hearts. Primary cultures of neonatal rat cardiomyocytes were prepared and high ambient pressure was produced using an incubator and pressure-overloading apparatus. Cells were exposed to one of two conditions for 72 h: atmospheric pressure conditions (APC) or high pressure conditions (HPC; HPC=APC+200 mmHg). The expression levels of RyR and Ca2+-ATPase were quantified and functional characteristics were monitored. The cell area was significantly greater under HPC. After 6 h exposure, the physiological properties of cardiomyocytes were impaired, but they returned to the baseline level within 24 h. After 24 h exposure, the expression level of RyR was significantly higher under HPC, and for Ca2+-ATPase, the expression level was significantly higher under HPC after 6 h exposure. HPC caused hypertrophy and up-regulated the expression of Ca2+ regulatory proteins and their genes. We suggest that this in vitro pressure-overloading model may prove useful, as is a stretch-overloading model, for investigation of the intracellular Ca2+ regulatory pathways responsible for the development of cardiac hypertrophy.

Extracellular signal-regulated kinase 1/2 (ERK1/2) is known to function in cell survival in response to various stresses; however, the mechanism of cell survival by ERK1/2 remains poorly elucidated in ischemic heart. Here we applied functional proteomics by two-dimensional electrophoresis to identify a cellular target of ERK1/2 in response to ischemic hypoxia. Approximately 1500 spots were detected by Coomassie Brilliant Blue staining of a sample from unstimulated cells. The staining intensities of at least 50 spots increased at 6-h reoxygenation after 2-h ischemic hypoxia. Of the 50 spots that increased, at least 4 spots were inhibited in the presence of PD98059, a MEK inhibitor. A protein with a molecular mass of 52 kDa that is strongly induced by ERK1/2 activation in response to ischemic hypoxia and reoxygenation was identified as alpha-enolase, a rate-limiting enzyme in the glycolytic pathway, by liquid chromatography-mass spectrometry and amino acid sequencing. The expressions of the alpha-enolase mRNA and protein are inhibited during reoxygenation after ischemic hypoxia in the cells containing a dominant negative mutant of MEK1 and treated with a MEK inhibitor, PD98059, leading to a decrease in ATP levels. alpha-Enolase expression is also observed in rat heart subjected to ischemia-reperfusion. The induction of alpha-enolase by ERK1/2 appears to be mediated by c-Myc. The introduction of the alpha-enolase protein into the cells restores ATP levels and prevents cell death during ischemic hypoxia and reoxygenation in these cells. These results show that alpha-enolase expression by ERK1/2 participates in the production of ATP during reoxygenation after ischemic hypoxia, and a decrease in ATP induces apoptotic cell death. Furthermore, alpha-enolase improves the contractility of cardiomyocytes impaired by ischemic hypoxia. Our results reveal that ERK1/2 plays a role in the contractility of cardiomyocytes and cell survival through alpha-enolase expression during ischemic hypoxia and reoxygenation.

Objectives The aim of this study was to investigate the effects of rapid electrical stimulation (RES) of contraction on the expression of connexin (Cx)43 gap junction in neonatal rat cultured ventricular myocytes and the consequent changes of conduction properties. Background The expression and distribution of gap junctions in cardiac muscle can be changed readily under a variety of pathological conditions because of dynamic turnover of Cxs. The effects of RES of contraction on gap junction remodeling are not well understood. Methods Neonatal rat ventricular myocytes cultured for five days were subjected to RES (field stimulation) at 3.0 Hz for up to 120 min. Results Rapid electrical stimulation resulted in a significant upregulation of Cx43 (by ∼1.5-fold in protein and by ∼1.9-fold in messenger ribonucleic acid at 60 min). Immunoreactive signal of Cx43 was also increased. Angiotensin II (AngII) content was increased significantly by RES >15 min. Phosphorylated forms of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinases, and p38 mitogen-activated protein kinases (MAPKs) were all increased dramatically by RES with peaks at 5 ∼ 60 min. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system. Conduction velocity was increased significantly by RES for 60 to 90 min (25% ∼ 27% increase). Treatment of myocytes with losartan (100 nmol/l) prevented most of these effects of RES; RES-induced upregulation of Cx43 was also prevented by specific inhibitors for ERK and p38 MAPKs. Conclusions A short-term RES causes upregulation of Cx43 in cardiomyocytes and a concomitant increase of conduction velocity, mainly through an autocrine action of AngII to activate ERK and p38 MAPKs.

An abnormal distribution of the gap junction occurs in chronic atrial fibrillation (AF). There are conflicting data regarding changes in connexins (Cxs) in experimental models of AF. We examined whether patients with chronic AF have alterations in atrial Cxs. We analyzed the expression of Cx40 and Cx43 in the right atrial myocardium from 10 patients with mitral valvular disease (MVD) who had AF (MVD/AF), 10 patients with MVD who were in normal sinus rhythm (MVD/NSR), and 10 control patients in NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained before surgery, and an electrophysiologic examination was performed during the operation. An immunohistochemical study was performed on atrial tissue. The relative expression level of Cx40 protein was significantly lower in MVD/AF patients (6.5 +/- 4.6) than in either MVD/NSR patients (17.7 +/- 8.9, p

The external lumen of a stent [defined as extra-stent lumen (ESL)] assessed by optical coherence tomography (OCT) may be related to the risk of thrombus formation after sirolimus-eluting stent (SES) implantation. An everolimus-eluting stent (EES) might provide relatively minimal inflammatory reaction and appropriate neointimal coverage. The purpose of this study was to compare the neointimal thickness and ESL between SES and EES. Patients who underwent OCT examination more than 7 months after either SES or EES implantation were enrolled. Stent area (SA), lumen area (LA), neointimal area (NIA) and neointimal thickness (NIT) of each strut were measured at 1-mm intervals between stented segments. The area, angle (summation per cross-section) and depth (maximum distance from adjacent vessel surface to the outline of stent) of ESL were analyzed. A total of 49 lesions were included (SES n = 20, EES n = 29). Mean follow-up period was 11 months. A total of 998 cross-sections and 9874 struts were analyzed. There were no differences in stent area, lumen area and neointimal area (SA: 6.01 ± 1.60 vs. 6.02 ± 1.40 mm2, p = 0.572, LA: 5.37 ± 1.52 vs. 5.29 ± 1.34 mm2, p = 0.692, NIA: 0.64 ± 0.49 vs. 0.72 ± 0.37 mm2, p = 0.493). Mean NIT of SES and EES were 0.11 ± 0.05 and 0.10 ± 0.05 mm, respectively (p = 0.367). Conversely, area, angle and depth of ESL in SES group were significantly greater than those in EES group (0.20 ± 0.39 vs. 0.03 ± 0.09 mm2, p

Aims We describe three-dimensional optical coherence tomography (3D-OCT) guided bifurcation stenting and the clinical utility of 3D-OCT. Methods and results Twenty-two consecutive patients who underwent OCT examination to confirm the recrossing position after stent implantation in a bifurcation lesion were enrolled. Frequency domain OCT images were obtained to check the recrossing position and 3D reconstructions were performed off-line. The recrossing position was clearly visualised in 18/22 (81.8%) cases. In 13 cases, serial 3D-OCT could be assessed both before and after final kissing balloon post-dilation (FKBD). We divided these cases into two groups according to the presence of the link between hoops at the carina: free carina type (n=7) and connecting to carina type (n=6). All free carina types complied with the distal rewiring. The percentage of incomplete stent apposition (%ISA) of free carina type at the bifurcation segment after FKBD was significantly smaller than that of the connecting to carina type (0.7±0.9% vs. 12.2±6.5%, p=0.0074). Conclusions 3D-OCT confirmation of the recrossing into the jailed side branch is feasible during PCI and may help to achieve distal rewiring and favourable stent positioning against the side branch ostium, leading to reduction in ISA and potentially better clinical outcomes.

A case of a 71-year-old Japanese woman with toxic shock-like syndrome is reported. She was admitted to the hospital because of swelling of the right leg. On admission, right lower leg was erythematous and swollen with an erosive lesion. On the second day, she rapidly fell into shock. Phlegmasia cerulea dolens caused by massive iliofemoral venous thrombosis was suspected because she had a history of deep venous thrombosis. But deep venous thrombus was not detected by venography at emergent surgery for thromboembolectomy. She died 38 hours after admission despite maximal supportive therapy. Group A beta-hemolytic streptococci were isolated from blood culture and soft tissue after the patient died.

Understanding of intraluminal structure and distribution of uncovered struts after drug-eluting stent implantation are limited by only 2-dimensional (2D) optical coherence tomography (OCT) images. We compared tissue coverage with 3-dimensional (3D) OCT and 2D quantitative analyses, and changes in intraluminal structure immediately after (baseline) everolimus-eluting stent (EES) implantation and at follow-up. The 2D analyses of uncovered struts ratio and tissue coverage thickness at a 0.5-mm interval were compared to 3D-OCT images and visually classified for the degree of tissue coverage. The difference in tissue coverage at baseline and follow-up after EES implantation was evaluated with tissue coverage scores (TCS) calculated by the 3D-OCT classification (Grade 0–3). 3D-OCT classifications were negatively correlated with uncovered-to-total struts (r = −0.864, P

Recently, we reported that low-dose landiolol (1.5 µg·kg(-1)·min(-1)), an ultra-short-acting β-blocker, safely decreased the heart rate (HR) in patients with acute decompensated heart failure (ADHF) and sinus tachycardia, thereby improving cardiac function. We investigated whether low-dose landiolol effectively decreased the HR in ADHF patients with rapid atrial fibrillation (AF).We enrolled 23 ADHF patients with rapid AF (HR ≥120 beats·min(-1) and New York Heart Association class III-IV) and systolic heart failure (SHF: n = 12) or diastolic heart failure (DHF: n = 11) who received conventional therapy with diuretics, vasodilators, and/or low-dose inotropes. They were administered continuous intravenous infusion of low-dose landiolol (1.0-2.0 µg·kg(-1)·min(-1)), and their electrocardiograms and blood pressures were monitored for 24 h thereafter.Two hours after starting landiolol, the HR was reduced significantly (22%), without a reduction in blood pressure, and remained constant thereafter. The HR reduction 2 h after landiolol administration was significantly greater in the DHF group than in the SHF group. No incidence of hypotension was recorded.Digitalis or amiodarone is currently recommended for HR control in ADHF patients with rapid AF. Our results showed that continuous infusion of low-dose landiolol may also be useful as first-line therapy in these patients.

Background: The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Methods and Results: Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6L·min-1·m-2; pulmonary capillary wedge pressure [PCWP], 26±8mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0μg·kg-1·min-1; i.v.), which is an ultra-short-acting β1-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5μg·kg-1·min-1) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0μg·kg-1·min-1) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5μg·kg-1·min-1), hemodynamic parameters such as PCWP, stroke volume index, SvO2, rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. Conclusions: A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR. (Circ J 2012; 76: 1646–1653)

BACKGROUND The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment. METHODS AND RESULTS Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment. CONCLUSIONS U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

The purpose of our study was to determine the relationship between the predictive factors and systolic reconstruction (SR) as an optimal reconstruction window in patients with low heart rate (LHR; less than 65 bpm).391 patients (262 male and 129 female, mean age; 67.1±10.1 years of age) underwent coronary CTA without the additional administration of a beta-blocker. Affecting factors for SR were analyzed in age, gender, body weight (BW), diabetes mellitus (DM), coronary arterial disease (CAD), ejection fraction (EF), systolic and diastolic body pressure (BP) and heart rate variability (HRV) during coronary CTA.In 29 (7.4%) of the 391 patients, SR was needed, but there was no apparent characteristic difference between the systolic and diastolic reconstruction groups in terms of gender, age, BW, DM, CAD and EF. In a multivariate analysis, the co-existence of DM [P0.05; OR, 0.27; 95% CI, 0.092-0.80], diastolic BP [P0.01; OR, 0.95; 95% CI, 0.92-0.98] and HRV [P0.01; OR, 0.98; 95% CI, 0.96-0.99] were found to be the factors for SR. In gender-related analysis, HRV was an important factor regardless of sex, but co-existence of DM affected especially for female and BP for male.Especially in the patients with LHR who had a medication of DM, high HRV or high BP, SR, in addition to DR, was needed to obtain high-quality coronary CTA images.

Aims Oxidative stress is known to play a crucial role in the pathogenesis of heart failure (HF). We investigated whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), a product of oxidative DNA damage, is a clinically useful biomarker of the severity of chronic heart failure (CHF) and oxidative stress levels in failing hearts. Methods and results We measured 8-OHdG in the serum obtained from the coronary sinus (CS) and aortic root (Ao) in small groups of control subjects and CHF patients. We then measured urinary 8-OHdG and other biomarkers (brain natriuretic peptide, 8-isoplastane, high-sensitivity C-reactive protein, interleukin-6, and tumour necrosis factor-α) in 31 control subjects and 194 patients with CHF [left-ventricular ejection fraction (LVEF): 28.3 ± 8.1%]. Serum 8-OHdG was significantly higher in the CS than the Ao in CHF patients only. Urinary 8-OHdG was also significantly higher in CHF patients than in control subjects, and urinary 8-OHdG became higher as New York Heart Association class increased. Moreover, there was a significant correlation between urinary 8-OHdG and LVEF (r = −0.27), pulmonary capillary wedge pressure (r = 0.31), or left-ventricular end-diastolic volume index (r = 0.22). In contrast, there was poor correlation between the severity of CHF and the other neurohumoral biomarkers. Conclusion In HF, urinary 8-OHdG seems to reflect the level of oxidative stress and various parameters related to symptomatic status and functional severity of CHF.

We investigated whether urinary (U) 8-hydroxy-2¢-deoxyguanosine (8-OHdG), an oxidative DNA damage marker, was related to inflammatory activity in cardiac sarcoidosis(CS). U-8-OHdG levels were measured in 31 CS patients, classified as active (n = 17) or non-active (n = 14) based on 18F-FDG-PET/CT.

(8-OHdG), a marker of oxidative stress, was related to LV remodeling in dilated cardiomyopathy (DCM). Methods: We performed full study of cardiac catheterization including endomyocardial biopsy from LV in 35 patients with DCM (left ventricular ejection fraction (LVEF)52865%). Biopsy samples were stained with sirius red to evaluate myocardial fibrosis, and also stained with immunohistochemical method using anti-8-OHdG antibody to evaluate myocardial oxidative stress. In 150 DCM patients, moreover, we examined whether urinary 8-OHdG levels correlated with LVEF, LV end-diastolic volume index (LVEDVI) and LV mass index (LVMI), peak early diastolic mitral annulus velocity (e’)by echocardiography. Results: Biopsy samples data showed that the ratio of oxidized nuclei in cardiomyocytes and CVF were significantly increased in patients with DCM as compared with normal subjects. A direct correlation was found between the positive staining ratio of nuclei and CVF (n535, r50.64, P!0.001). Urinary 8-OHdG was also significantly higher in DCM patients than in control subjects (DCM; n5150: 13.5 63.1 ng/ml vs control; n530: 8.061.9 ng/ml, P!0.001). There was a significant correlation between urinary 8-OHdG and LVEF, or LVEDVI, e’. Conclusions: These findings suggest that urinary 8-OHdG may be a clinically-useful marker for LV remodeling associated with DCM.

ObjectivesThe aim of this study was to investigate the effects of rapid electrical stimulation (RES) of contraction on the expression of connexin (Cx)43 gap junction in neonatal rat cultured ventricular myocytes and the consequent changes of conduction properties.BackgroundThe expression and distribution of gap junctions in cardiac muscle can be changed readily under a variety of pathological conditions because of dynamic turnover of Cxs. The effects of RES of contraction on gap junction remodeling are not well understood.MethodsNeonatal rat ventricular myocytes cultured for five days were subjected to RES (field stimulation) at 3.0 Hz for up to 120 min.ResultsRapid electrical stimulation resulted in a significant upregulation of Cx43 (by ∼1.5-fold in protein and by ∼1.9-fold in messenger ribonucleic acid at 60 min). Immunoreactive signal of Cx43 was also increased. Angiotensin II (AngII) content was increased significantly by RES >15 min. Phosphorylated forms of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinases, and p38 mitogen-activated protein kinases (MAPKs) were all increased dramatically by RES with peaks at 5 ∼ 60 min. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system. Conduction velocity was increased significantly by RES for 60 to 90 min (25% ∼ 27% increase). Treatment of myocytes with losartan (100 nmol/l) prevented most of these effects of RES; RES-induced upregulation of Cx43 was also prevented by specific inhibitors for ERK and p38 MAPKs.ConclusionsA short-term RES causes upregulation of Cx43 in cardiomyocytes and a concomitant increase of conduction velocity, mainly through an autocrine action of AngII to activate ERK and p38 MAPKs.