Showing papers in "Heart and Vessels in 2010"
TL;DR: Inhalation of fasudil is as effective as NO in patients with PAH, possibly through different mechanisms, and a positive correlation with serum levels of high-sensitivity C-reactive protein was noted for f asudil but not for NO.
Abstract: We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, as a more feasible option to locally deliver the drug for PAH. We examined 15 patients with PAH (13 women and 2 men, 45 ± 4 years old), including idiopathic PAH (n = 5), PAH associated with connective tissue disease (n = 6), PAH with congenital heart disease (n = 3), and portal PAH (n = 1). In those patients, we performed right heart catheterization with a Swan-Ganz catheter in the two protocols with inhalation of nitric oxide (NO) (40 ppm, 10 min) and fasudil (30 mg, 10 min) with a sufficient interval (>30 min). Both NO and fasudil inhalation significantly reduced mean pulmonary arterial pressure (PAP) (NO: P < 0.01, fasudil: P < 0.05) and tended to decrease pulmonary vascular resistance (NO: P = 0.07, fasudil: P = 0.1), but did not affect cardiac index. The ratio of pulmonary to systemic vascular resistance was significantly reduced both in NO and fasudil inhalation (NO: P < 0.01, fasudil: P < 0.05), indicating that both NO and fasudil inhalation selectively affect lung tissues. Interestingly, there was no correlation in the vasodilator effects between NO and fasudil, and a positive correlation with serum levels of high-sensitivity C-reactive protein was noted for fasudil but not for NO. These results suggest that inhalation of fasudil is as effective as NO in patients with PAH, possibly through different mechanisms.
136 citations
TL;DR: The results of this study demonstrate a significant relationship between OSA and several cardiac disorders, and also demonstrate the efficacy of CPAP in preventing OSA-associated arrhythmias in a large population of Japanese patients.
Abstract: The purpose of this study was to determine the relationship between obstructive sleep apnea (OSA) and cardiovascular disorders in a large Japanese population, and to assess the efficacy of continuous positive airway pressure (CPAP) in the treatment of OSA-associated arrhythmias. The study population comprised 1394 Japanese subjects (1086 men and 308 women) who were divided into four groups on the basis of polysomnography (PSG) analysis as follows: the no sleep apnea (N-SA) group (n = 44, apnea-hypopnea index [AHI] 2 s, P < 0.001) during the PSG recording. A total of 316 patients from the group underwent CPAP titration and were then re-evaluated. Continuous positive airway pressure therapy significantly reduced the occurrences of PAF (P < 0.001), PVC (P = 0.016), sinus bradycardia (P = 0.001), and sinus pause (P = 0.004). The results of this study demonstrate a significant relationship between OSA and several cardiac disorders, and also demonstrate the efficacy of CPAP in preventing OSA-associated arrhythmias in a large population of Japanese patients.
132 citations
TL;DR: It is suggested that caloric restriction reverses obesityinduced endothelial dysfunction and vascular oxidative stress, and underscores the importance of uncoupled eNOS in the pathogenesis.
Abstract: Obesity is frequently associated with endothelial dysfunction. We hypothesized that high-fat feeding dysregulates the balance between endothelial derived nitric oxide and superoxide formation. Furthermore, we examined whether caloric restriction could reverse the detrimental vascular effects related to obesity. Male C57Bl/6 mice were fed with normal-fat diet (fat 17%) or high-fat diet (fat 60%) for 150 days. After establishment of obesity at day 100, a subgroup of obese mice were put on caloric restriction (CR) (70% of ad libitum energy intake) for an additional 50 days. At day 100, aortic rings from obese mice receiving high-fat diet showed impaired endothelium-dependent vasodilation in response to acetylcholine (ACh). Caloric restriction reversed high-fat diet-induced endothelial dysfunction. At day 150, impaired vasodilatory responses to ACh in obese mice without caloric restriction were markedly improved by preincubation with the tetrahydrobiopterin (BH(4)) precursor sepiapterin and L-arginine, a substrate for endothelial nitric oxide synthase (eNOS). Additionally, inhibition of vascular arginase by L-norvaline partially, and superoxide scavenging by Tiron completely, restored endothelial cell function. Obese mice showed increased vascular superoxide production, which was diminished by endothelial denudation, pretreated of the vascular rings with apocynin (an inhibitor of reduced nicotinamide adenine dinucleotide phosphate [NADPH] oxidase), oxypurinol (an inhibitor of xanthine oxidase), N(G)-nitro-L-arginine methyl ester (LNAME; an inhibitor of eNOS), or by adding the BH(4) precursor sepiapterin. Caloric restriction markedly attenuated vascular superoxide production. In obese mice on CR, endothelial denudation increased superoxide formation whereas vascular superoxide production was unaffected by L-NAME. Western blot analysis revealed decreased phosphorylated eNOS (Ser1177)-to-total eNOS expression ratio in obese mice as compared to lean controls, whereas the phospho-eNOS/NOS ratio in obese mice on CR did not differ from the lean controls. In conclusion, the present study suggests that caloric restriction reverses obesity induced endothelial dysfunction and vascular oxidative stress, and underscores the importance of uncoupled eNOS in the pathogenesis.
69 citations
TL;DR: A low L% could be used as an independent predictor for ACS on admission and is associated with MACE during clinical follow-up in CHD patients.
Abstract: The physiological stress suffered by patients with coronary heart disease (CHD) may result in a shift in leukocyte differential toward a decreased percentage of lymphocytes (L%). The purpose of this study was to determine the prognostic value of a low L% in CHD. One hundred forty patients evaluated in our department between 2007 and 2008 were retrospectively reviewed. Thirty-eight patients had primary percutaneous coronary intervention (PCI), and 102 patients had elective PCI. Various statistical analyses were used to examine the association between a low L% or other clinical characteristics and CHD. Univariate analysis showed that low L% was significantly related to ACS compared with stable CHD or control. White blood cell (WBC) count, C-reactive protein (CRP) and left ventricular systolic dysfunction (LVSD) were also correlated with CHD. Multivariate analysis and logistic regression analysis revealed that L%, CRP, WBC count and LVSD were all independently significant risk factors to have predictive value for CHD and 1 year major adverse cardiac events (MACE). A low L% could be used as an independent predictor for ACS on admission and is associated with MACE during clinical follow-up in CHD patients.
63 citations
TL;DR: VKORC1 genotype and CYP2C9 polymorphism affect daily dose requirements and time to therapeutic INR in Turkish patients receiving warfarin for anticoagulation.
Abstract: In this study, we investigated the contribution of vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotypes, age, and body surface area (BSA) on warfarin dose requirements and in an adult Turkish population. Blood samples were collected from 100 Turkish patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the therapeutic range. Genetic analyses for CYP2C9 genotypes (*2 and *3 alleles) and VKORC1 −1639 G>A polymorphism were performed and venous INR determined. The mean warfarin daily dose requirement was higher in CYP2C9 homozygous wild-type patients, compared to those with the variant *3 allele (P 0.05) and highest in patients with the VKORC1 −1639 GG genotype compared to those with the GA genotype and the AA genotype (P < 0.01). The time to therapeutic INR was longer in CYP2C9 homozygous wild-type patients compared with those with the variant *2 and *3 alleles (P < 0.01), and longer in patients with the VKORC1 (position −1639) GG genotype compared with those with the GA genotype and the AA genotype (P < 0.01). The multivariate regression model including the variables of age (R2 = 4.4%), BSA (R2 = 27.4%), CYP2C9 (R2 = 8.1%), and VKORC1 genotype (R2 = 34.1%) produced the best model for estimating warfarin dose (R2 = 60.4%). VKORC1 genotype and CYP2C9 polymorphism affect daily dose requirements and time to therapeutic INR in Turkish patients receiving warfarin for anticoagulation.
46 citations
TL;DR: It is identified that high preoperative hemoglobin, a weight less than 3 kg at operation, and the presence of a patent duct are statistically significant risk factors for shunt blockage in the acute postoperative period.
Abstract: Factors relating to acute blockage of modified Blalock-Taussig shunts (MBTS) have not been well described in the literature. Our aim was to determine the outcomes in patients early after undergoing MBTS operations and to identify potential risk factors for acute shunt blockage in the early postoperative period. A retrospective study was performed in a tertiary referral congenital cardiac unit. All children who underwent first shunt insertion for cyanotic congenital heart disease during the study period from 2002 to 2006 were included. Seventy-six children underwent first shunt insertion with a median age of 37 days (range 2 days-8 years) and median weight of 3.75 kg (range 2.1-17.2 kg). The shunt sizes varied from 3 to 6 mm. The rate of acute shunt blockage was 11.8% (9/76), all within the first 24 h. There were 3 early deaths (3.9%), none of which were associated with shunt blockage. The main risk factors for blockage were preoperative high hemoglobin, weight less than 3 kg, and duct patency on echocardiogram after surgery. This study identifies that high preoperative hemoglobin, a weight less than 3 kg at operation, and the presence of a patent duct are statistically significant risk factors for shunt blockage in the acute postoperative period. Further work is needed to determine if reduction in preoperative hemoglobin concentration and attempts to reduce postoperative ductal patency may alter the outcome.
46 citations
TL;DR: It is demonstrated that patients with severe OSA have globalLeft ventricular dysfunction, and left ventricular MPI was significantly higher insevere OSA patients than in controls.
Abstract: Obstructive sleep apnea (OSA) is associated with cardiovascular mortality and morbidity. It may predispose patients to left ventricular hypertrophy and heart failure. The aim of this study was to determine the left ventricular mass (LVM) and myocardial performance index (MPI) reflecting left ventricular global function in uncomplicated OSA patients. Sixty-four subjects without hypertension, diabetes mellitus, and any cardiac or pulmonary disease referred for evaluation of OSA underwent overnight polysomnography and complete echocardiographic assessment. According to the apnea hypopnea index (AHI), subjects were divided into three groups: group 1, control subjects with nonapneic snorers (AHI 30, n = 21). Basic echocardiographic measurements, LVM, and LVM index were measured. Left ventricular MPI was calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic ejection time by Doppler echocardiography. There were no significant differences in age, sex, body mass index, heart rate, and systolic and diastolic blood pressure among the three groups. Left atrium, interventricular septum, left ventricular posterior wall, left ventricular end-diastolic and end-systolic diameters, LVM mass, and LVM index were not significantly different among the three groups. Left ventricular MPI was significantly higher in severe OSA patients (0.64 ± 0.18) than in controls (0.49 ± 0.18; P < 0.05). There was no significant difference between controls (0.49 ± 0.18) and mild to moderate OSA (0.61 ± 0.16; P = 0.08) and between mild to moderate OSA (0.61 ± 0.16) and severe OSA (0.64 ± 0.18; P = 0.84). The present study demonstrates that patients with severe OSA have global left ventricular dysfunction.
39 citations
TL;DR: Matching between the numerical simulation and experimental results was satisfactory, which proved that the finite element analysis could provide theoretical evidence and help design and optimize the stent structure.
Abstract: A computational and experimental method on biomechanics of stent is presented to analyze the stress distribution of different phases and evaluate the fatigue life according to Goodman criteria. As a result, the maximum stress and alternating stress were always located at the curvature area of rings, the fatigue bands in the experiment also verified the computation rationality. Matching between the numerical simulation and experimental results was satisfactory, which proved that the finite element analysis could provide theoretical evidence and help design and optimize the stent structure.
39 citations
TL;DR: Apelin-36 concentrations are reduced in lowrisk first STEMI patients during the first days regardless of the degree of LV dysfunction and prognosis, and after a 1-year follow-up, this finding is consistent with previous studies.
Abstract: To date, only animal studies have been concerned with apelin involvement in acute myocardial ischemia. The aim of this study was to investigate apelin measurements in low-risk patients with first ST-elevation myocardial infarction (STEMI) and to assess if apelin may feature as a marker of left ventricular (LV) injury and prognosis. In 78 consecutive patients (mean age 67 ± 11.5 years, 24 women) with first STEMI treated with primary percutaneous coronary intervention, plasma apelin-36 concentrations were measured twice: on admission and on the 5th day of hospitalization. Left ventricle ejection fraction (LVEF) was applied as marker of LV injury. Composite endpoint (CEP), which included death, stroke, and recurrent ischemic event, was assessed after 1 year follow-up. On the first day, median apelin-36 concentration was 2138.5 pg/ml and on the 5th day was significantly lower, 2008.3 pg/ml (P = 0.002). There were no significant differences found in apelin-36 concentrations between patients with normal and low LVEF. In both groups significant reductions were found in apelin-36 concentrations measured in 5-day intervals (P = 0.04 and P = 0.008, respectively). After a 1-year follow-up, only one patient died and 19 patients (24.3%) had reached CEP. No difference in baseline apelin-36 concentrations were found in the group of patients who reached CEP compared with those without CEP. However, in both groups concentrations significantly decreased after 5 days (P = 0.04 and P = 0.013, respectively). Apelin-36 concentrations are reduced in lowrisk first STEMI patients during the first days regardless of the degree of LV dysfunction and prognosis.
38 citations
TL;DR: This is the first reported case of use of tocilizumab in addition to steroids and conventional PAH therapy in a patient with PAH associated with Castleman’s disease.
Abstract: Castleman’s disease is a highly heterogeneous clinical-pathological entity that belongs to the lymphoproliferative disorders and is associated with pulmonary arterial hypertension (PAH) in some patients. It is linked to excessive immune stimulation by interleukin-6 (IL-6), which is also involved in the pathogenesis of PAH. A 31-year-old woman with Castleman’s disease demonstrated PAH characterized by severe right heart failure. Since she was resistant to various conventional therapies including steroids, prostacyclins, bosentan, and sildenafil, tocilizumab (anti-IL-6 receptor antibody) therapy was started. Her clinical course was followed for 6 months, with significant improvement without any adverse effect. This is the first reported case of use of tocilizumab in addition to steroids and conventional PAH therapy in a patient with PAH associated with Castleman’s disease.
37 citations
TL;DR: The low level of serum α-tocopherol was ameliorated during the remission phase as compared with the exacerbation phase in the patients with chronic fatigue syndrome, suggesting that increased oxidative stress may be involved in the pathogenesis of Chronic fatigue syndrome and might also be directly related to the severity of the symptoms of chronic fatigue Syndrome.
Abstract: The etiology of chronic fatigue syndrome remains unknown. Oxidative stress may be involved in its pathogenesis. Vitamin E is a major endogenous lipid-soluble antioxidative substance, and is consumed during the lipid peroxidation process. We studied a population comprising 27 patients with chronic fatigue syndrome (10 men and 17 women, 29 ± 6 years of age) and 27 age- and sex-matched control subjects. Serum vitamin E (α-tocopherol) concentrations were determined and expressed as mg/g total lipids (total cholesterol and triglyceride) to evaluate oxidative stress. Serum α-tocopherol concentrations (mg/g lipids) were significantly (P < 0.001) lower in the patients with chronic fatigue syndrome (2.81 ± 0.73) than in the control subjects (3.88 ± 0.65). The patients with chronic fatigue syndrome were re-examined during a follow-up interval. After 8 ± 2 months, 16 patients exhibited a status that warranted re-examination during remission of the symptoms at a regular visit to our hospital (Group 1), while the remaining 11 did not (Group 2). The serum α-tocopherol levels were significantly elevated during remission as compared with those at baseline in Group 1 (2.71 ± 0.62 → 3.24 ± 0.83, P < 0.001). The levels did not significantly change after the interval in Group 2 (2.97 ± 0.86 → 2.85 ± 0.73, not significant). In conclusion, serum α-tocopherol concentrations were significantly lower in the patients with chronic fatigue syndrome as compared with the control subjects, suggesting increased oxidative stress in the former. The low level of serum α-tocopherol was ameliorated during the remission phase as compared with the exacerbation phase in the patients with chronic fatigue syndrome, suggesting that increased oxidative stress may be involved in the pathogenesis of chronic fatigue syndrome and might also be directly related to the severity of the symptoms of chronic fatigue syndrome.
TL;DR: A novel role for AQP1 in postnatal angiogenesis is indicated, which has implications in diverse pathophysiological conditions including wound healing, tumor metastasis, and organ regeneration.
Abstract: Aquaporin-1 (AQP1) is a water channel protein expressed in endothelial and epithelial cells of many tissues, including the vasculature, where it serves to increase water permeability of the cell membrane. Prior studies have also reported that AQP1 plays a central role in tumor angiogenesis by promoting endothelial cell migration. To investigate whether AQP1 might also influence vascular angiogenesis in ischemic myocardium, the expression level of AQP1 for 21 days post myocardial infarction in rabbit hearts was observed. Aquaporin-1 mRNA and protein levels in day 3, and peaked on day 7 post surgery. This correlated well with the pattern of neovascularization and increased water content of infarct border tissue, and suggested that AQP1 may be involved in myocardial angiogenesis in response to ischemia injury. These AQP1-induced changes were tempered by acetazolamide, a carbonic anhydrase inhibitor, which acted by downregulating AQP1 expression. Acetazolamide treatment did not significantly affect the expression of vascular endothelial growth factor in the tissues studied. Our findings indicate a novel role for AQP1 in postnatal angiogenesis, which has implications in diverse pathophysiological conditions including wound healing, tumor metastasis, and organ regeneration.
TL;DR: In conclusion, the CYBA +242C/T and PPARD +294T/C variants modulate risk of CAD through their associations with atherogenic serum lipid profiles.
Abstract: Abnormalities in lipid metabolism and enhanced oxidative stress are considered as major risk factors for coronary atherosclerosis. Functional genetic variations in genes whose products are involved in lipid metabolism and antioxidant defense could therefore modulate risk of coronary artery disease (CAD). In this study, we evaluate whether the PPARGC1A Gly482Ser, PPARG3 (−681)C/G, PPARD +294T/C, and CYBA +242C/T gene variants confer the risk of CAD in a Russian population. A total of 313 CAD patients and 132 controls with no clinical sign of CAD were studied. The polymorphic markers were tested using a TaqMan assay. Allele and genotype frequencies in CAD patients and controls were compared using the Yates χ2 test. Association of the genetic markers with metabolic risk factors of arterial atherosclerosis was studied using the analysis of variance test and then adjusted for conventional risk factors in the multiple regression analysis. For CYBA +242C/T, both the allele T and genotype T/T showed significant association with higher risk of CAD (odds ratio =1.49 and 3.89, respectively). The allele C and genotype C/C of the +294T/C marker of PPARD were associated with increased risk of CAD providing an odds ratio of 2.12 and 2.78, respectively. The risk variants of CYBA +242C/T and PPARD +294T/C markers were associated with higher low-density lipoprotein cholesterol and increased total serum cholesterol, respectively. In conclusion, the CYBA +242C/T and PPARD +294T/C variants modulate risk of CAD through their associations with atherogenic serum lipid profiles.
TL;DR: An 18-year-old woman with catecholaminergic polymorphic ventricular tachycardia underwent pulmonary vein isolation (PVI) because of frequent and inappropriate shocks from an implantable cardioverter defibrillator associated with atrial fibrillation (AF).
Abstract: An 18-year-old woman with catecholaminergic polymorphic ventricular tachycardia (CPVT) underwent pulmonary vein isolation (PVI) because of frequent and inappropriate shocks from an implantable cardioverter defibrillator (ICD) associated with atrial fibrillation (AF) with a rapid ventricular response. While the PVI did not completely suppress the AF induced by an isoproterenol infusion, the Holter monitor recordings demonstrated a major decrease in the clinical episodes of AF and ventricular tachyarrhythmias in association with a reduced high-frequency (HF) component and ratio of the low-frequency (LF) component power to the HF component (LF/HF) after the PVI. The PVI can decrease the substrates that trigger and maintain the AF when it involves a pulmonary vein origin, and may exert an additional effect on the sympathetic nerve input to the heart. The PVI may be an adjunctive therapy for CPVT cases with drug refractory AF causing inappropriate ICD discharges.
TL;DR: The present study first time detected D1–D5 dopamine receptor subtypes in the native human heart simultaneously, found presence of D1, D2, D4, and D5 in cardiac tissues, and revealed distribution features of dopamine receptors subtype in the epicardium, myocardium, and endocardium.
Abstract: The present study first time detected D1-D5 dopamine receptor subtypes in the native human heart simultaneously, found presence of D1, D2, D4, and D5 in cardiac tissues, and revealed distribution features of dopamine receptor subtypes in the epicardium, myocardium, and endocardium. Samples from four native hearts coming from young brain-dead donors, which for technical reason were not used for transplants, were studied. Dopamine receptors were revealed by immunochemistry technique and immunoblot analysis. Morphometrical quantification of the density of each receptor subtype was performed by an image analyzer. Our results demonstrate that only four subtypes of dopamine receptors can be found in cardiac tissues: D1, D2, D4, and D5. These dopamine receptors have been detected in endocardium, myocardium, and epicardium. D1 receptors were stored primarily in the epicardial layer. Dopamine receptors are distributed in the wall of both atria and ventricles, and its transmural gradient can be described in the wall of the human heart. Sections of atria and ventricles exposed to antidopamine receptor antibodies showed fluorescent-positive reaction in the epicardium, myocardium and endocardium. D4 receptor immune reactivity was remarkably less intense than D2 receptor immune reactivity. All the subtypes of dopamine receptors are in close relationships with all cardiac structures. Our findings provide a favorable basis for researching the role of dopamine receptors in controlling functions of the human heart and in the pathogenesis of cardiovascular diseases.
TL;DR: Interestingly, a strong and positive significant correlation between neutrophil count and circulating sCD40L level is observed in unstable angina, indicating that Circulating s CD40L is associated with neutrophils count and may mediate interaction between neutophils and platelets in acute coronary syndrome, particularly in unstableAngina.
Abstract: Following plaque rupture, activated platelet will induce subsequent inflammatory process including neutrophil recruitment. In vitro study demonstrated an interaction between neutrophils and platelets via a mechanism involving CD40-CD40 ligand. However, whether this mechanism exists in the clinical setting remains unknown. Fifty-four patients with acute myocardial infarction (AMI) and 25 with unstable angina of pain onset of ≤24 h were enrolled consecutively. Acute myocardial infarction was diagnosed from three diagnostic criteria, i.e., anginal pain, electrocardiogram ST-T changes, and cardiac enzyme elevation. Unstable angina was diagnosed in patients without elevated cardiac enzymes. Peripheral venous blood was drawn at admission for routine blood count and soluble CD40 ligand (sCD40L) measurement. Neutrophil count was determined by an automated blood cell counter. Circulating sCD40L was measured using a standard enzyme-linked immunosorbent assay. Neutrophil count was significantly higher in AMI as compared with unstable angina (P < 0.001), whereas circulating sCD40L did not significantly differ. Despite marked elevation, no correlation was observed between neutrophil count and circulating sCD40L in AMI. Interestingly, we observed a strong and positive significant correlation between neutrophil count and circulating sCD40L level (r = 0.607, P = 0.002) in unstable angina. Circulating sCD40L is associated with neutrophil count and may mediate interaction between neutrophils and platelets in acute coronary syndrome, particularly in unstable angina.
TL;DR: The aim of this study is to investigate if serum asymmetric dimethylarginine (ADMA) levels can predict restenosis and major adverse cardiac events (MACE) in patients who undergo percutaneous coronary interventions.
Abstract: The aim of this study is to investigate if serum asymmetric dimethylarginine (ADMA) levels can predict restenosis and major adverse cardiac events (MACE) in patients who undergo percutaneous coronary interventions The most important cause of restenosis following percutaneous coronary intervention is neointimal hyperplasia Nitric oxide (NO) prevents the neointimal hyperplasia growing Asymmetric dimethylarginine is a competitive inhibitor of NO synthesis The effect of ADMA on the restenosis has not yet been investigated A total of 105 (80 male and 25 female) patients were included in our study All patients underwent elective percutaneous transluminal coronary angioplasty (PTCA) with bare metal stent implantation or direct stenting for one coronary artery between September 2004 and January 2006 All patients were clinically followed for a period of 6 months, and a control angiography was performed at the end of this period The probrain natriuretic peptide (pro-BNP), high-sensitivity Creactive protein (hs-CRP), and ADMA levels of the patients were evaluated before the procedure and 6 months afterwards Biochemical parameters and angiographic features were evaluated in order to determine if they could predict the development of restenosis and MACE by using univariate and multivariate Cox regression analysis The 65 (619%) patients (50 males and 15 females) who had not developed restenosis were designated as Group 1 The 27 (257%) patients (21 males and 6 females) who had developed restenosis were designated as Group 2 In terms of predicting the development of restenosis, the presence of diabetes mellitus (hazard ratio [HR]: 278; confidence interval [CI]: 125-620; P = 001), type of lesion (HR: 189; CI: 101-355; P = 004), form of procedure (HR: 030; CI: 011-081; P = 001), and ADMA (HR: 408; CI: 173-962; P = 0001) were found to be significant in univariate Cox regression analysis In contrast, only the levels of ADMA were found to be a significant predictor of restenosis in the multivariate Cox regression analysis (HR: 302; CI: 116-784; P = 002) The restenosis prediction of ADMA levels continued after excluding the patients with diabetes mellitus in the univariate and multivariate Cox regression analysis (HR: 523; CI: 199-1376; P = 0001 and HR: 561; CI: 179-1762; P = 0003, respectively) Regarding the development of cardiac events, hs-CRP (HR: 103; CI: 100-106; P = 001) and ADMA (HR: 171; CI: 306-958; P = 0001) were found to be significantly correlated with adverse cardiac events in univariate Cox regression analysis, whereas only ADMA levels were significant in the multivariate Cox regression analysis (HR: 283; CI: 127-631; P = 001) The levels of ADMA obtained before the procedure predict the development of restenosis and MACE in patients who underwent elective PTCA and bare metal stent procedures
TL;DR: Coronary artery calcium was found more frequently in LAD than in the other coronary arteries in patients with mild to high CAC, but not in those with veryhigh CAC.
Abstract: The distribution of coronary atherosclerosis has not been fully clarified. We measured coronary artery calcium score (CACS) in 624 consecutive patients for the right coronary artery (RCA), left main trunk (LMT), left anterior descending coronary artery (LAD), and left circumflex coronary artery (LCx), then calculated total CACS. Coronary artery calcium score was measured using the Agatston method. We divided these patients into four groups: CACS 1-100 (Group A, n = 267), CACS 101-400 (Group B, n = 160), CACS 401-1000 (Group C, n = 110), and CACS >1000 (Group D, n = 87). In Group A, B, and C, the CACS in LAD was significantly higher than in the other three arteries (P < 0.0001). In Group D, the CACS was not significantly different between LAD and RCA (P = 0.6930). In Groups A, B, and C, coronary artery calcium (CAC) was more frequently found in LAD compared with other arteries (P < 0.0001). However, in Group D the prevalence of CAC was not significantly different among the three arteries (P = 0.4435). Coronary artery calcium was found more frequently in LAD than in the other coronary arteries in patients with mild to high CAC, but not in those with very high CAC.
TL;DR: Nebivolol therapy may have a favorable effect on endothelial function in patients with CSX and further studies are needed to confirm the clinical significance.
Abstract: Endothelial dysfunction is major pathophysiologic mechanism in cardiac syndrome X (CSX), which causes a decrease in plasma nitrite oxide (NO) levels. It was demonstrated that nebivolol improves endothelial function and increases NO release. Despite this pathophysiologic relation, the effect of nebivolol therapy on endothelial function in patients with CSX is unknown. The aim of this study is to evaluate the effect of nebivolol on patients in CSX. Thirty-eight patients who were diagnosed with CSX were prospectively enrolled in the study. The treatment group consisted of 20 patients and the control group consisted of 18 patients. An oral 5-mg dose of nebivolol was given daily and maintained for 4 weeks in the treatment group. Ultrasonographic parameters (brachial artery flow-mediated dilatation [FMD], brachial artery lumen diameters) and inflammatory markers (high-sensitivity C-reactive protein [hsCRP], von Willebrand factor [vWf], and fibrinogen) were measured at baseline and end of the 4 weeks. Brachial baseline lumen diameter, brachial lumen diameter after reactive hyperemia, and FMD were 4.61 +/- 0.49 mm, 4.87 +/- 0.53 mm, and 5.6% +/- 2.3% at baseline. After the nebivolol therapy, there was a significant increase in both brachial artery baseline lumen diameter and lumen diameter after reactive hyperemia (P < 0.001 and P = 0.002). However, there was no significant change in FMD (5.6% +/- 2.2% vs 5.3% +/- 2.1%, P not significant). Levels of hsCRP, vWf, and fibrinogen were significantly decreased (hsCRP: 3.4 +/- 0.49 mg/dl vs 2.97 +/- 0.74 mg/dl, P = 0.001; vWf: 107 +/- 62 vs 86 +/- 58, P = 0.004; fibrinogen: 341 +/- 89 mg/dl vs 299 +/- 87 mg/ dl, P = 0.01) in the treatment group. Nebivolol therapy may have a favorable effect on endothelial function in CSX. Further studies are needed to confirm the clinical significance of nebivolol therapy in CSX.
TL;DR: Telmisartan is well tolerated, shows similar effects on the markers of left ventricular remodeling to those of enalapril, and suppresses vascular inflammation more effectively than enalAPril in AMI patients.
Abstract: Enalapril is effective in the suppression of left ventricular remodeling after acute myocardial infarction (AMI), but the effect of telmisartan is unclear. The consecutive 163 AMI patients underwent primary percutaneous coronary intervention and were randomized to telmisartan (n = 82) or enalapril (n = 81). Left ventriculography was performed in the acute and chronic (6 months) phases. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were measured by zymography in the acute (days 1, 7, and 14) and chronic (6 months) phases. Plasma pentraxin3 (PTX3), a marker of vascular inflammation, was also measured. There were no adverse effects in the telmisartan group. The analysis of the left ventriculograms in the acute and chronic phases revealed no difference between the two groups. MMP-9 activities at days 7 and 14 and in the chronic phase were decreased compared to that at day 1 in both groups. MMP-2 activity was also decreased in the acute phase, but increased in the chronic phase in both groups. There was no difference in the plasma PTX3 level in the acute phase, but in the chronic phase, PTX3 was significantly lower in telmisartan than in enalapril group (2.6 ± 1.4 vs. 3.2 ± 1.6 ng/ml, p = 0.04). Telmisartan is well tolerated, shows similar effects on the markers of left ventricular remodeling to those of enalapril, and suppresses vascular inflammation more effectively than enalapril in AMI patients. Telmisartan can be an alternative to angiotensin converting enzyme inhibitor in patients with AMI.
TL;DR: The incidence of renal impairment following exposure to the contrast medium was low, and this fact can be attributed to adequate parenteral hydratation and the use of the minimum amount of contrast medium necessary.
Abstract: Although the optimal strategy for preventing contrast-induced acute kidney injury (CI-AKI) has not yet been established, the current strategy focuses on adequate periprocedural hydration, the use of a low amount of low or iso-osmolar contrast medium, and the application of adjunctive therapies, including hemofiltration, hemodialysis and drugs. Previous trials and meta-analyses concerning the use of the adenosine antagonist theophylline have revealed contradictory results. We sought to evaluate the effect of theophylline in CI-AKI prevention in well-hydrated elderly patients with chronic kidney disease. We therefore conducted a randomized, double-blind, placebo-controlled trial involving 56 patients who had been referred for cardiac coronary angiography and/or angioplasty. 31 of these patients were randomly assigned to 200 mg theophylline IV before the procedure, and 25 to a placebo. The iso-osmolar contrast medium iodixanol was used. The primary endpoint was an increase in serum creatinine at study termination 48 h after contrast medium administration. Baseline characteristics in the placebo and theophylline groups were similar in terms of median age (75 years), estimated glomerular filtration rate (33 ± 10 vs. 33 ± 10 ml/min/1.73 m2; p = 0.87), diabetes mellitus (80 vs. 71%; p = 0.54), and amount of contrast used (94 ± 35 vs. 95 ± 38 ml; p = 0.89). There was no difference in serum creatinine at baseline (2.06 ± 0.59 vs. 2.02 ± 0.45 mg/dl; p = 0.62) or study termination (2.06 ± 0.68 vs. 2.10 ± 0.53; p = 0.79). A prophylactic effect of theophylline was not observed. The incidence of renal impairment following exposure to the contrast medium was low. This fact can be attributed to adequate parenteral hydratation and the use of the minimum amount of contrast medium necessary.
TL;DR: In patients with ACS undergoing PCI, obesity as assessed with BMI was not an independent correlate of 1-year mortality, after adjustment in the Cox proportional hazards model.
Abstract: Studies that have tested the relationship between body weight as assessed by body mass index (BMI) and clinical outcome after percutaneous coronary intervention (PCI) have given contradictory results. The aim of the study was to investigate the impact of BMI on clinical outcome and assess the impact of adjustment for other cardiovascular risk factors on the relationship between obesity and clinical outcome in patients with acute coronary syndromes (ACS) following PCI. This study included 9146 patients with ACS who underwent coronary angiography and PCI: 2610 patients with ST-segment elevation acute myocardial infarction, 2792 patients with non-ST-segment elevation acute myocardial infarction, and 3744 patients with unstable angina. The primary outcome of this analysis was 1-year mortality. Quartiles of BMI were: 12.8 to 29.1 to 50.7 (4th quartile). Within the first year following PCI, there were 756 deaths: 228 deaths in the 1st BMI quartile, 209 deaths in the 2nd BMI quartile, 161 deaths in the 3rd BMI quartile and 158 deaths in the 4th BMI quartile (Kaplan-Meier estimates of mortality 10.3%, 9.1%, 7.2%, and 7.0%, respectively; odds ratio [OR] = 1.51, 95% confidence interval [CI] 1.22-1.86, P < 0.001 for 1st vs 4th BMI quartile). After adjustment in the Cox proportional hazards model, the association between BMI and 1-year mortality was attenuated to the level of statistical insignificance (hazards ratio [HR] = 1.25, 95% CI 0.94-1.64; P = 0.127 for 1st vs 4th BMI quartile). In conclusion, in patients with ACS undergoing PCI, obesity as assessed with BMI was not an independent correlate of 1-year mortality.
TL;DR: It is concluded that low-dose nesiritide is more effective in suppressing the activation of the sympathetic and renin-angiotensin systems and improves the clinical symptoms and enhances renal function, but its effect on hospital readmission or mortality rate needs further investigation.
Abstract: This study was designed to investigate the effect of low-dose nesiritide on renal function and major cardiac events in patients with acute decompensated heart failure following acute myocardial infarction Sixty patients were randomized into nesiritide (loading dose 05 μg/kg, maintenance dose 00075 μg/kg/min) and nitroprusside groups Compared with the nitroprusside group, the nesiritide group had a greater heart rate reduction (P 005) The rehospitalization or mortality rate was similar between the two groups 3 months after the therapy (P > 005) We conclude that low-dose nesiritide is more effective in suppressing the activation of the sympathetic and renin-angiotensin systems It also improves the clinical symptoms and enhances renal function, but its effect on hospital readmission or mortality rate needs further investigation
TL;DR: Enhanced expression of the UPS colocalized with OMM in cardiomyocytes may be involved in the pathophysiology of DCM hearts.
Abstract: The ubiquitin (Ub)-proteasome system (UPS) is an important proteolytic mechanism for selecting and digesting cytotoxic proteins. The aim of this study is to elucidate expression and in situ localization of the UPS in the myocardium from patients with dilated cardiomyopathy (DCM) with refractory heart failure. The expression profile of the oxidative stress-induced cytotoxic proteins was also examined. Myocardium was obtained from 26 patients with DCM at the left ventriculoplasty. Ten normal autopsied hearts served as controls. Myocardial expressions of Ub and proteasomes were studied immunohistochemically. Oxidative stresses were examined in point of localization of the oxidation-induced modifier molecules (OMM). The relationship between immunohistochemical results and clinical parameters was also evaluated. Both Ub and proteasomes were stained positive in granular structures accumulating between the myofibrils and adjacent to nuclei in cardiomyocytes. The OMMs were also positive in the same Ub-positive granular structures. The area fraction of Ub, proteasomes and OMM was significantly higher in DCM hearts than in normal controls. Significant positive correlation was observed between the area fractions of Ub and plasma levels of brain natriuretic peptide (p = 0.046) in DCM hearts. In conclusion, enhanced expression of the UPS colocalized with OMM in cardiomyocytes may be involved in the pathophysiology of DCM hearts.
TL;DR: Since ET-1 and U-II levels may be increased in plasma of patients with CHD, their activation might have clinical significance in terms of early intervention in patients withCHD, especially after PTCA and stent therapy.
Abstract: Research has identified the vasoconstrictors endothelin-1 (ET-1) and urotensin-II (U-II) as having a role in the development of atherosclerotic cardiovascular disease. We aimed to observe alterations in plasma levels of both ET-1 and U-II in patients with coronary heart disease (CHD) undergoing percutaneous transluminal coronary angioplasty (PTCA) and stent therapy from November 2006 through May 2007. We examined plasma levels of ET-1 and U-II in 40 patients with CHD and 40 age-matched healthy subjects by radioimmunoassay (RIA). Chi-square test, Student’s t-test, and one-way analysis of variance were used for statistical analyses. Correlations between variables were tested by simple linear regression analysis. Coronary heart disease patients had significantly higher ET-1 and UII levels than healthy controls (20.05 ± 4.65 vs 8.16 ± 3.38 and 71.90 ± 11.61 vs 20.89 ± 7.00 pg/ml, respectively, all P 0.05). On day 7 after therapy, CHD patients had significantly lower ET-1 and U-II levels than before therapy (all P < 0.01). Since ET-1 and U-II levels may be increased in plasma of patients with CHD, their activation might have clinical significance in terms of early intervention in patients with CHD, especially after PTCA and stent therapy.
TL;DR: It was showed that renal function and anemia significantly affected the outcome of CHF, and it is clear that the preservation of renal functionand the management of anemia are important in addition to the conventional treatments for CHF.
Abstract: The purpose of this study is to investigate the effects of renal function and anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive patients who were hospitalized at the Division of Cardiology of Fujita Health University Hospital during a 5-year period. The subjects were divided into four groups according to their estimated glomerular filtration rate (e-GFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup comparisons were conducted for underlying heart diseases, clinical findings at the time of hospitalization, treatment, and outcome. Moreover, the patients were divided into two groups according to their serum hemoglobin concentration at the time of hospitalization, using 12.0 g/dl as the dividing point, to study the effects of anemia on the outcome. In the group with decreased renal function, the average age was higher, and ischemic heart disease and associated conditions such as hypertension and diabetes mellitus were observed in most of the patients. In addition, the rate of anemia development and the plasma B-type natriuretic peptide concentration were also high. The greater the deterioration in renal function, the poorer the outcome became (P < 0.0001). Chronic heart failure complicated by anemia showed an especially poor outcome (P < 0.0001). As this study showed that renal function and anemia significantly affected the outcome of CHF, it is clear that the preservation of renal function and the management of anemia are important in addition to the conventional treatments for CHF.
TL;DR: Valve surgery can be performed in octogenarian patients with acceptable mortality, good long-term results, and good quality of life and early referral to surgery should be important to obtain a better postoperative outcome.
Abstract: This study was performed to evaluate surgical outcomes in octogenarian patients undergoing valve surgery. Sixty patients (mean age 82.3 ± 1.9 years) who underwent valve surgery were reviewed. Aortic valve disease was found in 65% of the patients. Preoperatively, 20% of the patients were in NYHA class IV. An urgent operation and concomitant coronary artery bypass grafting were performed in ten patients each. A bioprosthetic valve was exclusively used for valve replacement except in two patients. Mitral valve repair was done in seven patients. Operative mortality was 13.3% for the period. No risk factors for operative mortality were detected by multivariate analysis; however, urgent operation, preoperative NYHA class IV, preoperative renal dysfunction, perioperative use of an intra-aortic balloon pumping, and prolonged cardiopulmonary bypass time had significant effects on operative mortality. The actuarial survival rate at 1 and 3 years after surgery was 82.6 and 71.5%, respectively, and 97.6% of late survivors reported that their activity level was equal to or better than the preoperative level. Valve surgery can be performed in octogenarian patients with acceptable mortality, good long-term results, and good quality of life. Early referral to surgery should be important to obtain a better postoperative outcome.
TL;DR: The evaluation of AoACS on chest radiography is a very simple tool in HD patients and active vitamin D therapy seems to protect patients from developing vascular calcification.
Abstract: The role of decreased active vitamin D levels on vascular calcification has not been elucidated in hemodialysis (HD) patients. The aim of the present study was to evaluate the relationship between progression of aortic arch calcification (AoAC) and prescribed dose of 1α-hydroxy vitamin D. The enrolled study subjects were 65 (40 men and 25 women) HD patients. Calcification of the aortic arch was semiquantitatively estimated with a score (AoACS) on plain chest radiology. Change in AoACS (ΔAoACS) was obtained by subtracting the baseline AoACS value from the follow-up AoACS value. The second assessment was performed from 2 years after the first determination. The nonprogressors (63.2 ± 14.5 years) were significantly younger than the progressors (68.2 ± 10.8 years) (P = 0.0419). In addition, prescribed dose of 1α-hydroxy vitamin D3 was significantly higher in the nonprogressors (125.5 ± 109.1 μg) than progressors (84.8 ± 81.1 μg) (P = 0.0371). Multiple regression analysis revealed prescribed dose of 1α-hydroxy vitamin D3 (β value = −0.324, P = 0.0051) as well as DBP (β value = −0.418, P = 0.007), serum levels of P (β value = 0.333, P = 0.006) and C-reactive protein (β value = 0.237, P = 0.0048) to be significant independent determinants of ΔAoACS. In conclusion, the evaluation of AoACS on chest radiography is a very simple tool in HD patients. Active vitamin D therapy seems to protect patients from developing vascular calcification.
TL;DR: Subjects with combined hyperlipidemia have increased levels of circulating ox-LDL compared to subjects with isolated hypercholesterolemia, but whether this reduction is related to clinical outcomes remains to be shown.
Abstract: Beyond lowering lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (statins) have been shown to possess antioxidant properties, which may explain some of their beneficial effects in reducing atherosclerosis. We sought to determine whether circulating oxidized low-density lipoprotein (ox-LDL) levels differ between subjects with isolated hypercholesterolemia and combined hyperlipidemia, as well as the effect of simvastatin on circulating ox-LDL according to the type of dyslipidemia. Twenty-five subjects with total cholesterol >200 mg/dl and triglycerides 200 mg/dl and triglycerides >150 mg/dl were treated with 40 mg simvastatin daily for 3 months. Serum lipids, C-reactive protein, fibrinogen, ox-LDL, and free radicals were measured at baseline and after 3 months of treatment. In both groups studied, simvastatin significantly improved lipids, and reduced C-reactive protein and fibrinogen levels. Free radicals were significantly reduced only in subjects with hypercholesterolemia. Subjects with combined hyperlipidemia had significantly higher baseline levels of ox-LDL compared to those with hypercholesterolemia (64.6 U/l vs 53.5 U/l, P = 0.03). Ox-LDL levels were reduced by 12% in subjects with hypercholesterolemia (P = 0.03) and by 26% in subjects with combined hyperlipidemia (P = 0.001) after simvastatin treatment. In conclusion, subjects with combined hyperlipidemia have increased levels of circulating ox-LDL compared to subjects with isolated hypercholesterolemia. Simvastatin significantly reduced circulating ox-LDL in both groups, but whether this reduction is related to clinical outcomes remains to be shown.
TL;DR: Dyspnea ameliorated, which was associated with decreased cardiac murmur, subsided abdominal bruit, normalization of the lowered diastolic pressure, and better renal function, and more microcoils can be applied, using the lodged plug as a framework, to achieve the best clinical improvement.
Abstract: A large renal arteriovenous fistula (RAF) may lead to heart failure, renal insufficiency, hematuria, and progressive increase in size of renal vessels Here we present the case of a 67-year-old man with a huge left RAF, who suffered from exertional dyspnea, nocturnal orthopnea, and impaired renal function The left renal vein and inferior vena cava were dilated to 4 cm An Amplatzer Vascular Plug with the largest size of 30 mm in disk diameter was deployed to block the fistula, with balloons inflated at renal artery and vein in advance, to reduce the renal flow in order to prevent plug migration The decrease of shunt flow after embolization was suboptimal However, dyspnea ameliorated, which was associated with decreased cardiac murmur, subsided abdominal bruit, normalization of the lowered diastolic pressure, and better renal function In addition, more microcoils can be applied, using the lodged plug as a framework, to achieve the best clinical improvement