Cardiovascular

Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease of left ventricular hypertrophy (LVH). Phenotypic expression varies widely from subclinical hypertrophy to gross asymmetric septal hypertrophy causing left ventricular outflow tract (LVOT) obstruction. On top of genetic and phenotypic heterogeneity, the prevalence of different types of HCM may have geographical, as well as, ethnic variation. Methods: This observational study was carried out during 2010 to 2020 to determine the echocardiographic profile of HCM in Bangladeshi population. All patients undergoing transthoracic echocardiography (TTE) in a private consultation centre of Dhaka, Bangladesh were included. HCM was defined as the presence of a maximal end-diastolic wall thickness of e”15 mm anywhere in the left ventricle (LV), in the absence of another cause of hypertrophy in adults. HCM was further classified according to the pattern of myocardial hypertrophy and presence or absence of LVOT, or mid...

Context: Flavonoids are natural polyphenolic compounds that are ubiquitous in plants. Numerous prospective epidemiological studies have found beneficial effects of flavonoid consumption on overall cardiovascular mortality. These effects have been attributed to nonspecific antioxidant, anti-atherosclerotic and antithrombotic properties of flavonoids. However, little is known about direct actions of flavonoids on cardiac and vascular smooth muscles.

Aims: To evaluate the effects of three flavonoids (naringenin, quercetin and genistein) on electrical and contractile activities of isolated rat hearts and on contraction of rat abdominal aortic rings.

Methods: Surface electrogram (ECG) and force of contraction (FC) were recorded in isolated rat hearts. The ventricular fibrillation threshold was evaluated with the flavonoids. The effects on aortic contraction were assessed in rat abdominal aortic rings pre-contracted with 60 mM of KCl.

Results: Genistein tended to prolong the QT interval while naringenin tended to decrease it. The effects of all flavonoids on QRS and RR interval were mild and not statistically significant. Genistein and naringenin produced a negative inotropic effect in isolated rat hearts with an IC50 of 13.8 μM and 33.8 μM, respectively. Quercetin at low concentrations had a positive inotropic effect; at high concentrations, it exerted a negative inotropic effect. Naringenin and quercetin increased the threshold for ventricular fibrillation, whereas genistein decreased it. Naringenin, quercetin, and genistein induced concentration-dependent relaxation in endothelium-denuded rat aortic rings.

Conclusions: These flavonoids have direct actions on rat cardiac and vascular smooth muscles.

Time for primary review: 15 days Aims A complex set of metabolic and inflammatory processes are involved in the development of cardiac hypertrophy. Accumulating evidence indicates an important role for Sirt1 in cardiac function, whereas peroxisome proliferatoractivated receptor-a (PPARa) is a master controller of cardiac lipid metabolism and plays a protective role on cardiac hypertrophy. The objective of the present study was to explore the relationships between Sirt1 and PPARa in the control of hypertrophy, metabolism, and inflammation processes in the heart. Methods and results Neonatal cardiomyocytes (NCMs) were used for studies in vitro. Both the activation of Sirt1 with resveratrol (RSV) and overexpression of Sirt1 inhibited phenylephrine (PE)-induced NCM hypertrophy and prevented PE-induced down-regulation of fatty acid oxidation genes. Sirt1 also inhibited the PE-induced increase in mRNA levels of the pro-inflammatory cytokine monocyte chemoattractant protein-1 in NCMs and blocked the enhanced nuclear factor-kB (NF-kB) activity associated with exposure to PE. Importantly, inhibition of PPARa suppressed the beneficial effects of Sirt1 on hypertrophy, fatty acid metabolism, and inflammation. Co-immunoprecipitation studies revealed that overexpression of Sirt1 enhanced PPARa binding to the p65 subunit of NF-kB and led to p65-deacetylation in NCMs. Moreover, Sirt1 overexpression led to the deacetylation of the PPARa co-activator PGC-1a. Consistent with these observations in vitro, isoproterenol-induced cardiac hypertrophy, metabolic dysregulation, and inflammation in vivo were prevented by RSV in wild-type mice but not in PPARa-null mice. Conclusions Collectively, these findings reveal a major involvement of the Sirt1-PPARa interaction in the protective role of Sirt1 against cardiac hypertrophy.

Chronic obstructive pulmonary disease (COPD) is an important and a growing cause of morbidity and mortality worldwide. Cardiovascular, musculoskeletal, metabolic, and mental comorbidities are considered to be part of the frequently prevalent non-pulmonary sequelae of the disease.1,2 Increasing evidence suggests that extra-pulmonary effects of COPD and airflow limitation are only poorly correlated.3 Waschki, et al. found that objectively measured physical activity is the strongest predictor of all-cause mortality in patients with COPD.

Background: The objective of this study was to analyse the impact of acute surgery for native aortic valve endocarditis and its influence on the long-term prognosis after surgery. Methods: A total of 161 patients underwent aortic valve replacement for native active aortic valve endocarditis (NAAVE) during a 29-year period, from 1967 to 1995 (age range: 10 to 72 years; mean 48 ± 12). The main indication for surgery was progressive congestive heart failure (76%). Other indications were unbeatable sepsis (27%), peripheral or central emboli (12%) and, from 1978, echocardiographic evidence of friable, pedunculated vegetations (3%). Streptococcal and staphylococcal infections predominated. Concomitant procedures were performed in 27% of the patients, including mitral and tricuspid valve surgery and coronary bypass procedures. Results: Operative mortality was 8% in the majority of cases caused by heart failure or multiorgan failure. Multivariate logistic regression analysis identified NYHA class IV to be an independent predictor for postoperative death. Long-term survival for discharged patients was 75% at 10 years and 58% at 15 years, with a mortality rate of 3.6%/patient/year. Cox regression analysis identified the year of operation, trivalvular endocarditis and staphylococcal infection as independent predictors of survival. At 10 and 15 years after aortic valve replacement, 91% and 84% of the patients, respectively, were free of recurrent endocarditis. The presence of an abscess cavity at first operation was found to be predictive of recurrent endocarditis. Conclusions: Valve replacement for NAAVE offers a good chance for a cure and satisfactory long-term survival. Improvements in pre- and per-op-rative management of the very ill patient, and the use of allograft valves are likely to further improve long-term results. Finally, the presence of staphylococcal endocarditis requires long-term postoperative antibiotic therapy.

Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, stroke, blindness, and end-stage renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Recent clinical studies have substantiated the concept of "hyperglycemic memory" in the pathogenesis of cardiovascular disease (CVD) in diabetes. Indeed, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that intensive therapy during the DCCT reduces the risk of cardiovascular events by about 50% in type 1 diabetic patients 11 years after the end of the trial. Among various biochemical pathways activated under diabetic conditions, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory "hyperglycemic memory." Further, there is a growing body of evidence that AGEs play an important role in CVD in diabetes. These observations suggest that the inhibition of AGEs formation may be a promising target for therapeutic intervention in diabetic vascular complications. Therefore, in this article, we review several agents with inhibitory effects on AGEs formation and their therapeutic implications in CVD in diabetes.

Cardiac fibroblasts form one of the largest cell populations, in terms of cell numbers, in the heart. They contribute to structural, biochemical, mechanical and electrical properties of the myocardium. Nonetheless, they are often disregarded by in vivo and in vitro studies into cardiac function. This review summarizes our understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart.

Introduction: Diabetes mellitus is associated with an increased risk of adverse clinical outcomes after percutaneous coronary intervention (PCI). The prognosis of patients with diabetes mellitus and chronic total occlusion (CTO) treated with PCI is poorly investigated. Current study evaluates outcome of successful PCI on CTO in patients with and without diabetes. Methods: One hundred and sixty three patients treated with successful PCI on CTO between January 2009 and March 2011 were prospectively identified from the PCI registry at the Madani Heart Center, Tabriz, Iran. Patients were followed for 15±3 months, were evaluated for the occurrence of major adverse cardiac events (MACE) comprising death, acute myocardial infarction, and need for repeat revascularization.Results: No differences were found in baseline clinical and procedural variables between patients with (n=34) and without diabetes (n=129), unless for hypertension (p=0.03). Hospitalization period after PCI in diabetics (3.26±0.61 days) and non-diabetics (2.86±0.52 days) was similar. In-hospital MACE occurred in 8 (23.5%) individuals of diabetics and 10 (7.8%) individuals of non-diabetics (p=0.02), among them revascularization was significantly higher in diabetics (20.6% vs. 7%, p=0.04). Follow-up events in diabetic and non-diabetic groups were 12 (35.3%) and 37 (28.5%), respectively (p was not significant). Conclusion: In patients undergoing successful PCI on CTO, diabetes is associated with higher in-hospital adverse events; however diabetes does not affect long term outcomes in these patients.

A B S T R A C T Ethnobotanical relevance: Pogostemon elsholtzioides Benth. (Lamiaceae) is an aromatic shrub, endemic to eastern Himalaya region. The leaves are used for treating goiter and high blood pressure (BP) by indigenous people in Arunachal Pradesh, India. Young leaves are used as vegetable and leaf decoction is also used for cough, cold and headache by some indigenous communities in Northeast India. Aim of the study: This species is used for treating hypertension and the genus Pogostemon is rich in essential oil. Therefore, the present study was aimed at investigation of the chemical constituents, vasorelaxant and cardiovascular effects of the essential oil of P. elsholtzioides. Materials and methods: P. elsholtzioides was collected from Pasighat, Arunachal Pradesh, India and essential oil was extracted from shade dried leaves. Essential oil was analyzed by GC-FID and GC-MS and the volatile constituents were identified. Vasorelaxant and cardiovascular properties of the essential oil were studied against phenylephrine induced contraction in isolated endothelium intact aortic preparations and by measuring systolic and diastolic BP, mean arterial pressure (MAP) and heart rate (HR) after carotid artery cannulation in Wistar rats. Results: The essential oil was rich in sesquiterpenes and curzerene, benzophenone, α-cadinol and germacrone were major constituents. The essential oil exhibited significant vasodilation effect in phenylephrine induced contracted aortic rings. Vasorelaxant effect of the essential oil was also observed both in the presence and absence of Nitro-L-arginine methyl ester against phenylephrine-contracted aortic rings. It also induced reduction of systolic and diastolic BP, MAP and HR. Conclusions: Essential oil of P. elsholtzioides exhibited significant vasorelaxant effect against endothelium intact aortic preparation mediated through nitric oxide dependent pathway and also reduced BP. However, further study is needed to screen the role of calcium ions in both intracellular and extracellular pathway.

Low doses of aspirin can injure the gastric mucosa. It is not clear whether other drugs such as the antiplatelet agent clopidogrel also cause gastric mucosal injury or exacerbate aspirin-induced injury, or whether proton pump inhibitors prevent damage. METHODS: Twenty Japanese subjects with different CYP2C19 genotypes were randomly assigned to groups that were given a low dose of aspirin (100 mg; A), clopidogrel (75 mg; C), low dose of aspirin and clopidogrel (AC), or low dose of aspirin in combination with clopidogrel and rabeprazole (10 mg; ACR) once daily for 7 days. Subjects underwent gastroduodenoscopy and platelet tests on days 3 and 7; gastric mucosal damage was assessed by using the modified Lanza score (MLS). We performed 24-hour intragastric pH monitoring on day 7 of each regimen. We also analyzed the effects of the AC regimen on 30 patients with different CYP2C19 genotypes. RESULTS: Subjects in groups A, C, and AC had significantly higher levels of gastric mucosal damage on days 3 and 7, compared with baseline. The median MLS for the AC group was similar to that of the A group. Helicobacter pylori-negative subjects in the ACR group with different CYP2C19 genotypes had significant differences in MLS, intragastric pH, and platelet function. Gastric mucosal injury was inhibited equally among H pylori-positive subjects in the ACR group. Rabeprazole did not appear to affect platelet function or intragastric pH in subjects given clopidogrel. CONCLU-SIONS: Clopidogrel and low doses of aspirin cause a similar degree of gastric mucosal damage. Rabeprazole prevented this damage without reducing the antiplatelet function of clopidogrel. However, its prophylactic effect varies with CYP2C19 genotype in H pylori-negative subjects.

Background: Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia, which confers a high risk of mortality and morbidity from stroke and thromboembolism. Altered platelet activation and platelet-dependent thromboembolism have been associated with the pathogenesis of cardiovascular or thromboembolic disorders, which include atherosclerosis, coronary disease and cerebrovascular disease. Platelet adhesion and activation are mediated by human platelet alloantigens (HPAs), a complex of platelet membrane glycoproteins (Gp) and other cellbound Factors. By altering platelet receptor sensitivity, polymorphisms in platelet Gp directly impact platelet susceptibility to activating stimuli, which is linked with an increased risk of atherothrombotic events, including acute myocardial infarction. We wanted to investigate HPA-1 polymorphism in patients with AF who have had a stroke than in healthy controls. Methods: The HPA-1 polymorphism was analysed in 70 patients with nonvalvuler AF who have had a stroke and 65 healthy individuals with no documented episode of AF matched for age, race and sex. Because ethnic differences have been reported for HPA-1. The HPA-1 gene polymorphism was identified by polymerase chain reaction (PCR) method. Distribution of the HPA-1 gene polymorphism alles (allel 1a, allel 1b) genotypes (1a1a, 1a1b and 1b1b) were determined in study population. Demographic characteristics and risk factors for AF and stroke were evaluated in the study groups. Results: There was no significant difference with respect to age and gender between groups. Genotype and allel distribution of AF patients who have had a stroke and control groups shown in the table. The frequency of 1a1a genotype of HPA-1 polymorphism was significantly lower in patients with AF patients who have had a stroke group compared with control group (49 (70%) vs 57 (87.7%), p¼0.012). The frequency of 1a1b genotype heterozygous genotype was significantly higher in AF patients who have had a stroke group than control (18 (25.7%) vs 6 (9.2%), p¼0.012). Between the two groups were compared according to the dominant genetic model (1a1b + 1b1b vs. 1a1a), The number of patients carrying at least one 1b mutant allele (1a1b + 1b1b) was significantly higher in AF patients who have had a stroke group than control (21 (30%) vs 7 (10.8%), p¼0.006). With respect to allelic distribution (1a vs 1b, additive model), the frequency of the 1b allele was significantly higher in AF patients who have had a stroke (24 (17.1%) vs 8 (6.1%), p¼0.009). Conclusıons: In this study, our data suggest that the HPA-1 gene polymorphisms may be associated with AF patients who have had a stroke from other clinical risk factors, but this should be confirmed in a much larger series of patients. Screening for this mutation may help in identifying patients at risk and in deciding the antithrombotic strategy.

Purpose: To assess selected balloon-expandable and selfexpanding stents for radial /brce, flexibility, radio-opacity, and trackability, and to relate these physical characteristics to potential indications for placement. Methods: Force-strain curves were plotted for each stent and the force required to produce 50% luminal narrowing was recorded. The ability of the stent to show elastic recoil following deformation was also noted. Flexibility was measured by bending the stents against a force transducer and recording the force required per degree of flexion. Radioopacity was measured by comparing each stent against a standard aluminum step wedge. Trackability was measured by testing the ability of the stent on its delivery system to track over angles of 90 ~ and 60 ~ . Results: The balloon-expandable stents showed greater radial strength and radio-opacity but, apart from the AVE Iliac Bridge stent, showed poorer flexibility and trackability. The self-expanding stents showed less radial force but were able to re-expand following deformity. They were generally more flexible and had better trackability but lower radio-opacity. Conclusion: There is no stent which exhibits all the ideal properties required and therefore the interventionist will need to keep a range of stents available if all lesions are to be addressed.

We investigated the influence of experimental hyperlipidemia on the formation of cardiac NO, superoxide, and peroxynitrite 2 (ONOO) in rat hearts. Methods: Wistar rats were fed 2% cholesterol-enriched diet or normal diet for 8 weeks. Separate groups of normal and hyperlipidemic rats were injected twice intraperitoneally with 2320 mmol / kg FeTPPS (5,10,15,20-tetrakis-[4-sul-2 fonatophenyl]-porphyrinato-iron[III]), a ONOO decomposition catalyst, 24 h and 1 h before isolation of the hearts. Results: A 21 21 cholesterol diet significantly decreased myocardial NO content, however, myocardial Ca-dependent and Ca-independent NO synthase activity and NO synthase protein level did not change. Myocardial superoxide formation and xanthine oxidase activity were significantly increased; however, cardiac superoxide dismutase activity did not change in the cholesterol-fed group. Dityrosine in the perfusate, a 2 2 marker of cardiac ONOO formation, and plasma nitrotyrosine, a marker for systemic ONOO formation, were both elevated in hyperlipidemic rats. In cholesterol-fed rats, left ventricular end-diastolic pressure (LVEDP) was significantly elevated as compared to controls. Administration of FeTPPS normalized LVEDP in the cholesterol-fed group. Conclusion: We conclude that cholesterol-enriched 2 diet-induced hyperlipidemia leads to an increase in cardiac ONOO formation and a decrease in the bioavailability of NO which contributes to the deterioration of cardiac performance and may lead to further cardiac pathologies.

Purpose: Posterior transverse plication (PTP) has gained popularity as a technique to correct redundancy of the internal carotid artery during endarterectomy. The safety of this technique in large series of patients has not been extensively studied. We investigated 876 primary carotid endarterectomies (CEAs) performed at our institution over the last six years to determine the safety of this technique.

The purpose of this investigation was to provide a detailed description of the angiographic results after stenting of high-grade intracranial stenosis using balloonexpandable stents. Forty consecutive patients with symptomatic atherosclerotic intracranial stenosis[50% received endovascular treatment by placement of balloon-expandable stents using the concept of slight underdilation and strict avoidance of overdilation. Intra-arterial digital subtraction angiography images before and after stenting in the same projection were reviewed for pre-and post-therapeutic measurement of the degree of stenosis and evaluation of morphologic criteria like plaque coverage, stent apposition, patency of side branches, and signs of dissection or vasospasm. Stenting decreased the mean percentage stenosis from 76.2 (WASID criteria) to 20.8%. Residual stenosis ranged from 0 to 55% with residual stenosis[50% in two of 40 cases. Technical success rate was 95%. There were no major vessel complications, but minor abnormalities like incomplete stent apposition (8/40) or plaque coverage (7/40), incomplete filling of side branches (13/40), and minor dissections after stenting (2/40) were seen. One case with incomplete stent apposition and two cases with side branch compromise were associated with clinical symptoms. In conclusion, intracranial stenting with slight underdilation avoided major vessel complication and created reliable luminal gain. Suboptimal recanalization results were frequently detected and may be the source of neurological complications in individual cases.

Epidemiologic studies have linked dioxin exposure to increased mortality caused by ischemic heart disease. To test the hypothesis that dioxin exposure may constitute an environmental risk factor for atherosclerosis, we exposed C57BL/6J mice to 5 µg/kg of dioxin daily for 3 d, and measured various molecular and physiological markers of heart disease. Dioxin treatment led to an increase in the urinary excretion of vasoactive eicosanoids and an elevation in the mean tail-cuff blood pressure. In addition, dioxin exposure led to an increase in triglycerides, but not in high-density lipoproteins, in both Apoe(+/+) mice and in hyperlipidemic Apoe(-/-) mice. Dioxin exposure also led to an increase in low-density lipoproteins in Apoe(-/-) mice. After treatment, dioxin was associated with low-density lipoprotein particles, which might serve as a vehicle to deliver the compound to atherosclerotic plaques. Dioxin treatment of vascular smooth-muscle cells taken from C57Bl/6J mice resulted in the deregulation of several genes involved in cell proliferation and apoptosis. Subchronic treatment of Apoe(-/-) mice with dioxin (150 ng/kg, three times weekly) for 7 or 26 wk caused a trend toward earlier onset and greater severity of atherosclerotic lesions compared to those of vehicle treated mice. These results suggest that dioxin may increase the incidence of ischemic heart disease by exacerbating its severity.

Cardiovascular disease is the leading cause of death and disability for women in Australia. Women living in rural areas are at greater risk of heart disease, because of limited access and availability of healthcare in rural areas. Lifestyle is a major determinant to the risk of heart disease. Risk factors such as smoking, hypertension, diet, physical activity and alcohol intake can be controlled or modified by lifestyle changes. As heart disease develops over many years, women need to be following healthy lifestyle practices and reduce their chance of a first or recurrent heart attack. To determine the effectiveness of primary health education or intervention programs for cardiac risk reduction in healthy women living in rural areas. Types of participants. Women aged 16-65 years, living in rural areas, who participated in primary healthcare education programs. Types of interventions. Primary health education or intervention programs aimed at improving rural women's knowledge of ...

We compared plasma biomarkers of antioxidant status, oxidative stress, inflammation, and risk for coronary heart disease in long-term vegetarians and age-and sex-matched omnivores. METHODS: Thirty vegetarians (mean age Ϯ standard deviation: 44.2 Ϯ 9.0 y) were recruited. The subjects had been vegetarian for 5 to 55 y (21.8 Ϯ 12.2 y). The control group comprised 30 adults selected by age-stratified sampling from a community health project (mean age: 44.0 Ϯ 9.2 y). Fasting plasma total antioxidant status (ferric-reducing antioxidant power), ascorbic acid (AA), ␣-tocopherol (total and lipid standardized), malondialdehyde, total cholesterol, triacylglycerol, uric acid (UA), and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Plasma AA was significantly higher in the vegetarians than in the omnivores (90.5 Ϯ 21.0 and 61.8 Ϯ 17.0 M; P Ͻ 0.001). The vegetarians had lower concentrations of triacylglycerol, UA, and hsCRP. Plasma total and lipid-standardized ␣-tocopherol concentrations were also lower in the vegetarians: 22.0 Ϯ 5.9 and 27.0 Ϯ 7.9 M versus 3.76 Ϯ 0.57 and 4.23 Ϯ 0.58 M per millimoles per liter of total cholesterol plus triacylglycerol, respectively. There was a significant inverse correlation between AA and UA (r ϭ Ϫ0.343, P Ͻ 0.01; n ϭ 60) and between AA and hsCRP (r ϭ Ϫ0.306, P Ͻ 0.05; n ϭ 55). Plasma ferric-reducing antioxidant power and malondialdehyde did not differ significantly between groups; however, the contribution of AA to the total antioxidant capacity of plasma was approximately 50% greater in the vegetarians. CONCLUSIONS: A long-term vegetarian diet is associated with markedly higher fasting plasma AA concentrations and lower concentrations of TAG, UA, and hsCRP. Long-term vegetarians have a better antioxidant status and coronary heart disease risk profile than do apparently healthy omnivores. Plasma AA may act a useful marker of overall health status.

BACKGROUND: Patients with obesity, diabetes, and chronic kidney disease (CKD) are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. METHODS: We performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (body mass index [BMI] > 30 kg/m2),

Left ventricular (LV) diastolic function is important because the enhanced systolic function that underpins high levels of cardio-respiratory fitness has to be matched by changes in LV filling, and LV diastolic dysfunction plays a key early role in the development and progression of a myriad of cardiovascular diseases. This review serves to detail knowledge in relation to: (1) the definition of diastole and the mechanical processes that occur during the diastolic period, (2) the quantitative assessment of diastolic function, predominantly focusing on non-invasive echocardiographic imaging modes such as tissue Doppler imaging and deformation analysis, (3) the impact of acute aerobic exercise on diastolic function, from the augmentation of function necessary to meet the demand for an increased cardiac output at exercise onset, to current concerns related to the impact of prolonged or ultraendurance activity on diastolic function during recovery, (4) the adaptation in diastolic function observed with chronic aerobic exercise training in athletes and sedentary individuals who undergo training programmes, and (5) directions for future research.

We report the case of a 52-year-old woman dying from a noninflammatory, occlusive vasculopathy. Histology showed marked intimal hyperplasia of small arteries of the intestines and myocardium with subsequent infarction of myocardium, large intestine and gallbladder. A comprehensive work up including laboratory studies, clinical investigations and postmortem failed to assign this condition to any of the known vascular diseases. D

The use of metallic stents in the management of benign and malignant superior vena cava syndrome (SVCS) is well documented. Symptomatic stenosis or occlusion of the SVC is a rare complication of a transvenous permanent pacemaker implant. Suggested treatments have included anticoagulation therapy, thrombolysis, balloon angioplasty and surgery. More recently, endovascular stenting has evolved as an attractive alternative but the data available in the literature are limited. We describe a case in which venous stenting with a Wallstent endoprosthesis was used successfully. The patient remains symptom free and with normal pacemaker function 36 months later.

Analysis of mice with genetically altered expression of cardiac connexins can provide insights into the role of individual gap junction channel proteins in cell-to-cell communication, impulse propagation, and arrhythmias. However, conflicting results have been reported regarding conduction velocity slowing in mice heterozygous for a null mutation in the gene encoding connexin43 (Cx43). Methods: High-resolution optical mapping was used to record

In this paper, we present design of a transdermal drug delivery system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The system comprises of integrated control electronics and microelectromechanical system devices such as micropump, micro blood pressure sensor and microneedle array. The objective is to overcome the limitations of oral therapy such as variable absorption profile and the need for frequent dosing, by fabricating a safe, reliable and cost effective transdermal drug delivery system to dispense various pharmacological agents through the skin for treatment of hemodynamic dysfunction such as hypertension. Moreover, design optimization of a piezoelectrically actuated valveless micropump is presented for the drug delivery system. Because of the complexity in analysis of piezoelectric micropump, which involves structural and fluid field couplings in a complicated geometrical arrangement, finite element (FE) numerical simulation rather than an analytical system has been used. The behavior of the piezoelectric actuator with biocompatible polydimethylsiloxane membrane is first studied by conducting piezoelectric analysis. Then the performance of the valveless micropump is analyzed by building a three dimensional electric-solid-fluid model of the micropump. The effect of geometrical dimensions on micropump characteristics and efficiency of nozzle/diffuser elements of a valveless micropump is investigated in the transient analysis using multiple code coupling method. The deformation results of the membrane using multifield code coupling analysis are in good agreement with analytical as well as results of single code coupling analysis of a piezoelectric micropump. The analysis predicts that to enhance the performance of the micropump, diffuser geometrical dimensions such as diffuser length, diffuser neck width and diffuser angle need to be optimized. Micropump flow rate is not strongly affected at low excitation frequencies from 10 to 200 Hz. The excitation voltage is the more dominant factor that affects the flow rate of the micropump as compared with the excitation frequency. However, at extremely high excitation frequencies beyond 8,000 Hz, the flow rate drops as the membrane exhibits multiple bending peaks which is not desirable for fluid flow. Following the extensive numerical analysis, actual fabrication and performance characterization of the micropump is presented. The performance of the micropump is characterized in terms of piezoelectric actuator deflection and micropump flow rate at different operational parameters. The set of multifield simulations and experimental measurement of deflection and flow rate at varying voltage and excitation frequency is a significant advance in the study of the electric-solid-fluid coupled field effects as it allows transient, three dimensional piezoelectric and fluid analysis of the micropump thereby facilitating a more realistic multifield analysis. The results of the present study will also help to conduct relevant strength duration tests of integrated drug delivery device with micropump and microneedle array in future.

The purpose of this article is to review the nerve sprouting hypothesis of sudden cardiac death. It is known that sympathetic stimulation is important in the generation of sudden cardiac death. For example, there is a diurnal variation of sudden death rate in patients with myocardial infarction. Beta blockers, or drugs with beta blocking effects, are known to prevent sudden cardiac death. It was unclear if the cardiac nerves in the heart play only a passive role in the mechanisms of sudden death. To determine if nerve sprouting and neural remodeling occur after myocardial infarction, we performed immunocytochemical studies of cardiac nerves in explanted native hearts of transplant recipients. We found that there was a positive correlation between nerve density and a clinical history of ventricular arrhythmia. Encouraged by these results, we performed a study in dogs to determine whether or not nerve growth factor (NGF) infusion to the left stellate ganglion can facilitate the development of ventricular tachycardia (VT), ventricular fibrillation (VF), and sudden cardiac death (SCD). The results showed that augmented myocardial sympathetic nerve sprouting through NGF infusion plus atrioventricular (AV) block and MI result in a 44% incidence (four of nine dogs) of SCD and a high incidence of VT in the chronic phase of MI. In contrast, none of the six dogs (with AV block and MI) without NGF infusion died suddenly or had frequent VT episodes. Based on these findings, we propose the nerve sprouting hypothesis of ventricular arrhythmia and SCD. The hypothesis states that MI results in nerve injury, followed by sympathetic nerve sprouting and regional (heterogeneous) myocardial hyperinnervation. The coupling between augmented sympathetic nerve sprouting with electrically remodeled myocardium results in VT, VF and SCD. Modification of nerve sprouting after MI may provide a novel opportunity for arrhythmia control.

Objective: The goal of this study was to evaluate effects on human stem cells in vitro and in vivo of an extract from the edible cyanobacterium Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human CD62L (L-selectin). Experimental approach: Ligands for CD62L provide a mechanism for stem cell mobilization in conjunction with down-regulation of the CXCR4 chemokine receptor for stromal derived factor 1. Affinity immunoprecipitation was used to identify a novel ligand for CD62L from a water extract from AFA. The effects of AFA water extract on CD62L binding and CXCR4 expression was tested in vitro using human bone marrow CD34 + cells and the two progenitor cell lines, KG1a and K562. A double-blind randomized crossover study involving 12 healthy subjects evaluated the effects of consumption on stem cell mobilization in vivo. Results: An AFA extract rich in the CD62L ligand reduced the fucoidan-mediated externalization of the CXCR4 chemokine receptor on bone marrow CD34 + cells by 30% and the CD62L + CD34 + cell line KG1A by 50% but did not alter the CXCR4 expression levels on the CD34 À cell line K562. A transient, 18% increase in numbers of circulating CD34 + stem cells maximized 1 hour after consumption ( Pb .0003). When 3 noncompliant volunteers were removed from analysis, the increase in CD34 + cells was 25% ( Pb.0001). Conclusion: AFA water extract contains a novel ligand for CD62L. It modulates CXCR4 expression on CD34 + bone marrow cells in vitro and triggers the mobilization of CD34 + CD133 + and CD34 + CD133 À cells in vivo. D

Aim-Generation of human induced pluripotent stem cell (hiPSC) lines by reprogramming of fibroblast cells with viral-free methods offers unique opportunities for translational cardiovascular medicine. The aim of the study was to reprogram fibroblast cells to hiPSCs, study cardiomyogenic property and ion channel characteristics of the viral-free hiPSC-derived cardiomyocytes. Methods and Results-hiPSCs generated by episomal based vectors generated teratomas in SCID mice, readily formed embryoid bodies and differentiated into cardiomyocytes with comparable efficiency to human embryonic stem cells. Temporal gene expression of these hiPSCs indicated that differentiation of cardiomyocytes was initiated by increasing expression of cardio/mesodermal markers, followed by cardiac-specific transcription factors, structural and ion channel genes. Furthermore, the cardiomyocytes showed characteristic cross-striations of sarcomeric proteins, expressed calcium handling and ion channel proteins, confirming their cardiac ontogeny. Microelectrode array recordings established the electrotonic development of a functional syncytium that responded predictably to pharmacologically active drugs. The cardiomyocytes showed chronotropic dose-response (0.1-10µM) to isoproterenol and Bay K8644. Furthermore, carbamycholine (5µM) suppressed the response to isoproterenol while verapamil (2.5µM) blocked Bay K8644 induced inotropic activity. Moreover, verapamil (1µM) reduced corrected field potential duration (cFPD) by 45% while tetrodotoxin (10µM) shortened minimal field potential (FP min) by 40% while E-4031 (50nM) prolonged field repolarization.

Background: Recent studies have shown that real-time three-dimensional (3D) echocardiography (RT3DE) gives more accurate and reproducible left ventricular (LV) volume and ejection fraction (EF) measurements than traditional two-dimensional methods. A new semi-automated tool (4DLVQ) for volume measurements in RT3DE has been developed. We sought to evaluate the accuracy and repeatability of this method compared to a 3D echo standard. Methods: LV end-diastolic volumes (EDV), end-systolic volumes (ESV), and EF measured using 4DLVQ were compared with a commercially available semi-automated analysis tool (TomTec 4D LV-Analysis ver. 2.2) in 35 patients. Repeated measurements were performed to investigate interand intra-observer variability. Results: Average analysis time of the new tool was 141s, significantly shorter than 261s using TomTec (p < 0.001). Bland Altman analysis revealed high agreement of measured EDV, ESV, and EF compared to TomTec (p = NS), with bias and 95% limits of agreement of 2.1 ± 21 ml,-0.88 ± 17 ml, and 1.6 ± 11% for EDV, ESV, and EF respectively. Intra-observer variability of 4DLVQ vs. TomTec was 7.5 ± 6.2 ml vs. 7.7 ± 7.3 ml for EDV, 5.5 ± 5.6 ml vs. 5.0 ± 5.9 ml for ESV, and 3.0 ± 2.7% vs. 2.1 ± 2.0% for EF (p = NS). The inter-observer variability of 4DLVQ vs. TomTec was 9.0 ± 5.9 ml vs. 17 ± 6.3 ml for EDV (p < 0.05), 5.0 ± 3.6 ml vs. 12 ± 7.7 ml for ESV (p < 0.05), and 2.7 ± 2.8% vs. 3.0 ± 2.1% for EF (p = NS). Conclusion: In conclusion, the new analysis tool gives rapid and reproducible measurements of LV volumes and EF, with good agreement compared to another RT3DE volume quantification tool.

Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT 1 ) receptor that is indicated for the treatment of essential hypertension. It selectively and insurmountably inhibits stimulation of the AT 1 receptor by angiotensin II without affecting other receptor systems involved in cardiovascular regulation. Very high lipophilicity, a unique feature of telmisartan, coupled with a high volume of distribution, indicate that the compound offers the clinically important advantage of good tissue penetration. Telmisartan is not a prodrug and has a longer terminal elimination half-life than other commercially available sartans (~24 h), making it suitable for once-daily dosing. The compound is not metabolized by cytochrome P450 isoenzymes and has a low risk for P450-based drug interactions. In animal models, telmisartan exhibits pronounced cardioand reno-protective effects in animals with severe, essential hypertension. In clinical studies, telmisartan shows comparable antihypertensive activity to members of other major antihypertensive classes, such as ACE inhibitors, beta blockers and calcium antagonists. These trials have confirmed the placebo-like safety and tolerability of telmisartan in hypertensive patients. Based on these data, telmisartan offers advantages over other sartans and represents an important new treatment option for hypertension. FIG. 4. Effect of solvent, telmisartan or co-incubation of telmisartan in the presence of losartan on the log concentration-contractile response curve for AII in rabbit aortic rings; numbers of experiments are given in parentheses. From ref. 61.

Interventional radiology is a relatively new speciality and may be referred to as ''image-guided surgery without a scalpel.'' Training and accreditation bodies regard interventional radiology training as being ''different'' from general radiology because of the additional need for dexterity and clinical acumen. Due to the multidimensional role of an interventional radiologist, a practitioner in this discipline must have a number of the competencies of anesthetists, surgeons, and radiologists. The attributes required of an interventional radiologist are akin to those required of a surgeon. This paper gives an overview of the skills required to be a competent interventional radiologist along with a succinct introduction to methods of assessment of technical and non-technical skills.

The purpose was to determine the prevalence of the rheumatic heart disease in Okédama’s secondary school of Parakou. It was a cross-sectional descriptive study conducted for two months (07 May to 05 July 2012). We included all students present during the survey and whose parents have signed the consent paper. The diagnosis of rheumatic disease was done on the basis of the criteria of Jones. The rheumatic carditis was retained according to the echographic criteria. A total of 483 students were examined among which 220 male. The mean age was 14,2 ±3,2 years. After investigations, no student presented major criteria of Jones but the accumulation of two minor criteria was found in 1,9 % of them.  No student has biological confirmation of rheumatic disease. Finally, no case of rheumatic disease was retained. A large-scale study is necessary to verify these data.

Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.

Sleep disordered breathing (SDB) ranges in severity from primary snoring (PS) to obstructive sleep apnoea (OSA). In adults, SDB is associated with adverse cardiovascular consequences which are mediated, in part, by autonomic dysfunction. Although SDB is common in children, fewer paediatric studies have investigated these cardiovascular effects. Initial research focused on those with OSA, indeed children with PS were occasionally utilised as the comparison control group. However, it is essential to understand the ramifications of this disorder in all its severities, as currently the milder forms of SDB are often untreated. Methodologies used to assess autonomic function in children with SDB include blood pressure (BP), BP variability, baroreflex sensitivity, heart rate variability, peripheral arterial tonometry and catecholamine assays. The aim of this review was to summarise the findings of paediatric studies to date and explore the relationship between autonomic dysfunction and SDB in children, paying particular attention to the roles of disease severity and/or age. This review found evidence of autonomic dysfunction in children with SDB during both wakefulness and sleep. BP dysregulation, elevated generalised sympathetic activity and impairment of autonomic reflexes occur in school-aged children and adolescents with SDB. The adverse effects of SDB seem somewhat less in young children, although more studies are needed. There is mounting evidence that the cardiovascular and autonomic consequences of SDB are not limited to those with OSA, but are also evident in children with PS. The severity of disease and age of onset of autonomic consequences may be important guides for the treatment of SDB.

To determine the frequency of adopting a healthy lifestyle (5 or more fruits and vegetables daily, regular exercise, BMI 18.5-29.9 kg/m 2 , no current smoking) in a middle-aged cohort, and determine the subsequent rates of cardiovascular disease (CVD) and mortality among those who adopt a healthy lifestyle.

Stents have revolutionized percutaneous coronary interventions (PCI), impacting on both acute and long-term results. However, despite improvements in stent design, stent deployment failure is not an unusual event. The aim of the present study was to assess the frequency and causes of stent deployment failure, as well as the outcome of these patients. Between 1997 and 2001, a total of 3,537 patients underwent stent-assisted PCI and delivery of 5,275 stents was attempted. In the majority of patients (118; 78.1%), stenting was performed as provisional; in the remaining 33 (21.8%) as a bailout procedure. A total of 175 (3.3%) stents in 151 (4.3%) patients failed. Failure to deliver the stent to the lesion site was the main cause in 139 patients (92%) and failure either to expand adequately the stent or premature disengagement of the stent from the balloon in only 12 patients (8%). Peripheral stent embolization occurred in 10 (0.3%) patients. Deployment of a different stent in place of the failed one was attempted in 122 patients and was successful in the majority (108; 88.5%). In-hospital major adverse cardiac events were observed in six patients (4%): three patients required emergency coronary artery bypass surgery, two had a myocardial infarction (MI), and one patient underwent urgent repeat coronary intervention. At a mean follow-up of 32.2 ؎ 17.7 months, 22 major adverse cardiac event occurred in 17 patients (11.2%): 1 cardiac death, 3 patients had an MI, and 18 patients required target vessel revascularization. One-year event-free survival for the whole group was 91.2%. Patients with stent embolization did not have any major adverse cardiac or vascular events. Thus, the rate of stent deployment failure in our series was 3.3%, mainly due to failure to deliver the stent to the site. Another stent was successfully deployed in the majority of cases and these patients had favorable short-and long-term outcomes. Cathet Cardiovasc Intervent 2003;59:324 -328.