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26.  A new method of building permanent A-V block model: ablating his-bundle potential through femoral artery with pre-implanted biventricular pacemaker 
Background
To explore the feasibility of a new method of achieving a permanent A-V block animal model.
Methods
16 beagles were randomly divided into two groups based on the method of their pre-implanted biventricular pacemakers. (1) In the first group (8 beagles), the A-V block model was achieved by ablating his-bundle potential at the site of the left ventricular superior-septum, under the aortic sinus, through femoral artery. (2) In the second group (8 beagles), the A-V block model was achieved by ablating his-bundle potential at the triangle of Koch, through femoral vein. A complete A-V block model was achieved as a standard in this study. The success rates, intraoperative arrhythmias, operative and X-ray exposure time, intraoperative bleeding amount were assessed in this two groups, both animal models were followed up for four weeks and then fasted to monitor myocardial pathological changes.
Results
The success rate of the first group, which with fewer intraoperative arrhythmias, and less operative and X-ray exposure time, was significantly higher than the second group.
Conclusions
Compared with traditional animal method, our new method of ablating his-bundle potential at the left ventricle from the femoral artery has a higher success rate, fewer occurrence of malignant arrhythmias, and less operation and X-ray time. Thus, our new method should be preferred in the building of Permanent A-V Block Model.
doi:10.1186/1471-2261-14-164
PMCID: PMC4246545  PMID: 25410685
A-V block; His-bundle potential; Biventricular pacemaker; Radiofrequency ablation; Beagle; Disease models
27.  Validation of the pooled cohort risk score in an Asian population – a retrospective cohort study 
Background
The Pooled Cohort Risk Equation was introduced by the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 in their Blood Cholesterol Guideline to estimate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. However, absence of Asian ethnicity in the contemporary cohorts and limited studies to examine the use of the risk score limit the applicability of the equation in an Asian population. This study examines the validity of the pooled cohort risk score in a primary care setting and compares the cardiovascular risk using both the pooled cohort risk score and the Framingham General Cardiovascular Disease (CVD) risk score.
Methods
This is a 10-year retrospective cohort study of randomly selected patients aged 40–79 years. Baseline demographic data, co-morbidities and cardiovascular (CV) risk parameters were captured from patient records in 1998. Pooled cohort risk score and Framingham General CVD risk score for each patient were computed. All ASCVD events (nonfatal myocardial infarction, coronary heart disease (CHD) death, fatal and nonfatal stroke) occurring from 1998–2007 were recorded.
Results
A total of 922 patients were studied. In 1998, mean age was 57.5 ± 8.8 years with 66.7% female. There were 47% diabetic patients and 59.9% patients receiving anti-hypertensive treatment. More than 98% of patients with pooled cohort risk score ≥7.5% had FRS >10%. A total of 45 CVD events occurred, 22 (7.2%) in males and 23 (3.7%) in females. The median pooled cohort risk score for the population was 10.1 (IQR 4.7-20.6) while the actual ASCVD events that occurred was 4.9% (45/922). Our study showed moderate discrimination with AUC of 0.63. There was good calibration with Hosmer-Lemeshow test χ2 = 12.6, P = 0.12.
Conclusions
The pooled cohort risk score appears to overestimate CV risk but this apparent over-prediction could be a result of treatment. In the absence of a validated score in an untreated population, the pooled cohort risk score appears to be appropriate for use in a primary care setting.
doi:10.1186/1471-2261-14-163
PMCID: PMC4246627  PMID: 25410585
Pooled cohort risk score; Atherosclerotic cardiovascular disease; Validation; Asian population; Framingham risk score; Cardiovascular events; Primary care; Retrospective cohort; Malaysia
28.  Clinical course and outcomes of type-2 diabetic patients after treatment intensification for insufficient glycaemic control - results of the 2 year prospective DiaRegis follow-up 
Background
In cases where antidiabetic monotherapy is unable to sufficiently control glucose levels in patients with type-2 diabetes, treatment needs to be intensified. Determining factors that may be predictors for the occurrence of comorbidities in these patients is essential for improving the efficacy of clinical diabetes care.
Methods
The DiaRegis prospective cohort study included 3,810 type-2 diabetics for whom the treating physician aimed to intensify and optimise antidiabetic treatment due to insufficient glucose control. Treatment intensification was defined as increasing the dose of the originally prescribed drug, and/or selecting an alternative drug, and/or prescribing an additional drug. The aims were to monitor the co-morbidity burden of type-2 diabetic patients over a follow-up of two years, and to identify multivariable adjusted predictors for the development of comorbidity and cardiovascular events.
Results
A total of 3,058 patients completed the 2 year follow-up. A substantial proportion of these patients had co-morbidities such as vascular disease, neuropathy, and heart failure at baseline. After treatment intensification, there was an increased use of DPP-4 inhibitors, insulin, and GLP-1 analogues, achieving reductions in HbA1c, fasting plasma glucose, and postprandial glucose. During the 2 year period 2.5% of patients (n = 75) died, 3.2% experienced non-fatal macrovascular events, 11.9% experienced microvascular events, and 4.3% suffered onset of heart failure. Predictors for combined macro-/microvascular complications/heart failure/death were found to be age (OR 1.36; 95% CI 1.10–1.68), prior vascular disease (1.73; 1.39–2.16), and history of heart failure (2.78; 2.10–3.68).
Conclusions
Determining the factors that contribute to co-morbidities during intensive glucose-lowering treatment is essential for improving the efficacy of diabetes care. Our results indicate that age, prior vascular disease, and heart failure constitute important predictors of poor cardiovascular outcomes in patients receiving such therapy.
doi:10.1186/1471-2261-14-162
PMCID: PMC4247562  PMID: 25410473
Diabetes type 2; Glucose control; Co-morbidities; Treatment intensification; Oral antidiabetic drug; Macrovascular; Microvascular; Heart failure
29.  Idiopathic left ventricular outflow tract ectopy: a single focus with extremely divergent breakouts 
Background
Idiopathic ventricular tachycardia (VT) and/or premature ventricular contractions (PVCs) arise most commonly from the right ventricular outflow tract and less frequently from the left ventricular outflow tract (LVOT), either below or above the semilunar valves.
Case presentation
We report a case of 24-year-old man with idiopathic ventricular tachycardia from a single focus in the supravalvular left ventricular outflow tract with two extremely divergent breakouts observed during the ablation procedure.
Conclusion
Focal sources of ventricular arrhythmia in the aortic root may have different preferential exits and meticulous activation sequence mapping is the preferable strategy to delineate the site of origin.
doi:10.1186/1471-2261-14-161
PMCID: PMC4247694  PMID: 25406950
Ventricular tachycardia; Premature ventricular contractions; Left ventricular outflow tract; Preferential conduction; Non-coronary aortic cusp; Catheter ablation
30.  Balloon expandable transcatheter aortic valve implantation with or without pre-dilation of the aortic valve – rationale and design of a multicenter registry (EASE-IT) 
Background
In patients with severe calcific aortic stenosis, balloon aortic valvuloplasty (BAV) is routinely performed in order to pre-dilate the stenosed aortic valve prior to transcatheter aortic valve implantation (TAVI). Although pre-dilation is considered to be essential for the preparation of the valve landing zone, there is no clear evidence to support its clinical value. In contrast, BAV has been suggested to be linked to several complications. Notably, while preliminary evidence has supported the feasibility and safety of TAVI without pre-dilation, larger studies directly comparing the benefit/risk profile of TAVI in the presence and absence of pre-dilation are required.
Methods/Design
Therefore, a prospective, two-armed, multicenter registry (EASE-IT) was designed to obtain essential data concerning procedural success rates, adverse events, and mortality in a large cohort of patients undergoing transapical (TA)-TAVI using the Edwards SAPIEN 3 balloon expandable heart valves with and without pre-ballooning.
Discussion
Data provided by EASE-IT will be used to assess the relevance of BAV during the TAVI procedure and to investigate associations between patient characteristics and outcomes. Therefore, results obtained from the EASE-IT registry could contribute to reduced rates of TAVI-associated morbidity and mortality in patients with severe, calcific aortic stenosis.
Trial registration
ClinicalTrials.gov Identifier: NCT02127580
doi:10.1186/1471-2261-14-160
PMCID: PMC4247728  PMID: 25403092
EASE-IT; Transcatheter aortic valve implantation; TAVI; Balloon aortic valvuloplasty; BAV
31.  Association between serum free fatty acid levels and possible related factors in patients with type 2 diabetes mellitus and acute myocardial infarction 
Background
Free fatty acids (FFAs) play importance roles in the development of diabetes and cardiovascular diseases. We measured serum FFA levels from type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) patients and assay the correlation between serum FFA levels and related factors. The present study was undertaken to investigate a possible relation between the changes in serum free fatty acid concentration with acute myocardial infarction and type 2 diabetes mellitus.
Methods
The study population consisted of 540 healthy individuals and 103 patients with T2DM, 59 patients with AMI and 21 volunteers. Serum FFAs were measured with high pressure liquid chromatography. Blood urea nitrogen and uric acid were measured in clinical laboratory, as were glycemic, lipid and blood routine parameters. We selected 242 individuals with age over 60 years, 143 healthy individuals and 52 patients with T2DM, 47 patients with AMI were incorporated into three groups as control group, T2DM group and AMI group. Associations were analyzed with stepwise regression analysis with adjusted for age, sex, body mass index.
Results
Serum FFA levels were significantly higher in the age over 60 years individuals compared to 20 ~ 50 years (logFFA μmmol/L:2.60 ± 0.16 vs. 2.73 ± 0.18, P < .001) in the healthy group. We found lower FFA levels in the AMI compared to the T2DM and control group (2.64 ± 0.22 vs. 2.72 ± 0.13&2.72 ± 0.16, respectively, P < .05&P < 0.01) in the age over 60, fasting blood glucose level higher in the AMI and T2DM (5.78 ± 1.32&7.75 ± 2.93 mmol/L vs. 4.90 ± 0.47 mmol/L, P < .01&P < .001) compared with the normal group, HDL level (1.01 ± 0.22&0.98 ± 0.18 mmol/L vs.1.30 ± 0.22 mmol/L, P < .001&P < .001). With stepwise regression analysis, the serum FFA levels was positively associated with the HDL in the control group (YlogFFA = 2.32 + 0.33XHDL, R = 0.26, P < .01) and T2MD (YlogFFA = 2.46 + 0.27XHDL, R = 0.36, P < .05), AST in AMI (YlogFFA =2.24 + 0. 015XAST, R = 0.49, P < .01).
Conclusions
Compared to control group, serum FFA levels were decreased only in AMI group, while HDL level was increased in both AMI and T2DM group. The serum FFA levels were positive association with the HDL level in both T2DM and control group, FFA levels were positive association with AST in AMI.
doi:10.1186/1471-2261-14-159
PMCID: PMC4236447  PMID: 25399059
Acute myocardial infarction (AMI); Type 2 diabetes mellitus (T2DM); Free fatty acid (FFA); High density lipoprotein cholesterol (HDL-c); Aspartate aminotransferase (AST)
32.  Assessment of vitamin D and its association with cardiovascular disease risk factors in an adult migrant population: an audit of patient records at a Community Health Centre in Kensington, Melbourne, Australia 
Background
Vitamin D deficiency is a global public health problem associated with increased risk of cardio-metabolic diseases and osteoarthritis. Migrants with dark skin settled in temperate climates are at greater risk of both vitamin D deficiency and cardiovascular diseases. This study aims to identify the risk of vitamin D deficiency and associations with cardiovascular disease in a migrant population in Australia.
Methods
An audit was carried out at a Community Health Service in Kensington, Melbourne which, services a large migrant population. Data from the clinical records of all adults who visited the medical centre at least once during the period from 1st January 2010 to 31st December 2012 was extracted. The future (10 year) coronary heart disease risk was estimated using Framingham Risk Score.
Results
The centre has given higher priority to vitamin D testing in migrants, those middle-aged, females and those with diabetes and osteoarthritis. Migrants from countries located in lower latitude regions (Latitude N230 to S230) were 1.48 (95% C.I. 1.32-1.65) times more likely to develop vitamin D deficiency post migration and 0.44 (95% C.I. 0.31-0.62) times less likely to have a >15% 10-year risk of coronary heart disease when compared to their Australian-born counterparts.
Conclusions
Adherence to a high risk strategy for vitamin D testing was observed in the centre. Pre-migration latitude is an important factor for vitamin D deficiency (lower the latitude higher the risk) and in predicting future risk of cardiovascular disease in migrants. These findings suggest that a targeted approach for vitamin D testing, including zone of origin might better identify individuals at higher risk of both vitamin D deficiency and cardiovascular disease.
doi:10.1186/1471-2261-14-157
PMCID: PMC4233056  PMID: 25387481
Vitamin D deficiency; Migrants; Cardiovascular diseases; Framingham 10 year risk score
33.  Mapping of a blood pressure QTL on chromosome 17 in American Indians of the strong heart family study 
Background
Blood pressure (BP) is a complex trait, with a heritability of 30 to 40%. Several genome wide associated BP loci explain only a small fraction of the phenotypic variation. Family studies can provide an important tool for gene discovery by utilizing trait and genetic transmission information among relative-pairs. We have previously described a quantitative trait locus at chromosome 17q25.3 influencing systolic BP in American Indians of the Strong Heart Family Study (SHFS). This locus has been reported to associate with variation in BP traits in family studies of Europeans, African Americans and Hispanics.
Methods
To follow-up persuasive linkage findings at this locus, we performed comprehensive genotyping in the 1-LOD unit support interval region surrounding this QTL using a multi-step strategy. We first genotyped 1,334 single nucleotide polymorphisms (SNPs) in 928 individuals from families that showed evidence of linkage for BP. We then genotyped a second panel of 306 SNPs in all SHFS participants (N = 3,807) for genes that displayed the strongest evidence of association in the region, and, in a third step, included additional genotyping to better cover the genes of interest and to interrogate plausible candidate genes in the region.
Results
Three genes had multiple SNPs marginally associated with systolic BP (TBC1D16, HRNBP3 and AZI1). In BQTN analysis, used to estimate the posterior probability that any variant in each gene had an effect on the phenotype, AZI1 showed the most prominent findings (posterior probability of 0.66). Importantly, upon correction for multiple testing, none of our study findings could be distinguished from chance.
Conclusion
Our findings demonstrate the difficulty of follow-up studies of linkage studies for complex traits, particularly in the context of low powered studies and rare variants underlying linkage peaks.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-158) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-158
PMCID: PMC4246441  PMID: 25387527
34.  A randomized control trial to assess the impact of vitamin D supplementation compared to placebo on vascular stiffness in chronic kidney disease patients 
Background
Vitamin D deficiency is associated with cardiovascular (CV) risk in multiple populations, including those with chronic kidney disease (CKD). The active form of the hormone (1,25 OH2D3) binds to receptors in multiple organs. CKD patients are deficient in both 25 Vitamin D and 1,25 OH2D3. Clinical trial data demonstrating the benefits of vitamin D formulations are limited, and fail to show significant benefits on CV outcomes, and have compared different compounds, in various populations, and focused on a variety of outcomes. A understanding of the mechanism by which different vitamin D compounds confer CV protection in CKD is important for the design of future studies.
Methods/Design
This 3 arm randomized prospective double-blinded placebo-controlled study examining the impact of calcitriol (1,25 OH2D3) and 25-hydroxyvitamin D3 supplementation compared to placebo on vascular stiffness, as measured by pulse wave velocity (PWV). Patients are enrolled from 2 tertiary care institutions if they meet inclusion criteria (stable estimated glomerular filtration rate (eGFR) between 15-45ml/min, <±5ml/min change in previous 6 months), on stable doses of renin-angiotensin aldosterone system blockade. For those already receiving vitamin D therapies, a 3 month washout period before randomization is mandatory. Treatment duration is 6 months; medications are given thrice weekly in fixed doses. The primary outcome measure is Vascular stiffness, measured non-invasively by pulse wave velocity (PWV). Other measurements include BP, kidney function and serial blood levels of biomarkers. The primary analysis will compare any vitamin D therapy versus placebo for the primary outcome defined as the change of PWV from baseline to 6 months. Analysis of covariance will be used to detect differences between vitamin D preparations in the magnitude of reduction in PWV.
Discussion
This study is novel in that we are using a robust study design in CKD patients (not on dialysis) comparing placebo to different forms of vitamin D supplementation in fixed doses, irrespective of baseline values. We hope to demonstrate the biological mechanistic effect of vitamin D supplementation on vascular function in order for this information to be used in designing larger randomized controlled trials.
Trial registration
Current Controlled Trials NCT01247311. Date of Registration: November 12, 2010.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-156) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-156
PMCID: PMC4230794  PMID: 25381032
Chronic kidney disease; Vitamin D; Vascular stiffness; PWV; Randomized protocol study
35.  High prevalence of overweight, obesity, and hypertension with increased risk to cardiovascular disorders among adults in northwest Ethiopia: a cross sectional study 
Background
Overweight and obesity are components of a defined cluster of risk factors for non-communicable diseases, once problems for only the high-income countries, in recent days became rampant in developing countries. Despite the lack of extensive data on metabolic and cardio vascular disorders in Ethiopia, the prevalence of obesity among young adults (15–24 years), in a cross sectional study conducted in 1997, was 0.7% for men and 6% for women. The prevalence of hypertension (HTN) was found to be 7.1% of the population. The objective of this study was to see the prevalence and association of overweight, obesity and HTN and to check if there was any agreement among the various anthropometric measurements in detecting overweight and obesity.
Methods
This cross-sectional study was conducted in Gondar city, Northwest Ethiopia. A total of 68 participants with age >18 year were randomly selected and included. Data were collected using questionnaires and through physical measurements of weight, height and blood pressure, using the WHO recommendations.
Result
The prevalence of hypertension was 13.3% (9/68). The prevalence of overweight based on calculated body mass index (BMI) was 32.4% (22/68) while the prevalence of obesity was 16.2% (11/68). Body fat percentage (BFP) effectively classified all of the ‘overweight’ and ‘obese’ values according to the BMI as ‘overweight/obese’ (P = 0.016). Risk level classification with waist circumference enabled to correctly classify most (90.9%) and all of the ‘overweight’ and ‘obese’ BMI values as ‘increased risk/substantially increased risk’ (P < 0.001). Similarly, waist-to-height ratio (WHtR) was able to classify all ‘overweight’ and ‘obese’ BMI values as ‘increased risk/substantially increased risk’ (P < 0.001).
Conclusion
In conclusion, the current study was able to detect a high prevalence of overweight, obesity, and HTN among adult population in Gondar town. There is a prevalent high level of general adiposity and central obesity. WHtR and BFP were the most efficient measurements to identify all ‘high risk’ groups of individuals as ‘high risk’ irrespective of their gender. Further study is recommended to elucidate the risk factors and complications of obesity and overweight in the study area and beyond.
doi:10.1186/1471-2261-14-155
PMCID: PMC4228065  PMID: 25373922
Obesity; Overweight; Metabolic disorder; Hypertension; Anthropometry; Ethiopia
36.  Contrasting clinical evidence for market authorisation of cardio-vascular devices in Europe and the USA: a systematic analysis of 10 devices based on Austrian pre-reimbursement assessments 
Background
European medical device regulation is under scrutiny and will be re-regulated with stricter rules concerning requirements for clinical evidence for high-risk medical devices. It is the aim of this study to analyse the differences between Europe and USA in dealing with risks and benefits of new cardio-vascular devices.
Methods
Since no information is available on clinical data used by the Notified Body for CE-marking, data from Austrian pre-reimbursement assessments close to European market approval were used as proxy and compared with clinical data available at time of market approval by FDA in the USA.
Results
10 cardio-vascular interventions with 27 newly CE approved medical devices were analysed. The time lag between market authorisation in Europe and in the USA is 3 to 7 years. Only 7 CE-marked devices also hold a FDA market approval, 7 further devices are in FDA approved ongoing efficacy trials. For 4 of the CE-marked devices the FDA market application or the approval-trial was either suspended due to efficacy or safety concerns or the approval was denied. Evidence available at time of CE-marking are most often case-series or small feasibility RCTs, while large RCTs and only in rare cases prospective cohort studies are the basis of FDA approvals. Additionally, the FDA often requires post-approval studies for high-risk devices.
Conclusions
Market authorisation based on mature clinical data deriving from larger RCTs and longer follow-ups do not only change the perspective on the risk-benefit ratio, but also secures real patient benefit and safety and assures payers of investing only in truly innovative devices.
doi:10.1186/1471-2261-14-154
PMCID: PMC4232631  PMID: 25366498
Approval; Market authorisation; Medical devices; Evidence based medicine/EbM; Health Technology Assessment/HTA; Cardio-vascular disease; Surgery; Safety
37.  Relationships between obesity, glycemic control, and cardiovascular risk factors: a pooled analysis of cross-sectional data from Spanish patients with type 2 diabetes in the preinsulin stage 
Background
Obesity is associated with the onset of type 2 diabetes mellitus (T2D), but reports conflict regarding the association between obesity and macrovascular complications. In this study, we investigated associations between cardiovascular risk factors and body mass index (BMI) and glycemic control in non–insulin-treated patients with T2D.
Methods
Authors gathered cross-sectional data from five observational studies performed in Spain. Generalized logit models were used to analyze the relationship between cardiovascular risk factors (independent variables) and 5 BMI strata (<25 kg/m2, 25 to <30 kg/m2, 30 to <35 kg/m2, 35 to <40 kg/m2, ≥40 kg/m2) and 5 glycated hemoglobin (HbA1c) strata (≤6.5%, >6.5–7%, >7–8%, >8–9%, >9%) (dependent outcomes).
Results
In total, data from 6442 patients were analyzed. Patients generally had mean values of investigated cardiovascular risk factors outside recommended thresholds. Younger patients had higher BMI, triglyceride levels and HbA1c than their older counterparts. Diastolic blood pressure, systolic blood pressure and triglyceride levels were directly correlated with BMI strata, whereas an inverse correlation was observed between BMI strata and high-density lipoprotein cholesterol (HDL-C) levels, patient age, and duration of T2D. Increased duration of T2D and total cholesterol levels, and decreased HDL-C levels were associated with a higher HbA1c category. BMI and HbA1c levels were not associated with each other.
Conclusions
As insulin-naïve patients with T2D became more obese, cardiovascular risk factors became more pronounced. Higher BMI was associated with younger age and shorter duration of T2D, consistent with the notion that obesity at an early age may be key to the current T2D epidemic. Glycemic control was independent of BMI but associated with abnormal lipid levels. Further efforts should be done to improve modifiable cardiovascular risk factors.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-153) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-153
PMCID: PMC4228158  PMID: 25361574
Cardiovascular disease; Glycosylated hemoglobin A; Prevalence; Obesity; Observational research; Risk factors
38.  Transaortic transcatheter aortic valve implantation - rationale and design of the multicenter, multinational prospective ROUTE registry 
Background
Transaortic transcatheter aortic valve implantation (TAo-TAVI) is a recently developed approach that provides an alternative delivery route for valve replacement in patients with vascular abnormalities or existing comorbidities. While initial studies have shown the principal efficacy and safety, the real world effectiveness and safety of this approach remains to be fully assessed.
Methods/Design
In this regard, the Registry Of the Utilization of the TAo-TAVI approach using the Edwards SAPIEN Valve (ROUTE) represents the first multicenter, multinational prospective documentation of the course and outcome of patients with severe calcific aortic stenosis (AS) undergoing TAo-TAVI. ROUTE commenced in February 2013 with the goal of consecutively enrolling 300 patients at up to 22 sites across Europe. The primary objective of ROUTE is to determine the 30-day mortality associated with TAo-TAVI using the Edwards SAPIEN THV (Edwards Lifesciences, Irvine, CA). In addition, ROUTE aims to quantify complications, predictors of patient outcome and the value of CT guided valve sizing.
Discussion
Findings from this landmark registry will provide important information regarding procedural success rates and early mortality in patients undergoing TAo-TAVI.
Trial registration
Identifier: NCT01991431.
doi:10.1186/1471-2261-14-152
PMCID: PMC4271489  PMID: 25361564
Transaortic transcatheter aortic valve implantation; TAVI; TAo-TAVI; ROUTE; Registry; Mortality
39.  Hypovolaemia was associated with clustering of major cardiovascular risk factors in general population 
Background
Previous studies indicated that the clustering of major cardiovascular disease (CVD) risk factors is common, and multiple unhealthy lifestyles are responsible for the clustering of CVD risk factors. However, little is known about the direct association between the volume load and the clustering of CVD risk factors in general population.
Methods
We investigated the association of the clustering of CVD risk factors (defined as two or more of the following factors: hypertension, diabetes, dyslipidemia and overweight) with volume load, which was evaluated by bioelectrical impedance analysis. Hypovolaemia was defined as extracellular water/total body water (ECW/TBW) at and under the 10th percentile for the normal population.
Results
Among the 7900 adults, only 29.3% were free of any pre-defined CVD risk factors and 40.8% had clustering of CVD risk factors. Hypovolaemia in clustering group was statistically higher than that either in the single or in the none risk factor group, which was 23.7% vs. 17.0% and 10.0%, respectively (P <0.001). As a categorical outcome, the percentage of the lowest quartiles of ECW/TBW and TBW/TBWwatson in clustering group were statistically higher than either those in the single or in the none risk factor group, which were 44.9% vs. 36.9% and 25.1% (P <0.001), 36.2% vs. 32.2% and 25.0%, respectively (P <0.001). After adjusting of potential confounders, hypovolaemia was significantly associated with clustering of CVD risk factors, with an OR of 1.66 (95% CI, 1.45-1.90).
Conclusions
Hypovolaemia was associated with clustering of major CVD risk factors, which further confirms the importance of lifestyle for the development of CVD.
doi:10.1186/1471-2261-14-151
PMCID: PMC4223830  PMID: 25361538
Volume load; Cardiovascular disease; Bioelectrical impedance analysis; Body fluid composition
40.  I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice 
Background
Ivabradine (IVBD), a novel I(f)-channel inhibitor and specific heart rate-lowering agent, is known to have anti-oxidative activity that promotes endothelial function. However, the molecular mechanism through which IVBD acts on cardiac function has yet to be elucidated, especially in experimental diabetic animals.
Methods
For this reason, twenty diabetic mice were randomly assigned to IVBD-treated (10 mg/kg/day) and control (saline) groups. After a 3-month treatment, microarray assay was performed to identify differentia expressed genes, and cardiac function was measured by echocardiography, with subsequent immunohistochemistry analysis and western blotting.
Results
Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB. Ivabradine treatment led to a significant improvement in cardiac function.
Conclusion
Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.
doi:10.1186/1471-2261-14-150
PMCID: PMC4230832  PMID: 25361902
Diabetes; Gene; Microarray; Signal pathway; Immunohistochemistry; Apoptosis
41.  Revisiting the J shaped curve, exploring the association between cardiovascular risk factors and concurrent depressive symptoms in patients with cardiometabolic disease: Findings from a large cross-sectional study 
Background
Depression is common in patients with cardiometabolic diseases but little is known about the relationship, if any, between cardiovascular risk factor values and depressive symptoms in patients with these conditions. The objective of this paper is to study the association between cardiovascular risk factors and concurrent depressive symptoms in patients with three common cardiometabolic conditions: coronary heart disease (CHD), stroke and diabetes.
Methods
We retrospectively reviewed primary care data for N = 35537 with 1 of the above 3 conditions who underwent depression screening using the depressive subscale of hospital anxiety and depression score (HADS-D). We reviewed 4 cardiometabolic risk factors (Systolic Blood Pressure [SBP], Diastolic Blood Pressure [DBP], BMI and total cholesterol) recorded concurrently in all patients and HbA1c in patients with diabetes (n = 18453). We analysed the association between individual risk factor value and a positive HADS-D screening result (>7) using logistic regression.
Results
SBP and BMI were noted to have a non-linear “J-shaped” relationship with the probability of having a positive HADS-D and observed nadirs (levels with the lowest probability) of 148 mm Hg and 30.70 kg/m2, respectively. Total cholesterol and DBP found to have a weaker curvilinear association with concurrent depression symptoms and nadirs of 3.60 mmol/l and 74 mmHg. Among patients with Diabetes, HbA1c was also found to have a “J-shaped” relationship with probability of having a positive HADS-D with an observed nadir of 7.06% DCCT. The above relationships remain significant after adjusting for age, sex, socio-economic status and number of co-morbid conditions.
Conclusion
In patients with cardiometabolic disease, cardiovascular risk factor values at both extremes were associated with higher positive depression screening after adjusting for confounders. These findings have potentially important implications for clinical practice in relation to both risk stratification for depression and approaches to secondary prevention in individuals with cardiometabolic disease and merit further investigation to determine the nature and direction of the observed association.
Please see related article: http://www.biomedcentral.com/1741-7015/12/199.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-139) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-139
PMCID: PMC4271339  PMID: 25352020
Cardiovascular risk factors; J-curve; Depression; Blood pressure; Body mass index; Total cholesterol; HbA1C; Diabetes; Stroke; Coronary heart disease
42.  Partial anomalous pulmonary venous connection to superior vena cava that overrides across the intact atrial septum and has bi-atrial connection in a 75-year-old female presenting with pulmonary hypertension 
Background
Partial anomalous venous connection (PAPVC) is a rare congenital heart disease where the blood flow from one or more pulmonary veins (but not all) returns to the right atrium or systemic venous circulation and is often associated with a sinus venosus atrial defect (SVD). Transthoracic echocardiography (TTE) can provide limited information for this anomaly and the diagnosis of this congenital defect has been a clinical challenge.
Case presentation
We report here a case of a 75-year-old female with adult-onset pulmonary arterial hypertension (PAH), hypoxemia and right-sided chamber dilatation. The diagnosis of PAPVC was made incidentally by multidetector computed tomographic angiography (MCTA) that was performed to exclude pulmonary embolism. In this type of PAPVC, the atrial septum is intact, the right upper pulmonary vein (RUPV) connects to the superior vena cava (SVC), and the SVC overrides across the atrial septum and has bi-atrial connection, all of which are clearly manifested by MCTA.
Conclusions
This case indicates the need to exclude a PAPVC and SVD in unexplained pulmonary hypertension, and MCTA is a reliable non-invasive imaging technique with high resolution and wide anatomic coverage. The case also demonstrates that the coexisting SVD with PAPVC is an anomalous venous connection instead of atrial septal defect (ASD) and its key feature is the overriding of SVC or IVC across the intact atrial septum.
doi:10.1186/1471-2261-14-149
PMCID: PMC4219022  PMID: 25344786
Sinus venosus atrial defect (SVD); Partial anomalous pulmonary venous connection (PAPVC); Pulmonary hypertension
43.  Effects of ACEI/ARB in hypertensive patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled studies 
Background
The effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on cardiovascular (CV) risk in hypertensive patients with type 2 diabetes mellitus (T2 DM) are uncertain. Our objective was to analyze the effects of ACE/ARBs, on the incidence of myocardial infarction, stroke, CV events, and all-cause mortality in hypertensive patients with T2 DM.
Method
PubMed and Embase databases were searched through January 2014 to identify studies meeting a priori inclusion criteria and references in the published articles were also reviewed. Two investigators independently extracted the information with either fixed-effect model or random-effect model to assess the effects of ACE/ARBs treatment in hypertensive patients with T2 DM.
Results
Ten randomized controlled studies were included with a total of 21,871 participants. Overall, treatment with ACE/ARBs in hypertensive patients with T2 DM was associated with a statistically significant 10% reduction in CV events, pooled hazard ratio (HR) of 0.90 [95% confidence intervals (CI): 0.82-0.98] with no heterogeneity (I2 = 19.50%; P = 0.275);and 17% reduction in CV mortality, pooled HR of 0.83 [95% CI: 0.72-0.96] with no heterogeneity (I2 = 0.9%; P = 0.388). ACE/ARBs was not associated with MI, stroke and all-cause mortality.
Conclusions
Treatment with ACE/ARBs results in significant reduction in CV events and mortality in hypertensive patients with T2 DM.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-148) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-148
PMCID: PMC4221690  PMID: 25344747
44.  Prevalence, associated factors and management implications of left ventricular outflow tract obstruction in takotsubo cardiomyopathy: a two-year, two-center experience 
Background
Some patients with Takotsubo cardiomyopathy (TTC) develop cardiogenic shock due to left ventricular outflow tract (LVOT) obstruction – there is, however, a paucity of data regarding this condition.
Methods
Prevalence, associated factors and management implications of LVOT obstruction in TTC was explored, based on two-year data from two Belgian heart centres.
Results
A total of 32 patients with TTC were identified out of 3,272 patients presenting with troponin-positive acute coronary syndrome. In six patients diagnosed with TTC (19%), a significant LVOT obstruction was detected by transthoracic echocardiography. Patients with LVOT obstruction were older and had more often septal bulging, and presented more frequently in cardiogenic shock as compared to those without LVOT obstruction (P < 0.05). Moreover, all patients with LVOT obstruction showed systolic anterior motion (SAM) of the anterior mitral valve leaflet, which was associated with a higher grade of mitral regurgitation (2.2±0.7 vs. 1.0±0.6, P<0.001). Adequate therapeutic management including fluid resuscitation, cessation of inotropic therapy, intravenous β-blocker, and the use of intra-aortic balloon pump resulted in non-inferior survival in TTC patients with LVOT obstruction as compared to those without LVOT obstruction.
Conclusions
TTC is complicated by LVOT obstruction in approximately 20% of cases. Older age, septal bulging, SAM-induced mitral regurgitation and hemodynamic instability are associated with this condition. Timely and accurate diagnosis of LVOT obstruction by echocardiography is key to successful management of these TTC patients with LVOT obstruction and results in a non-inferior outcome as compared to those patients without LVOT obstruction.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2261-14-147) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2261-14-147
PMCID: PMC4210484  PMID: 25339604
Takotsubo cardiomyopathy; Apical ballooning; Outflow tract obstruction; Systolic anterior motion; Cardiogenic shock
45.  Effect of atorvastatin on the expression of gamma-glutamyl transferase in aortic atherosclerotic plaques of apolipoprotein E–knockout mice 
Background
Gamma-glutamyl transpeptidase (GGT) is now considered to be one of the risk factors for cardiovascular disease. However, whether statins can alter GGT levels in arterial atheromatous plaque has not yet been studied. Therefore, the aim of this study is to determine whether statins can effectively decrease the expression of GGT in arterial atheromatous plaques.
Methods
We randomly divided 45 apolipoprotein E–knockout (ApoE KO) male mice into three groups: normal diet (ND) group,high-cholesterol diet (HCD) group and high-cholesterol diet and atorvastatin (HCD + Ato) group. We fed high-cholesterol food to the HCD and HCD + Ato group. After eight weeks, atorvastatin 5 mg•kg−1•d−1 was given to HCD + Ato group mice. The serum GGT-1, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell-adhesion molecule-1 (VCAM-1) levels were measured at end of 16 weeks by using ELISA methods. The expressions of GGT-1, ICAM-1 and VCAM-1 in aorta were measured by RT-PCR and Western Blot.
Results
The ApoE KO mice with HCD were associated with a marked increase in plasma lipid, inflammatory factors, GGT-1, ICAM-1 and VCAM-1. The expressions of GGT-1, ICAM-1 and VCAM-1 in HCD aortic tissue were increased. At the HCD + Ato group were treated with atorvastatin, the levels of lipid, GGT-1, ICAM-1 and VCAM-1were suppressed. Meanwhile, the expressions of GGT-1, ICAM-1 and VCAM-1 were significantly decreased in the whole aorta plaques.
Conclusions
The effect of statins on the expression of GGT in aorta plaque was firstly observed in animal model. The research shows that statins can significantly decrease the expression of GGT in aortic atherosclerotic plaques.
doi:10.1186/1471-2261-14-145
PMCID: PMC4210575  PMID: 25326709
Statins; Atherosclerosis; Gamma-glutamyltransferase; Inflammation
46.  Comparison of clinical outcomes in patients undergoing mitral valve replacement with mechanical or biological substitutes: a 20 years cohort 
Background
The choice of prosthesis for mitral valve replacement still remains controversial. This study assessed mortality, bleeding events and reoperation in patients who underwent mitral valve replacement surgery with biological or mechanical substitutes.
Methods
A total of 352 patients who underwent mitral valve replacement surgery between 1990 and 2008 with 5 to 23 years of follow-up were retrospectively evaluated in a cohort study.
Results
The 5, 10, 15 and 20 year survival rates after surgery using a mechanical substitute were 87.7%, 74.2%, 69.3% and 69.3%, respectively, while after surgery with a biological substitute, they were 87.6%, 71.0%, 64.2% and 56.6%, respectively. There was no significant difference between the two groups (p = 0.38). In the multivariate analysis, the factors associated with death were age, bleeding events and renal failure. The probabilities of remaining free of reoperation at 5, 10, 15 and 20 years after surgery using a mechanical substitute were 94.4%, 92.7%, 92.7% and 92.7%; after surgery with a bioprosthesis, they were 95.9%, 86.4%, 81.2% and 76.5%, respectively (p = 0.073). There was a significantly higher incidence of reoperation for the bioprosthetic valve replacement group (p = 0.008). The probabilities of remaining free of bleeding events at 5, 10, 15 and 20 years after surgery using a mechanical substitute were 95.0%, 91.0%, 89.6% and 89.6%, respectively, while after surgery with a bioprosthesis, they were 96.9%, 94.0%, 94.0% and 94.0%, (p = 0.267).
Conclusions
The authors concluded that: 1) mortality during follow-up was statistically similar for both groups; 2) there was a greater tendency to reoperation in the bioprosthesis group; 3) the probability of remaining free from reoperation remained unchanged after 10 years’ follow-up for patients with mechanical substitute valves; 4) the probability of remaining fee from bleeding events remained unchanged after 10 years’ follow-up for patients given bioprostheses; 5) the baseline characteristics of patients were the greatest determinants of later mortality after surgery; 6) the type of prosthesis was not an independent predictive factor of any of the outcomes tested in the multivariate analysis.
doi:10.1186/1471-2261-14-146
PMCID: PMC4271332  PMID: 25326757
Mitral valve surgery; Mitral prosthesis; Bioprostheses; Mechanical prostheses; Predictors; Mortality
47.  Lower serum triglyceride level is a risk factor for in-hospital and late major adverse events in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention- a cohort study 
Background
Whether serum triglyceride level correlates with clinical outcomes of patients with ST segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI) remains unclear.
Methods
From June 2008 to February 2012, all patients with STEMI who were treated with pPCI in this tertiary referral hospital and then had fasting lipid profiles measured within 24 hours were included and dichotomized into lower- (≦150 mg/dl) and higher-triglyceridemic (>150 mg/dl) groups. Baseline characteristics, in-hospital outcomes, and late major adverse cardiovascular events (MACE) were compared in-between. Independent predictors for in-hospital death and late adverse events were identified by multivariate logistic and Cox regression analyses.
Results
A total of 247 patients were enrolled, including 163 lower-triglyceridemic and 84 higher-triglyceridemic subjects. The angiographic characteristics, pPCI results and in-hospital outcomes were similar between the two groups. However, multivariate logistic analysis identified triglyceride level as a negative predictor for in-hospital death (OR 0.963, 95% CI 0.931-0.995, p = 0.023). At follow-up for a mean period of 1.23 to 1.40 years, compared with the high-triglyceridemic group, low-triglyceridemic patients had fewer cumulative incidences of target vessel revascularization (TVR) (21.7% vs. 9.5%, p = 0.011) and overall MACE (26.1% vs. 11.9%, p = 0.0137). Cox regression analysis confirmed serum triglyceride as a negative predictor for TVR and overall MACE.
Conclusions
Serum triglyceride level inversely correlates with in-hospital death and late outcomes in patients with STEMI treated with pPCI. Thus, when managing such patients, a high serum triglyceride level can be regarded as a benign factor but not a target for aggressive therapy.
doi:10.1186/1471-2261-14-143
PMCID: PMC4197277  PMID: 25303974
Triglyceride; Myocardial infarction; Coronary; Revascularization; Restenosis; Outcome
48.  Sex-dependent association between coronary vessel dominance and cardiac syndrome X: a case-control study 
Background
Previous studies have demonstrated the relevance of left coronary artery dominance in the outcome and prognosis of obstructive coronary artery disease (CAD). However, no studies have investigated the influence of coronary vessel dominance on non obstructive CAD. The aim of this study was to establish the association of left and mixed dominance of the major epicardial arteries with the development of non obstructive CAD and evaluate potential sex-dependent differences in the coronary artery supply.
Methods
A total of 484 patients underwent the same diagnostic procedures. The patients were divided into two groups based on their coronary angiogram results: the control group (242 patients with obstructive CAD; coronary artery stenosis of ≥50%) and the experimental group (242 patients with non obstructive CAD; coronary artery stenosis of <50%).
Results
Significantly more women than men were affected by non obstructive CAD (P = 0.005). Left dominance was more frequent in the non obstructive CAD group than in the control group (P = 0.018) and was more pronounced in women than in men (P = 0.013). Among men with non obstructive CAD, a left supply was more frequent than a mixed supply (P = 0.012). Women with non obstructive CAD had a higher frequency of a left supply, whereas a mixed supply was less frequent in men than in patients with obstructive CAD (P = 0.013 and 0.018, respectively).
Conclusion
These results suggest that left dominance (particularly in women) and the absence of a mixed supply in men could cause regional ischemia, thus affecting the development of non obstructive CAD. Furthermore, sex may determine the incidence of specific coronary artery supply types, therefore influencing disease development and prognosis.
doi:10.1186/1471-2261-14-142
PMCID: PMC4197336  PMID: 25300376
Non obstructive coronary artery disease; Left coronary artery dominance; Mixed coronary artery dominance; Sex; Obstructive coronary artery disease
49.  Speckle tracking echocardiography in the diagnosis of early left ventricular systolic dysfunction in type II diabetic mice 
Abstracts
Background
The leptin receptor-deficient db/db mouse is a well-established type II diabetes animal model used to investigate diabetic cardiomyopathy. Previous reports have documented diabetic cardiomyopathy is accompanied by cardiac structural and functional abnormalities. To better elucidate early or subtle changes in cardiac performance in db/db mice, we used speckle tracking echocardiography to assess systolic myocardial strain in vivo with diabetic db/db mice in order to study early changes of left ventricle contractile function in type II diabetes model.
Methods
Male diabetic db/db mice and age-matched control mice from C57BL/6J strain at 8,12 and 16 weeks of age were subjected to echocardiography. At the midpapillary level in the parasternal left ventricular short-axis view, end diastolic and systolic left ventricular diameter, interventricular septal thickness and posterior wall thicknesses, ejection fraction, fractional shortening were determined by M-mode echocardiography. Using speckle-tracking based strain analysis of two-dimensional echocardiographic images acquired from the parasternal short-axis views at the mid-papillary level, systolic global radial and circumferential strain values were analyzed.
Results
There was no significant difference in interventricular septal thickness, posterior wall thicknesses, end diastolic and systolic left ventricular diameter, ejection fraction and fractional shortening between db/db and age-matched control mice at 8,12 or 16 weeks of age (P > 0.05). At 8 and 12 weeks of age, there was no significant difference in left ventricular radial strain and circumferential strain between db/db mice and age-matched controls (P > 0.05). But at 16 weeks of age, the left ventricular radial strain and circumferential strain in db/db mice were lower than in control mice (P < 0.01).
Conclusion
The present study shows that speckle tracking echocardiography can be used to evaluate cardiac functional alterations in mouse models of cardiovascular disease. Radial and circumferential strain are more sensitive and can be used for detection of early left ventricular contractile dysfunction in db/db type II diabetic mice.
doi:10.1186/1471-2261-14-141
PMCID: PMC4197287  PMID: 25292177
Diabetic cardiomyopathy; db/db mice; Echocardiography; Strain; Cardiac function
50.  Sudden cardiac death in the young (5-39 years) in the canton of Vaud, Switzerland 
Background
Sudden cardiac death (SCD) among the young is a rare and devastating event, but its exact incidence in many countries remains unknown. An autopsy is recommended in every case because some of the cardiac pathologies may have a genetic origin, which can have an impact on the living family members. The aims of this retrospective study completed in the canton of Vaud, Switzerland were to determine both the incidence of SCD and the autopsy rate for individuals from 5 to 39 years of age.
Methods
The study was conducted from 2000 to 2007 on the basis of official statistics and analysis of the International Classification of Diseases codes for potential SCDs and other deaths that might have been due to cardiac disease.
Results
During the 8 year study period there was an average of 292′546 persons aged 5-39 and there were a total of 1122 deaths, certified as potential SCDs in 3.6% of cases. The calculated incidence is 1.71/100′000 person-years (2.73 for men and 0.69 for women). If all possible cases of SCD (unexplained deaths, drowning, traffic accidents, etc.) are included, the incidence increases to 13.67/100′000 person-years. However, the quality of the officially available data was insufficient to provide an accurate incidence of SCD as well as autopsy rates. The presumed autopsy rate of sudden deaths classified as diseases of the circulatory system is 47.5%. For deaths of unknown cause (11.1% of the deaths), the autopsy was conducted in 13.7% of the cases according to codified data.
Conclusions
The incidence of presumed SCD in the canton of Vaud, Switzerland, is comparable to the data published in the literature for other geographic regions but may be underestimated as it does not take into account other potential SCDs, as unexplained deaths. Increasing the autopsy rate of SCD in the young, better management of information obtained from autopsies as well developing of structured registry could improve the reliability of the statistical data, optimize the diagnostic procedures, and the preventive measures for the family members.
doi:10.1186/1471-2261-14-140
PMCID: PMC4198689  PMID: 25291980
Sudden cardiac death; Autopsy rate; Death certification

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