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1.  Impact of adiposity on cardiac structure in adult life: the childhood determinants of adult health (CDAH) study 
Background
We have examined the association between adiposity and cardiac structure in adulthood, using a life course approach that takes account of the contribution of adiposity in both childhood and adulthood.
Methods
The Childhood Determinants of Adult Health study (CDAH) is a follow-up study of 8,498 children who participated in the 1985 Australian Schools Health and Fitness Survey (ASHFS). The CDAH follow-up study included 2,410 participants who attended a clinic examination. Of these, 181 underwent cardiac imaging and provided complete data. The measures were taken once when the children were aged 9 to 15 years, and once in adult life, aged 26 to 36 years.
Results
There was a positive association between adult left ventricular mass (LVM) and childhood body mass index (BMI) in males (regression coefficient (β) 0.41; 95% confidence interval (CI): 0.14 to 0.67; p = 0.003), and females (β = 0.53; 95% CI: 0.34 to 0.72; p < 0.001), and with change in BMI from childhood to adulthood (males: β = 0.27; 95% CI: 0.04 to 0.51; p < 0.001, females: β = 0.39; 95% CI: 0.20 to 0.58; p < 0.001), after adjustment for confounding factors (age, fitness, triglyceride levels and total cholesterol in adulthood). After further adjustment for known potential mediating factors (systolic BP and fasting plasma glucose in adulthood) the relationship of LVM with childhood BMI (males: β = 0.45; 95% CI: 0.19 to 0.71; p = 0.001, females: β = 0.49; 95% CI: 0.29 to 0.68; p < 0.001) and change in BMI (males: β = 0.26; 95% CI: 0.04 to 0.49; p = 0.02, females: β = 0.40; 95% CI: 0.20 to 0.59; p < 0.001) did not change markedly.
Conclusions
Adiposity and increased adiposity from childhood to adulthood appear to have a detrimental effect on cardiac structure.
doi:10.1186/1471-2261-14-79
PMCID: PMC4090182  PMID: 24980215
2.  Acute effects of using an electronic nicotine-delivery device (electronic cigarette) on myocardial function: comparison with the effects of regular cigarettes 
Background
Electronic cigarettes have been developed and marketed in recent years as smoking substitutes. However, no studies have evaluated their effects on the cardiovascular system. The purpose of this study was to examine the immediate effects of electronic cigarette use on left ventricular (LV) function, compared to the well-documented acute adverse effects of smoking.
Methods
Echocardiographic examinations were performed in 36 healthy heavy smokers (SM, age 36 ± 5 years) before and after smoking 1 cigarette and in 40 electronic cigarette users (ECIG, age 35 ± 5 years) before and after using the device with “medium-strength” nicotine concentration (11 mg/ml) for 7 minutes. Mitral flow diastolic velocities (E, A), their ratio (E/A), deceleration time (DT), isovolumetric relaxation time (IVRT) and corrected-to-heart rate IVRT (IVRTc) were measured. Mitral annulus systolic (Sm), and diastolic (Em, Am) velocities were estimated. Myocardial performance index was calculated from Doppler flow (MPI) and tissue Doppler (MPIt). Longitudinal deformation measurements of global strain (GS), systolic (SRs) and diastolic (SRe, SRa) strain rate were also performed.
Results
Baseline measurements were similar in both groups. In SM, IVRT and IVRTc were prolonged, Em and SRe were decreased, and both MPI and MPIt were elevated after smoking. In ECIG, no differences were observed after device use. Comparing after-use measurements, ECIG had higher Em (P = 0.032) and SRe (P = 0.022), and lower IVRTc (P = 0.011), MPI (P = 0.001) and MPIt (P = 0.019). The observed differences were significant even after adjusting for changes in heart rate and blood pressure.
Conclusions
Although acute smoking causes a delay in myocardial relaxation, electronic cigarette use has no immediate effects. Electronic cigarettes’ role in tobacco harm reduction should be studied intensively in order to determine whether switching to electronic cigarette use may have long-term beneficial effects on smokers’ health.
Trial registration
Current Controlled Trials ISRCTN16974547
doi:10.1186/1471-2261-14-78
PMCID: PMC4077146  PMID: 24958250
Electronic cigarette; Smoking; Myocardial function; Diastolic function; Tobacco harm reduction; Nicotine
3.  Effect of seasonal variation on hospital admission due to cardiovascular disease - findings from an observational study in a divisional hospital in Bangladesh 
Background
Seasonal variation in the hospital admission due to cardiovascular disease (CVDs) has been widely reported. However, very limited data on Bangladesh is available regarding this matter. The aim of the current study was to investigate the effect of seasonal variation on hospital admission due to CVDs in a leading hospital of Bangladesh.
Methods
Over a period of two years (from May 2010 to April 2012), the number of patients hospitalized due to various CVDs and number of death among these hospitalized patients were recorded on a day-to-day basis. The data were recorded according to the chief reason of hospital admission such as myocardial infarction or MI (acute, old and non-ST elevation), unstable angina (UA), exaggeration of stable angina, acute left ventricular failure (LVF), cardiomyopathy (ischemic and dilated) or heart failure, syncope and arrhythmia. The data were cumulated and analyzed on month-wise and season-wise manner.
Results
A total of 8371 patients were admitted over the study period (5909 male and 2462 female; M/F ratio - 2.4:1). The highest number of patients were admitted during winter (n = 2839, 33.9%) and lowest during summer (n = 1648, 19.7%). The hospital admission was also significantly higher in winter compared to other seasons (p-value versus summer, autumn and spring was 0.018, 0.020 and 0.023 respectively). Acute MI (n = 2374), Acute LVF (n = 1582) and UA (n = 1277) were the top three reasons for hospitalization. Number of death also significantly higher in winter compared to other seasons (p-value versus summer, winter and spring was 0.044, 0.050 and 0.014 respectively).
Conclusion
A seasonal variation in the hospital admission due to CVDs with a peak in winter was clearly demonstrated in the study. These data could be useful to improve causative prevention measures, therapeutic management, and educational strategies.
doi:10.1186/1471-2261-14-76
PMCID: PMC4064511  PMID: 24927754
Seasonal variation; Cardiovascular disease; Hospital admission; Bangladesh
4.  High-sensitive Troponin T assay for the diagnosis of acute myocardial infarction: an economic evaluation 
Background
Delayed diagnosis and treatment of Acute Myocardial Infarction (AMI) has a major adverse impact on prognosis in terms of both morbidity and mortality. Since conventional cardiac Troponin assays have a low sensitivity for diagnosing AMI in the first hours after myocardial necrosis, high-sensitive assays have been developed. The aim of this study was to assess the cost effectiveness of a high-sensitive Troponin T assay (hsTnT), alone or combined with the heart-type fatty acid-binding protein (H-FABP) assay in comparison with the conventional cardiac Troponin (cTnT) assay for the diagnosis of AMI in patients presenting to the hospital with chest pain.
Methods
We performed a cost-utility analysis (quality adjusted life years-QALYs) and a cost effectiveness analysis (life years gained-LYGs) based on a decision analytic model, using a health care perspective in the Dutch context and a life time time-horizon. The robustness of model predictions was explored using one-way and probabilistic sensitivity analyses.
Results
For a life time incremental cost of 30.70 Euros, use of hsTnT over conventional cTnT results in gain of 0.006 Life Years and 0.004 QALY. It should be noted here that hsTnT is a diagnostic intervention which costs only 4.39 Euros/test more than the cTnT test. The ICER generated with the use of hsTnT based diagnostic strategy comparing with the use of a cTnT-based strategy, is 4945 Euros per LYG and 7370 Euros per QALY. The hsTnT strategy has the highest probability of being cost effective at thresholds between 8000 and 20000 Euros per QALY. The combination of hsTnT and h-FABP strategy’s probability of being cost effective remains lower than hsTnT at all willingness to pay thresholds.
Conclusion
Our analysis suggests that hsTnT assay is a very cost effective diagnostic tool relative to conventional TnT assay. Combination of hsTnT and H-FABP does not offer any additional economic and health benefit over hsTnT test alone.
doi:10.1186/1471-2261-14-77
PMCID: PMC4065542  PMID: 24927776
Cost-effectiveness; Decision model; Acute myocardial infarction; High-sensitive troponin T
5.  Prevalence of lower extremity Peripheral artery disease among adult diabetes patients in Southwestern Uganda 
Background
Peripheral artery disease (PAD) is a major complication of atherosclerosis. PAD can be diagnosed with low-cost diagnostic techniques and is associated with significant morbidity and mortality. While the major epidemiologic risk factors for PAD have been established in the western world, data from resource-poor countries are limited. We performed a cross-sectional study to determine the prevalence and correlates of PAD among patients with diabetes at Mbarara Referral Hospital in southwestern Uganda.
Methods
We consecutively enrolled diabetes patients aged 50 years or greater presenting to the outpatient clinic. We collected blood for fasting lipid profile, HIV serology, and glycosylated hemoglobin, measured blood pressure and ankle brachial index, and administered the Edinburgh Claudication Questionnaire (ECQ). We also surveyed patients for other PAD risk factors. We used logistic regression to determine correlates of PAD.
Results
We enrolled 229 diabetes patients. The median age of 60 years (IQR 55–66), and 146 (63.7%) were female. Fifty five patients (24%) had PAD (ABI of ≤ 0.9). Of these, 48 /55 (87.27%) had mild PAD (ABI 0.71-0.9) while 7/55 (12.73%) had moderate to severe PAD (ABI < 0.7). Amongst those with PAD, 24/55 (43.64%) reported claudication by the ECQ. Correlates of PAD included female sex (AOR 2.25, 95% CI 1.06 - 4.77, p = 0.034), current high blood pressure (AOR 2.59, 95% CI 1.25-5.33, p = 0.01), and being on a sulfonylurea–glibenclamide (AOR 3.47, 95% CI 1.55 - 7.76, p = 0.002).
Conclusion
PAD was common in diabetic patients in southwestern Uganda. Given its low cost and ease of measurement, ABI deserves further assessment as a screening tool for both PAD and long term cardiovascular risk amongst diabetics in this region.
doi:10.1186/1471-2261-14-75
PMCID: PMC4057935  PMID: 24913468
6.  Percutaneous closure of large VSD using a home-made fenestrated atrial septal occluder in 18-year-old with pulmonary hypertension 
Background
Hemodynamically significant muscular ventricular septal defects in children after the infantile period are a rare occurrence and ideal for transcatheter closure. In cases of severe concomitant pulmonary hypertension, it may be necessary to fenestrate the device. In this report, we present an 18-year old patient with a large mid-trabecular ventricular septal defect and severe pulmonary hypertension that underwent percutaneous closure of the defect with a home-made fenestrated atrial septal occluder.
Case presentation
An 18-year-old female patient referred to us with complaints of dyspnea (NYHA score of 2–3). Physical examination revealed an apical rumble and a harsh second heart sound. Echocardiographic examination revealed a large mid-trabecular ventricular septal defect with bidirectional shunt and the widest diameter measuring 22 mm on 2D echocardiography. Left and right heart cavities were enlarged. Before and after the vasoreactivity test performed during cardiac catheterization, average aortic pressure was 65 → 86 mmHg, average pulmonary artery pressure: 58 → 73 mmHg, Qp/Qs: 1.6 → 3.2, PVR: 4.6 → 4.3 Wood/U/m2 and PVR/SVR: 0.5 → 0.2. On left-ventricular angiocardiogram, the largest end-diastolic defect diameter was 21 mm. The closure procedure was performed with transthoracic echocardiographic guidance, using a 24 mm Cera septal occluder and a 14 F sheath dilator to make a 4.5-5 mm opening. Measured immediately after the procedure and during cardiac catheterization one month later, average aortic pressure was 75 → 75 mmHg, average pulmonary artery pressure: 66 → 30 mmHg, Qp/Qs 1.5 → 1.4, PVR: 4.4 → 2.9 Wood/U/m2 and PVR/SVR: 0.4 → 0.2. Transthoracic echocardiographic examination performed 24 hours after the procedure showed a max 35–40 mmHg gradient between the left and right ventricles through the fenestration. After the procedure, we observed sporadic early ventricular systoles and a nodal rhythm disorder that started after approximately 12 hours and spontaneously reverted to normal 9 days later.
Conclusion
In patients with large ventricular septal defects, large atrial septal occluders may be used. In cases with risk of pulmonary vascular disease, a safer option would be to close the defect using a manually fenestrated device.
doi:10.1186/1471-2261-14-74
PMCID: PMC4060098  PMID: 24913354
Transcatheter closure; Home-made fenestration; Muscular ventricular septal defect
7.  Comorbidity profiles and inpatient outcomes during hospitalization for heart failure: an analysis of the U.S. Nationwide inpatient sample 
Background
Treatment of heart failure (HF) is particularly complex in the presence of comorbidities. We sought to identify and associate comorbidity profiles with inpatient outcomes during HF hospitalizations.
Methods
Latent mixture modeling was used to identify common profiles of comorbidities during adult hospitalizations for HF from the 2009 Nationwide Inpatient Sample (n = 192,327).
Results
Most discharges were characterized by "common" comorbidities. A "lifestyle" profile was characterized by a high prevalence of uncomplicated diabetes, hypertension, chronic pulmonary disorders and obesity. A "renal" profile had the highest prevalence of renal disease, complicated diabetes, and fluid and electrolyte imbalances. A "neurovascular" profile represented the highest prevalence of cerebrovascular disease, paralysis, myocardial infarction and peripheral vascular disease. Relative to the common profile, the lifestyle profile was associated with a 15% longer length of stay (LOS) and 12% greater cost, the renal profile was associated with a 30% higher risk of death, 27% longer LOS and 24% greater cost, and the neurovascular profile was associated with a 45% higher risk of death, 34% longer LOS and 37% greater cost (all p < 0.001).
Conclusions
Comorbidity profiles are helpful in identifying adults at higher risk of death, longer length of stay, and accumulating greater costs during hospitalizations for HF.
doi:10.1186/1471-2261-14-73
PMCID: PMC4057902  PMID: 24898986
Heart failure; Comorbidity; Outcomes; Inpatient
8.  Cardiac tamponade and para-aortic hematoma post elective surgical myocardial revascularization on a beating heart – a possible complication of the Lima-stitch and sequential venous anastomosis 
Background
Off-pump coronary artery bypass (OPCAB) surgery can be associated with some intrinsic, but relatively rare complications. A pericardial effusion is a common finding after cardiac surgeries, but the prevalence of a cardiac tamponade does not exceed 2% and is less frequent after myocardial revascularization.
Authors believe that in our patient an injury of a nutritional pericardial or descending aorta vessel caused by the Lima stitch resulted in oozing bleeding, which gradually leaded to cardiac tamponade. The bleeding increased after introduction of double antiplatelet therapy and caused life-threatening hemodynamic destabilization. According to our knowledge it is the first report of such a complication after OPCAB.
Case presentation
We present a case of a 61-year old man, who underwent elective surgical myocardial revascularization on a beating heart. On the 11th postoperative day the patient was readmitted emergently to the intensive care unit for severe chest pain, dyspnoea and hypotension. Coronary angiographic control showed a patency of the bypass grafts and significant narrowing of circumflex artery, treated with angioplasty and stenting. The symptoms and hemodynamic instability exacerbated. A suspicion of dissection of the ascending aorta and para-aortic hematoma was stated on 16-slice cardiac computed tomography. The patient was referred to the Cardiovascular Surgery Clinic. Transthoracic echocardiography revealed cardiac tamponade. On transesophageal echocardiography there were no signs of the ascending aorta dissection, but a possible lesion of the descending aorta with para-aortic hematoma was visualized. Emergent rethoracotomy and cardiac tamponade decompression were performed. 12 days after intervention the control 64-slice computed tomography showed no lesions of the ascending or descending aorta. On one-year follow-up patient is in a good condition, the left ventricular function is preserved and there is no pathology in thoracic aorta on echocardiography.
Conclusions
Mechanical complications of surgical myocardial revascularization on a beating heart should be considered as a cause of the clinical and hemodynamic instability relatively early in the postoperative period. Echocardiographic examination must be the first step in diagnostics process in a patient after cardiac surgery.
doi:10.1186/1471-2261-14-72
PMCID: PMC4078092  PMID: 24898884
Lima-stitch; Cardiac tamponade; Aortic dissection
9.  Do gender differences in primary PCI mortality represent a different adherence to guideline recommended therapy? a multicenter observation 
Background
It is uncertain whether gender differences in outcome after primary percutaneous coronary intervention (PCI) are only attributable to different baseline characteristics or additional factors.
Methods
Databases of two German myocardial infarction network registries were combined with a total of 1104 consecutive patients admitted with acute ST-elevation myocardial infarction (STEMI) and treated according to standardized protocols.
Results
Approximately 25% of patients were females. Mean age (69 vs 61 years), incidence of diabetes (28% vs 20%), hypertension (68 vs 58%) and renal insufficiency (26% vs 19%) was significantly higher compared to males. Mean prehospital delay was numerically longer in females (227 vs 209 min) as was in hospital delay (35 vs 30 min). PCI was finally performed in 92% of females and 95% of males with comparable procedural success (95% vs 97%). Use of drug eluting stents (55% vs 68%) and application of GP 2b 3a blockers (75% vs 89%) was significantly less frequent in women. At discharge, prescription of beta blockers and lipid lowering drugs was also significantly lower in females (84% vs 90% and 71% vs 84%). Unadjusted in-hospital mortality was significantly higher in females (10% vs 5%) without attenuation after 12 months. Adjusted mortality however did not differ significantly between genders.
Conclusion
Higher unadjusted mortality in females after primary PCI was accompanied by significant differences in baseline characteristics, interventional approach and secondary prophylaxis in spite of the same standard of care. Lower guideline adherence seems to be less gender specific but rather a manifestation of the risk-treatment paradox.
doi:10.1186/1471-2261-14-71
PMCID: PMC4061506  PMID: 24893930
Primary PCI; Myocardial infarction network; Gender differences
10.  The impact of omega-3 polyunsaturated fatty acid supplementation on the incidence of cardiovascular events and complications in peripheral arterial disease: a systematic review and meta-analysis 
Background
Individuals with peripheral arterial disease are at higher risk for cardiovascular events than the general population. While supplementation with omega-3 polyunsaturated fatty acids (PUFA) has been shown to improve vascular function, it remains unclear if supplementation decreases serious clinical outcomes. We conducted a systematic review and meta-analysis to determine whether omega-3 PUFA supplementation reduces the incidence of cardiovascular events and complications in adults with peripheral arterial disease.
Methods
We searched five electronic databases (MEDLINE, EMBASE, CENTRAL, Scopus and the International Clinical Trials Registry Platform) from inception to 6 December 2013 to identify randomized trials of omega-3 PUFA supplementation (from fish or plant oils) that lasted ≥12 weeks in adults with peripheral arterial disease. No language filters were applied. Data on trial design, population characteristics, and health outcomes were extracted. The primary outcome was major adverse cardiac events; secondary outcomes included myocardial infarction, cardiovascular death, stroke, angina, amputation, revascularization procedures, maximum and pain-free walking distance, adverse effects of the intervention, and quality of life. Trial quality was assessed using the Cochrane Risk of Bias tool.
Results
Of 741 citations reviewed, we included five trials enrolling 396 individuals. All included trials were of unclear or high risk of bias. There was no evidence of a protective association of omega-3 PUFA supplementation against major adverse cardiac events (pooled risk ratio 0.73, 95% CI 0.22 to 2.41, I 2 75%, 2 trials, 288 individuals) or other serious clinical outcomes. Adverse events and compliance were poorly reported.
Conclusions
Our results showed that insufficient evidence exists to suggest a beneficial effect of omega-3 PUFA supplementation in adults with peripheral arterial disease with regard to cardiovascular events and other serious clinical outcomes.
doi:10.1186/1471-2261-14-70
PMCID: PMC4065588  PMID: 24885361
Omega-3 polyunsaturated fatty acid; Peripheral arterial disease; Intermittent claudication
11.  Birth weight and the risk of atrial fibrillation in whites and African Americans: the Atherosclerosis Risk In Communities (ARIC) study 
Background
Low birth weight (LBW) has been associated with an increased risk of cardiovascular disease (CVD). A previous study, however, found higher risk of atrial fibrillation (AF) in individuals with higher birth weight (BW). To further understand this apparent paradox, we examined the relationship between AF and BW in the Atherosclerosis Risk in Communities (ARIC) cohort.
Methods
The analysis included 10,132 individuals free of AF at baseline (1996–1998), who provided BW information, were not born premature, and were not a twin. Self-reported BW was categorized as low (<2.5 kg), medium (2.5-4 kg), and high (>4.0 kg). AF incidence was ascertained from hospital discharge codes and death certificates. We used multivariable Cox proportional hazard models to determine the hazard ratios (HR) and 95% confidence intervals (CI) of AF across BW groups.
Results
During an average follow-up of 10.3 years, we identified 882 incident AF cases. LBW was associated with higher risk of AF. Compared to individuals in the medium BW category, the HR (95% CI) of AF was 1.33 (0.99, 1.78) for LBW and 1.00 (0.81, 1.24) for high BW after adjusting for sociodemographic variables (p for trend = 0.29). Additional adjustment for CVD risk factors did not attenuate the associations (HR 1.42, 95% CI 1.06, 1.90 for LBW and HR 0.86, 95% CI 0.69-1.07 for high BW, compared to medium BW, p for trend = 0.01).
Conclusion
LBW was associated with a higher risk of AF. This association was independent of known predictors of AF and is consistent with that observed for other cardiovascular diseases.
doi:10.1186/1471-2261-14-69
PMCID: PMC4045869  PMID: 24885251
Atrial fibrillation; Birth weight; Race; Sex
12.  Association of body mass index with risk of acute myocardial infarction and mortality in Norwegian male and female patients with suspected stable angina pectoris: a prospective cohort study 
Background
A number of previous studies have suggested that overweight or obese patients with coronary artery disease (CAD) may have lower morbidity and mortality than their leaner counterparts. Few studies have addressed possible gender differences, and the results are conflicting. We examined the association between body mass index (BMI) and risk of acute myocardial infarction (AMI), cardiovascular (CV) death and all-cause mortality in men and women with suspected stable angina pectoris.
Method
The cohort included 4164 patients with suspected stable angina undergoing elective coronary angiography between 2000 and 2004. Events were registered until the end of 2006. Hazard ratios (HR) (95% confidence intervals) were estimated using Cox regression by comparing normal weight (18.5-24.9 kg/m2) with overweight (25–29.9 kg/m2) and obese (≥30 kg/m2) patients. Underweight (<18.5 kg/m2) patients were excluded from the study.
Results
Of 4131 patients with complete data, 72% were males and 75% were diagnosed with significant CAD. The mean (standard deviation (SD)) age in the total population was 62 (10) years. Mean (SD) BMI was 26.8 (3.9) kg/m2, 34% was normal weight, 48% overweight and 19% obese. During follow up, a total of 337 (8.2%) experienced an AMI and 302 (7.3%) patients died, of whom 165 (4.0%) died from cardiovascular causes. We observed a significant interaction between BMI groups and gender with regards to risk of AMI (p = 0.011) and CV death (p = 0.031), but not to risk of all-cause mortality; obese men had a multivariate adjusted increased risk of AMI (HR 1.80 (1.28, 2.52)) and CV death (HR 1.60 (1.00, 2.55)) compared to normal weight men. By contrast, overweight women had a decreased risk of AMI (HR 0.56 (0.33, 0.98)) compared to normal weight women. The risk of all-cause mortality did not differ between BMI categories.
Conclusion
Compared with normal weight subjects, obese men had an increased risk of AMI and CV death, while overweight women had a decreased risk of AMI. These findings may potentially explain some of the result variation in previous studies reporting on the obesity paradox.
Trial registration
Clinicaltrials.gov Identifier: NCT00354081
doi:10.1186/1471-2261-14-68
PMCID: PMC4032453  PMID: 24885137
Acute myocardial infarction; Body mass index; Cardiovascular disease; Obesity paradox
13.  Plasma NT pro-BNP, hs-CRP and big-ET levels at admission as prognostic markers of survival in hospitalized patients with dilated cardiomyopathy: a single-center cohort study 
Background
Circulating N-terminal pro-B-type natriuretic peptide (NT pro-BNP), high- sensitivity C-reactive protein (hs-CRP) and big endothelin (big-ET) have been shown to be increased in heart failure and to contribute to both hemodynamic deterioration and cardiovascular remodeling. Here, we examined the prognostic value of the three neurohormones at admission in a population of hospitalized patients with dilated cardiomyopathy (DCM).
Methods and results
This cohort study was undertaken in 622 hospitalized patients with DCM in Fuwai Hospital from January 2005 to September 2011 (female 26.5%, 51.4 ± 14.6 years old). Standard demographics, echocardiography and routine blood samples were obtained shortly after admission. NT pro-BNP, hs-CRP and big-ET were measured, and their concentrations in relation to all-cause mortality were assessed through a mean follow-up of 2.6 ± 1.6 years. Kaplan-Meier curves showed that the all-cause mortality rates were higher in patients with NT pro-BNP > 2247 pmol/L compared to patients with NT pro-BNP < 2247 pmol/L (11.9% vs 34.8%, log-rank χ2 = 35.588, P < 0.001), in patients with hs-CRP > 3.90 mg/L compared to patients with hs-CRP < 3.90 mg/L (12.8% vs 33.6%, log-rank χ2 = 39.662, P < 0.001) and in patients with big-ET > 0.95 pmol/L compared to patients with big-ET <0.95 pmol/L (12.5% vs 31.0%, log-rank χ2 = 17.890, P < 0.001). High circulating concentrations of NT pro-BNP (HR 2.217, 95% CI 1.015-4.846, P = 0.046) and hs-CRP (HR 1.922, 95% CI 1.236-2.988, P = 0.004), but not big-ET, in addition to left atrial diameter and fasting blood glucose, were independent predictors of the outcome defined as all-cause mortality.
Conclusions
In a large population of patients with DCM, the circulating concentrations of NT pro-BNP and hs-CRP, but not big-ET, were independent markers of all-cause mortality.
doi:10.1186/1471-2261-14-67
PMCID: PMC4041639  PMID: 24885051
Dilated cardiomyopathy; NT pro-BNP; Hs-CRP; Big-endothelin; Prognosis
14.  Distal end side-to-side anastomoses of sequential vein graft to small target coronary arteries improve intraoperative graft flow 
Background
End-to-side anastomoses to connect the distal end of the great saphenous vein (GSV) to small target coronary arteries are commonly performed in sequential coronary artery bypass grafting (CABG). However, the oversize diameter ratio between the GSV and small target vessels at end-to-side anastomoses might induce adverse hemodynamic condition. The purpose of this study was to describe a distal end side-to-side anastomosis technique and retrospectively compare the effect of distal end side-to-side versus end-to-side anastomosis on graft flow characteristics.
Methods
We performed side-to-side anastomoses to connect the distal end of the GSV to small target vessels on 30 patients undergoing off-pump sequential CABG in our hospital between October 2012 and July 2013. Among the 30 patients, end-to-side anastomoses at the distal end of the GSV were initially performed on 14 patients; however, due to poor graft flow, those anastomoses were revised into side-to-side anastomoses. We retrospectively compared the intraoperative graft flow characteristics of the end-to-side versus side-to-side anastomoses in the 14 patients. The patient outcomes were also evaluated.
Results
We found that the side-to-side anastomosis reconstruction improved intraoperative flow and reduced pulsatility index in all the 14 patients significantly. The 16 patients who had the distal end side-to-side anastomoses performed directly also exhibited satisfactory intraoperative graft flow. Three-month postoperative outcomes for all the patients were satisfactory.
Conclusions
Side-to-side anastomosis at the distal end of sequential vein grafts might be a promising strategy to connect small target coronary arteries to the GSV.
doi:10.1186/1471-2261-14-65
PMCID: PMC4023697  PMID: 24884776
Coronary artery bypass grafts; venous graft; off-pump surgery
15.  Rhabdomyomas and Tuberous sclerosis complex: our experience in 33 cases 
Background
Rhabdomyomas are the most common type of cardiac tumors in children. Anatomically, they can be considered as hamartomas. They are usually randomly diagnosed antenatally or postnatally sometimes presenting in the neonatal period with haemodynamic compromise or severe arrhythmias although most neonatal cases remain asymptomatic. Typically rhabdomyomas are multiple lesions and usually regress spontaneously but are often associated with tuberous sclerosis complex (TSC), an autosomal dominant multisystem disorder caused by mutations in either of the two genes, TSC1 or TSC2. Diagnosis of tuberous sclerosis is usually made on clinical grounds and eventually confirmed by a genetic test by searching for TSC genes mutations.
Methods
We report our experience on 33 cases affected with rhabdomyomas and diagnosed from January 1989 to December 2012, focusing on the cardiac outcome and on association with the signs of tuberous sclerosis complex. We performed echocardiography using initially a Philips Sonos 2500 with a 7,5/5 probe and in the last 4 years a Philips IE33 with a S12-4 probe. We investigated the family history, brain, skin, kidney and retinal lesions, development of seizures, and neuropsychiatric disorders.
Results
At diagnosis we detected 205 masses, mostly localized in interventricular septum, right ventricle and left ventricle. Only in 4 babies (12%) the presence of a mass caused a significant obstruction. A baby, with an enormous septal rhabdomyoma associated to multiple rhabdomyomas in both right and left ventricular walls died just after birth due to severe heart failure. During follow-up we observed a reduction of rhabdomyomas in terms of both number and size in all 32 surviving patients except in one child. Eight patients (24,2%) had an arrhythmia and in 2 of these cases rhabdomyomas led to Wolf-Parkinson-White Syndrome. For all patients the arrhythmia spontaneously totally disappeared or was reduced gradually. With regarding to association with tuberous sclerosis, we diagnosed tuberous sclerosis clinically in 31 babies (93,9%).
Conclusion
Rhabdobyomas are tumors with favorable prognosis because they frequently do not cause symptoms and they often regress in numbers and size. Nevertheless, due to frequent association with tuberous sclerosis complex and the resulting neurological impairment, the prognosis can result unfavorable.
doi:10.1186/1471-2261-14-66
PMCID: PMC4039990  PMID: 24884933
Cardiac masses; Rhabdomyomas; Tuberous sclerosis complex; Echocardiography
16.  Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis 
Background
We investigated whether right ventricular dysfunction (RVD) as assessed by echocardiogram can be used as a prognostic factor in hemodynamically stable patients with acute pulmonary embolism (PE). Short-term mortality has been investigated only in small studies and the results have been controversial.
Methods
A PubMed search was conducted using two keywords, “pulmonary embolism” and “echocardiogram”, for articles published between January 1st 1998 and December 31st 2011. Out of 991 articles, after careful review, we found 12 articles that investigated the implications of RVD as assessed by echocardiogram in predicting short-term mortality for hemodynamically stable patients with acute PE. We conducted a meta-analysis of these data to identify whether the presence of RVD increased short-term mortality.
Results
Among 3283 hemodynamically stable patients with acute PE, 1223 patients (37.3%) had RVD, as assessed by echocardiogram, while 2060 patients (62.7%) had normal right ventricular function. Short-term mortality was reported in 167 (13.7%) out of 1223 patients with RVD and in 134 (6.5%) out of 2060 patients without RVD. Hemodynamically stable patients with acute PE who had RVD as assessed by echocardiogram had a 2.29-fold increase in short-term mortality (odds ratio 2.29, 95% confidence interval 1.61-3.26) compared with patients without RVD.
Conclusions
In hemodynamically stable patients with acute PE, RVD as assessed by echocardiogram increases short-term mortality by 2.29 times. Consideration should be given to obtaining echocardiogram to identify high-risk patients even if they are hemodynamically stable.
doi:10.1186/1471-2261-14-64
PMCID: PMC4029836  PMID: 24884693
Echocardiography; Pulmonary embolism; Right ventricular dysfunction
17.  A comparison of risk factors for mortality from heart failure in Asian and non-Asian populations: An overview of individual participant data from 32 prospective cohorts from the Asia-Pacific Region 
Background
Most of what is known regarding the epidemiology of mortality from heart failure (HF) comes from studies within Western populations with few data available from the Asia-Pacific region where the burden of heart failure is increasing.
Methods
Individual level data from 543694 (85% Asian; 36% female) participants from 32 cohorts in the Asia Pacific Cohort Studies Collaboration were included in the analysis. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality from HF were estimated separately for Asians and non-Asians for a quintet of cardiovascular risk factors: systolic blood pressure, diabetes, body mass index, cigarette smoking and total cholesterol. All analyses were stratified by sex and study.
Results
During 3,793,229 person years of follow-up there were 614 HF deaths (80% Asian). The positive associations between elevated blood pressure, obesity, and cigarette smoking were consistent for Asians and non-Asians. There was evidence to indicate that diabetes was a weaker risk factor for death from HF for Asians compared with non-Asians: HR 1.26 (95% CI: 0.74-2.13) versus 3.04 (95% CI 1.76-5.25) respectively; p for interaction = 0.022. Additional adjustment for covariates did not materially change the overall associations. There was no good evidence to indicate that total cholesterol was a risk factor for HF mortality in either population.
Conclusions
Most traditional cardiovascular risk factors including elevated blood pressure, obesity and cigarette smoking appear to operate similarly to increase the risk of death from HF in Asians and non-Asians populations alike.
doi:10.1186/1471-2261-14-61
PMCID: PMC4037783  PMID: 24884382
Meta-analysis; Heart failure; Epidemiology
18.  Transfers to metropolitan hospitals and coronary angiography for rural Aboriginal and non‐Aboriginal patients with acute ischaemic heart disease in Western Australia 
Background
Aboriginal people have a disproportionately higher incidence rate of ischaemic heart disease (IHD) than non-Aboriginal people. The findings on Aboriginal disparity in receiving coronary artery procedures are inconclusive. We describe the profile and transfers of IHD patients admitted to rural hospitals as emergency admissions and investigate determinants of transfers and coronary angiography.
Methods
Person-linked hospital and mortality records were used to identify 28-day survivors of IHD events commencing at rural hospitals in Western Australia. Outcome measures were receipt of coronary angiography, transfer to a metropolitan hospital, and coronary angiography if transferred to a metropolitan hospital.
Results
Compared to non-Aboriginal patients, Aboriginal patients with IHD were more likely to be younger, have more co-morbidities, reside remotely, but less likely to have private insurance. After adjusting for demographic characteristics, Aboriginal people with MI were less likely to be transferred to a metropolitan hospital, and if transferred were less likely to receive coronary angiography. These disparities were not significant after adjusting for comorbidities and private insurance. In the full multivariate model age, comorbidities and private insurance were adversely associated with transfer to a metropolitan hospital and coronary angiography.
Conclusion
Disparity in receiving coronary angiography following emergency admission for IHD to rural hospitals is mediated through the lower likelihood of being transferred to metropolitan hospitals where this procedure is performed. The likelihood of a transfer is increased if the patient has private insurance, however, rural Aboriginal people have a lower rate of private insurance than their non-Aboriginal counterparts. Health practitioners and policy makers can continue to claim that they treat Aboriginal and non-Aboriginal people alike based upon clinical indications, as private insurance is acting as a filter to reduce rural residents accessing interventional cardiology. If health practitioners and policy makers are truly committed to reducing health disparities, they must reflect upon the broader systems in which disparity is perpetuated and work towards a systems improvement.
doi:10.1186/1471-2261-14-58
PMCID: PMC4021447  PMID: 24886321
Oceanic ancestry group; Ischaemic heart disease; Myocardial infarction; Healthcare Disparities; Rural Hospitals; Health Insurance; Coronary angiography
19.  Usefulness of the heart-rate variability complex for predicting cardiac mortality after acute myocardial infarction 
Background
Previous studies indicate that decreased heart-rate variability (HRV) is related to the risk of death in patients after acute myocardial infarction (AMI). However, the conventional indices of HRV have poor predictive value for mortality. Our aim was to develop novel predictive models based on support vector machine (SVM) to study the integrated features of HRV for improving risk stratification after AMI.
Methods
A series of heart-rate dynamic parameters from 208 patients were analyzed after a mean follow-up time of 28 months. Patient electrocardiographic data were classified as either survivals or cardiac deaths. SVM models were established based on different combinations of heart-rate dynamic variables and compared to left ventricular ejection fraction (LVEF), standard deviation of normal-to-normal intervals (SDNN) and deceleration capacity (DC) of heart rate. We tested the accuracy of predictors by assessing the area under the receiver-operator characteristics curve (AUC).
Results
We evaluated a SVM algorithm that integrated various electrocardiographic features based on three models: (A) HRV complex; (B) 6 dimension vector; and (C) 8 dimension vector. Mean AUC of HRV complex was 0.8902, 0.8880 for 6 dimension vector and 0.8579 for 8 dimension vector, compared with 0.7424 for LVEF, 0.7932 for SDNN and 0.7399 for DC.
Conclusions
HRV complex yielded the largest AUC and is the best classifier for predicting cardiac death after AMI.
doi:10.1186/1471-2261-14-59
PMCID: PMC4023175  PMID: 24886422
Acute myocardial infarction; Cardiac death; Support vector machine; Heart-rate variability; Machine learning
20.  Microvascular obstruction assessed by 3-tesla magnetic resonance imaging in acute myocardial infarction is correlated with plasma troponin I levels 
Background
Microvascular obstruction (MVO) at the acute phase of myocardial infarction (MI) is associated with poor prognosis. We aimed to evaluate the correlation between plasma cardiac troponin I (cTnI) at the acute phase of MI and extent of no-reflow, as assessed by 3-T cardiac magnetic resonance imaging (MRI). Secondly, we defined a cut-off value for cTnI predictive of no-reflow.
Methods
51 consecutive patients with no previous history of cardiovascular disease, presenting ST elevation MI within <12 h. Infarct size and extent of no-reflow were evaluated by 3-T MRI at day 5. Extent of no-reflow at 15 minutes (MVO) was correlated with cTnI at admission, 6, 12, 24, 48 and 72 hours. At 6 months, MRI was performed to evaluate the impact of MVO on LV remodeling.
Results
MVO was diagnosed in 29 patients (57%). Extent of MVO was significantly correlated to peak troponin, cTnI (except admission values) and area under the curve. Using Receiver-operating characteristic (ROC) curve analysis, a cut-off cTnI value >89 ng/mL at 12 h seemed to best predict presence of early MVO (sensitivity 63%, specificity 88%). At 6 months, MVO was associated with left ventricular (LV) remodeling, resulting in higher LV volumes.
Conclusion
There is a relationship between cTnI at the acute phase of AMI and extent of MVO as assessed by 3-T cardiac MRI. A cut-off cTnI value of 89 ng/mL at 12 h seems to best predict presence of MVO, which contributes to LV remodeling.
doi:10.1186/1471-2261-14-57
PMCID: PMC4013057  PMID: 24886208
Myocardial infarction; MRI; Troponin; Microvascular obstruction
21.  Chemerin and CMKLR1 expression in human arteries and periadventitial fat: a possible role for local chemerin in atherosclerosis? 
Background
Depending on their anatomical location, different fat depots have a different capacity to produce bioactive peptides, called adipokines. Adipokines produced by periadventitial fat have been implicated in the pathogenesis of vascular disease, including atherosclerosis. Chemerin is an adipokine with an established role in immunity, adipose tissue function and metabolism, acting in autocrine, paracrine and endocrine manners. We investigated the protein expression of chemerin and its receptor, CMKLR1, in human aortas, coronary vessels and the respective periadventitial adipose tissue and correlated their expression with the presence of atherosclerosis.
Methods
Immunohistochemistry for chemerin and CMKLR1 was performed on human aortic and coronary artery samples including the periadventitial adipose tissue. Aortic and coronary atherosclerotic lesions were assessed using the AHA classification.
Results
Chemerin immunopositivity was noticed in both periadventitial fat depots, in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Periadventitial fat and foam cell chemerin immunopositivity was statistically significantly correlated with the severity of atherosclerosis in both locations. CMKLR1 was expressed in vascular smooth muscle cells and foam cells in aortic and coronary vessels with atherosclerotic lesions. CMKLR1 immunostaining in foam cells was statistically significantly correlated with aortic atherosclerosis.
Conclusions
Our results lend some support to a presumable role of locally produced chemerin in the progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor. Further research will elucidate the role of chemerin signaling in atherosclerosis.
doi:10.1186/1471-2261-14-56
PMCID: PMC4022413  PMID: 24779513
Periadventitial adipose tissue; Chemerin; CMKLR1; Atherosclerosis; Coronary arteries; Aorta
22.  Predictors of positive response to cardiac resynchronization therapy 
Background
Approximately 30% of patients treated with cardiac resynchronization therapy (CRT) do not achieve favourable response. The purpose of the present study was to identify echocardiographic and clinical predictors of a positive response to CRT.
Methods
The study included 82 consecutive heart failure (HF) patients in New York Heart Association (NYHA) functional class III or IV with left bundle branch block (LBBB), QRS duration ≥ 120 ms and left ventricular ejection fraction (LVEF) ≤ 35%. Statistical analysis was performed using IBM SPSS statistical software (SPSS v.21.0 for Mac OS X). A p value < 0.05 was considered statistically significant.
Results
Echocardiographic response was established in 81.6% and clinical response was achieved in 82.9% of patients. Significant univariate predictors of favourable echocardiographic response after 12 months were smaller left ventricular end-diastolic diameter (LVEDD) (odds ratio [OR] 0.89; 95% confidence interval [CI] 0.82 - 0.97, p = 0.01), and smaller left ventricular end-systolic diameter (LVESD) (OR 0.91; 95% CI 0.85 - 0.98, p = 0.01). Lower uric acid concentration was associated with better echocardiographic response (OR 0.99; 95% CI 0.99 - 1.0, p = 0.01). Non-ischemic HF etiology (OR 4.89; 95% CI 1.39 - 17.15, p = 0.01) independently predicted positive clinical response. Multiple stepwise regression analysis demonstrated that LVEDD lower than 75 mm (OR 5.60; 95% confidence interval [CI] 1.36 - 18.61, p = 0.01) was the strongest independent predictor of favourable echocardiographic response.
Conclusions
Smaller left ventricular end-diastolic and end-systolic diameters and lower serum uric acid concentration were associated with better response to CRT. Left ventricular end-diastolic diameter and non-ischemic heart failure etiology were the strongest independent predictors of positive response to CRT.
doi:10.1186/1471-2261-14-55
PMCID: PMC4016658  PMID: 24779476
Cardiac resynchronization therapy; Heart failure; Response
23.  Circulating CD36 and oxLDL levels are associated with cardiovascular risk factors in young subjects 
Background
Cardiovascular disease (CVD) results from a combination of abnormalities in lipoprotein metabolism, oxidative stress, chronic inflammation, and susceptibility to thrombosis. Atherosclerosis is the major cause of CVD. CD36 has been shown to play a critical role in the development of atherosclerotic lesions by its capacity to bind and promote endocytosis of oxidized low-density lipoprotein (oxLDL) and is implicated in the formation of foam cells. The purpose of this research was to evaluate whether there is an association of sCD36 and oxLDL levels with cardiovascular risk factors in young subjects.
Methods
A total of 188 subjects, 18 to 25 years old, 133 normal-weight and 55 obese subjects from the state of Guerrero, Mexico were recruited in the study. The lipid profile and glucose levels were measured by enzymatic colorimetric assays. Enzyme-linked immunosorbant assays (ELISA) for oxLDL and sCD36 were performed. Statistical analyses of data were performed with Wilcoxon- Mann Whitney and chi-square tests as well as with multinomial regression.
Results
TC, LDL-C, TG, oxLDL and sCD36 levels were higher in obese subjects than in normal-weight controls, as well as, monocyte and platelet counts (P < 0.05). Obese subjects had 5.8 times higher risk of sCD36 in the third tertil (>97.8 ng/mL) than normal-weight controls (P = 0.014), and 7.4 times higher risk of oxLDL levels in third tertile (>48 U/L) than control group. The subjects with hypercholesterolemia, hypertriglyceridemia, fasting impaired LDL-C had a higher risk of oxLDL levels in the third tertile (>48 U/L) than the control group (P < 0.05).
Conclusions
Circulating CD36 and oxLDL levels are associated with cardiovascular risk factors in young subjects and may be potential early markers for cardiovascular disease (CVD).
doi:10.1186/1471-2261-14-54
PMCID: PMC4012526  PMID: 24766787
CD36; OxLDL; Cardiovascular risk factors; Obesity
24.  Cardioprotective activity of placental growth factor in a rat model of acute myocardial infarction: nanoparticle-based delivery versus direct myocardial injection 
Background
To comparatively evaluate the cardioprotective activity of placental growth factor (PGF) delivered through direct injection and a nanoparticle-based system respectively and to study the underlying mechanisms in a rat model of acute myocardial infarction (AMI).
Methods
Poly lactic-co-glycolic acid (PLGA)-based PGF-carrying nanoparticles (PGF-PLGANPs) were created. The mean size and morphology of particles were analyzed with particle size analyzer and transmission electronic microscopy (TEM). Encapsulation efficiency and sustained-release dose curve were analyzed by ELISA. Sprague-Dawley rats were randomized into four groups (n = 10). While animals in the first group were left untreated as controls, those in the other 3 groups underwent surgical induction of AMI, followed by treatment with physiological saline, PGF, and PGF-PLGANPs, respectively. Cardiac function was evaluated by transthoracic echocardiography at 4 weeks after treatment. At 6 weeks, rats were sacrificed, infarction size was analyzed with Masson trichrome staining, and protein contents of TIMP-2, MT1-MMP and MMP-2 at the infarction border were determined by immunohistochemistry and western blotting analysis.
Results
PGF was released for at least 15 days, showing successful preparation of PGF-PLGANPs. Coronary artery ligation successfully induced AMI. Compared to physiological saline control, PGF, injected to the myocardium either as a nude molecule or in a form of nanoparticles, significantly reduced infarction size, improved cardiac function, and elevated myocardial expression of TIMP-2, MT1-MMP, and MMP-2 (P < 0.05). The effect of PGF-PLGANPs was more pronounced than that of non-encapsulated PGF (P < 0.05).
Conclusion
Target PGF delivery to myocardium may improve cardiac function after AMI in rats. PLGA-based nanoparticles appear to be a better approach to delivery PGF. PGF exerts its cardioprotective effect at least partially through regulating metalloproteinase-mediated myocardial tissue remodeling.
doi:10.1186/1471-2261-14-53
PMCID: PMC4014437  PMID: 24742302
Placental growth factor; Acute myocardial infarction; Cardiac function; Nanoparticles-mediated drug delivery; Vicious ventricular remodeling
25.  Efficacy of N-acetylcysteine in preventing atrial fibrillation after cardiac surgery: a meta-analysis of published randomized controlled trials 
Background
Atrial fibrillation is a common complication after cardiac surgery. The aim of this study is to evaluate whether N-acetylcysteine (NAC) could prevent postoperative atrial fibrillation (POAF).
Methods
PubMed, Embase and Cochrane Center Register of Controlled Trials were searched from the date of their inception to 1 July 2013 for relevant randomized controlled trials (RCTs), in which NAC was compared with controls for adult patients undergoing cardiac surgery. Outcome measures comprised the incidence of POAF, all-cause mortality, length of intensive care unit (ICU) stay, hospital length of stay, and the incidence of cerebrovascular events. The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity.
Results
We retrieved ten studies enrolling a total of 1026 patients. Prophylactic NAC reduced the incidence of POAF (OR 0.56; 95% CI 0.40 to 0.77; P < 0.001) and all-cause mortality (OR 0.40; 95% CI 0.17 to 0.93; P = 0.03) compared with controls, but failed to reduce the stay in ICU and overall stay in hospital. No difference in the incidence of cerebrovascular events was observed.
Conclusions
Prophylactic use of NAC could reduce the incidence of POAF and all-cause mortality in adult patients undergoing cardiac surgery. However, larger RCTs evaluating these and other postoperative complication endpoints are needed.
doi:10.1186/1471-2261-14-52
PMCID: PMC4012554  PMID: 24739515
N-acetylcysteine; Postoperative atrial fibrillation; Cardiac surgery; Meta-analysis

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