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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  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
20.  Gender-dependent associations between socioeconomic status and metabolic syndrome: a cross-sectional study in the adult Saudi population 
Background
To determine the gender-dependent association of socio-economic status variables with the prevalence of metabolic syndrome (MetS) in the adult Saudi population.
Methods
A total of 9164 adult Saudis (aged 18–70 years) were included in this cross-sectional study. Marital status, income, education, and occupation were used as socio-economic indicators while behavioral factor like physical exercise was also taken into account. MetS was defined using the criteria based from the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III).
Results
In males, the odds ratio (OR) of harboring MetS was higher in married [OR1.6 (Confidence Interval (CI) 1.1, 2.4); p < 0.03], and high income class [OR 2.3(CI 1.5, 3.5); p < 0.001] and lowest in retired and unemployed individuals [1.4(1.0, 1.9); p < 0.04, 0.61(0.45, 0.82); p < 0.001] respectively. In females, MetS was inversely related to high income [OR 0.70 (CI 0.46, 1.1); p < 0.09] and education level [OR 0.38 (CI 0.26, 0.56); p < 0.001], and was significantly higher in the unemployed class [OR 1.6 (CI 1.2, 2.2); p < 0.004].
Conclusions
The prevalence of MetS is significantly high among retired, married and high-earning Saudi males while in females, high earners and high education seem to confer a protective effect against MetS.
doi:10.1186/1471-2261-14-51
PMCID: PMC3990270  PMID: 24735007
Gender; Socioeconomic status; Marital status; Income; Education; Saudi Arabia
21.  Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure 
Background
This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF).
Methods
From June 2011 to December 2012, a total of 104 CHF patients and 30 healthy controls were enrolled in this study. We obtained a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN), and resting heart rate (RHR). The relationships between HRT parameters and the prognosis of CHF patients were determined.
Results
The assessment follow-up period lasted until January 31, 2013. The overall mortality of CHF patients was 9.6% (10/104). Our results revealed that CHF patients had higher levels of TO than those of healthy subjects, but the TS levels of CHF patients were lower than that of the control group. CHF patients with NYHA grade IV had higher HRT1/2 rate than those with NYHA grade II/III. There were statistical differences in TS, LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor group. Significant differences in TS among the three groups were also found. Furthermore, CHF patients in the non-survivor group had lower levels of TS than those in the deteriorating group. Correlation analyses indicated that TO negatively correlate with SDNN, while TS positively correlated with SDNN and left ventricular ejection fraction (LVEF). We also observed negative correlations between TS and left ventricular end-diastolic cavity dimension (LVEDD), RHR, homocysteine (Hcy) and C-reactive protein (CRP). Multivariate Cox regression analysis further confirmed that LVEF (≤30%), HRT2, SDNN and RHR were independent risk factors which can indicate poor prognosis in CHF patients.
Conclusions
Our findings indicate that HRT may have good clinical predictive value in patients with CHF. Thus, quantifying HRT parameters could be a useful tool for predicting mortality in CHF patients.
doi:10.1186/1471-2261-14-50
PMCID: PMC3996196  PMID: 24725657
Heart rate turbulence; Chronic heart failure; Prognosis
22.  The prevalence of coronary anomalies in a single center of Korea: origination, course, and termination anomalies of aberrant coronary arteries detected by ECG-gated cardiac MDCT 
Background
Coronary anomalies are rare congenital abnormalities often found incidentally on conventional coronary angiography (CCA) or coronary CT angiography (CTA). They may result in various clinical outcomes. CCA is invasive and not able to demonstrate all coronary anomalies in detail, especially those with complex courses. Multidetector computed tomography (MDCT) enables visualization of the origin and course of coronary arteries. The objective of this study was to investigate the prevalence of origin and termination coronary artery anomalies and the course of these anomalies in patients in a single center in Korea.
Methods
To diagnose coronary anomalies, the angiographic data of 8,864 consecutive patients undergoing 64- or 320-MDCT from September 2005 to November 2011 were analyzed retrospectively.
Results
Among the 8,864 patients, 103 (1.16%) had coronary anomalies. Ninety (87.4%) patients had origin and distribution anomalies, and 13 (12.6%) patients had a coronary artery fistula. The most common anomaly (41, 39.8%) was an anomalous origin of the right coronary artery (RCA). Of these, three patients received a coronary artery bypass graft.
Conclusions
The prevalence of coronary anomalies in a single center of Korea was 1.16%. The incidence and patterns of coronary artery anomalies in our patient population were similar to those of previous studies.
doi:10.1186/1471-2261-14-48
PMCID: PMC3991863  PMID: 24725604
Coronary vessel anomalies; Multidetector computed tomography; Prevalence
23.  Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation 
Background
Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin.
Methods and results
In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products.
Conclusions
Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.
doi:10.1186/1471-2261-14-49
PMCID: PMC4021258  PMID: 24725620
Thalassaemia; Ventricular rotation; Ventricular mechanics; Exercise echocardiography; Titin
24.  Possible extracardiac predictors of aortic dissection in Marfan syndrome 
Background
According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS.
Methods
A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-β (TGF-β) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and −9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed.
Results
Among patients with aortic dissection, TGF-β serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2α = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group.
Conclusions
We found three easily measurable parameters (striae atrophicae, TGF-β serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.
doi:10.1186/1471-2261-14-47
PMCID: PMC4021409  PMID: 24720641
Marfan syndrome; Aortic dissection; Predictors; Cardiac surgery
25.  Determining the prevalence and predictors of sleep disordered breathing in patients with chronic heart failure: rationale and design of the SCHLA-HF registry 
Background
The objective of the SCHLA-HF registry is to investigate the prevalence of sleep-disordered breathing (SDB) in patients with chronic heart failure with reduced left ventricular systolic function (HF-REF) and to determine predictors of SDB in such patients.
Methods
Cardiologists in private practices and in hospitals in Germany are asked to document patients with HF-REF into the prospective SCHLA-HF registry if they meet predefined inclusion and exclusion criteria. Screening was started in October 2007 and enrolment was completed at the end of May 2013. After enrolment in the registry, patients are screened for SDB. SDB screening is mainly undertaken using the validated 2-channel ApneaLink™ device (nasal flow and pulse oximetry; ResMed Ltd., Sydney, Australia). Patients with a significant number of apneas and hypopneas per hour recording time (AHI ≥15/h) and/or clinical symptoms suspicious of SDB will be referred to a cooperating sleep clinic for an attended in-lab polysomnography with certified scoring where the definite diagnosis and, if applicable, the differentiation between obstructive and central sleep apnea will be made. Suggested treatment will be documented.
Discussion
Registries play an important role in facilitating advances in the understanding and management of cardiovascular disease. The SCHLA-HF registry will provide consistent data on a large group of patients with HF-REF that will help to answer questions on the prevalence, risk factors, gender differences and stability of SDB in these patients by cross-sectional analyses. Further insight into the development of SDB will be gained by extension of the registry to include longitudinal data.
doi:10.1186/1471-2261-14-46
PMCID: PMC3983862  PMID: 24716484
Registry; Prevalence; Heart failure; Sleep-disordered breathing; Obstructive sleep apnea; Central sleep apnea; Cheyne-Stokes respiration; Predictors

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