PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation : Part 1(Patient Dynamics): Preoperative demographics and preoperative and operative risk factors.

OBJECTIVES: The PROSE trial purpose is to investigate whether the incidence of thromboembolic-related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.-On-X) compared with a previous generation mechanical prosthesis (St Jude Medical-SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. METHODS: The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. RESULTS: The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. CONCLUSIONS: The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Linking world bank development indicators and outcomes of congenital heart surgery in low-income and middle-income countries: retrospective analysis of quality improvement data.

OBJECTIVE: Many low-income and middle-income countries (LMICs) struggle to provide the health services investment required for life-saving congenital heart disease (CHD) surgery. We explored associations between risk-adjusted CHD surgical mortality from 17 LMICs and global development indices to identify patterns that might inform investment strategies. DESIGN: Retrospective analysis: country-specific standardised mortality ratios were graphed against global development indices reflective of wealth and healthcare investment. Spearman correlation coefficients were calculated. SETTING AND PARTICIPANTS: The International Quality Improvement Collaborative (IQIC) keeps a volunteer registry of outcomes of CHD surgery programmes in low-resource settings. Inclusion in the IQIC is voluntary enrolment by hospital sites. Patients in the registry underwent congenital heart surgery. Sites that actively participated in IQIC in 2013, 2014 or 2015 and passed a 10% data audit were asked for permission to share data for this study. 31 sites in 17 countries are included. OUTCOME MEASURES: In-hospital mortality: standardised mortality ratios were calculated. Risk adjustment for in-hospital mortality uses the Risk Adjustment for Congenital Heart Surgery method, a model including surgical risk category, age group, prematurity, presence of a major non-cardiac structural anomaly and multiple congenital heart procedures during admission. RESULTS: The IQIC registry includes 24 917 congenital heart surgeries performed in children<18 years of age. The overall in-hospital mortality rate was 5.0%. Country-level congenital heart surgery standardised mortality ratios were negatively correlated with gross domestic product (GDP) per capita (r=-0.34, p=0.18), and health expenditure per capita (r=-0.23, p=0.37) and positively correlated with under-five mortality (r=0.60, p=0.01) and undernourishment (r=0.39, p=0.17). Countries with lower development had wider variation in mortality. GDP per capita is a driver of the association between some other measures and mortality. CONCLUSIONS: Results display a moderate relationship among wealth, healthcare investment and malnutrition, with significant variation, including superior results in many countries with low GDP per capita. These findings provide context and optimism for investment in CHD procedures in low-resource settings.

Tetralogy of Fallot Repair in Developing Countries: International Quality Improvement Collaborative.

BACKGROUND: Isolated reports from low- and middle-income countries (LMICs) for surgical results in tetralogy of Fallot (TOF) are available. The International Quality Improvement Collaborative for Congenital Heart Disease (IQIC) seeks to improve surgical results promoting reductions in infection and mortality in LMICs. METHODS: All cases of TOF in the IQIC database performed between 2010 and 2014 at 32 centers in 20 LMICs were included. Excluded from the analysis were TOF with any associated lesions. A logistic regression analysis was performed to identify risk factors for in-hospital mortality after surgery for TOF. RESULTS: A total of 2,164 patients were identified. There were 1,839 initial primary repairs, 200 with initial systemic-to-pulmonary artery shunt, and 125 underwent secondary repair after initial palliation. Overall mortality was 3.6% (78 of 2,164), initial primary repair was 3.3% (60 of 1,839), initial systemic-to-pulmonary artery shunt was 8.0% (16 of 200), and secondary repair was 1.6% (2 of 125; p = 0.003). Major infections occurred in 5.9% (128 of 2,164) of the entire cohort. Risk factors for death after the initial primary repair were oxygen saturation less than 90% and weight/body mass index for age below the fifth percentile (p < 0.001). The initial primary repair occurred after age 1 year in 54% (991 of 1,839). Older age at initial primary repair was not a risk factor for death (p = 0.21). CONCLUSIONS: TOF patients are often operated on after age 1 year in LMICs. Unlike in developed countries, older age is not a risk factor for death. Nutritional and hypoxemic status were associated with higher mortality and infection. This information fills a critical knowledge gap for surgery in LMIC.

Use of Indigenous Decellularized Valved Xenograft Conduit for Double-Barrel Right Ventricular Outflow Tract Reconstruction: Nine-Year Follow-Up.

Over the last two decades, numerous conduit options and implantation techniques have been described for right ventricular outflow tract (RVOT) reconstruction in the management of tetralogy of Fallot (TOF) with hypoplastic pulmonary annulus. The limited availability of homografts and the cost factor have led us to explore the use of decellularized xenografts as an alternative. Here we present a nine-year follow-up of an adult patient with TOF with hypoplastic pulmonary annulus, who underwent reconstruction of the RVOT by the double-barrel technique, using a decellularized porcine pulmonary artery xenograft valved conduit.

Reducing mortality and infections after congenital heart surgery in the developing world.

BACKGROUND: There is little information about congenital heart surgery outcomes in developing countries. The International Quality Improvement Collaborative for Congenital Heart Surgery in Developing World Countries uses a registry and quality improvement strategies with nongovernmental organization reinforcement to reduce mortality. Registry data were used to evaluate impact. METHODS: Twenty-eight sites in 17 developing world countries submitted congenital heart surgery data to a registry, received annual benchmarking reports, and created quality improvement teams. Webinars targeted 3 key drivers: safe perioperative practice, infection reduction, and team-based practice. Registry data were audited annually; only verified data were included in analyses. Risk-adjusted standardized mortality ratios (SMRs) and standardized infection ratios among participating sites were calculated. RESULTS: Twenty-seven sites had verified data in at least 1 year, and 1 site withdrew. Among 15,049 cases of pediatric congenital heart surgery, unadjusted mortality was 6.3% and any major infection was 7.0%. SMRs for the overall International Quality Improvement Collaborative for Congenital Heart Surgery in Developing World Countries were 0.71 (95% confidence interval [CI] 0.62-0.81) in 2011 and 0.76 (95% CI 0.69-0.83) in 2012, compared with 2010 baseline. SMRs among 7 sites participating in all 3 years were 0.85 (95% CI 0.71-1.00) in 2011 and 0.80 (95% CI 0.66-0.96) in 2012; among 14 sites participating in 2011 and 2012, the SMR was 0.80 (95% CI 0.70-0.91) in 2012. Standardized infection ratios were similarly reduced. CONCLUSIONS: Congenital heart surgery risk-adjusted mortality and infections were reduced in developing world programs participating in the collaborative quality improvement project and registry. Similar strategies might allow rapid reduction in global health care disparities.

Estimation of Ischemia Modified Albumin (IMA) Levels in Patients with Acute Coronary Syndrome.

Myocardial ischemia produces free radicals that catalyze a series of oxidative reactions that damage healthy tissues. The N-terminal sequence of albumin is one of the proteins modified by these highly reactive oxygen species and forms the ischemia modified albumin (IMA). This study involves investigations undertaken in different study groups to assess the levels of IMA. Mean serum IMA levels (U/mL) in patients with ST-segment elevated myocardial infarction (92.1 ± 10.6), non-ST-segment elevated myocardial infarction (87.3 ± 5.95) and unstable angina (UA) (88.9 ± 6.16) were significantly higher than non-cardiac chest pain (77.9 ± 6.69) and also healthy subjects (54.7 ± 17.2) (p < 0.001). IMA is a highly sensitive marker and has a high predictive value, which might prove the usefulness of this biomarker for early detection of myocardial ischemia. These data indicate a possible role of the IMA test in the early triage of patients with chest pain.

Hybrid intraoperative pulmonary artery stenting in redo congenital cardiac surgeries.

OBJECTIVE: Reconstruction of branch pulmonary arteries (PAs) can be challenging in redo congenital heart surgeries. Treatment options like percutaneous stent implantation and surgical patch angioplasty may yield suboptimal results. We present our experience with hybrid intraoperative stenting which may be an effective alternative option. METHODS: We retrospectively analyzed data of all patients with PA stenosis who underwent intraoperative PA branch stenting in our institution between January 2011 and December 2012. RESULTS: Ten patients [6 females, median age 10 (1.4 to 37) years], underwent hybrid stenting of the PA. Primary cardiac diagnoses were pulmonary atresia with ventricular septal defect (VSD) in three patients, pulmonary atresia with intact ventricular septum in two, Tetralogy of Fallot (TOF) in one, Double outlet right ventricle (DORV) with pulmonary stenosis (PS) in one, complex single ventricle in two and VSD with bilateral branch PA stenosis in one patient. Concomitant surgeries were revision/reconstruction of RV-PA conduit in 4, Fontan completion in 4, repair of TOF with conduit placement in 1 and VSD closure in 1 patient. The left PA was stented in 7, the right in 2 and both in 1, with a total of 11 stents. There were no complications related to stent implantation. Two early postoperative deaths were unrelated to stent implantation. At mean follow-up period of 14.8 (12-26) months, stent position and patency were satisfactory in all survivors. None of them needed repeat dilatation or surgical reintervention. CONCLUSION: Hybrid stenting of branch PA is a safe and effective option for PA reconstruction in redo cardiac surgeries. With meticulous planning, it can be safely performed without fluoroscopy.

Emergence of omentin as a pleiotropic adipocytokine.

"Less is more" - this is becoming the global quote on event of alarming rise in the prevalence of obesity among all age groups. The perspective of adipose tissue as merely a fat depot has changed in recent times. Focus is now being laid on the metabolic and inflammatory functions of the adipose tissue which is modulated through adipocytokines. Adipocytokines have been found to control insulin sensitivity, inflammatory activity, neuroendocrine activity, cardiovascular function, food and water intake, breeding, and bone metabolism. Few of these adipokines play a role in the positive metabolism promoting good health, while few of them pose adverse effects. Omentin is a recently identified novel adipocytokine and it falls under the category of being a good adipokine. Plasma omentin-1 levels are significantly decreased in patients with obesity, insulin resistance, and diabetes that contribute to the major components of the metabolic syndrome and other disease conditions like atherosclerosis, autoimmune disorders etc and that the review focuses on the comprehensive effects of omentin on all the major systems of the body.

The clinical and biochemical parameters in relation to the serum neopterin levels in Indian children and adolescents.

INTRODUCTION: An adverse pattern of blood lipids and cardiovascular abnormalities starts in obese children during childhood and neopterin serves as a marker for cardiovascular disease. Unfortunately, the data for children and adolescents, particularly, in the Indian population, are scarce. The present study aimed at evaluating the levels of serum neopterin in obese and overweight children and adolescents of the Indian population. METHODS: The study groups included 296 school going children and adolescents. (96 obese and 97 overweight subjects were compared with 103 normal controls who were aged between 10-17 years). The anthropometric variables, the lipid profile, the fasting serum glucose which was analyzed by using an autoanalyzer and the serum neopterin levels were assayed by HPLC (Shimazdu) by using the method of Palfrey et al., 1993. The serum insulin levels were measured by using ELISA kits. RESULTS: The serum neopterin levels (nmol/l) were elevated significantly in the obese (7.4±1.4) and overweight (6.4±0.8) (p<0.001) children and adolescents than in the controls (4.9±0.9). The serum neopterin levels showed a positive correlation with the BMI (r=0.79), WHR (r=0.5), systolic (r=0.44) and diastolic blood pressures (r= 0.25), insulin (r=0.57), HOMAIR (r=0.55), total cholesterol (r=0.35), triglycerides (r=0.20) and LDL-C (r=0.27) and they showed a negative correlation with HDL-C (r=-0.15) and fasting glucose (r= -0.3). CONCLUSION: This study revealed a good relationship between serum neopterin and the anthropometric and biochemical parameters. We, therefore, aim to conduct regular camps at schools to counsel and advise the identified overweight and obese children to go for physical exercise and a balanced diet. The implementation of preventive measures from early childhood will have far reaching benefits, as even the prevalence of other obesity related disorders could decline.

Physician assistant education in India.

The first PA program in India was established in 1992 with a focus on expanding cardiovascular surgery. Since then, eight additional programs have developed (in total seven baccalaureate and two master's level programs). Approximately 850 graduates are distributed throughout southern India with concentrations near their home universities. While all PAs are trained as generalists, most work in hospitals in specialized roles such as surgery. With service delivery a looming issue in India, there is an increased interest in the PA profession, and existing PA programs are beginning to work together to advance the field.

Hybrid stage I palliation for hypo-plastic left heart condition without a hybrid suite: suggestions for developing nations.

Cardiac hybrid procedures are performed in modern, spacious, and highly equipped hybrid suites in developed countries. Organizing such expensive suites in countries with an emerging economy is difficult from both a financial and logistics point of view. We share our experience of safely performing a Hybrid stage I palliation procedure for Aortic atresia with ventricular septal defect on a 2-month-old infant weighing 3.35 kg using minimal resources in a conventional catheterization laboratory.

Pregnancy associated plasma protein-A (PAPP-A) as an early marker for the diagnosis of acute coronary syndrome.

AIMS AND OBJECTIVES: Pregnancy associated plasma protein-A (PAPP-A), a metalloproteinase plays a pivotal role in the pathogenesis of atherosclerosis. Recent studies have reported that elevated levels of PAPP-A, signal the onset of acute coronary syndrome (ACS). We, therefore, proposed to study the analytical competence of PAPP-A in patients admitted to the emergency department with chest pain and finally diagnosed as ACS. METHODS AND RESULTS: Pregnancy associated plasma protein-A was measured using enzyme-linked immunosorbent assay (ELISA) in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as Non-cardiac chest pain (NCCP). Elevated levels of PAPP-A were observed in patients diagnosed as ACS on comparison with the controls. Receiver operator characteristic (ROC) curve analysis showed PAPP-A to be a good discriminator between ischaemic and non-ischaemic patients. The area under the curve was found to be 0.904, 95% CI (0.874-0.929) with 90% sensitivity and 85% specificity (P< 0.0001). The cut-off value from the ROC curve was 0.55 µg/mL above which PAPP-A was considered to be positive. CONCLUSION: Pregnancy associated plasma protein-A seems to be a promising biomarker for identification and risk stratification for patients with ACS.

The curious case of a button which led to the needle.

Foreign bodies in the heart are uncommon in children. These are often removed even if asymptomatic to prevent complications like erosion, embolization, bleeding, thrombosis, and endocarditis. We report the case of a one-and-a-half-year-old child with a hypodermic needle in the heart which was found incidentally and removed successfully by surgery.

Statistical tools for analysing the data obtained from repeated dose toxicity studies with rodents: a comparison of the statistical tools used in Japan with that of used in other countries.

In the present study, an attempt was made to compare the statistical tools used for analysing the data of repeated dose toxicity studies with rodents conducted in 45 countries, with that of Japan. The study revealed that there was no congruence among the countries in the use of statistical tools for analysing the data obtained from the above studies. For example, to analyse the data obtained from repeated dose toxicity studies with rodents, Scheffé's multiple range and Dunnett type (joint type Dunnett) tests are commonly used in Japan, but in other countries use of these statistical tools is not so common. However, statistical techniques used for testing the above data for homogeneity of variance and inter-group comparisons do not differ much between Japan and other countries. In Japan, the data are generally not tested for normality and the same is true with the most of the countries investigated. In the present investigation, out of 127 studies examined, data of only 6 studies were analysed for both homogeneity of variance and normal distribution. For examining homogeneity of variance, we propose Levene's test, since the commonly used Bartlett's test may show heterogeneity in variance in all the groups, if a slight heterogeneity in variance is seen any one of the groups. We suggest the data may be examined for both homogeneity of variance and normal distribution. For the data of the groups that do not show heterogeneity of variance, to find the significant difference among the groups, we recommend Dunnett's test, and for those show heterogeneity of variance, we recommend Steel's test.

Absent pulmonary valve syndrome: prenatal cardiac ultrasound diagnosis with autopsy correlation.

Absent pulmonary valve syndrome (APVS) is a rare conotruncal anomaly consisting of a severely hypoplastic pulmonary valve with annular stenosis, aneurysmal dilatation of main pulmonary artery with dilatation of one or both pulmonary artery branches, and a ventricular septal defect. Here, we report a prenatal echo diagnosis of APVS in a 27-year-old primi gravida at 20 weeks of gestation confirmed on fetal autopsy. A 'bow tie'-like hypoechoic shadow in fetal cardiac ultrasound observed by us in a modified four-chamber view was suggestive of aneurysmal dilatation of branch pulmonary arteries. The consequences of continuation of pregnancy including immediate neonatal complications and possible medical and multistaged surgical interventions were well explained. Parents opted for medical termination of pregnancy. Autopsy findings of the fetus were consistent with the prenatal echo diagnosis of APVS. The presence of patent ductus arteriosus seen in the autopsy may be the cause of severe heart failure evidenced by the abnormally large congested liver, dilated right heart chambers, and tricuspid valve annulus. We infer that the prenatal diagnosis of APVS may be possible with a high degree of accuracy with characteristic fetal echocradiographic findings such as 'bow tie'-like or 'ballooning'-like shadows observed in this case. The presence of ductus confirms definite fetal loss and the parents can be counselled accordingly. However, when the ductus is absent, decision-making is difficult as the fetus is going to survive.

"Humanized" stem cell culture techniques: the animal serum controversy.

Cellular therapy is reaching a pinnacle with an understanding of the potential of human mesenchymal stem cells (hMSCs) to regenerate damaged tissue in the body. The limited numbers of these hMSCs in currently identified sources, like bone marrow, adipose tissue, and so forth, bring forth the need for their in vitro culture/expansion. However, the extensive usage of supplements containing xenogeneic components in the expansion-media might pose a risk to the post-transplantation safety of patients. This warrants the necessity to identify and develop chemically defined or "humanized" supplements which would make in vitro cultured/processed cells relatively safer for transplantation in regenerative medicine. In this paper, we outline the various caveats associated with conventionally used supplements of xenogenic origin and also portray the possible alternatives/additives which could one day herald the dawn of a new era in the translation of in vitro cultured cells to therapeutic interventions.