Cardiac Effects of Highly Active Antiretroviral Therapy in Perinatally HIV-Infected Children: The CHAART-2 Study.

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), cardiac mortality and morbidity were common in HIV-infected children. OBJECTIVES: This study sought to identify long-term cardiovascular effects of HAART in HIV-infected children. METHODS: The CHAART-2 (HAART-Associated Cardiotoxicity in HIV-Infected Children) study prospectively compared 148 echocardiograms from 74 HAART-exposed children to 860 echocardiograms from 140 HAART-unexposed but HIV-infected children from the Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) study. Both studies used similar protocol, centralized echocardiographic interpretation, and measures expressed as z-scores referenced to healthy controls. Associations between HAART exposure and echocardiographic measures were evaluated using generalized estimating equations. RESULTS: Comparing the HAART-exposed and HAART-unexposed groups, any HAART exposure was positively associated with left ventricular (LV) fractional shortening (z-score for difference = 1.07; p = 0.02) and HAART exposure duration (z-score difference per year = 0.17; p = 0.003. LV mass was negatively associated with any HAART exposure (z-score difference = -0.64; p = 0.01) as was septal thickness (z-score difference = -0.93; p = 0.001). Duration of HAART exposure was negatively associated with LV end-systolic dimension and heart rate (z-score difference per year= -0.11; p = 0.05; and z-score difference per year = -0.10; p = 0.002, respectively). During 11 years of follow-up, in the HAART-exposed group, LV mass and LV end-diastolic septal thickness were lower whereas LV contractility and LV fractional shortening were higher when compared to the HAART-unexposed group. CONCLUSIONS: Cardiac structure and function were better in perinatally HIV-infected children exposed to HAART than in those of similar children from the pre-HAART era but did decline over time. Evidence-based strategies for cardiovascular monitoring are needed to inform treatment decisions to improve long-term cardiovascular health.

Treatment options for the closure of secundum atrial septal defects: A systematic review and meta-analysis.

BACKGROUND: Secundum atrial septal defects (ASDs) are treated by surgical closure (SC) or transcatheter device closure (TCC). Due to a scarcity of data directly comparing these approaches, it remains unclear which is superior. This meta-analysis compares the clinical outcomes of the two treatment options. METHODS: A literature search was performed in MEDLINE, Embase, PubMed, Google Search, and Cochrane databases for studies directly comparing SC and TCC of ASDs. Outcomes studied were major and minor acute complications, all-cause mortality, residual shunt, reinterventions, and length of stay (LOS). Relative risk (RR), difference in mean (DM) and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method with a fixed effect model. In cases of heterogeneity (defined as I2>25%), random effect models were used. Sensitivity and meta-regression analyses were performed for each outcome. RESULTS: Of the 1742 manuscripts screened, 26 observational studies fulfilled the inclusion criteria (total n=14,559 patients). TCC was superior to SC for the following outcomes: all-cause mortality (RR, 0.66; 95% CI 0.64-0.99), total complications (RR, 0.48; 95% CI 0.35-0.65), major complications (RR, 0.57; 95% CI 0.40-0.81), minor complications (RR, 0.35; 95% CI 0.23-0.53), and LOS (DM, -2.92; 95% CI -3.25 to (-2.58)). Residual shunts were more common with TCC (RR, 3.35; 95% CI 1.72-6.51). No difference was observed regarding the need of reintervention (RR, 1.45; 95% CI 0.60-3.51). Meta-regression analysis showed that older age increases the risk of death and complications in patients undergoing TCC. CONCLUSIONS: Though both approaches are effective, TCC is associated with lower mortality, complications, and LOS while SC has a lower rate of residual shunting.

Observations on obesity patterns in tetralogy of Fallot patients from childhood to adulthood.

Obesity is increasingly prevalent, and abnormal body mass index is a risk factor for cardiovascular disease. There are limited data published regarding body mass index and CHD. We tested the hypothesis that body mass index and obesity prevalence are increasing in patients with tetralogy of Fallot over time by analysing time since surgery, age, height, weight, and body mass index among tetralogy of Fallot patients and demographic data from age-matched controls. NYHA class and left ventricular ejection fraction were analysed in adults. Body mass index was categorised into normal, overweight, and obese in this single-centre, retrospective chart review. Data were collected from 137 tetralogy of Fallot patients (71 men:66 women), of whom 40 had body mass index >25 kg/m2. Tetralogy of Fallot patients aged <6 years had lower body mass index (15.9 versus 17.1; p=0.042) until 16-20 years of age (27.4 versus 25.4; p=0.43). For adult tetralogy of Fallot patients, the mean body mass index was 26.5 but not statistically significantly different from the control cohort. Obese adult patients had significantly higher average NYHA class compared with those of normal weight (p=0.03), but no differences in left ventricular ejection fraction by echocardiography (p=0.55) or cardiac MRI (p=0.26) were noted. Lower body mass index was observed initially in tetralogy of Fallot patients, but by late adolescence no significant difference was observed. As adults, tetralogy of Fallot patients with higher body mass index had increased NYHA class but similar left ventricular ejection fraction.

Current attitudes and clinical practice towards the care of pregnant women with underlying CHD: a paediatric cardiology perspective.

OBJECTIVES: The growing number of women with CHD presents unique challenges, including those related to pregnancy, which can lead to significant morbidity and mortality. We sought to evaluate the perception of paediatric cardiologists towards the reproductive health of women with CHD. METHODS: Paediatric cardiologists in the United States of America were invited to participate in a cross-sectional, anonymous survey. Information solicited included knowledge of contraceptive methods, experience caring for pregnant women with CHD, and referral patterns including the utilisation of high-risk obstetric and adult CHD specialists. RESULTS: A total of 110 cardiologists responded - 90% with an academic affiliation and 70% with ⩾10 years' clinical experience. Although 95% reported an understanding of available contraceptive options, 32% did not feel comfortable recommending birth control. Pregnant women with CHD were seen by 83% of responders, and 37% of the responders reported a low level of comfort in doing so. Among all respondents, 73% indicated that they would refer a pregnant CHD patient to a high-risk obstetrician and 60% to an adult CHD specialist - almost all respondents would not transfer care to a non-adult CHD cardiologist. Among paediatric cardiologists, 81% indicated that they would resume their patient's care following delivery. CONCLUSION: Our results illustrate a gap in what physicians feel should be done and the care that they feel comfortable providing pregnant women with CHD. As this population continues to grow, training adult CHD cardiologists with specific skills in reproductive health in women with CHD is the first step to closing the care gap that exists in the management of such patients.

Health Care Costs for Adults With Congenital Heart Disease in the United States 2002 to 2012.

More adults than children with congenital heart disease (CHD) are alive today. Few studies have evaluated adult congenital heart disease (ACHD) health care utilization in the United States. Data from the National Inpatient Sample from 2002 to 2012, using International Classification of Diseases, Ninth Revision, codes for moderate and complex CHD were analyzed. Hospital discharges, total billed and reimbursed amounts, length of stay, and gender/age disparities were evaluated. There was an increase in CHD discharges (moderate CHD: 4,742 vs 6,545; severe CHD: 807 vs 1,115) and total billed and reimbursed dollar amounts across all CHD (billed: $2.7 vs $7.0 billion, 155% increase; reimbursed: $1.3 vs $2.3 billion, 99% increase) and in the ACHD subgroup (billed: $543 million vs $1.5 billion, 178% increase; reimbursed: $221 vs $433 million, 95% increase). Women comprised more discharges in 2002 but not in 2012 (men:women, 2002: 6,503 vs 7,805; 2012: 7,715 vs 7,200, p = 0.39). Gender-based billed amounts followed similar trends (2002: $263 vs $280 million; 2012: $845 vs $662 million, p = 0.006) as did reimbursements (2002: $108 vs $114 million; 2012: $243 vs $190 million, p = 0.008). All age subgroups demonstrated increased health care expenditures, including the >44 versus 18- to 44-year-old age subgroup (billed: $618 vs $347 million, p <0.001; reimbursed: $136 vs $75 million, p <0.001). Our results reveal increased ACHD billed and reimbursed amounts and hospital discharges with a shift in gender-based ACHD hospitalizations: men now account for more hospitalizations in the United States. In conclusion, increased health care expenditure in older patients with ACHD is likely to increase further as health care system use and costs continue to grow.

Berry syndrome: the importance of genetic evaluation before surgical intervention.

Berry syndrome is a rare CHD. Approximately 29 cases have been described in the literature. Surgical correction has been successfully performed as well. We report the case of a newborn diagnosed with Berry syndrome who was subsequently diagnosed with trisomy 13. Cytogenetic analysis should be performed before surgical repair for optimal management.

Pediatric cardiomyopathies: causes, epidemiology, clinical course, preventive strategies and therapies.

Pediatric cardiomyopathies, which are rare but serious disorders of the muscles of the heart, affect at least one in every 100,000 children in the USA. Approximately 40% of children with symptomatic cardiomyopathy undergo heart transplantation or die from cardiac complications within 2 years. However, a significant number of children suffering from cardiomyopathy are surviving into adulthood, making it an important chronic illness for both pediatric and adult clinicians to understand. The natural history, risk factors, prevalence and incidence of this pediatric condition were not fully understood before the 1990s. Questions regarding optimal diagnostic, prognostic and treatment methods remain. Children require long-term follow-up into adulthood in order to identify the factors associated with best clinical practice including diagnostic approaches, as well as optimal treatment approaches. In this article, we comprehensively review current research on various presentations of this disease, along with current knowledge about their causes, treatments and clinical outcomes.

Analysis and reproducibility of 3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging in patients with non-small cell lung cancer.

PURPOSE: Imaging tumor proliferation with 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) and positron emission tomography is being developed with the goal of monitoring antineoplastic therapy. This study assessed the methods to measure FLT retention in patients with non-small cell lung cancer (NSCLC) to measure the reproducibility of this approach. EXPERIMENTAL DESIGN: Nine patients with NSCLC who were untreated or had progressed after previous therapy were imaged twice using FLT and positron emission tomography within 2 to 7 days. Reproducibility (that is, error) was measured as the percent difference between the two patient scans. Dynamic imaging was obtained during the first 60 min after injection. Activity in the blood was assessed from aortic images and the fraction of unmetabolized FLT was measured. Regions of interest were drawn on the plane with the highest activity and the adjacent planes to measure standardized uptake value (SUV(mean)) and kinetic variables of FLT flux. RESULTS: We found that the SUV(mean) obtained from 30 to 60 min had a mean error of 3.6% (range, 0.6-6.9%; SD, 2.3%) and the first and second scans were highly correlated (r(2) = 0.99; P < 0.0001). Using shorter imaging times from 25 to 30 min or from 55 to 60 min postinjection also resulted in small error rates; SUV(mean) mean errors were 8.4% and 5.7%, respectively. Compartmental and graphical kinetic analyses were also fairly reproducible (r(2) = 0.59; P = 0.0152 and r(2) = 0.58; P = 0.0175 respectively). CONCLUSION: FLT imaging of patients with NSCLC was quite reproducible with a worst case SUV(mean) error of 21% when using a short imaging time.

A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and retention.

PURPOSE: [18F]3'-deoxy-3'-fluorothymidine (FLT) is a thymidine analog developed for imaging tumor proliferation with positron emission tomography (PET). To quantitatively assess images, the blood activities of FLT and its glucuronidated metabolite were measured and its kinetics analyzed. This study sought to limit the number of blood samples needed to measure FLT retention. METHODS: Total FLT activity was measured from 18 venous samples obtained over the first hour and dynamic imaging performed on 33 patients (average dose 350 MBq/mmol). The 5-, 10-, 30- and 60-min samples were analyzed to measure the fraction of activity in FLT and its glucuronide. HPLC analysis was compared against a two-step column (Sep-Pak) and metabolic rates measured using full and limited sampling. Probenecid (2 g, oral) was given to two patients to determine whether imaging of the liver improved. RESULTS: At 60 min, 74% of the blood activity was unmetabolized (range 57-85%). HPLC and Sep-Pak gave comparable results (r=0.97; average difference 2.1%). For kinetic analysis, eight venous samples were sufficient to accurately measure total activity; for metabolite analysis, a single sample at 60 min yielded data with mean errors of 2.2%. The metabolic rate correlated with average SUV (r2=0.85; p=0.0002). An aorta input function gave kinetic results comparable to venous blood (r2=0.82). Probenecid did not improve imaging of the liver. CONCLUSION: Dynamic measurements of FLT retention can be used to calculate metabolic rates using a limited set of samples and correction for metabolites measured in a single sample obtained at 60 min.