Salil Ginde

Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein.

Immune activation results in the activation of adrenal steroidogenesis and inhibition of gonadal steroidogenesis. Previous studies indicated that these effects were caused primarily by activation and suppression of the secretion of ACTH and LH, respectively. However, other evidence indicated a direct effect of the immune system on the gonads. In this study, serum testosterone, quantitated by RIA after lipopolysaccharide injection, showed a significant decrease within 2 h. Parallel measurement of serum LH showed no change. There were no differences in LH receptor or cAMP produced in Leydig cells between vehicle- and lipopolysaccharide-injected mice. The 30-kDa form of the steroidogenic acute regulatory (StAR) protein was quantitated, by Western blot, in Leydig cells and was found to decrease in a time-dependent manner. No change in StAR protein messenger RNA (mRNA) was detected by Northern analysis during this time, nor were any changes found in the levels of mRNA for the steroidogenic enzymes P450scc, 3β-...

Noninvasive Assessment of Liver Fibrosis in Adult Patients Following the Fontan Procedure

OBJECTIVE   Recent data indicate that patients after the Fontan procedure are at risk for significant liver dysfunction; however, the prevalence and extent of liver disease in the Fontan population remains unknown. Furthermore, limited data exist in regard to screening for liver disease in adult Fontan patients. We sought to determine the prevalence of liver disease in adult patients following the Fontan procedure using computed tomography (CT) and serum biomarkers of liver fibrosis. DESIGN   Adult Fontan patients underwent screening for liver disease as part of their annual evaluation. Screening consisted of laboratory evaluation and dual-phase liver CT scan. Laboratory evaluation included analysis of liver function, viral hepatitis serologies, and FibroSURE panel (LabCorp), a test that analyzes the results of serum biomarkers to provide a quantitative surrogate marker for liver fibrosis. RESULTS   Sixteen patients, mean age 30.3 (range 20-41) years, were enrolled in the study. Mean length of follow-up from time of Fontan palliation was 20.5 (range 11-33) years. No patients had serologic evidence of viral hepatitis or synthetic liver dysfunction. Twelve patients (75%) had abnormal FibroSURE scores, seven (44%) had elevated FibroSURE scores predictive of Metavir fibrosis stage F2 or greater on liver biopsy, and one (6%) had a FibroSURE score predictive of cirrhosis on biopsy. All 16 patients had abnormal radiologic liver findings identified on CT, including heterogeneous enhancement in 11 (69%), varices in six (38%), and liver nodules in five patients (31%). Length of time since Fontan surgery correlated significantly with an elevated FibroSURE score (P = .05) and having more CT scan abnormalities (P = .04). CONCLUSIONS   Liver fibrosis detected by serum biomarkers and dual phase CT scan is common in adult patients following the Fontan procedure. Further studies are needed to determine the long-term clinical significance of these findings.

Restrictive Lung Disease is an Independent Predictor of Exercise Intolerance in the Adult with Congenital Heart Disease

BACKGROUND/OBJECTIVES Following repair of congenital heart disease (CHD), adult patients are at risk for reduced exercise capacity. Restrictive lung disease (RLD) may contribute to reduced exercise capacity in this population. The aim of this study was to determine the prevalence of RLD and its impact on exercise tolerance in the adult with CHD. METHODS One hundred consecutive adult patients with CHD, who underwent routine cardiopulmonary exercise testing with spirometry, were evaluated. Clinical data were obtained by retrospective chart review. RESULTS Patients from 10 major diagnostic groups were identified. The median age for the cohort was 31 years (range 18-63) and included 43 males and 57 females. Most patients, 79%, had at least one previous surgical procedure. Based on spirometry and flow/volume loops, 50 patients were classified as normal pulmonary function, 44 patients had patterns suggestive of RLD, 4 suggestive of mixed (obstructive and restrictive), and 2 indeterminate. Risk factors associated with RLD include history of multiple thoracotomies (odds ratio = 9.01, P =.05) and history of atrial arrhythmias (odd ratio = 4.25, P =.05). Overall, 56% of the patients had abnormal exercise capacity. Spirometry suggestive of RLD was a significant risk factor for decreased exercise capacity (odds ratio = 3.65, P =.03). Patients with spirometry suggesting RLD also had lower exercise duration (P =.004) and a higher New York Heart Association Functional Class (P =.02). History of previous surgery and decreased heart rate reserve were also significant risk factors for decreased exercise capacity. CONCLUSION Abnormal spirometry suggestive of RLD is common in the adult with CHD and is a significant risk factor for decreased exercise tolerance in this population. Further studies are needed to evaluate the relationship between RLD and exercise intolerance and its relationship to mortality in the adult with CHD.

Extracardiac Complications in Adults with Congenital Heart Disease

With the increasing number of adults living with repaired, or unrepaired, congenital heart disease, there is a growing incidence of extracardiac comorbidities. These comorbidities can affect various organ systems in complex ways, and may have a significant impact on a patients quality of life and survival. Many of these potential complications may go undiagnosed until there is already a significant bearing on the patients life. Therefore, it is important for physicians who care for the adult congenital patient to be mindful of these potential extracardiac complications, and actively assess for these complications in their adult congenital practice. Continued research to identify modifiable risk factors is needed so that both preventative and therapeutic management options for these extracardiac complications may be developed.

Long-term outcomes of the neoaorta after arterial switch operation for transposition of the great arteries.

BACKGROUND After the arterial switch operation (ASO) for transposition of the great arteries (TGA), the native pulmonary root and valve function in the systemic position, and the long-term risk for neoaortic root dilation and valve regurgitation is currently undefined. The aim of this study was to determine the prevalence and progression of neoaortic root dilation and neoaortic valve regurgitation in patients with TGA repaired with the ASO. METHODS Measurements of the neoaortic annulus, neoaortic root at the level of the sinuses of Valsalva, and the degree of neoaortic regurgitation were assessed by serial transthoracic echocardiograms on 124 patients with TGA at a median follow-up of 7.2 years (range, 1 to 23 years) after the ASO at our institution. RESULTS Neoaortic root dilation with z scores of 2.5 or greater was identified in 66%, and the root diameter z score increased at an average rate of 0.08 per year over time after ASO. Freedom from neoaortic root dilation at 1, 5, 10, and 15 years after ASO was 84%, 67%, 47%, and 32%, respectively. Risk factors for root dilation include history of double-outlet right ventricle (p = 0.003), previous pulmonary artery banding (p = 0.01), and length of follow-up (p = 0.04). Neoaortic valve regurgitation of at least moderate degree was present in 14%. Neoaortic root dilation was a significant risk factor for neoaortic valve regurgitation (p < 0.0001). No patient required reintervention on the neoaorta or neoaortic valve during follow-up. CONCLUSIONS Progressive neoaortic root dilation is common in patients with TGA after the ASO. Continued surveillance of this population is required.

Can a Home-based Cardiac Physical Activity Program Improve the Physical Function Quality of Life in Children with Fontan Circulation?

OBJECTIVE Patients after Fontan operation for complex congenital heart disease (CHD) have decreased exercise capacity and report reduced health-related quality of life (HRQOL). Studies suggest hospital-based cardiac physical activity programs can improve HRQOL and exercise capacity in patients with CHD; however, these programs have variable adherence rates. The impact of a home-based cardiac physical activity program in Fontan survivors is unclear. This pilot study evaluated the safety, feasibility, and benefits of an innovative home-based physical activity program on HRQOL in Fontan patients. METHODS A total of 14 children, 8-12 years, with Fontan circulation enrolled in a 12-week moderate/high intensity home-based cardiac physical activity program, which included a home exercise routine and 3 formalized in-person exercise sessions at 0, 6, and 12 weeks. Subjects and parents completed validated questionnaires to assess HRQOL. The Shuttle Test Run was used to measure exercise capacity. A Fitbit Flex Activity Monitor was used to assess adherence to the home activity program. RESULTS Of the 14 patients, 57% were male and 36% had a dominant left ventricle. Overall, 93% completed the program. There were no adverse events. Parents reported significant improvement in their childs overall HRQOL (P < .01), physical function (P < .01), school function (P = .01), and psychosocial function (P < .01). Patients reported no improvement in HRQOL. Exercise capacity, measured by total shuttles and exercise time in the Shuttle Test Run and calculated VO2 max, improved progressively from baseline to the 6 and 12 week follow up sessions. Monthly Fitbit data suggested adherence to the program. CONCLUSION This 12-week home-based cardiac physical activity program is safe and feasible in preteen Fontan patients. Parent proxy-reported HRQOL and objective measures of exercise capacity significantly improved. A 6-month follow up session is scheduled to assess sustainability. A larger study is needed to determine the applicability and reproducibility of these findings in other age groups and forms of complex CHD.

Surgical Valvotomy Versus Balloon Valvuloplasty for Congenital Aortic Valve Stenosis: A Systematic Review and Meta‐Analysis

Background Optimal initial treatment for congenital aortic valve stenosis in children remains unclear between balloon aortic valvuloplasty (BAV) and surgical aortic valvotomy (SAV). Methods and Results We performed a contemporary systematic review and meta‐analysis to compare survival in children with congenital aortic valve stenosis. Secondary outcomes included frequency of at least moderate regurgitation at hospital discharge as well as rates of aortic valve replacement and reintervention. Single‐ and dual‐arm studies were identified by a search of PubMed (Medline), Embase, and the Cochrane database. Overall 2368 patients from 20 studies were included in the analysis, including 1835 (77%) in the BAV group and 533 (23%) in the SAV group. There was no difference between SAV and BAV in hospital mortality (OR=0.98, 95% CI 0.5–2.0, P=0.27, I2=22%) or frequency of at least moderate aortic regurgitation at discharge (OR=0.58, 95% CI 0.3–1.3, P=0.09, I2=54%). Kaplan–Meier analysis showed no difference in long‐term survival or freedom from aortic valve replacement but significantly more reintervention in the BAV group (10‐year freedom from reintervention of 46% [95% CI 40–52] for BAV versus 73% [95% CI 68–77] for SAV, P<0.001). Results were unchanged in a sensitivity analysis restricted to infants (<1 year of age). Conclusions Although higher rates of reintervention suggest improved outcomes with SAV, indications for reintervention may vary depending on initial intervention. When considering the benefits of a less‐invasive approach, and clinical equipoise with respect to more clinically relevant outcomes, these findings support the need for a randomized controlled trial.

Quantitative echocardiographic measures in the assessment of single ventricle function post‐Fontan: Incorporation into routine clinical practice

Quantitative echocardiographic measurements of single ventricular (SV) function have not been incorporated into routine clinical practice.

Outcomes of a hepatitis C screening protocol in at-risk adults with prior cardiac surgery.

Background: Symptoms associated with hepatitis C infection often do not develop until an advanced stage of liver disease. Prior to 1992, reliable testing for hepatitis C was unavailable, resulting in potential patient exposure during cardiopulmonary bypass. As the hepatitis C prevalence in our center was unknown, a screening protocol for patients who underwent surgery prior to 1992 was developed. Methods: Patients evaluated in the Wisconsin Adult Congenital Heart Disease program who underwent surgery prior to 1992 were screened for hepatitis C as part of their initial clinical evaluation. The hepatitis C-positive patients were assessed for risk factors, level of hepatic involvement, whether they received treatment, and whether viral clearance was obtained. Results: A total of 147 patients (53% male) underwent testing. Seven (4.8%) patients had evidence of chronic hepatitis C infection, which is higher than the Wisconsin reported prevalence of 0.3%. Six of the seven patients had elevated liver enzymes at time of diagnosis. No relationship was found between hepatitis C infection and number of surgeries, year of surgery, or age at surgery. Four patients had hepatitis C genotype 1, but none achieved viral clearance despite three having received treatment. Three had genotype 2, were treated, and had viral clearance. No hepatitis C-positive patient developed cirrhosis or required liver transplant. Conclusion: Hepatitis C infection in patients with congenital heart disease who underwent surgical palliation prior to 1992 is common, with prevalence higher than the general population. Our data emphasize the continued importance of screening the high-risk adult congenital heart disease patients.

The Impact of Obesity on Postoperative Outcomes in Adults with Congenital Heart Disease Undergoing Pulmonary Valve Replacement

OBJECTIVE The impact of obesity on surgical morbidity in adults with congenital heart disease is currently unknown. The aim of our study was to investigate the impact of obesity on postoperative outcomes in adults with congenital heart disease undergoing reoperation for pulmonary valve replacement. METHODS A retrospective analysis was performed assessing the influence of obesity on surgical outcomes. Obesity was defined as a body mass index ≥30 kg/m2. RESULTS The mean body mass index of the cohort was 25.9 ± 6.9 kg/m2 . The cohort included 71 patients with 17 patients (24%) being obese. There was no postoperative mortality. Obese patients had a longer hospital length of stay (6.6 vs. 4.7 days; P < .001) and increased incidence of postoperative arrhythmias (29% vs. 5.6%; P = .003) compared with nonobese patients. Multivariable analysis performed using logistic regression with backwards elimination demonstrated obesity was independently associated with hospital length of stay >5 days (odds ratio [OR] = 5.2; 95% confidence interval [CI]: 1.5-18.2, P = .01) and with increased postoperative arrhythmias (OR = 4.2; 95% CI: 1.7-40, P < .01). CONCLUSIONS Obesity is associated with increased morbidity in adults with congenital heart disease undergoing pulmonary valve replacement, including longer hospitalization and higher risk for postoperative arrhythmias.