Peter J. Bartz

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.

Paradoxical emboli in children and young adults: role of atrial septal defect and patent foramen ovale device closure.

OBJECTIVE To describe a multicenter experience with patent foramen ovale (PFO) and atrial septal defect (ASD) device closure for presumed paradoxical emboli in children and young adults (<35 years old). PATIENTS AND METHODS Medical records were reviewed of patients who had device closure of an ASD or PFO, who were younger than 35 years, and who had a history of presumed paradoxical embolus between January 1999 and August 2005 at Mayo Clinic, Rochester, Minn, University of Parma, Parma, Italy, and Loyola University Medical Center, Maywood, Ill. RESULTS Forty-five patients fulfilled the inclusion criteria. Median patient age was 29.0 years (range, 5.0-34.9 years), and 23 patients (51%) were male. Clinical diagnoses included the following: stroke, 30 (67%); transient ischemic attack, 13 (29%); myocardial infarction, 1 (2%); and renal infarct, 1 (2%). Overall, 42 patients (93%) had a PFO, and 3 (7%) had an ASD. Seventeen patients had known cardiovascular disease risk factors: tobacco use (10 patients), hypercoagulable states (7 patients), systemic hypertension (3 patients), and hyperilpidemia (2 patients). No major procedural complications occurred. Median follow-up evaluation was performed at 5.3 months (range, 2.5-40.0 months). Forty-four patients (98%) had no recurrent neurologic events and no residual atrial shunt by contrast transthoracic echocardiography. CONCLUSIONS Cryptogenic ischemic events occur in young patients and have serious sequelae. The potential for paradoxical embolization through a PFO or an ASD should be assessed in all such patients. In our short-term follow-up, device closure was a safe alternative therapeutic option for children and young adults with presumed paradoxical emboli.

Naloxone administration following operant training of sucrose/water discrimination in the rat

The suppression of food intake observed following naloxone administration has often been ascribed to palatability or taste. Unfortunately, many confounds become apparent when attempts are made to isolate such factors in the investigation of ingestive behaviors. In the present study, rats (two groups) were trained to discriminate either a 10% or 5% sucrose solution from water (0.1 ml). These mildly food deprived subjects (95% of free-feeding weight) were trained to press the appropriate lever in a two-lever operant chamber following sampling of sucrose or water; successful responding was reinforced by delivery of a 45 mg grain food pellet. Following random exposure to reduced sucrose concentrations tested under extinction, a sucrose concentration gradient (1.0, 0.5, 0.1, 0.05, 0.01 and 0.005% sucrose solution) was established for both training groups under IP saline administration. Data collected under IP saline were then compared to those collected following random IP naloxone administration (3.0, 1.0, 0.3 and 0.1 mg/kg). No significant differences were observed between the sucrose concentration gradients obtained under saline and those obtained under naloxone, suggesting that the anorectic effect of naloxone is not primarily determined by discrimination of sweet taste.

Improving interstage survival after Norwood operation: outcomes from 10 years of home monitoring.

OBJECTIVE Infants who undergo Norwood stage 1 palliation (S1P) continue with high-risk circulation until stage 2 palliation (S2P). Routine care during the interstage period is associated with 10% to 20% mortality. This report illustrates the sustained reduction of interstage mortality over 10 years associated with use of home monitoring. METHODS Daily monitoring of oxygen saturation and weight was done for all patients discharged to home after S1P. Notification of the care team occurred for oxygen saturation<75% or >90%, weight gain<20 g over 3 days, weight loss>30 g, or intake<100 cc/kg/d. Breach of these criteria marked an interstage event. Interstage outcomes are reported. Patient characteristics and perioperative variables were compared between patients with and without interstage events. RESULTS Over 10 years, 157 patients were discharged after S1P with home monitoring. Interstage survival was 98%. Breach of home criteria occurred in 59% (93 out of 157), with violation of oxygen saturation<75% the most common event. Patient characteristics, operative data, and early postoperative morbidity did not differ between patients with and without events. CONCLUSIONS Home monitoring after S1P is associated with excellent interstage survival. Although a breach of monitoring criteria occurred in more than half of patients, our analysis failed to identify independent predictors of interstage events. Analysis of variables predicting mortality could not be assessed due to the low frequency of death in this cohort. Failure to identify specific variables for interstage events suggests that home monitoring, as part of an interstage surveillance program, should be applied to all S1P hospital survivors.

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.

Timing and Technique of Pulmonary Valve Replacement in the Patient With Tetralogy of Fallot

Residual right ventricular (RV) outflow tract pathology is universal among patients with repaired tetralogy of Fallot, and pulmonary regurgitation (PR) is also commonly present. Although tolerated in early life, by the second decade of life PR is associated with an increased risk of death because of ventricular arrhythmias. Pulmonary valve replacement (PVR) is a safe procedure that will eliminate PR, but timing and indications are evolving. Patients with arrhythmias or prolonged QRS duration are candidates for PVR. Patients with symptomatic exercise intolerance are likely to have improvement in symptoms and quality of life and should be offered PVR. Cardiac magnetic resonance has become an essential component of the management of the patient with tetralogy of Fallot with PR, and has identified the potential for and limitations of RV remodeling following PVR. Among patients with severe RV enlargement, particularly those with diminished RV or left ventricular function, there is an increased risk of adverse events and even asymptomatic patients with severe PR should be considered for PVR. Valve replacement is accomplished with homografts or heterografts, either stented bioprosthetic valves or valved conduits. In a retrospective analysis of the Childrens Hospital of Wisconsin experience with PVR, there was no difference in survival or freedom from reintervention between heterografts and homografts.

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.

Effect of feeding modality on interstage growth after stage I palliation: A report from the National Pediatric Cardiology Quality Improvement Collaborative

OBJECTIVES Achieving adequate growth after stage 1 palliation for children with single-ventricle heart defects often requires supplemental nutrition through enteral tubes. Significant practice variability exists between centers in the choice of feeding tube. The impact of feeding modality on the growth of patients with a single ventricle after stage 1 palliation was examined using the multiinstitutional National Pediatric Cardiology Quality Improvement Collaborative data registry. METHODS Characteristics of patients were compared by feeding modality, defined as oral only, nasogastric tube only, oral and nasogastric tube, gastrostomy tube only, and oral and gastrostomy tube. The impact of feeding modality on change in weight for age z-score during the interstage period, from stage 1 palliation discharge to stage 2 palliation, was evaluated by multivariable linear regression, adjusting for important patient characteristics and postoperative morbidities. RESULTS In this cohort of 465 patients, all groups demonstrated improved weight for age z-score during the interstage period with a mean increase of 0.3±0.8. In multivariable analysis, feeding modality was not associated with differences in the change in weight for age z-score during the interstage period (P=.72). Risk factors for poor growth were a diagnosis of hypoplastic left heart syndrome (P=.003), vocal cord injury (P=.007), and lower target caloric goal at discharge (P=.001). CONCLUSIONS In this large multicenter cohort, interstage growth improved for all groups and did not differ by feeding modality. With appropriate caloric goals and interstage monitoring, adequate growth may be achieved regardless of feeding modality and therefore local comfort and complication risk should dictate feeding modality.

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.

Urinary interleukin-18 and urinary neutrophil gelatinase-associated lipocalin predict acute kidney injury following pulmonary valve replacement prior to serum creatinine.

BACKGROUND It is becoming increasingly recognized that manifestations of congenital heart disease (CHD) extend beyond the cardiovascular system. The factors contributing to renal dysfunction in patients with CHD are multifactorial, with acute kidney injury (AKI) at time of cardiac surgery playing a major role. AKI is often diagnosed based on changes in serum creatinine and estimated glomerular filtration rate (eGFR). Such measurements are often late and imprecise. Recent data indicate that urinary biomarkers interleukin-18 (IL-18) and neutrophil gelatinase-associated lipocalin (NGAL) are earlier markers of AKI. We sought to determine the efficacy of urinary IL-18 and NGAL for detecting early AKI in patients undergoing surgical pulmonary valve replacement (PVR). METHODS Twenty patients presenting for surgical PVR with a history of previous repair of a conotruncal anomaly were enrolled. Preoperative clinical data were measured and urine samples and serum creatinine were collected at 6, 12, 24, and 72 hours post bypass. Urine was evaluated for NGAL and IL-18. AKI was determined using the Risk, Injury, Failure, Loss and End Stage Renal Disease (RIFLE) classification system. RESULTS Using the RIFLE classification system, seven patients (35%) were found to have AKI defined as a drop in the eGFR or an increase in serum creatinine. All seven patients with AKI had marked increase from preoperative baseline in urine IL-18 (sixfold) and NGAL (26-fold). Using NGAL and IL-18, AKI was detected at 6 hours postoperatively, resulting in AKI being identified 12-36 hours prior to detection by conventional methods. No preoperative predictors for AKI were identified. CONCLUSION Both NGAL and IL-18 are early predictive biomarkers of AKI, and both increase in tandem after surgical PVR. Importantly, both rise before an increase in creatinine or a decrease in eGFR is present. Monitoring both biomarkers may allow for earlier detection and subsequent interventions to prevent AKI at time of surgery for CHD.