Abstract Background Protein-losing enteropathy (PLE), characterized by loss of proteins in the intestine, is a devastating complication in patients with congenital heart disease. The cause of PLE is ...unknown, but lymphatic involvement has been suspected. Objectives The authors evaluated the use of lymphangiographic imaging and liver lymphatic embolization as a treatment for PLE. Methods This was a single-center, retrospective review of imaging and interventions used in 8 consecutive patients with liver lymphatic embolization and congenital heart disease with elevated central venous pressure complicated by PLE. Results Liver lymphangiography was performed in 8 patients (5 males, 3 females; median age, 21 years), 7 of whom demonstrated leakage of liver lymph into the duodenum through abnormal hepatoduodenal lymphatic communications. This was confirmed by duodenoscopy with simultaneous injection of isosulfan blue dye into the liver lymphatics in 6 of 7 patients. Liver lymphatic embolization with ethiodized oil in 2 patients resulted in a temporary increase in albumin blood level and symptom improvement in 1 patient, but was complicated by duodenal bleeding in both patients. Of the remaining 6 patients, liver lymphatic embolization with n-butyl cyanoacrylate glue resulted in sustained improvement of the serum albumin level and symptoms in 3 patients, temporary improvement in 2 patients, and no change in 1 patient with median follow-up of 135 days (range, 84 to 1,005 days). Conclusions The authors demonstrated liver lymph leakage as a cause of PLE in patients with congenital heart disease and elevated central venous pressure. Lymphatic embolization led to improved albumin levels and relief of symptoms. Further experience with the technique is needed to determine long-term outcome of this procedure.
Abstract Objective Existing studies of patients palliated with the Fontan operation are limited by heterogeneous patient populations and incomplete follow-up. This study aimed to describe long-term ...post-Fontan survival in a modern patient cohort. Methods All 773 patients who underwent a first Fontan operation at our institution between 1992 and 2009 were reviewed. The primary outcome was the composite endpoint of Fontan takedown, heart transplantation, or death before 2013. Results Follow-up rate was 99.2%. Survival with intact Fontan circulation was 94% at 1 year (95% confidence interval 95% CI, 92%-95%), 90% at 10 years (95% CI, 88%-92%), 85% at 15 years (95% CI, 82%-88%), and 74% at 20 years (95% CI, 67%-80%). Distinct risk factors were identified for early (≤1 year) and late composite outcomes. Independent risk factors for early outcome included prolonged pleural drainage (hazard ratio HR, 4.4; P < .001), intensive care unit stay >1 week (HR, 2.4; P < .001), Fontan before 1997 (HR, 3.3; P < .001), preoperative atrioventricular valve regurgitation (HR, 2.0; P < .001), and longer crossclamp time (HR, 1.3 per 10 minutes; P < .001). Late outcome was predicted by atrioventricular valve regurgitation prior to Fontan (HR, 2.0; P ≤ .001), and post-Fontan ICU stay >1 week (HR, 2.4; P < .001). Conclusions Long-term mortality after Fontan operation remains substantial. Risk factors for death or loss of Fontan circulation differ between the early and late postoperative periods. Long-term survival has not improved appreciably over the last decade, suggesting that alternatives to the Fontan are warranted.
Objective To determine whether prenatal diagnosis of congenital heart disease (CHD) increases maternal stress. Study design Self-report instruments were administered to mothers carrying a fetus with ...CHD. Domains included: (1) traumatic stress (Impact of Events Scale-Revised); (2) depression (Beck Depression Index II); and (3) anxiety (State-Trait Anxiety Index). Modifiers included: (1) coping skills (COPE Inventory); (2) partner satisfaction (Dyadic Adjustment Scale); and (3) demographics. Multivariate linear regression models were used to assess relationships between stress measures and modifiers. Results Fifty-nine mothers (gestational age 27 ± 3 weeks) completed all measures. Clinically important traumatic distress was seen in 39%, depression in 22%, and state anxiety in 31%. Lower partner satisfaction was associated with higher depression ( P < .01) and higher anxiety ( P < .01). After controlling for partner satisfaction and income, “denial” was most associated with increased traumatic stress, anxiety, and depression ( P < .01). Conclusions Posttraumatic stress, depression, and anxiety are common after prenatal diagnosis of CHD. Healthy partner relationships and positive coping mechanisms can act as buffers.
Abstract Although survival after the Fontan operation has improved, little is known about the burden of major medical morbidities associated with the modern total cavopulmonary connection (TCPC). A ...total of 773 consecutive patients who underwent a first Fontan operation at our institution between 1992 and 2009 were retrospectively reviewed. All subjects underwent TCPC (53% lateral tunnel, 47% extracardiac conduit). Median length of follow-up was 5.3 years (IQR 1.4-11.2), and 30% had follow-up >10 years. Freedom from a composite medical morbidity outcome (protein-losing enteropathy, plastic bronchitis, serious thromboembolic event, or tachyarrhythmia) was 47% at 20 years (95% CI 38-55%). Independent risk factors for morbidity included pre-Fontan atrioventricular valve regurgitation (HR 1.7, 95% CI 1.2-2.4; p=0.001), pleural drainage > 14 days (HR 1.5, 95% CI 1.01-2.2, p=0.04), and longer cross-clamp time (HR 1.2 per 10 minutes, 95% CI 1.06-1.3; p=0.004) at the time of TCPC. Surgical era, Fontan type, and ventricular morphology were not associated with the composite outcome. Presence of Fontan-associated morbidity was associated with a 36-fold increase in the risk of subsequent Fontan takedown, heart transplantation, or death (95% CI 17– 76, p<0.001). For patients without any component of the composite outcome, freedom from Fontan failure was 98% at 20 years (95% CI 96-99%). Medical morbidities after TCPC are common and significantly reduce the longevity of the Fontan circulation. However, for those patients who remain free from the composite morbidity outcome, 20-year survival with intact Fontan circulation is encouraging.
Summary The Fontan operation is a widely used palliative procedure in patients with single ventricle anatomy that results in liver injury. As timely identification of liver fibrosis may result in ...management changes to Fontan patients, the aim of our study was to identify clinically meaningful semi-quantitative/quantitative pathologic parameters for biopsy assessment. We performed a retrospective review of 74 liver needle biopsies from Fontan patients. Fibrosis was assessed using quantitative % collagen deposition (%CD) by Sirius red image analysis, METAVIR, congestive hepatic fibrosis score (CHFS), sinusoidal fibrosis (SF) score, and sinusoidal dilation score. Contemporaneous laboratory, hemodynamic, and ultrasound data were collected. Centrilobular and peri-sinusoidal fibrosis was observed in all cases, with 39.2% high grade. Portal fibrosis was observed in 93.2%, with 36.2% high grade (METAVIR F3-F4). Cirrhosis was observed in 5.4%. %CD was increased over control tissue (p<0.001) and correlated with time from Fontan (r=0.3, p=0.009) and prothrombin time (PT) (r=0.25, p=0.034). Mildly elevated PT/INR was the only measure of liver function consistently associated with multiple high-grade fibrosis scores (METAVIR p=0.046, SF p=0.018). Abnormal liver echotexture on ultrasound was associated with high grade CHFS (p=0.03). Pathologic gradings and %CD correlated with each other (r=0.48-0.8, p<0.001). Hepatic fibrosis in Fontan patients in our study is universally present, appears to be time dependent, and correlates with few laboratory measurements of liver function. Careful assessment of needle liver biopsies lends a more meaningful measure of liver fibrosis in the Fontan patient than clinical and laboratory data, allowing for appropriate changes to patient management.
Objective Current means of grading twin-twin transfusion syndrome does not characterize cardiovascular aspects adequately. We sought to develop a score that describes the magnitude of cardiovascular ...severity in twin-twin transfusion syndrome. Study Design Fetal echocardiograms of 150 monochorionic/diamniotic twins were reviewed. Blinded to Quintero stage, we applied a cardiovascular score to each twin set and compared it to the Quintero grade. The score is a composite of variables that include ventricular hypertrophy, dilation, function, valve regurgitation, great artery size, and diastolic properties in the recipient and umbilical artery flow in the donor. Doppler indices of vascular and ventricular function were measured. Results Mean age was 21 ± 3 weeks. Discrepancy was noted in degree of severity between Quintero and cardiovascular stages. The score correlated well with myocardial performance index of the recipient right ventricle ( r2 = .65). Conclusion We describe the spectrum of cardiovascular abnormalities that are seen in twin-twin transfusion syndrome and propose a scoring system for assessment of severity.
Background Intrapericardial teratoma is a rare, lethal tumor often detected in fetal life. Tumor mass and pericardial effusion cause cardiac tamponade that, if relieved, could be life-saving. Optimal ...timing of intervention and methods for effective fetal treatment are unknown. Objective We describe our single-center experience with fetal intrapericardial teratoma including the first report of successful in utero surgical resection with survival to term. Study Design We reviewed our database for suspected fetal intrapericardial teratoma. On fetal ultrasound and echocardiography tumor size was estimated by calculation of an ellipse and analyzed in relation to Doppler-derived fetal cardiac output, venous flow patterns, hydrops, and outcome. Results Eight fetuses with suspected intrapericardial teratoma were seen from 2009 through 2015. Gestational age at initial presentation ranged from 21-34 (median 26) weeks. Two cases mimicked the appearance of intrapericardial teratoma, but had no serial change in cardiac output over time and were ultimately determined to be other types of tumor. In 6 cases of true intrapericardial teratoma, tumor growth was extremely rapid and associated with progressive decline in cardiac output (to <400 mL/kg/min) manifesting in hydrops and death if left untreated. One case was treated successfully at 31 weeks through ex utero intrapartum delivery with tumor resection while on placental support. Another case underwent open fetal surgery and resection at 24 weeks, with resumption of gestation until delivery at 37 weeks with excellent outcome. Conclusion Fetal intrapericardial teratoma can be successfully managed utilizing serial surveillance and by treatment in a timely manner prior to the predictable onset of hydrops, determined through increasing tumor size and a declining cardiac output. Surgical resection in utero is possible, with good results.
Background Plastic bronchitis is a rare, potentially life-threatening complication after Fontan operation. Hemodynamic alterations (elevated central venous pressure and low cardiac output) likely ...contribute to the formation of tracheobronchial casts composed of inflammatory debris, mucin, and fibrin. Pathologic studies of cast composition support medical treatment with fibrinolytics such as inhaled tissue plasminogen activator (t-PA). Methods This was a retrospective case series of medical, surgical, and catheter-based treatment of patients with plastic bronchitis after cavopulmonary palliation. Results Included were 14 patients (86% male, 93% white). Median age at Fontan operation was 2.7 years (range, 1.2 to 4.1 years), with median interval to plastic bronchitis presentation of 1.5 years (range, 9 days to 15.4 years). Cast composition was available for 11 patients (79%) and included fibrin deposits in 7. All patients were treated with pulmonary vasodilators, and 13 (93%) were treated with inhaled t-PA. Hemodynamically significant lesions in the Fontan pathway were addressed by catheter-based (n = 9) and surgical (n = 3) interventions. Three patients (21%) underwent heart transplantation. Median follow-up was 2.7 years (range, 0.6 to 8.7 years). Symptoms improved, such that 6 of 13 patients (46%) were weaned off t-PA. Rare or episodic casts are successfully managed with outpatient t-PA in most of the other patients. Of the 3 patients who underwent heart transplant, 2 are asymptomatic and 1 has recurrent casts in the setting of elevated filling pressures and rejection. Conclusions A systematic step-wise algorithm that includes optimization of hemodynamics, aggressive pulmonary vasodilation, and inhaled t-PA is an effective treatment strategy for patients with plastic bronchitis after cavopulmonary connection.
Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, ...volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 ± 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement for qualitative grading of ventricular function by echocardiography was modest for left ventricular (LV) morphology (κ = 0.42) and weak for right ventricular (RV) morphology (κ = 0.12). For quantitative assessment, high intraclass correlation coefficients were found for echocardiographic interobserver agreement (LV 0.87 to 0.92, RV 0.82 to 0.85) of systolic and diastolic volumes, respectively. In contrast, intraclass correlation coefficients for LV and RV mass were moderate (LV 0.78, RV 0.72). The corresponding intraclass correlation coefficients by CMR were high (LV 0.96, RV 0.85). Volumes by echocardiography averaged 70% of CMR values. Interobserver reproducibility for the EF was similar for the 2 modalities. Although the absolute mean difference between modalities for the EF was small (<2%), 95% limits of agreement were wide. In conclusion, agreement between observers of qualitative FSV function by echocardiography is modest. Measurements of FSV volume by 2-dimensional echocardiography underestimate CMR measurements, but their reproducibility is high. Echocardiographic and CMR measurements of FSV EF demonstrate similar interobserver reproducibility, whereas measurements of FSV mass and LV diastolic volume are more reproducible by CMR.
Growth hormone and its mediator, insulinlike growth factor 1 (IGF-1), are key determinants of growth in children and young adults. As patients with Fontan physiology often experience diminished ...longitudinal growth, we sought to describe IGF-1 levels in this population and to identify factors associated with IGF-1 deficiency. Forty-one Fontan subjects ≥5 years were evaluated in this cross-sectional study. Age- and gender-specific height Z scores were generated using national data. Laboratory testing included IGF-1 and brain natriuretic peptide (BNP) levels. IGF-1 levels were converted to age-, gender-, and Tanner stage–specific Z scores. BNP levels were log transformed to achieve a normal distribution (log-BNP). Medical records were reviewed for pertinent clinical variables. Predictors of IGF-1 Z score were assessed through the Student t test and Pearson's correlation. Median age was 11.1 years (range 5.1 to 33.5 years), and time from Fontan was 8.2 years (1.1 to 26.7). Mean height Z score was −0.2 ± 0.9 with a mean IGF-1 Z score of −0.1 ± 1.3. There was no association between IGF-1 Z score and height Z score. Longer interval since Fontan ( R = −0.32, p = 0.04), higher log-BNP ( R = −0.40; p = 0.01), and lower indexed systemic flow on cardiac magnetic resonance ( R = 0.55, p = 0.02) were associated with lower IGF-1 Z scores. In conclusion, in this cohort with Fontan physiology, higher BNP and lower systemic flow were associated with lower IGF-1 Z score. Longitudinal studies are needed to determine if these relations represent a mechanistic explanation for diminished growth in children with this physiology and with other forms of congenital heart disease.
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