Resolution of Acquired Pulmonary Arteriovenous Malformations in a Patient with Total Anomalous Systemic Venous Return

An 11-year-old male with total anomalous systemic venous return had surgical repair except for the hepatic venous return, which drained to the left atrium. He developed progressive cyanosis and fatigue and was diagnosed with large pulmonary arteriovenous malformations (PAVMs) during cardiac catheterization with the use of bubble contrast echocardiography. After surgical redirection of hepatic venous flow to the right heart and pulmonary arterial system, resolution of these PAVMs was demonstrated clinically and by contrast echocardiography. This unique case report demonstrates the development of PAVMs with exclusion of hepatic venous return through the pulmonary vascular bed while pulsatile pulmonary blood flow remains intact. It reinforces the likelihood of the absence of an as yet unidentified hepatic vasoactive substance as the source for development of PAVMs.     

Endostatin, an Inhibitor of Angiogenesis, Decreases After Bidirectional Superior Cavopulmonary Anastamosis

Pulmonary arteriovenous malformations (PAVMs) are a common source of morbidity after bidirectional superior cavopulmonary anastomosis (Glenn). The diversion of hepatic venous effluent away from the pulmonary circulation after Glenn appears to play a significant role in the pathogenesis of PAVMs. Although the liver is known to produce factors that regulate vascular development, specific hepatic inhibitors of angiogenesis have not been described in the post-Glenn population. Endostatin, produced from its precursor collagen XVIII, is a potent inhibitor of angiogenesis produced by the liver. This study aimed to investigate the hypothesis that endostatin levels decrease in patients after Glenn. Levels of endostatin and its precursor, long-type collagen XVIII, were determined by enzyme-linked immunoassay and immunoprecipitation, respectively, for serum samples from 38 patients undergoing Glenn, total cavopulmonary anastomosis (Fontan), or biventricular repair of cardiac defects. Samples were obtained before surgery and 24 h afterward. In patients undergoing a bidirectional Glenn procedure, endostatin levels decreased after surgery (n = 17; 4.42 vs 3.34 ng/ml; p < 0.001), and long type-collagen XVIII levels increased by 200 % (n = 10; p = 0.0001). However, endostatin levels did not change after surgery in patients undergoing Fontan (n = 13) or biventricular repair (n = 8). In patients undergoing Fontan, long-type collagen XVIII increased by 18 % (p < 0.01), whereas in control subjects, the levels were unchanged. These data suggest that the diversion of hepatic blood flow away from the pulmonary circulation in patients after the Glenn procedure inhibits endostatin production from collagen XVIII, resulting in decreased circulating serum endostatin levels. A decrease in endostatin may promote angiogenesis. The mechanism whereby the pulmonary circulation processes endostatin and its potential role in the pathogenesis of PAVMs warrant further study.     

Surgical Removal of Pulmonary Arteriovenous Malformations Subsequent to Total Cavopulmonary Connection Conversion Long After a Björk Procedure

Because the cavopulmonary shunt procedure is widely used for palliation of complex congenital heart diseases, pulmonary arteriovenous malformations (PAVMs) are relatively well-known complications. The reported patient was a 23-year-old woman who experienced PAVMs in the right lower lobe after a classical Glenn anastomosis and Björk procedure for tricuspid atresia. Her arterial oxygen saturation (SaO₂) 14 years after the Björk procedure was ~80 %. She then underwent a total cavopulmonary connection (TCPC) conversion to reduce her PAVMs in the right lower lobe using the “hepatic factor.” However, her situation remained unchanged, and she experienced severe systemic cyanosis (SaO₂, 70 %) and dyspnea during physical exertion without hemoptysis due to increased blood flow to the PAVMs. Although interventional embolization was considered, it was impossible due to considerable dilation of the main PAVM. Thus, right lower lung lobectomy was performed. After surgery, the patient’s SaO₂ increased to 90 %. To the authors’ knowledge, this is the first case report of a lung resection for residual PAVMs after TCPC conversion.     

Cardiac surgery for the adolescent with univentricular heart

Univentricular heart is a complex congenital anomaly with an extremely dismal prognosis. Left untreated the majority of patients will die in infancy. This poor outlook has prompted an aggressive surgical approach consisting of early palliation followed by eventual complete repair. The initial palliative efforts are aimed at providing adequate arterial oxygen saturation and normalizing pulmonary artery pressure. Infants with severe cyanosis due to diminished pulmonary blood flow are best treated with a systemic to pulmonary artery shunt. Those with excessive pulmonary flow and hypertension must be banded early to prevent pulmonary vascular occlusive disease. Most patients who are properly palliated will become acceptable candidates for an eventual corrective procedure. For the majority, this will be a direct atriopulmonary connection, known as the Fontan procedure. In this operation, systemic venous blood is routed directly to the pulmonary artery, excluding the ventricular mass. Although not corrective in the usual sense, this procedure provides normal arterial saturation without ventricular volume overload. A small group of patients with univentricular heart may best be treated by partitioning the ventricular chamber into 2 halves. Septation procedures, however, carry a high operative mortality and are likely to result in complete heart block. These surgical options, when properly selected and timed, have improved the outlook for many children with univentricular heart.     

Redirection of the Hepatic Venous Flow for the Treatment of Pulmonary Arteriovenous Malformations after Fontan Operation

A 45-month-old boy who had complex cardiac anomalies with interrupted inferior vena cava and polysplenia underwent extracardiac Fontan operation. He redeveloped deep cyanosis postoperatively. Cardiac catheterization showed a preferential flow of the hepatic venous blood to the right lung and arteriovenous malformations (PAVMs) in the left lung. He underwent revision of the conduit to attain balanced hepatic venous drainage with subsequent regression of the PAVMs and disappearance of cyanosis. Our experience shows that deficiency of hepatic venous flow played a crucial role in the development of PAVMs and that redistribution of the flow retained potential to ameliorate the pathological condition.     

Evaluation of patients undergoing Senning repair with two-dimensional contrast echocardiography

Summary The postoperative anatomy of the Senning interatrial diversion was defined by two-dimensional contrast echocardiography in ten patients. A modified apical four-chamber view proved most valuable, allowing for simultaneous visualization of both the systemic venous atrium and the pulmonary venous atrium. The anatomy was confirmed with two-dimensional contrast echocardiography utilizing catheters placed in the systemic venous atrium and pulmonary venous atrium at the time of surgery. In addition, in several of the patients, we were able to detect atrial or ventricular level shunts which were not clinically apparent. One patient who was judged to have a significant shunt by two-dimensional contrast echocardiography had no anatomic site found at autopsy to explain the shunting. We conclude that two-dimensional contrast echocardiography can define the postoperative anatomy following Senning repair allowing for immediate and future evaluation. Shunting at the atrial and ventricular levels can also be detected, but the method is very sensitive and difficult to quantitate or correlate clinically.     

Posterior reversible encephalopathy syndrome after pediatric heart transplantation: Increased risk for children with preexisting Glenn/Fontan physiology

Identification of risk factors for PRES after organ transplant can improve early detection and avoid permanent neurological injury. High calcineurin‐inhibitor levels and hypertension are recognized risk factors for PRES in adult transplant recipients. Limited data exist regarding PRES after pediatric HTx, with studies limited to case reports. We performed a retrospective review of 128 pediatric HTx recipients to identify risk factors for PRES. Seven of 128 (5.5%) recipients developed PRES at a median of 10 days (5–57) after HTx. The median age of recipients with PRES was 10.0 yr (5.7–19.0), compared to 1.4 yr (0.0–19.8) for recipients without PRES (p = 0.010). Fewer than half of recipients with PRES had elevated post‐transplant calcineurin‐inhibitor levels (n = 3) and/or preceding severe hypertension (n = 3). Four of seven who developed PRES (57%) had pretransplant Glenn or Fontan physiology (G/F). G/F was a significant risk factor for PRES (RR 4.99, 95% CI: 1.19–21.0, p = 0.036). Two recipients (29%), both with severe PRES, had residual neurological symptoms. In summary, PRES occurred in 5.5% of pediatric HTx recipients and presented early after HTx. All recipients with PRES were > 5 yr. Patients with pretransplant G/F were at increased risk, a risks factor not previously described.     

Transcatheter closure of extracardiac fontan fenestration in a cyanotic patient

Fontan operation is the connection of the systemic venous return to the pulmonary arteries, performed in patients with single ventricle physiology. The Fontan circuit is commonly fenestrated because of early postoperative risks such as high systemic venous pressure and low cardiac output. As it causes progressive cyanosis and increased risk of paradoxical embolism in the follow-up period, occlusion of these fenestrations is generally suggested. Successful closure of extracardiac Fontan fenestration with atrial septal occluder in a 10-year-old girl is reported herein. To our knowledge, this is the first such report from Turkey.     

Device Closure of an Atrial Septal Defect Following Successful Balloon Valvuloplasty in a Neonate with Critical Pulmonary Valve Stenosis and Persistent Cyanosis

Persistent cyanosis after successful balloon valvuloplasty for neonatal critical pulmonary valve stenosis is often related to poor right ventricular compliance and right-to-left shunting at the atrial level. A successful catheter closure of an atrial septal defect was performed with a dramatic increase in systemic oxygen saturation alleviating the need for a surgical systemic-to-pulmonary artery shunt.     

Stepwise interventional approach in a neonate with pulmonary valve atresia and intact ventricular septum

In neonates with pulmonary atresia and intact ventricular septum the aims of therapy are maintenance of pulmonary blood flow and right ventricular decompression in order to achieve right ventricular support of the pulmonary circulation. Recent developments in interventional heart catheterization with pulmonary radiofrequency-assisted balloon valvuloplasty and ductal stent implantation offer an alternative to the classical surgical approach. We report on a neonate with membranous pulmonary atresia and intact ventricular septum, in whom a large interatrial right-to-left shunt via the foramen ovale persisted after radiofrequency-assisted pulmonary balloon valvuloplasty on the 2nd day of life. The interatrial shunt prevented adequate right ventricular filling and antegrade pulmonary perfusion leading to severe cyanosis (transcutaneous oxygen saturation 40%). In order to increase pulmonary blood flow and raise left atrial pressure, the arterial duct was stented. After ductal stenting, prostaglandin was discontinued and the transcutaneous oxygen saturation remained stable around 89%. At follow up after 7 weeks the foramen ovale had decreased in size and only a small left-to-right shunt was present, documenting the effectiveness of this approach. Conclusion Based on the present case we propose a stepwise interventional approach for the neonate with pulmonary atresia and intact ventricular septum. If cyanosis persists after isolated pulmonary valvuloplasty despite adequate right ventricular function, ductal stent implantation can reduce interatrial shunting and thus improve oxygen saturation. Received: 12 January 1998 / Accepted: 15 February 1998     

Risk factors for late renal dysfunction after pediatric heart transplantation: a multi-institutional study

Renal dysfunction is a major determinant of outcome after HTx. Using a large, multi-institutional database, we sought to identify factors associated with late renal dysfunction after pediatric HTx. All patients in the PHTS database with eGFR ≥60 mL/min/1.73 m(2) at one yr post-HTx (n = 812) were analyzed by Cox regression for association with risk factors for eGFR <60 mL/min/1.73 m(2) at >1 yr after HTx. Freedom from late renal dysfunction was 71% and 57% at five and 10 yr. Multivariate risk factors for late renal dysfunction were earlier era of HTx (HR 1.84; p < 0.001), black race (HR 1.42; p = 0.048), rejection with hemodynamic compromise in the first year after HTx (HR 1.74; p = 0.038), and lowest quartile eGFR at one yr post-HTx (HR 1.83; p < 0.001). Renal function at HTx was not associated with onset of late renal dysfunction. Eleven patients (1.4%) required chronic dialysis and/or renal transplant during median follow-up of 4.1 yr (1.5-12.6). Late renal dysfunction is common after pediatric HTx, with blacks at increased risk. Decreased eGFR at one yr post-HTx, but not at HTx, predicts onset of late renal dysfunction. Future research on strategies to minimize late renal dysfunction after pediatric HTx may be of greatest benefit if focused on these subgroups.     

Fulminant development of pulmonary arteriovenous fistulas in an infant after total cavopulmonary shunt

An infant with cyanotic congenital heart disease and polysplenia syndrome developed profound cyanosis within months of undergoing bilateral cavopulmonary anastomoses. Intrapulmonary shunting was diagnosed by contrast echocardiography with peripheral venous and selective pulmonary artery injection. Histopathology revealed abnormal, thin-walled vessels within the interstitium of the lung lobule. These vessels have not been reported previously and are likely to be the anatomic site of arteriovenous shunting. This case demonstrates that pulmonary arteriovenous fistulas (PAVFs) may develop rapidly after cavopulmonary anastomosis in young infants. It also illustrates the use of contrast echocardiography for following PAVF progression in these patients.     

Exercise Performance Following Repair of Hypoplastic Left Heart Syndrome: A Comparison with Other Types of Fontan Patients

Reports of exercise performance after Fontan surgery for hypoplastic left heart syndrome (HLHS) are lacking. We compared the exercise performance of total cavopulmonary connection type (TCPC) of Fontan subjects with HLHS (group 1, n= 7) to those not requiring a Norwood procedure having a systemic right ventricle (group 2, n= 6) or a systemic left ventricle (group 3, n= 8). The subjects underwent assessment of resting pulmonary mechanics followed by maximal exercise testing with a bicycle or treadmill protocol. ECG, oxygen consumption, and carbon dioxide production were measured continuously. There was not a significant difference seen between HLHS and the comparison groups for the following parameters: maximum heart rate, maximum oxygen consumption, respiratory exchange ratio, breathing reserve, and arterial oxygen saturation at rest or exercise. Exercise performance in the TCPC type of Fontan patients was comparable regardless of ventricular morphology or surgical approach.     

Modified Fontan Operation in Patients with Anomalies of Systemic and Pulmonary Venous Connection

The presence of anomalies of the systemic and pulmonary venous connection associated with single ventricle anomalies has been considered a contraindication for the Fontan operation (FO). The aim of this study is to outline the technical considerations associated with the presence of anomalies of systemic and/or pulmonary venous connections and to identify the risk factors for mortality in this group of patients undergoing the modified FO. Between 1989 and 2004, 63 patients (median age, 3.2 years) with anomalous systemic or pulmonary venous connection underwent a Fontan procedure at our institution. Nine patients had a combination of anomalous systemic and pulmonary venous connection, 49 patients had anomalous drainage only from the systemic circulation, and 5 patients had isolated anomalies of pulmonary venous return. Visceral heterotaxy syndrome was diagnosed in 25 patients. Previous palliative operations had been performed in 51 patients (81%). There was 1 early death, and 2 patients required take down of Fontan procedures. Two patients required reoperation for revision of the atrial baffle. At a mean follow-up of 4.6 ± 3.4 years, there have been 5 late deaths (8%) and 45 patients (71%) have undergone Fontan completion. Actuarial survival was 92% at 1 year and 91% at 5 and 10 years-not significantly different from the overall survival of the Fontan patients. We conclude that the modified FO can be successfully performed in patients with anomalous systemic or pulmonary venous connections, including those with visceral heterotaxy syndrome, with morbidity and mortality rates that do not differ significantly from those achieved in all patients with normal connections.     

Restrictive Ventilatory Impairment and Arterial Oxygenation Characterize Rest and Exercise Ventilation in Patients After Fontan Operation

The objective of this study was evaluate the relationships between abnormal pulmonary circulation, lung function, and respiratory response during exercise in Fontan patients. Pulmonary function and cardiopulmonary exercise tests were performed in 101 Fontan patients and 122 controls. A small vital capacity (VC) with a high residual volume-to-total lung capacity ratio and a slight but significant low arterial saturation with hypocapnia were observed in Fontan patients. The number of surgical procedures determined VC. Total cavopulmonary connection, fenestration, higher pulmonary arterial wedge pressure, and smaller VC were independent determinants of low arterial saturation, which was the only determinant of hypocapnia. Arterial saturation decreased during exercise and resting arterial saturation correlated with that at peak exercise. Improvement in dead space ventilation was less in Fontan patients and was independently determined by resting arterial saturation. A steeper minute ventilation–carbon dioxide production slope was determined by resting arterial saturation, arterial carbon dioxide tension, and peak oxygen uptake. In Fontan patients, in addition to dead space ventilation, surgery-related reduced VC, the type of repair, and high pulmonary arterial wedge pressure cause arterial desaturation with subsequent hypocapnia, resulting in accelerated inefficient ventilation at rest and during exercise.     

Results of Exercise Stress Testing in Patients with Diffuse Pulmonary Arteriovenous Malformations

Patients with diffuse pulmonary arteriovenous malformations (PAVMs) are subject to frequent complications and need to be followed closely. As part of this follow-up, we have employed exercise stress testing (EST) as an aid to assess their status. Twenty patients from a cohort of 35 with diffuse PAVMs have undergone EST using a standard cycle ergometer test. All patients had previously undergone pulmonary angiography, noncontrast chest computed tomography (CT), and repair of large focal PAVMs, prior to EST. Mean room air oxygen saturation at baseline and at maximum exercise (85% of maximum heart rate) were tabulated. Serial studies in six children and young adults were plotted by year and compared using the patient as their own control. Fourteen females and six males ranging in age from 4 to 50 years (mean 22 years) were studied. Baseline mean oxygen saturation was 84% and fell to 73% at maximum exercise. There was no significant difference between those with unilateral and bilateral involvement (P = 0.09). In four of the six patients with serial EST, the baseline and exercise oxygen saturations were quite stable. In the two patients who became symptomatic, with age, growth, and more activity, complete embolization of one or more segments of the lung improved their EST and functionality. Based on our previous work in patients with diffuse PAVMs, EST appears to offer a relatively safe and noninvasive method for assessing these patients. Our limited experience with serial EST suggests a good correlation with decreased functionality in these patients.     

Ventricular energetics in Fontan circulation: Evaluation with a theoretical model

BACKGROUND: Both pulmonary and systemic circulation must be maintained by a single pump in Fontan circulation. This unique property of Fontan circulation may be related to decreased exercise tolerance or increased instantaneous postoperative mortality rate, often observed in patients with this circulation. To better understand Fontan physiology, the present study theoretically investigated cardiac performance of Fontan circulation by using ventricular-vascular coupling framework analysis. METHODS: End-systolic volume elastance (Ees), as a chamber contractile property, and effective arterial elastance (Ea), a lumped measure of ventricular afterload, were estimated both in normal left ventricular systemic circulation and in Fontan circulation. RESULTS: End-systolic volume elastance was decreased and Ea was increased in Fontan circulation. Both ventricular external stroke work (SW) and mechanical efficiency (EFF) under Fontan circulation were lower compared with those under normal circulation. Furthermore, the Ees-Ea relationship in Fontan circulation predicted limited cardiac reserve in terms of SW and EFF. Such cardiac performance in Fontan circulation stemmed from increased impedance due to the additional connection of the pulmonary vascular bed to the systemic vasculature and from the lack of a compensatory increase in contractility for increased afterload. CONCLUSIONS: Thus, it was inferred that Fontan circulation had intrinsic disadvantages and this may explain, in part, abnormal functional status and decline in survival following this procedure.     

Morphological Studies of Pulmonary Arteriovenous Shunting in a Lamb Model of Superior Cavopulmonary Anastomosis

We sought to identify and characterize the abnormal vascular structures responsible for pulmonary arteriovenous shunting following the Glenn cavopulmonary shunt. Superior cavopulmonary shunt is commonly performed as part of the staged pathway to total cavopulmonary shunt to treat univentricular forms of congenital heart disease, however, clinically significant pulmonary arteriovenous malformations develop in some patients after the procedure. The causes of pulmonary arteriovenous malformations and other pulmonary vascular changes that occur after cavopulmonary shunt are not known. Using a juvenile lamb model of superior cavopulmonary anastomosis that reliably produces pulmonary arteriovenous malformations, we performed echocardiography and morphological analyses to determine the anatomic site of shunting and to identify the vascular structures involved. Pulmonary arteriovenous shunting was identified by contrast echocardiography in all surviving animals (n = 40) following superior cavopulmonary anastomosis. Pulmonary vascular corrosion casts revealed abnormal tortuous vessels joining pulmonary arteries and veins in cavopulmonary shunt animals but not control animals. In conclusion, unusual channels that bridged pulmonary arteries and veins were identified. These may represent the vascular structures responsible for arteriovenous shunting following the classic Glenn cavopulmonary shunt. Detailed analysis of these structures may elucidate factors responsible for their development.     

Cerebral Hemodynamics in the Presence of Decreased Systemic Venous Compliance in Patients with Fontan Physiology May Limit Anaerobic Exercise Capacity

Patients who have had the Fontan procedure report poor exercise performance. Fontan subjects can tolerate a higher level of sub maximal activity than might be anticipated from Vo ₂, suggesting a different mechanism of exercise limitation. Near-infrared spectroscopy (NIRS) provides a non-invasive, continuous method to monitor regional tissue oxygenation (rSO2) and thereby a window into regional oxygen supply–demand relationships. We hypothesized that Fontan patients would have altered rSO2 trends from normal population that might reflect the mechanisms of exercise limitation. All the patients without structural or acquired heart disease and Fontan patients were eligible for inclusion if they were ordered to undergo cardiopulmonary exercise testing (CPET). Four-site regional rSO2 were recorded continuously during exercise. The difference between the oxyhemoglobin saturation measured by pulse oximetry (Spo ₂) and NIRS (rSO2) was computed as the regional arterial–venous saturation difference (AVDO2). A total of 33 normal subjects and five Fontan subjects scheduled for CPET were recruited. None of the Fontan subjects had a fenestration of the conduit. In the cerebral circulation, the Fontan patients have a significantly higher initial slope of increasing AVDO2 compared with normals. After vAT, the AVDO2 slope is flat for Fontan patients (p = 0.02). There is also a substantially larger rebound of cerebral rSO2 than in normal subjects after QT (p < 0.0001). Reduced anaerobic exercise capacity in Fontan patients may be secondary to limitation of cerebral blood flow, secondary to low systemic venous compliance due to absence of a sub-pulmonary ventricle, and augmented hyperventilatory response during exercise.     

Changes in Pulmonary Venous Flow Patterns in Patients with Ventricular Septal Defect

We studied pulmonary venous (PV) flow patterns using Doppler echocardiography in 26 patients with ventricular septal defect less than 3 years of age. Fifteen patients had moderate or severe symptoms, and the remaining 11 had no significant symptoms. Peak velocity of PV diastolic flow and flow velocity integral of PV diastolic flow in the symptomatic patients were significantly larger than those in either asymptomatic patients or the normal controls. The ratio of PV diastolic flow velocity to PV systolic flow velocity and the ratio of flow velocity integral of PV diastolic flow to that of PV systolic flow in the symptomatic patients were significantly larger than those in either asymptomatic patients or the normal controls. The ratio of PV diastolic flow velocity to PV systolic flow velocity as well as the ratio of flow velocity integral of PV diastolic flow to that of PV systolic flow correlated with V wave in left atrial or pulmonary capillary wedge pressure and indexes of left ventricular mass and left atrial volume. We conclude that the abnormal pulmonary venous flow patterns in ventricular septal defect might be associated with large left-to-right shunting and left atrial pressure V wave.