Pulmonary vascular disease and optical coherence tomography imaging in patients with Fontan palliation.

INTRODUCTION: The Fontan procedure is the palliative procedure of choice for patients with single ventricle physiology. Pulmonary vascular disease (PVD) is an important contributor to Fontan circulatory failure. AREAS COVERED: We review the pathophysiology of PVD in patients with Fontan palliation and share our initial experience with optical coherence tomography (OCT) in supplementing standard hemodynamics in characterizing Fontan-associated PVD. In the absence of a sub-pulmonary ventricle, low pulmonary vascular resistance (PVR; ≤2 WU/m2) is required to sustain optimal pulmonary blood flow. PVD is associated with adverse pulmonary artery (PA) remodeling resulting from the non-pulsatile low-shear low-flow circulation. Predisposing factors to PVD include impaired PA growth, endothelial dysfunction, hypercoagulable state, and increased ventricular end-diastolic pressure. OCT parameters that show promise in characterizing Fontan-associated PVD include the PA intima-to-media ratio and wall area ratio (i.e. difference between the whole-vessel area and the luminal area divided by the whole-vessel area). EXPERT OPINION: OCT carries potential in characterizing PVD in patients with Fontan palliation. PA remodeling is marked by intimal hyperplasia, with medial regression. Further studies are required to determine the role of OCT in informing management decisions and assessing therapeutic responses.

Comparison of definitive approaches for conotruncal defects following bidirectional Glenn procedure.

BACKGROUND: Staged repair is common for complex conotruncal defects, often involving bidirectional Glenn (BDG) procedure. Following the cavopulmonary shunt, both Fontan completion and biventricular conversion (BiVC) serve as definitive approaches. The optimal strategy remains controversial. METHODS: The baseline, perioperative and follow-up data were obtained for all paediatric patients with conotruncal defects who underwent BDG procedure as palliation in Fuwai Hospital from 2013 to 2022. Patients with single ventricle were excluded. The primary outcome was mortality. The secondary outcome was reintervention, including any cardiovascular surgeries and non-diagnostic catheterisations. RESULTS: A total of 232 patients were included in the cohort, with 142 underwent Fontan (61.2%) and 90 underwent BiVC (38.8%). The median interstage period from BDG to the definitive procedure was 3.83 years (IQR: 2.72-5.42) in the overall cohort, 3.62 years (IQR: 2.57-5.15) in the Fontan group and 4.15 years (IQR: 3.05-6.13) in the BiVC group (p=0.03). The in-hospital outcomes favoured the Fontan group, including duration of cardiopulmonary bypass, aortic cross-clamp, mechanical ventilation and intensive care unit stay. Postoperative mortality was generally low and comparable, as was the reintervention rate (HR=1.42, 95% CI: 0.708 to 2.85, p=0.32). The left ventricular size was smaller at baseline and within the normal range at follow-up for both Fontan and BiVC groups; however, it was significantly larger with BiVC at follow-up. CONCLUSION: In paediatric patients with conotruncal heart defects who underwent BDG procedure, BiVC is a feasible option, especially for patients with certain Fontan risk factors, and are not ideal candidates for successful Fontan completion.

Effect of patient factors, center, and era on Fontan timing: An observational study using the Pediatric Health Information Systems Database.

BACKGROUND: There are no consensus guidelines defining optimal timing for the Fontan operation, the last planned surgery in staged palliation for single-ventricle heart disease. OBJECTIVES: Identify patient-level characteristics, center-level variation, and secular trends driving Fontan timing. METHODS: A retrospective observational study of subjects who underwent Fontan from 2007 to 2021 at centers in the Pediatric Health Information Systems database was performed using linear mixed-effects modeling in which age at Fontan was regressed on patient characteristics and date of operation with center as random effect. RESULTS: We included 10,305 subjects (40.4% female, 44% non-white) at 47 centers. Median age at Fontan was 3.4 years (IQR 2.6-4.4). Hypoplastic left heart syndrome (-4.4 months, 95%CI -5.5 to -3.3) and concomitant conditions (-2.6 months, 95%CI -4.1 to -1.1) were associated with younger age at Fontan. Subjects with technology-dependence (+4.6 months, 95%CI 3.1-6.1) were older at Fontan. Black (+4.1 months, 95%CI 2.5-5.7) and Asian (+8.3 months, 95%CI 5.4-11.2) race were associated with older age at Fontan. There was significant variation in Fontan timing between centers. Center accounted for 10% of variation (ICC 0.10, 95%CI 0.07-0.14). Center surgical volume was not associated with Fontan timing (P = .21). Operation year was associated with age at Fontan, with a 3.1 month increase in age for every 5 years (+0.61 months, 95%CI 0.48-0.75). CONCLUSIONS: After adjusting for patient-level characteristics there remains significant inter-center variation in Fontan timing. Age at Fontan has increased. Future studies addressing optimal Fontan timing are warranted.

Bidirectional glenn surgery without palliative pulmonary artery banding in univentricular heart with unrestricted pulmonary flow. Retrospective multicenter experience.

BACKGROUND: Although pulmonary artery banding (PAB) has been generally acknowledged as an initial palliative treatment for patients having single ventricle (SV) physiology and unrestrictive pulmonary blood flow (UPBF), it may result in unfavorable outcomes. Performing bidirectional Glenn (BDG) surgery without initial PAB in some selected cases may avoid the complications associated with PAB and reduce the number of operative procedures for these patients. This research aimed to assess the outcome of BDG surgery performed directly without doing initial PAB in patients with SV-UPBF. METHODS: This Multicenter retrospective cohort includes all patients with SV-UPBF who had BDG surgery. Patients were separated into two groups. Patients in Group 1 included patients who survived till they received BDG (20 Patients) after initial PAB (28 patients), whereas patients in Group 2 got direct BDG surgery without first performing PAB (16 patients). Cardiac catheterization was done for all patients before BDG surgery. Patients with indexed pulmonary vascular resistance (PVRi) ≥ 5 WU.m2 at baseline or > 3 WU.m2 after vasoreactivity testing were excluded. RESULTS: Compared with patients who had direct BDG surgery, PAB patients had a higher cumulative mortality rate (32% vs. 0%, P = 0.016), with eight deaths after PAB and one mortality after BDG. There were no statistically significant differences between the patient groups who underwent BDG surgery regarding pulmonary vascular resistance, pulmonary artery pressure, postoperative usage of sildenafil or nitric oxide, intensive care unit stay, or hospital stay after BDG surgery. However, the cumulative durations in the intensive care unit (ICU) and hospital were more prolonged in patients with BDG after PAB (P = 0.003, P = 0.001respectively). CONCLUSION: Direct BDG surgery without the first PAB is related to improved survival and shorter hospital stays in some selected SV-UPBF patients.

Extremely Long-Term Follow-Up of Dr William Glenn's Original Patient Cohort With Superior Cavopulmonary Anastomosis (1958-1990).

BACKGROUND: Historically, Dr William Glenn performed the first classic superior cavopulmonary anastomosis in a seven-year-old child at Yale in 1958. By 1990, this operation was performed consecutively in over 90 patients. With over 60 years of follow-up, this is the longest survival record of early Glenn patients from the first 30 years. METHODS: We performed a single center, retrospective evaluation of patients undergoing a Glenn operation. A collected list of surviving patients, previously updated in 1988, included demographics, age at procedure, and underlying diagnosis. Follow-up data were obtained in May 2022 using electronic medical records to determine survival, age of survivors, and age of deceased. RESULTS: Ninety-five patients underwent the Glenn operation from 1958 to 1990: 58.9% (n = 56) were male and 41.1% (n = 39) female. Fifteen patients were lost to follow-up, but 12 were alive in 1988. Sixty patients were deceased (68.1%), with an average age of 33.5 ± 18.3(range, 2-78, excluding seven early deaths) years. The oldest patient who passed away was a 78-year-old male with tetralogy of Fallot. Twenty patients remain alive, with an average age of 47.5 (range, 32-66) years. Four patients who are still alive today (20% survivors) are older than 60 years. CONCLUSIONS: Since Dr Glenn's original operation, the technique, timing, and indications have been modified (ie, bidirectional Glenn) to adapt to the current era. By following this initial group of patients, we can approach completion of the survival rates for adult congenital patients who were some of the first pediatric patients to receive this ground-breaking palliative procedure.

Textbook Outcome for Superior Cavopulmonary Connection: A Metric for Single Ventricle Heart Surgery.

Background: To develop a more holistic measure of congenital heart center performance beyond mortality, we created a composite "textbook outcome" (TO) for the Glenn operation. We hypothesized that meeting TO would have a positive prognostic and financial impact. Methods: This was a single center retrospective study of patients undergoing superior cavopulmonary connection (bidirectional Glenn or Kawashima ± concomitant procedures) from 2005 to 2021. Textbook outcome was defined as freedom from operative mortality, reintervention, 30-day readmission, extracorporeal membrane oxygenation, major thrombotic complication, length of stay (LOS) >75th percentile (17d), and mechanical ventilation duration >75th percentile (2d). Multivariable logistic regression and Cox proportional hazards modeling were used. Results: Fifty-one percent (137/269) of patients met TO. Common reasons for TO failure were prolonged LOS (78/132, 59%) and ventilator duration (67/132, 51%). In multivariable analysis, higher weight [odds ratio, OR: 1.44 (95% confidence interval, CI: 1.15-1.84), P = .002] was a positive predictor of TO achievement while right ventricular dominance [OR 0.47 (0.27-0.81), P = .007] and higher preoperative pulmonary vascular resistance [OR 0.58 (0.40-0.82), P = .003] were negative predictors. After controlling for preoperative factors and excluding operative mortalities, TO achievement was independently associated with a decreased risk of death over long-term follow-up [hazard ratio: 0.50 (0.25-0.99), P = .049]. Textbook outcome achievement was also associated with lower direct cost of care [$137,626 (59,333-167,523) vs $262,299 (114,200-358,844), P < .0001]. Conclusion: Achievement of the Glenn TO is associated with long-term survival and lower costs and can be predicted by certain risk factors. As outcomes continue to improve within congenital heart surgery, operative mortality will become a less informative metric. Textbook outcome analysis may represent a more balanced measure of a successful outcome.

Hemoadsorption Contribution in Failing Fontan Pediatric Heart Transplantation.

INTRODUCTION: A systemic inflammatory response is triggered in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). This response is particularly evident in pediatric patients, especially those of low weight and after undergoing long CPB, and can severely impair the surgical result. Adsorptive blood purification techniques have been proposed to limit this systemic inflammatory response. To test its efficacy, we added the hemoadsorption filter Jafron HA 380 to CPB in a much compromised pediatric patient who underwent heart transplantation. METHODS: A 10-year-old single ventricle patient previously treated with Fontan operation was listed for heart transplantation due to the evidence of failing Fontan condition. He experienced many episodes of cardiac arrest and underwent heart transplantation in much compromised general and hemodynamic conditions. The hemoadsorption filter Jafron HA 380 was used for all the duration of CPB, and the inflammatory biomarker interleukin 6 (IL-6) was assayed. RESULTS: Postoperative outcome was uneventful and comparable to that of elective pediatric heart transplantation. IL-6 levels showed an impressive postoperative reduction, and after 2 days, the IL-6 level was comparable with a typical uneventful post-transplant course. CONCLUSIONS: The use of hemoadsorption filter can contribute to improve the pediatric transplant results, especially in very high-risk patients.

In vitro investigation of axial mechanical support devices implanted in the novel convergent cavopulmonary connection Fontan.

OBJECTIVES: The 2 opposing inflows and 2 outflows in a total cavopulmonary connection make mechanical circulatory support (MCS) extremely challenging. We have previously reported a novel convergent cavopulmonary connection (CCPC) Fontan design that improves baseline characteristics and provides a single inflow and outflow, thus simplifying MCS. This study aims to assess the feasibility of MCS of this novel configuration using axial flow pumps in an in vitro benchtop model. METHODS: Three-dimensional segmentations of 12 single-ventricle patients (body surface area 0.5-1.75 m2) were generated from cardiovascular magnetic resonance images. The CCPC models were designed by connecting the inferior vena cava and superior vena cava to a shared conduit ascending to the pulmonary arteries, optimized in silico. The 12 total cavopulmonary connection and their corresponding CCPC models underwent in vitro benchtop characterization. Two MCS devices were used, the Impella RP® and the PediPump. RESULTS: MCS successfully and symmetrically reduced the pressure in both vena cavae by >20 mmHg. The devices improved the hepatic flow distribution balance of all CCPC models (Impella RP®P = 0.045, PediPump P = 0.055). CONCLUSIONS: The CCPC Fontan design provides a feasible MCS solution for a failing Fontan by balancing hepatic flow distribution and symmetrically decompressing the central venous pressure. Cardiac index may also improve with MCS. Additional studies are needed to evaluate this concept for managing Fontan failure.

Utility of Balloon Occlusion Testing in Determining Fontan Suitability Among Patients with Elevated Pulmonary Artery Pressure and Additional Antegrade Pulmonary Blood Flow.

In individuals with a single ventricle undergoing evaluation before Fontan surgery, the presence of excessive pulmonary blood flow can contribute to increased pulmonary artery pressure, notably in those who had a Glenn procedure with antegrade pulmonary flow. 28 patients who had previously undergone Glenn anastomosis with antegrade pulmonary blood flow (APBF) and with elevated mean pulmonary artery (mPAP) pressure > 15 mmHg in diagnostic catheter angiography were included in the study. After addressing other anatomical factors that could affect pulmonary artery pressure, APBF was occluded with semi-compliant, Wedge or sizing balloons to measure pulmonary artery pressure accurately. 23 patients (82% of the cohort) advanced to Fontan completion. In this group, median mPAP dropped from 20.5 (IQR 19-22) mmHg to 13 (IQR 12-14) mmHg post-test (p < 0.001). Median PVR post-test was 1.8 (IQR 1.5-2.1) WU m2. SpO2 levels decreased from a median of 88% (IQR 86%-93%) pre-test to 80% (IQR 75%-84%) post-test (p < 0.001). In five patients, elevated mPAP post-test occlusion on diagnostic catheter angiography led to non-completion of Fontan circulation. In this group, median pre- and post-test mPAP were 23 mmHg (IQR 21.5-23.5) and 19 mmHg (IQR 18.5-20), respectively (p = 0.038). Median post-test PVR was 3.8 (IQR 3.6-4.5) WU m2. SpO2 levels decreased from a median of 79% (IQR 76%-81%) pre-test to 77% (IQR 73.5%-80%) post-test (p = 0.039). Our study presents a specialized approach for patients initially deemed unsuitable for Fontan due to elevated pulmonary artery pressures. We were able to successfully complete the Fontan procedure in the majority of these high-risk cases after temporary balloon occlusion test.

Does the External Pericardial Lateral Tunnel Fontan Pathway Enlarge to Accommodate Somatic Growth? A Preliminary Analysis.

Objectives: An ideal Fontan pathway should be capable of adapting to changes in circulatory demands. The external pericardial lateral tunnel Fontan (EPLTF) is constructed of viable, autologous tissue and may be capable of changing in size. We investigated the ability of the EPLTF to enlarge with increasing physiologic demands of somatic growth. Methods: Retrospective review of echocardiographic images for patients with a minimum of five years follow-up after EPLTF. Serial echocardiographic measurements of the EPLTF pathway were obtained at three distinct locations: the inferior vena cava junction with the EPLTF, midsection of the EPLTF, and cross-sectional area of the EPLTF visualized in a four-chamber view. Body surface area (BSA) was calculated at the time of each echocardiographic measurement. Changes in echocardiographic measurements over time were analyzed and compared with changes in BSA. Results: A total of 332 echocardiographic studies from 38 patients were reviewed. Significant enlargement of the EPLTF pathway is observed at the inferior vena caval junction (P < .001), midsection (P < .01), and cross-sectional area (P < .001). Repeated measures correlation between pathway measurements and BSA is highly significant (P < .001). Conclusions: The EPLTF pathway enlarges over time in correlation with increasing BSA. Further research is needed to define ideal pathway size, differentiate normal physiologic growth from pathologic enlargement, and correlate changes with clinical outcomes.

Outcomes of the Kawashima: A Society of Thoracic Surgeons Congenital Heart Surgery Database Analysis.

BACKGROUND: We aimed to evaluate the effect of age at operation on postoperative outcomes in children undergoing a Kawashima operation. METHODS: The Society of Thoracic Surgeons Congenital Heart Surgery Database was queried for Kawashima procedures from January 1, 2014, to June 30, 2020. Patients were stratified by age at operation in months: 0 to <4, 4 to <8, 8 to <12, and >12. Subsequently, outcomes for those in whom the Kawashima was not the index operation and for those undergoing hepatic vein incorporation (Fontan completion or hepatic vein-to-azygos vein connection) were evaluated. RESULTS: We identified 253 patients who underwent a Kawashima operation (median age, 8.6 months; median weight, 7.4 kg): 12 (4.7%), 0 to <4 months; 96 (37.9%), 4 to <8 months; 81 (32.0%), 8 to <12 months; and 64 (25.3%), >12 months. Operative mortality was 0.8% (n = 2), with major morbidity or mortality in 17.4% (n = 44), neither different across age groups. Patients <4 months had a longer postoperative length of stay (12.5 vs 9.3 days; P = .03). The Kawashima was not the index operation of the hospital admission in 15 (5.9%); these patients were younger (6.0 vs 8.4 months; P = .05) and had more preoperative risk factors (13/15 [92.9%] vs 126/238 [52.9%]; P < .01). We identified 173 patients undergoing subsequent hepatic vein incorporation (median age, 3.9 years; median weight, 15.0 kg) with operative mortality in 6 (3.5%) and major morbidity or mortality in 30 (17.3%). CONCLUSIONS: The Kawashima is typically performed between 4 and 12 months with low mortality. Morbidity and mortality were not affected by age. Hepatic vein incorporations may be higher risk than in traditional Fontan procedures, and ways to mitigate this should be sought.

Fontan surgery failure: risk factors and experience in a Colombian reference centre.

BACKGROUND: The Fontan procedure is considered one of the most remarkable achievements in paediatric cardiology and cardiac surgery. Its final anatomical objective is a venous return through the superior and inferior vena cava. The complications inherent to this procedure and subsequent failure are its limitations. OBJECTIVE: To describe the clinical and haemodynamic characteristics of patients with Fontan failure and define the risk factors associated with it, with its short- and long-term outcomes during a 21-year observation period. METHODS: This is a retrospective follow-up study in which 15 patients diagnosed with Fontan failure in the single-ventricle programme of a high-complexity hospital in Medellín, Colombia, between 2001 and 2022 were included. RESULTS: One hundred and eight patients were identified in whom the Fontan procedure was performed, and 17 met the failure criteria. 82.4% were men, with a median age of 4.3 years. Ebstein's anomaly was the most common diagnosis, 29.4%. All patients underwent Fontan with an extracardiac tube following the procedure. According to the type of failure, 58.8% of patients presented protein-losing enteropathy and 17.6% plastic bronchitis. During follow-up, 5.9% of patients died. CONCLUSION: Fontan surgery in our centre is an option for patients with univentricular physiology. The correct selection of the patient is essential to mitigate failure risks.

Bidirectional Glenn operation without cardiopulmonary bypass: Single center experience and results.

BACKGROUND: The bidirectional Glenn (BDG) shunt operation serves as temporary surgery for the treatment of single-ventricle physiology with the eventual Fontan procedure. In some cases, the procedure can be performed without the support of a cardiopulmonary bypass (CPB) machine. In this study, we present the surgical outcomes of off-pump BDG operation with the use of a temporary veno-atrial shunt to decompress the superior vena cava (SVC) during clamping time. METHODS: A cohort of 23 patients underwent off-pump BDG operations at Cardiovascular Center, E Hospital. All patients were operated on using a veno-atrial shunt to decompress the SVC. RESULTS: Satisfactory results with mean oxygen saturation increased from 79.6 ± 11.2% to 87.2 ± 4.7%. The SVC clamping time was 14 ± 2.4 min (ranging from 12 to 21 min). Among 23 patients, only six patients required blood transfusion, 17 patients had BDG without blood transfusion. No neurological complications or deaths occurred after the surgery, and the post-operative period was uneventful. CONCLUSIONS: The use of veno-atrial shunts to decompress SVC during off-pump BDG operation is safe with good surgical outcomes and can avoid the deleterious effects caused by CPB. It is easily reproducible, at low cost and economically effective.

Living to Tell the Tale: A First-Person Chronicle of the Development of the Fontan-Kreutzer Procedure.

The current surgical approach for patients with a single ventricle is the culmination of decades of dedicated research and groundbreaking innovation. From 1971 to the present day, a series of incremental advancements have significantly extended the life expectancy of these patients. Since the very beginning, Dr Guillermo Kreutzer and his team have pioneered different techniques with the ultimate goal of improving outcomes for these individuals. This is, narrated by him, the story of how it all began.

Impact of Optimal Fenestration Size on Outcomes of High-Risk Fontan Patients.

BACKGROUND: We aimed to analyze mid-term outcomes of the fenestrated Fontan procedure, focusing on the fenestration size. METHODS: We retrospectively reviewed the outcomes of the fenestrated Fontan procedure. Among 165 patients who underwent the Fontan procedure from 2011 to 2021, fenestration was created in 27 patients with the highest risks, including those with hypoplastic left heart syndrome, hypoplastic pulmonary arteries, heterotaxy syndrome with high pulmonary vascular resistance, and pulmonary arterial pressure >15 mm Hg. The patients underwent the procedure at a median age of three years (body weight, 11.4 kg; body surface area, 0.54 m2). Fenestration sizes were 3.5 to 5 mm. RESULTS: Spontaneous fenestration closure occurred within one year postoperatively in nine patients. Among them, three experienced Fontan failure, necessitating refenestration. Although fenestration size did not differ, the size corrected by body surface area at the time of surgery was smaller in patients with fenestration closure (6.4 mm/m2 vs 8.3 mm/m2, P < .05). Patients with a fenestration <7 mm/m2 were more likely to have fenestration closure within one year postoperatively, and those with a fenestration >9 mm/m2 were more likely to have severe desaturation and require home oxygen therapy following discharge. CONCLUSIONS: Spontaneous fenestration closure affected the frequency of Fontan complications. A very small fenestration size corrected by body surface area was a significant risk factor for spontaneous closure. Conversely, a very large fenestration size corrected by body surface area resulted in severe desaturation. The optimal fenestration size to prevent early spontaneous closure and severe desaturation is approximately 8 mm/m2.

Introduction of transcatheter edge-to-edge repair in patients with congenital heart disease at a children's hospital.

BACKGROUND: Atrioventricular valve regurgitation (AVVR) is a devastating complication in children and young adults with congenital heart disease (CHD), particularly in patients with single ventricle physiology. Transcatheter edge-to-edge repair (TEER) is a rapidly expanding, minimally invasive option for the treatment of AVVR in adults that avoids the morbidity and mortality associated with open heart surgery. However, application of TEER in in CHD and in children is quite novel. We describe the development of a peri-procedural protocol including image-derived pre-intervention simulation, with successful application to four patients. AIMS: To describe the initial experience using the MitraClip system for TEER of dysfunctional systemic atrioventricular valves in patients with congential heart disease within a pediatric hospital. METHODS: A standardized screening and planning process was developed using cardiac magnetic resonance imaging, three dimensional echocardiography and both virtual and physical simulation. Procedures were performed using the MitraClip G4 system and patients were clinically followed post-intervention. RESULTS: A series of four CHD patients with at least severe AVVR were screened for suitability for TEER with the MitraClip system: three patients had single ventricle physiology and Fontan palliation, and one had repair of a common atrioventricular canal defect. Each patient had at least severe systemic AVVR and was considered at prohibitively high risk for surgical repair. Each patient underwent a standardized preprocedural screening protocol and image-derived modeling followed by the TEER procedure with successful clip placement at the intended location in all cases. CONCLUSIONS: The early results of our protocolized efforts to introduce TEER repair of severe AV valve regurgitation with MitraClip into the CHD population within our institution are encouraging. Further investigations of the use of TEER in this challenging population are warranted.

Five decades of Fontan palliation: What have we learned? What should we expect?

The Fontan procedure is the final palliative surgery in a series of staged surgeries to reroute the systemic venous blood flow directly to the lungs, with the ventricle(s) pumping oxygenated blood to the body. Advances in medical and surgical techniques have improved patients' overall survival after the Fontan procedure. However, Fontan-associated chronic comorbidities are common. In addition to chronic cardiac dysfunction and arrhythmias, complications involving other organs such as the liver, lungs, intestine, lymphatic system, brain, and blood frequently occur. This narrative review focuses on the immediate and late consequences in children, pregnant women, and other adults with Fontan circulation. In addition, we describe the technical advancements that might change the way single-ventricle patients are managed in future.

Intravenous infusion of cardiac progenitor cells in animal models of single ventricular physiology.

OBJECTIVES: The goal of this study was to identify the practical applications of intravenous cell therapy for single-ventricle physiology (SVP) by establishing experimental SVP models. METHODS: An SVP with a three-stage palliation was constructed in an acute swine model without cardiopulmonary bypass. A modified Blalock-Taussig (MBT) shunt was created using an aortopulmonary shunt with the superior and inferior venae cavae (SVC and IVC, respectively) connected to the left atrium (n = 10). A bidirectional cavopulmonary shunt (BCPS) was constructed using a graft between the IVC and the left atrium with an SVC cavopulmonary connection (n = 10). The SVC and the IVC were connected to the pulmonary artery to establish a total cavopulmonary connection (TCPC, n = 10). The survival times of half of the animal models were studied. The other half and the biventricular sham control (n = 5) were injected intravenously with cardiosphere-derived cells (CDCs), and the cardiac retention of CDCs was assessed after 2 h. RESULTS: All SVP models died within 20 h. Perioperative mortality was higher in the BCPS group because of lower oxygen saturation (P < 0.001). Cardiac retention of intravenously delivered CDCs, as detected by magnetic resonance imaging and histologic analysis, was significantly higher in the modified Blalock-Taussig and BCPS groups than in the TCPC group (P < 0.01). CONCLUSIONS: Without the total right heart exclusion, stage-specific SVP models can be functionally constructed in pigs with stable outcomes. Intravenous CDC injections may be applicable in patients with SVP before TCPC completion, given that the initial lung trafficking is efficiently bypassed and sufficient systemic blood flow is supplied from the single ventricle.

Long-term follow-up of atrioventricular valve function in Fontan patients: effect of atrioventricular valve surgery.

OBJECTIVES: The aim of this study was to evaluate the relationship between atrioventricular valve and ventricular function in Fontan survivors, including the effect of atrioventricular valve surgery. METHODS: Analysis focused on transplant-free survival and the need for atrioventricular valve surgery in single ventricle patients after Fontan completion. Longitudinal echocardiographic examination of long-term valve and ventricular function was performed. RESULTS: Fontan completion was performed in 113 patients, having a right univentricular morphology in 33.6%, a left ventricle morphology in 62.8% and ambiguous in 3.6%. Perioperative mortality was 2.7% (n = 3). Within a median follow-up of 16.3 years (interquartile range 10.6-23.6), transplant-free survival was 96.1 ± 1.9% and 90.4 ± 5.8% at 10-25 years. Twenty AV valve procedures were performed in 14 (12.4%) children, respectively, pre-Fontan (n = 10), per-Fontan (n = 8) and post-Fontan (n = 2), resulting in a cumulative incidence of AV valve surgery is 5.7 ± 2.2% and 12.3 ± 3.2% at 1-5 years. Atrio-ventricular valve function deteriorated over time [hazard ratio (HR) 1.112, 95% confidence interval (CI) 1.089-1.138, P < 0.001], without difference for valve morphology (P = 0.736) or ventricular dominance (P = 0.484). AV valve dysfunction was greater in patients requiring AV valve surgery (HR 20.383, 95% CI 6.223-36.762, P < 0.001) but showed a comparable evolution since repair to those without valve surgery (HR 1.070, 95% CI 0.987-1.160, P = 0.099). Progressive time-related ventricular dysfunction was observed (HR 1.141, 95% CI 1.097-1.182, P < 0.001), significantly less in left ventricle-dominance (HR 0.927, 95% CI 0.860-0.999, P = 0.047) but more after AV valve surgery (HR 1.103, 95% CI 1.014-1.167, P = 0.022). CONCLUSIONS: In a homogeneously treated Fontan population, 25-year transplant-free survival is encouraging. Atrio-ventricular valve surgery was necessary in 12.4%, resulting mostly in a durable valve function. However, a slow time-related decline of atrioventricular valve function as of ventricular function is worrisome, evoking a role for additional heart failure therapy.