Impact of Age-Related Change in Caval Flow Ratio on Hepatic Flow Distribution in the Fontan Circulation.

BACKGROUND: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling. METHODS: SVC and IVC flow from 414 patients with Fontan were collected to establish a relationship between SVC:IVC flow ratio and age. Computational fluid dynamics modeling was performed in 60 (30 extracardiac and 30 lateral tunnel) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. RESULTS: SVC:IVC flow ratio inverted at ≈8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC, 2, 1, and 0.5 corresponded to ages, 3, 8, and 15+, respectively) was not significant for extracardiac but statistically significant for lateral tunnel cohorts. For all 3 caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2 to 0.5 (age, 3-15+) years, the correlation's strength decreased from 0.87 to 0.64, due to potential flow perturbation as IVC flow momentum increased. CONCLUSIONS: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of SVC:IVC variations over time on Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes.

Real-world use of apixaban for the treatment and prevention of thrombosis in children with cardiac disease.

BACKGROUND: Direct oral anticoagulants use in pediatric cardiology is poorly defined. OBJECTIVE: We present the largest experience of apixaban use in children with heart disease, using weight- and level-based dosing. METHODS: Retrospective single-center analysis of cardiac patients ≤19 years treated with apixaban. Patients were evaluated for safety (clinically relevant non-major [CRNM] or major bleeding; thrombotic events) and effectiveness (thrombus improvement by imaging). Peak drug-specific anti-Xa chromogenic assay results ("apixaban levels") were analyzed. RESULTS: Over 3 years (5/2018-9/2021), 219 children, median age 6.8 years (0.3-19), median weight 20.8 kg (4.8-160) received apixaban, totaling 50,916 patient days. Of them, 172 (79%) warranted thromboprophylaxis and 47 (21%) thrombosis treatment (with 10 arterial, 19 venous, 15 intracardiac, and 3 pulmonary). The median initial peak apixaban level was 165 ng/mL (23-474; n = 125) in the prophylaxis subgroup and 153 ng/mL (30-450; n = 33) in the treatment subgroup; dosage was adjusted in response to levels in 25% of the patients. There were 4 bleeding safety events (3 CRNM; 1 major, hemoptysis complicating empyema); the serious bleeding event rate was 2.9 per 100 patient-years of apixaban. Minor bleeding events (42) were noted in 18 patients, with an additional 2 having leukopenia, 1 transaminitis, and 3 rashes. An improvement in thrombosis was seen in 95% of the treated patients with available follow-up imaging (37/39 patients). CONCLUSION: Apixaban use was feasible with a low rate of adverse events across a diverse pediatric cardiac population using commercially available tablets dosed to weight and adjusted based on peak apixaban levels.

Apixaban Anticoagulation in Children and Young Adults Supported With the HeartMate 3 Ventricular Assist Device.

There is a growing population of pediatric and adult patients supported with the HeartMate 3 ventricular assist device (HM3 VAD) all of whom require anticoagulation. Apixaban is an anticoagulant requiring less testing than warfarin which has been shown to be effective in other indications. We report five pediatric and young adult patients managed on HM3 VAD with apixaban anticoagulation for 1589 days of VAD support between January 6, 2019 and January 7, 2022. The median age was 17 years and the weight was 69 kg. Four patients had congenital heart disease (2 single-ventricle Fontan circulation, and 2 biventricular circulations) and one had dilated cardiomyopathy. Apixaban was initiated at a median of 7 days postoperatively and doses were titrated based on peak apixaban-specific anti-Xa chromogenic analysis levels (goal 150-250 ng/ml). All patients received aspirin 81 mg daily. There was one major hemocompatibility-related event observed (outflow graft thrombus in the setting of medication nonadherence and chronic VAD infection); there was no major bleeding, death, or stroke. Three patients underwent heart transplantation and two remain on VAD support. In this limited series, apixaban paired with a level-based dosing regimen and low-dose aspirin provided safe and effective antithrombosis with only one hemocompatibility-related event related to medication non-adherence.

Is Doppler Echocardiography Adequate for Surgical Planning of Single Ventricle Patients?

PURPOSE: Surgical planning has shown great potential for optimizing outcomes for patients affected by single ventricle (SV) malformations. Phase-contrast magnetic resonance imaging (PC-MRI) is the routine technique used for flow acquisition in the surgical planning paradigm. However, PC-MRI may suffer from possible artifacts in certain cases; furthermore, this technology may not be readily available for patients in low and lower-middle-income countries. Therefore, this study aims to investigate the effectiveness of using Doppler echocardiography (echo-Doppler) for flow acquisitions of SV surgical planning. METHODS: This study included eight patients whose blood flow data was acquired by both PC-MRI and echo-Doppler. A virtual surgery platform was used to generate two surgical options for each patient: (1) a traditional Fontan conduit and (2) a Y-graft. Computational fluid dynamics (CFD) simulations were conducted using the two flow acquisitions to assess clinically relevant hemodynamic metrics: indexed power loss (iPL) and hepatic flow distribution (HFD). RESULTS: Differences exist in flow data acquired by PC-MRI and echo-Doppler, but no statistical significance was obtained. Flow fields, therefore, exhibit discrepancies between simulations using flow acquisitions by PC-MRI and echo-Doppler. In virtual surgery, the two surgical options were ranked based on these metrics. No difference was observed in the ranking of surgical options between using different flow acquisitions. CONCLUSION: Doppler echocardiography is an adequate alternative approach to acquire flow data for SV surgical planning. This finding encourages broader usage of SV surgical planning with echo-Doppler when MRI may present artifacts or is not available, especially in low and lower-middle-income countries.

An Anterior Anastomosis for the Modified Fontan Connection: A Hemodynamic Analysis.

This hemodynamic feasibility study examined total cavopulmonary connection (TCPC) designs connecting the extracardiac conduit to the anterior surface of pulmonary arteries (PAs) or superior vena cava (SVC) rather than to the inferior PA surface (traditional TCPC). The study involved twenty-five consecutive Fontan patients meeting inclusion criteria from a single institution. A virtual surgical platform mimicked the completed traditional TCPC and generated three anterior anastomosis designs: Anterior-PA, Middle-SVC, and SVC-Inn (Inn: innominate vein). Hemodynamic performance of anterior anastomosis designs was compared with the traditional TCPC regarding indexed power loss (iPL) and hepatic flow distribution (HFD). Compared to the traditional TCPC, the Anterior-PA design produces a similar iPL. The Middle-SVC design is also similar, though the iPL difference is positively correlated with the anastomosing height. The SVC-Inn design had significantly more iPL. The three anterior anastomosis designs did not have a significant difference in HFD (from traditional TCPC). Pulmonary flow distribution (PFD) has a stronger correlation with HFD from the anterior anastomosis designs than the traditional TCPC. This hemodynamic feasibility study examined anterior anastomosis, extracardiac TCPC designs that may offer surgeons clinical dexterity. The Anterior-PA design may be equivalent to the traditional TCPC. Fontan extracardiac conduit anastomosis just superior to the PAs (Middle-SVC) also preserves hemodynamic performance and avoids direct PA anastomosis. These designs could simplify surgical Fontan completion, and may particularly benefit patients requiring surgical dissection, having atypical PA orientation, or after PA stent angioplasty.