Impact of 2016 UNOS pediatric heart allocation policy changes on VAD utilization, waitlist, and post-transplant survival outcomes in children with CHD versus Non-CHD.

AIMS: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post-heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non-CHD patients before (Era-1) and after (Era-2) pediatric heart allocation policy implementation. METHODS: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era-1 and Era-2. RESULTS: 5551 patients were listed for HT, of whom 2447(44%) were in Era-1 and 3104(56%) were in Era-2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era-2, whereas the number of non-CHD patients listed as status 1A decreased, but status 1B increased. In Era-2 compared to Era-1, both temporary (1% to 4%, p < .001) and durable VAD (13.6% to 17.8%, p < .001) utilization increased, and the transplantation rate per 100-patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p = .06), whereas for non-CHD patients it decreased from 61 to 54 days (p < .001). Adjusted 90-day WL survival increased from 84% to 88%, p = .016 in CHD, but there was no significant change in non-CHD patients (p = .57). There was no significant difference in 1-year post-HT survival in CHD and non-CHD patients between Era-1 and Era-2. CONCLUSIONS: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non-CHD cohort, and 90-day WL survival probability improved in children with CHD without significant change in 1-year post-HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post-HT survival.

Heart Failure with Preserved Ejection Fraction in Children.

Diastolic dysfunction (DD) refers to abnormalities in the mechanical function of the left ventricle (LV) during diastole. Severe LVDD can cause symptoms and the signs of heart failure (HF) in the setting of normal or near normal LV systolic function and is referred to as diastolic HF or HF with preserved ejection fraction (HFpEF). Pediatric cardiologists have long speculated HFpEF in children with congenital heart disease and cardiomyopathy. However, understanding the risk factors, clinical course, and validated biomarkers predictive of the outcome of HFpEF in children is challenging due to heterogeneous etiologies and overlapping pathophysiological mechanisms. The natural history of HFpEF varies depending upon the patient's age, sex, race, geographic location, nutritional status, biochemical risk factors, underlying heart disease, and genetic-environmental interaction, among other factors. Pediatric onset HFpEF is often not the same disease as in adults. Advances in the noninvasive evaluation of the LV diastolic function by strain, and strain rate analysis with speckle-tracking echocardiography, tissue Doppler imaging, and cardiac magnetic resonance imaging have increased our understanding of the HFpEF in children. This review addresses HFpEF in children and identifies knowledge gaps in the underlying etiologies, pathogenesis, diagnosis, and management, especially compared to adults with HFpEF.

SARS-CoV-2 infection induced thyroid storm and heart failure in an adolescent girl.

We report a case of thyroid storm precipitated by SARS-CoV-2 infection in an adolescent girl with a history of Graves disease and dilated cardiomyopathy. This case highlights that SARS-CoV-2 infection can potentially trigger a thyrotoxicosis crisis and acute decompensated heart failure in a patient with underlying thyroid disease and myocardial dysfunction even in the absence of multi-system inflammatory syndrome in children. We systematically reviewed the thyrotoxicosis cases with SARS-CoV-2 infection and described its impact on pre-existing dilated cardiomyopathy.

Mechanical Circulatory Support Devices for Pediatric Patients With Congenital Heart Disease.

The use of mechanical circulatory support (MCS) devices is a viable therapeutic treatment option for patients with congestive heart failure. Ventricular assist devices, cavopulmonary assist devices, and total artificial heart pumps continue to gain acceptance as viable treatment strategies for both adults and pediatric patients as bridge-to-transplant, bridge-to-recovery, and longer-term circulatory support alternatives. We present a review of the current and future MCS devices for patients having congenital heart disease (CHD) with biventricular or univentricular circulations. Several devices that are specifically designed for patients with complex CHD are in the development pipeline undergoing rigorous animal testing as readiness experiments in preparation for future clinical trials. These advances in the development of new blood pumps for patients with CHD will address a significant unmet clinical need, as well as generally improve innovation of the current state of the art in MCS technology.

Three-dimensional laser flow measurements of a patient-specific fontan physiology with mechanical circulatory assistance.

Mechanical assistance of the Fontan circulation is hypothesized to enhance ventricular preload and improve cardiac output; however, little is known about the fluid dynamics. This study is the first to investigate the three-dimensional flow conditions of a blood pump in an anatomic Fontan. Laser measurements were conducted having an axial flow impeller in the inferior vena cava. Experiments were performed for a physiologic cardiac output, pulmonary arterial flows, and pump speeds of 1000-4000 rpm. The impeller had a modest effect on the flow conditions entering the total cavopulmonary connection at low pump speeds, but a substantial impact on the velocity at higher speeds. The higher speeds of the pump disrupted the recirculation region in the center of the anastomosis, which could be advantageous for washout purposes. No retrograde velocities in the superior vena cava were measured. These findings indicate that mechanical assistance is a viable therapeutic option for patients having dysfunctional single ventricle physiology.

Stereo-particle image velocimetry measurements of a patient-specific Fontan physiology utilizing novel pressure augmentation stents.

Single ventricle anomalies are a challenging set of congenital heart defects that require lifelong clinical management due to progressive decline of cardiovascular function. Few therapeutic devices are available for these patients, and conventional blood pumps are not designed for the unique anatomy of the single ventricle physiology. To address this unmet need, we are developing an axial flow blood pump with a protective cage or stent for Fontan patients. This study investigates the 3-D particle image velocimetry measurements of two cage designs being deployed in a patient-specific Fontan anatomy. We considered a control case without a pump, impeller placed in the inferior vena cava, and two cases where the impeller has two protective stents with unique geometric characteristics. The experiments were evaluated at a cardiac output of 3 L/min, a fixed vena caval flow split of 40%/60%, a fixed pulmonary arterial flow split of 50%/50%, and for operating speeds of 1000-4000 rpm. The introduction of the cardiovascular stents had a substantial impact on the flow conditions leaving the pump and entering the cavopulmonary circulation. The findings indicated that rotational speeds above 4000 rpm for this pump could result in irregular flows in this specific circulatory condition. Although retrograde flow into the superior vena cava was not measured, the risk of this occurrence increases with higher pump speeds. The against-with stent geometry outperformed the other configurations by generating higher pressures and more energetic flows. These results provide further support for the viability of mechanical cavopulmonary assistance as a therapeutic treatment strategy for Fontan patients.

Design of axial blood pumps for patients with dysfunctional fontan physiology: computational studies and performance testing.

Limited treatment options for patients having dysfunctional single ventricle physiology motivate the necessity for alternative therapeutic options. To address this unmet need, we are developing a collapsible axial flow blood pump. This study investigated the impact of geometric simplicity to facilitate percutaneous placement and maintain optimal performance. Three new pump designs were numerically evaluated. A transient simulation explored the impact of respiration on blood flow conditions over the entire respiratory cycle. Prototype testing of the top performing pump design was completed. The top performing Rec design generated the highest pressure rise range of 2-38 mm Hg for flow rates of 1-4 L/min at 4000-7000 RPM, exceeding the performance of the other two configurations by more than 26%. The blood damage indices for the new pump designs were determined to be below 0.5% and predicted hemolysis levels remained low at less than 7 × 10(-5) g/100 L. Prototype testing of the Rec design confirmed numerical predictions to within an average of approximately 22%. These findings demonstrate that the pumps are reasonably versatile in operational ability, meet pressure-flow requirements to support Fontan patients, and are expected to have low levels of blood trauma.

Experimental measurements of energy augmentation for mechanical circulatory assistance in a patient-specific Fontan model.

A mechanical blood pump specifically designed to increase pressure in the great veins would improve hemodynamic stability in adolescent and adult Fontan patients having dysfunctional cavopulmonary circulation. This study investigates the impact of axial-flow blood pumps on pressure, flow rate, and energy augmentation in the total cavopulmonary circulation (TCPC) using a patient-specific Fontan model. The experiments were conducted for three mechanical support configurations, which included an axial-flow impeller alone in the inferior vena cava (IVC) and an impeller with one of two different protective stent designs. All of the pump configurations led to an increase in pressure generation and flow in the Fontan circuit. The increase in IVC flow was found to augment pulmonary arterial flow, having only a small impact on the pressure and flow in the superior vena cava (SVC). Retrograde flow was neither observed nor measured from the TCPC junction into the SVC. All of the pump configurations enhanced the rate of power gain of the cavopulmonary circulation by adding energy and rotational force to the fluid flow. We measured an enhancement of forward flow into the TCPC junction, reduction in IVC pressure, and only minimally increased pulmonary arterial pressure under conditions of pump support.

Aerosolised heparin in the treatment of Fontan-related plastic bronchitis.

Patients with Fontan palliation and single-ventricle physiology encounter multiple comorbidities including plastic bronchitis, a disease characterised by the plugging of small and large airways by rubbery, white casts. To date, no controlled clinical trials have demonstrated effective treatment of plastic bronchitis. We report the application of aerosolised heparin, which has published success in non-cardiac-related pulmonary disease, for this complication in a Fontan patient.

Dual-pump support in the inferior and superior vena cavae of a patient-specific fontan physiology.

The implementation of simultaneous mechanical cavopulmonary assistance having blood pumps located in both of the vena cavae is investigated as an approach to treating patients with an ailing Fontan physiology. Identical intravascular blood pumps are employed to model the hemodynamic support of a patient-specific Fontan. Pressure flow characteristics, energy gain calculations, and blood damage analyses are assessed for each model. The performance of the dual-support scenario is compared to conditions of mechanical support in the inferior vena cava only and to a nonsupported cavopulmonary circuit. The blood pump in the superior vena cava generates pressures ranging from 1 to 22 mm Hg for flow rates of 1-4 L/min at operating speeds of 1250-2500 rpm. The blood pump in the inferior vena cava produces pressures at levels approximately 20% lower. The blood pumps positively augment the hydraulic energy in the total cavopulmonary connection circuit as a function of flow rate and rotational speed. Scalar stress levels and fluid residence times are at acceptable levels. Damage indices for the dual-support case, however, are elevated slightly above 3.5%. These results suggest that concurrent, mechanical assistance of the inferior vena cava and superior vena cava in Fontan patients has the potential to be beneficial, but additional studies are needed to further explore this approach.

A viable therapeutic option: mechanical circulatory support of the failing Fontan physiology.

A blood pump specifically designed to augment flow from the great veins through the lungs would ameliorate the poor physiology of the failing univentricular circulation and result in a paradigm shift in the treatment strategy for Fontan patients. This study is the first to examine mechanical cavopulmonary assistance with a blood pump in the inferior vena cava (IVC) and hepatic blood flow. Five numerical models of mechanical cavopulmonary assistance were investigated using a three-dimensional, reconstructed, patient-specific Fontan circulation from magnetic resonance imaging data. Pressure flow characteristics of the axial blood pump, energy augmentation calculations for the cavopulmonary circulation with and without pump support, and hemolysis estimations were determined. In all of the pump-supported scenarios, a pressure increase of 7-9.5 mm Hg was achieved. The fluid power of the cavopulmonary circulation was also positive over the range of flow rates. No retrograde flow from the IVC into the hepatic circulation was evident during support cases. Vessel suction risk, however, was found for greater operating rotational speeds. Fluid shear stresses and hemolysis predictions remained at acceptable levels with normalized index of hemolysis estimations at 0.0001 g/100 L. The findings of this study support the continued design and development of this blood pump technology for Fontan patients with progressive cardiovascular insufficiency. Validation of these flow and performance predictions will be completed in the next round of experimental testing with blood bag evaluation.

Trends in Contemporary Use of Ventricular Assist Devices in Children Awaiting Heart Transplantation and Their Outcomes by Race/Ethnicity.

This retrospective study included children aged ≤18 years who had durable ventricular assist devices (VADs) as a bridge to transplantation from the United Network Organ Sharing (UNOS) database between 2011 and 2020. We evaluated 90 day waitlist mortality and 1 year posttransplant mortality after VAD implantation in children stratified by race/ethnicity: Black, White, and Others. The VAD was used in a higher proportion of Black children listed for heart transplantation (HT) (26%) versus Other (25%) versus White (22%); p < 0.01. Black children had Medicaid health insurance coverage (67%) predominantly at the time of listing for HT. There was no significant overall difference in waitlist survival among the three groups supported with VAD at the time of listing (log-rank p = 0.4). On the other hand, the 90 day waitlist mortality after the VAD implantation at listing and while listed was the lowest among Black (6%) compared with White (13%) and Other (14%) ( p < 0.01). The multivariate regression analysis showed that Other race (hazard ratio [HR], 2.29; p < 0.01), Black race (HR, 2.13; p < 0.01), use of mechanical ventilation (HR, 1.72; p = 0.01), and Medicaid insurance (HR, 1.54; p = 0.04) were independently associated with increased 1 year posttransplant mortality. In conclusion, Black children had more access to durable VAD support than White children. The 90 day waitlist mortality was significantly lower in Black children compared with White and Other after VAD implantation. However, Black and Other racial/ethnic children with VAD at transplant had higher 1 year posttransplant mortality than White children. Future studies to elucidate the reasons for these disparities are needed.

Racial and Ethnic Disparity in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 in Mississippi, USA.

We aimed to study the disparity in the clinical profile and outcomes of hospitalized Multisystem Inflammatory Syndrome in Children (MIS-C) patients at our center. The second goal was to examine the temporal association with preceding SARS-CoV-2 infection by race/ethnicity in our community in Mississippi. We found the racial disparity in the prevalence of MIS-C exceeded its temporal association with SARS-CoV-2 infections. We included 51 consecutive MIS-C patients hospitalized, whose median age was 9 (interquartile range [IQR] 5-12) years, 58% were male, 71% were black, 25% were white, and 4% belonged to other groups. We found a delay between onset of symptoms and hospitalization in black patients compared with white patients with a median of 2 (IQR 0-7) vs median of 0 (0-5) urgent care visits (P = .022), respectively. Black patients were hospitalized longer (median 8, IQR 2-39 days) than whites (median 5, IQR 3-14 days), P = .047. A total of 38.9% of blacks and 23.1% of whites were admitted to intensive care unit (P = .498); 36.1% of blacks had severe cardiac involvement vs 23.1% of white patients, P = .531. Future studies of MIS-C are required to improve health equity for children.

Steady flow analysis of mechanical cavopulmonary assistance in MRI-derived patient-specific fontan configurations.

This numerical study examined the performance of an intravascular axial flow blood pump for mechanical hemodynamic support of patients in the setting of Fontan failure, which presently has few treatment options. Three anatomically accurate geometries of the total cavopulmonary connection (TCPC) were generated using patients' magnetic resonance imaging data. These patient-specific geometries, as well as an idealized version with cylindrical vessels, were computationally analyzed with and without a pump in the inferior vena cava. Pressure flow characteristics, energy gain calculations, and blood damage analyses were performed for each model. The pump produced pressures of 1-14 mm Hg for 1500-4000 revolutions per minute, flow rates of 1-4 L/min, and pulmonary artery pressures of 8-24 mm Hg. Comparison of pump performance among the four models showed minimal intermodel differences (<5% deviation) in the pressure rise generated by the pump, the IVC pressure, and the energy imparted to the system by the pump. Blood damage analysis showed maximum fluid scalar stress values of 372 Pa or less, and the blood damage index was less than 2% in all of the models. These results suggest that this axial flow blood pump performs consistently in a variety of TCPC vessel geometries with low risk of blood trauma.

Posterior reversible encephalopathy syndrome in a pediatric heart transplant recipient with coarctation of aorta.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome reported in children with hypertension due to renal diseases, immunosuppression after solid organ transplant, cytotoxic agents for chemotherapy, and many others rare instances. We described PRES in a 6-year-old child with hypertension secondary to an incidental postoperative coarctation of the aorta after heart transplantation (HT). Her blood pressure was well controlled with amlodipine during the outpatient visits and home monitoring of blood pressure, but she had hypertension when presented with neurological symptoms. This case's unique feature is that although PRES has been described after pediatric HT, this is the first case report due to a postoperative coarctation of the proximal descending aorta related to scarring from previous multiple sternotomies leading to inadvertent external compression of the aorta with scar tissue. We discussed the risk factors associated with hypertension before PRES and the correlation of brain magnetic resonance imaging findings with clinical outcomes.

Telehealth: Opportunities to Improve Access, Quality, and Cost in Pediatric Care.

The use of telehealth technology to connect with patients has expanded significantly over the past several years, particularly in response to the global coronavirus disease 2019 pandemic. This technical report describes the present state of telehealth and its current and potential applications. Telehealth has the potential to transform the way care is delivered to pediatric patients, expanding access to pediatric care across geographic distances, leveraging the pediatric workforce for care delivery, and improving disparities in access to care. However, implementation will require significant efforts to address the digital divide to ensure that telehealth does not inadvertently exacerbate inequities in care. The medical home model will continue to evolve to use telehealth to provide high-quality care for children, particularly for children and youth with special health care needs, in accordance with current and evolving quality standards. Research and metric development are critical for the development of evidence-based best practices and policies in these new models of care. Finally, as pediatric care transitions from traditional fee-for-service payment to alternative payment methods, telehealth offers unique opportunities to establish value-based population health models that are financed in a sustainable manner.

Pediatric catheterization laboratory anticoagulation with bivalirudin.

BACKGROUND: Pediatric physicians regularly face the problem of uncertain procedural anticoagulation in children, especially in neonates. We sought to evaluate the safety, plasma concentration (pharmacokinetics, PK), pharmacodynamics (PD), and dosing guidelines of bivalirudin when used as a procedural anticoagulant in pediatric percutaneous intravascular procedures. METHODS AND RESULTS: Pediatric subjects undergoing percutaneous intravascular procedures for congenital heart disease were enrolled and received the current weight-based dose used in percutaneous coronary interventions (0.75 mg/kg bolus, 1.75 mg/kg/hr infusion). Blood samples for PK/PD analyses were drawn, and safety was evaluated by monitoring bleeding and thrombosis events. A total of 110 patients (11 neonates, 33 infants, 32 young children, and 34 older children) were enrolled; 106 patients received the protocol dose. The PK/PD response of bivalirudin was predictable and behaved in a manner similar to that in adults. Weight-normalized bivalirudin clearance rates were more rapid in neonates and decreased with increasing age. Bivalirudin concentrations were slightly lower in neonates, with a trend to an increase with age. Activating clotting time response was consistent with adult studies and prolonged in all age groups, and there was reasonable correlation between activating clotting time and bivalirudin plasma concentrations across all age groups. There were few major bleeding (2 of 110, 1.8%) or thrombotic events (9 of 110, 8.2%) reported. CONCLUSIONS: PK/PD response of bivalirudin in the pediatric population is predictable and behaves in a manner similar to that in adults. Using adult dosing, bivalirudin safely provided the expected anticoagulant effect in the pediatric population undergoing intravascular procedures for congenital heart disease.

Mechanical cavopulmonary assistance of a patient-specific Fontan physiology: numerical simulations, lumped parameter modeling, and suction experiments.

This study investigated the performance of a magnetically levitated, intravascular axial flow blood pump for mechanical circulatory support of the thousands of Fontan patients in desperate need of a therapeutic alternative. Four models of the extracardiac, total cavopulmonary connection (TCPC) Fontan configuration were evaluated to formulate numerical predictions: an idealized TCPC, a patient-specific TCPC per magnetic resonance imaging data, and each of these two models having a blood pump in the inferior vena cava (IVC). A lumped parameter model of the Fontan physiology was used to specify boundary conditions. Pressure-flow characteristics, energy gain calculations, scalar stress levels, and blood damage estimations were executed for each model. Suction limitation experiments using the Sylgard elastomer tubing were also conducted. The pump produced pressures of 1-16 mm Hg for 2000-6000 rpm and flow rates of 0.5-4.5 L/min. The pump inlet or IVC pressure was found to decrease at higher rotational speeds. Maximum scalar stress estimations were 3 Pa for the nonpump models and 290 Pa for the pump-supported cases. The blood residence times for the pump-supported cases were shorter (0.9 s) as compared with the nonsupported configurations (2.5 s). However, the blood damage indices were higher (1.5%) for the anatomic model with pump support. The pump successfully augmented pressure in the TCPC junction and increased the hydraulic energy of the TCPC as a function of flow rate and rotational speed. The suction experiments revealed minimal deformation (<3%) at 9000 rpm. The findings of this study support the continued design and development of this blood pump.

Current and Future Drug and Device Therapies for Pediatric Heart Failure Patients: Potential Lessons from Adult Trials.

This review discusses the potential drug and device therapies for pediatric heart failure (HF) due to reduced systolic function. It is important to realize that most drugs that are used in pediatric HF are extrapolated from adult cardiology practices or consensus guidelines based on expert opinion rather than on evidence from controlled clinical trials. It is difficult to conclude whether the drugs that are well established in adult HF trials are also beneficial for children because of tremendous heterogeneity in the mechanism of HF in children and variations in the pharmacokinetics and pharmacodynamics of drugs from birth to adolescence. The lessons learned from adult trials can guide pediatric cardiologists to design clinical trials of the newer drugs that are in the pipeline to study their efficacy and safety in children with HF. This paper's focus is that the reader should specifically think through the pathophysiological mechanism of HF and the mode of action of drugs for the selection of appropriate pharmacotherapy. We review the drug and device trials in adults with HF to highlight the knowledge gap that exists in the pediatric HF population.

Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination: What Do We Know So Far?

This is a cross-sectional study of 29 published cases of acute myopericarditis following COVID-19 mRNA vaccination. The most common presentation was chest pain within 1-5 days after the second dose of mRNA COVID-19 vaccination. All patients had an elevated troponin. Cardiac magnetic resonance imaging revealed late gadolinium enhancement consistent with myocarditis in 69% of cases. All patients recovered clinically rapidly within 1-3 weeks. Most patients were treated with non-steroidal anti-inflammatory drugs for symptomatic relief, and 4 received intravenous immune globulin and corticosteroids. We speculate a possible causal relationship between vaccine administration and myocarditis. The data from our analysis confirms that all myocarditis and pericarditis cases are mild and resolve within a few days to few weeks. The bottom line is that the risk of cardiac complications among children and adults due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection far exceeds the minimal and rare risks of vaccination-related transient myocardial or pericardial inflammation.