A prospective multicenter feasibility study of a miniaturized implantable continuous flow ventricular assist device in smaller children with heart failure.

BACKGROUND: There is no FDA-approved left ventricular assist device (LVAD) for smaller children permitting routine hospital discharge. Smaller children supported with LVADs typically remain hospitalized for months awaiting heart transplant-a major burden for families and a challenge for hospitals. We describe the initial outcomes of the Jarvik 2015, a miniaturized implantable continuous flow LVAD, in the NHLBI-funded Pumps for Kids, Infants, and Neonates (PumpKIN) study, for bridge-to-heart transplant. METHODS: Children weighing 8 to 30 kg with severe systolic heart failure and failing optimal medical therapy were recruited at 7 centers in the United States. Patients with severe right heart failure and single-ventricle congenital heart disease were excluded. The primary feasibility endpoint was survival to 30 days without severe stroke or non-operational device failure. RESULTS: Of 7 children implanted, the median age was 2.2 (range 0.7, 7.1) years, median weight 10 (8.2 to 20.7) kilograms; 86% had dilated cardiomyopathy; 29% were INTERMACS profile 1. The median duration of Jarvik 2015 support was 149 (range 5 to 188) days where all 7 children survived including 5 to heart transplant, 1 to recovery, and 1 to conversion to a paracorporeal device. One patient experienced an ischemic stroke on day 53 of device support in the setting of myocardial recovery. One patient required ECMO support for intractable ventricular arrhythmias and was eventually transplanted from paracorporeal biventricular VAD support. The median pump speed was 1600 RPM with power ranging from 1-4 Watts. The median plasma free hemoglobin was 19, 30, 19 and 30 mg/dL at 7, 30, 90 and 180 days or time of explant, respectively. All patients reached the primary feasibility endpoint. Patient-reported outcomes with the device were favorable with respect to participation in a full range of activities. Due to financial issues with the manufacturer, the study was suspended after consent of the eighth patient. CONCLUSION: The Jarvik 2015 LVAD appears to hold important promise as an implantable continuous flow device for smaller children that may support hospital discharge. The FDA has approved the device to proceed to a 22-subject pivotal trial. Whether this device will survive to commercialization remains unclear because of the financial challenges faced by industry seeking to develop pediatric medical devices. (Supported by NIH/NHLBI HHS Contract N268201200001I, clinicaltrials.gov 02954497).

Successful implementation of telehealth visits in the paediatric heart failure and heart transplant population.

The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and Pediatric Heart Transplant Society (PHTS) convened a working group at the beginning of 2020 during the COVID-19 pandemic, with the aim of using telehealth as an alternative medium to provide quality care to a high-acuity paediatric population receiving advanced cardiac therapies. An algorithm was developed to determine appropriateness, educational handouts were developed for both patients and providers, and post-visit surveys were collected. Telehealth was found to be a viable modality for health care delivery in the paediatric heart failure and transplant population and has promising application in the continuity of follow-up, medication titration, and patient education/counselling domains.

Expanding use of the HeartMate 3 ventricular assist device in pediatric and adult patients within the Advanced Cardiac Therapies Improving Outcomes Network (ACTION).

BACKGROUND: We report current outcomes in patients supported with the HeartMate 3 (HM3) ventricular assist device in a multicenter learning network. METHODS: The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HM3 implants between 12/2017 and 5/2022. Clinical characteristics, postimplant course, and adverse events were collected. Patients were stratified according to body surface area (BSA) (<1.4 m2, 1.4-1.8 m2, and >1.8 m2) at device implantation. RESULTS: During the study period, 170 patients were implanted with the HM3 at participating network centers, with median age 15.3years; 27.1% were female. Median BSA was 1.68 m2; the smallest patient was 0.73 m2 (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with BSA <1.4 m2 had a higher incidence of infection, renal dysfunction, and ischemic stroke. CONCLUSIONS: In this updated cohort of predominantly pediatric patients supported with the HM3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care.

Impact of Weight on Ventricular Assist Device Outcomes in Dilated Cardiomyopathy Patients in Pediatric Centers: An ACTION Registry Study.

Ventricular assist device (VAD) options vary for children in different weight groups. This study evaluates contemporary device usage and outcomes for children based on weight. Data from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were examined for patients with dilated cardiomyopathy (DCM) in 4 weight cohorts: <8 kg, 8-20 kg, 21-40 kg, and >40 kg, for devices implanted 3/2013-10/2020. Adverse event rates and ultimate outcome (deceased, alive on device, transplanted, or ventricular recovery) were analyzed. 222 DCM patients were identified with 24% in cohort 1, 23% in cohort 2, 15% in cohort 3, and 38% in cohort 4. Of 272 total implants, paracorporeal pulsatile devices were most common (95%) in cohorts 1 and 2 and intracorporeal continuous devices (81%) in cohorts 3 and 4. Stroke was noted in 17%, 12%, 6%, and 4% of cohorts, respectively (Cohort 1 vs. 4 and 2 vs. 4 - p = 0.01; other comparisons - not significant). Incidences of major bleeding, device malfunction, and infection was not different. All cohorts had >90% positive outcomes. Stroke incidence was higher in smaller cohorts, but other outcomes were similar. Positive outcomes were attained in over 90% across all weight groups, demonstrating excellent outcomes using current VADs in this DCM population.

Bivalirudin Compared to Heparin as the Primary Anticoagulant in Pediatric Berlin Heart Recipients.

Bivalirudin has been used in increasing frequency as an alternative to unfractionated heparin (UFH) in pediatric recipients of Berlin Heart EXCOR ventricular assist devices (VAD). This single-center, retrospective review characterizes anticoagulant trends and outcomes in pediatric Berlin Heart VAD recipients implanted between September 1, 2013, and August 31, 2021, anticoagulated with either bivalirudin or UFH. Thirty-one patients were included; 65% who received bivalirudin and 35% who received UFH. The median age was 2.9 years, included 64.5% females, with 61.3% of patients diagnosed with dilated cardiomyopathy and 25.8% of patients with congenital heart disease. Therapeutic anticoagulation was achieved sooner in the bivalirudin group compared to UFH via anti-Xa monitoring (median 5.7 and 69.5 hours, respectively, p < 0.001). Bivalirudin had a greater number of therapeutic values comparatively to UFH (52% and 24%, respectively; p < 0.001) and a superior number of hours in the therapeutic range (67% and 32%, respectively; p < 0.001). Secondary outcomes were similar among the two groups, apart from greater chest tube output (UFH), more frequent events of elevated plasma-free hemoglobin (bivalirudin), and more frequent elevated inflammatory markers postimplant (bivalirudin). Prevalence of pump replacements secondary to significant clot burden and prevalence of stroke was comparable. In this patient cohort, bivalirudin demonstrated greater anticoagulation stability comparatively to UFH. Multicenter collaboration would be necessary to identify whether this further translates into improved patient outcomes.

Sixth Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: The Society Of Thoracic Surgeons Pedimacs Annual Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs). METHODS: From September 19, 2012, to December 31, 2021, there were 1355 devices in 1109 patients (<19 years) from 42 North American Hospitals. RESULTS: Cardiomyopathy was the most common underlying cause (59%), followed by congenital heart disease (25%) and myocarditis (9%). Regarding device type, implantable continuous (IC) VADs were most common at 40%, followed by paracorporeal pulsatile (PP; 28%) and paracorporeal continuous (PC; 26%). Baseline demographics differed, with the PC cohort being younger, smaller, more complex (ie, congenital heart disease), and sicker at implantation (P < .0001). At 6 months after VAD implantation, a favorable outcome (transplantation, recovery, or alive on device) was achieved in 84% of patients, which was greatest among those on IC VADs (92%) and least for PC VADs (69%). Adverse events were not uncommon, with nongastrointestinal bleeding (incidence of 14%) and neurologic dysfunction (11% [stroke, 4%]), within 2 weeks after implantation being the most prevalent. Stroke and bleeding had negative impacts on overall survival (P = .002 and P < .001, respectively). CONCLUSIONS: This Sixth Pedimacs Report demonstrates the continued evolution of the pediatric field. The complexity of cardiac physiologies and anatomic constraint mandates the need for multiple types of devices used (PC, PP, IC). Detailed analyses of each device type in this report provide valuable information to further advance the care of this challenging and vulnerable population.

Initial multicenter experience with ventricular assist devices in children and young adults with muscular dystrophy: An ACTION registry analysis.

PURPOSE: Cardiac disease results in significant morbidity and mortality in patients with muscular dystrophy (MD). Single centers have reported their ventricular assist device (VAD) experience in specific MDs and in limited numbers. This study sought to describe the outcomes associated with VAD therapy in an unselected population across multiple centers. METHODS: We examined outcomes of patients with MD and dilated cardiomyopathy implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers from 9/2012 to 9/2020. RESULTS: A total of 19 VADs were implanted in 18 patients across 12 sites. The majority of patients had dystrophinopathy (66%) and the median age at implant was 17.2 years (range 11.7-29.5). Eleven patients were non-ambulatory (61%) and 6 (33%) were on respiratory support pre-VAD. Five (28%) patients were implanted as a bridge to transplant, 4 of whom survived to transplant. Of 13 patients implanted as bridge to decision or destination therapy, 77% were alive at 1 year and 69% at 2 years. The overall frequencies of positive outcome (transplanted or alive on device) at 1 year and 2 years were 84% and 78%, respectively. Two patients suffered a stroke, 2 developed sepsis, 1 required tracheostomy, and 1 experienced severe right heart failure requiring right-sided VAD. CONCLUSIONS: This study demonstrates the potential utility of VAD therapies in patients with muscular dystrophy. Further research is needed to further improve outcomes and better determine which patients may benefit most from VAD therapy in terms of survival and quality of life.

Quality of life and lifetime achievement in adult survivors of pediatric heart transplant.

BACKGROUND: Survival in pediatric heart transplantation has improved since the first successful transplant over 35 years ago leading to increasing numbers of patients entering adulthood. We sought to examine quality of life and various lifetime achievements in our institutional population of long-term adult survivors of pediatric heart transplant. METHODS: Participants ≥18 years of age who received a heart transplant as a pediatric patient (<18 years old), and who have survived ≥10 years post-transplant, completed two self-report surveys: (1) Ferrans and Powers QLI cardiac version which reports a measure of life satisfaction with a range of 0 (very dissatisfied) to 1 (very satisfied); and (2) CHONY Pediatric Heart Transplant Life Achievement Survey to examine lifetime achievement. RESULTS: Sixty-two and sixty-five participants completed the Ferrans and Powers QLI cardiac version and CHONY Pediatric Heart Transplant Life Achievement Survey. The mean overall QLI was 0.75 ± 0.14 with the most satisfaction in the family domain. QLI scores were analyzed by age at initial transplant, gender, indication for transplant, and whether patients currently followed by pediatric or adult providers, with no statistically significant differences noted. Seventy-two percent of participants demonstrated stable employment or schooling. Around thirty percent of participants showed the ability to reach academic milestones including college and post-graduate education and ten percent to start their own families. CONCLUSIONS: Our cohort of long-term adult survivors of pediatric heart transplant report a quality of life with scores thought to be reflective of a satisfactory quality of life, and many demonstrate achievement of major life milestones.

Diversity of Dystrophin Gene Mutations and Disease Progression in a Contemporary Cohort of Duchenne Muscular Dystrophy.

Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1-6). Subjects with mutations starting at exon positions 40-54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18-∞), p = 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12-15) in subjects with mutations that started between exons 55-79, p = 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability.

Fifth Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) provides detailed information on pediatric patients supported with ventricular assist devices (VADs). METHODS: From September 19, 2012, to December 31, 2020, 1229 devices in 1011 patients were reported to the registry from 47 North American Hospitals in patients aged younger than 19 years. RESULTS: Cardiomyopathy was the most common underlying etiology (58%), followed by congenital heart disease (CHD; 25%) and myocarditis (10%). The most common devices implanted were implantable continuous (IC; 419 [41%]), followed by paracorporeal pulsatile (PP; 269 [27%]), paracorporeal continuous (PC; 263 [26%]), and percutaneous (53 [5%]). Overall, at 6 months after VAD implantation, 83% had a positive outcome (transplant, explant, or alive on device). The freedom from stroke at 3 months was highest in IC VADs (93%), compared with PP VADs (84%) and with PC VADs (75%). There were differences in survival by device type, with patients on IC VADs having the best overall survival and those on PC having the lowest overall survival, though the patient populations being supported by each VAD type differed significantly from each other. CONCLUSIONS: This Fifth Pedimacs Report demonstrates the continued robust growth of VADs in the pediatric community, now with more than 1000 patients reported to the registry. The multiple available device types (PC, PP, IC) serve different populations with different pre-VAD risk profiles, which may account for differences in survival and adverse events between device types.

Right heart failure considerations in pediatric ventricular assist devices.

Right heart failure (RHF) is a vexing problem in children after left ventricular assist device (LVAD) implantation that can negatively impact transplant candidacy and survival. Anticipation, prevention, early identification and appropriate medical and device management of RHF are important to successful LVAD outcomes. However, there is limited pediatric evidence to guide practice. This pediatric-focused review summarizes the relevant literature and describes the harmonized approach to RHF from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). This review seeks to improve RHF outcomes through the sharing of best practices and experience across the pediatric VAD community.

Atretic Coronary Artery Ostia in a Full-Term Infant with Early Postnatal Demise.

Congenital coronary artery anomalies are extremely rare causes of early cardiac failure. Several cardiac lesions are associated with coronary anomalies such as pulmonary atresia with intact ventricular septum. Isolated coronary ostial atresia is extremely rare and described in only a few published case reports. To our knowledge, there were two reports of bilateral coronary ostial atresia in which the entire coronary arterial system originated from the right ventricle without other intracardiac defects. We present a case of a full-term infant who presented with severely depressed biventricular function secondary to bilateral coronary ostial atresia.

Varying presentations of COVID-19 in young heart transplant recipients: A case series.

BACKGROUND: Immunosuppression is considered a risk factor for more severe clinical presentation of COVID-19. Limited data regarding clinical outcome exist in adults, whereas very little is known about the spectrum of the disease in pediatric heart transplant recipients. METHODS: We retrospectively reviewed the charts of young heart transplant patients from our tertiary care center during the coronavirus pandemic in New York City and identified patients infected with SARS-CoV-2. RESULTS: We present four cases with COVID-19 disease and elaborate on their presentation and clinical course. CONCLUSIONS: Although far from conclusive and limited by the small sample size and selection bias, these cases demonstrate mild and self-limited disease despite immunosuppressive therapy and various comorbidities that are expected to increase the severity of the clinical picture based on extrapolation from the adult experience with this novel disease.

Evolution of pediatric ventricular assist devices and their neurologic and renal complications-A 24-year single-center experience.

Utilization of ventricular assist devices (VADs) in adult populations with severe heart failure as a bridge to transplant has become the standard of care over the past two decades. Analogously, the use of VADs in pediatric populations has become more commonplace as pediatric heart transplantation has become more prevalent. We still have much to learn, however, about the complications after VAD placement in pediatric patients, their impact on transplantation and, in particular, how outcomes have changed over time. The objectives of this study were to (a) review the experience of a single pediatric VAD center, (b) identify risk factors that could lead to poor outcomes in patients on the transplant waitlist after VAD implantation and (c) demonstrate changes in outcomes over time. A retrospective cohort analysis was performed comparing death as a primary outcome and stroke and acute kidney injury (AKI) as secondary outcomes, across the study period divided into three timed eras. We analyzed 88 patients supported by a VAD over a 24-year timeframe. The duration, age at implant and indication for VAD support did not change significantly across the eras. We found that the incidence of stroke decreased over the study period and, while the rates of AKI did not change over the study period, those who developed AKI, while supported on VAD, had an increased risk of death.

Implantable Cardioverter Defibrillator Use in Males with Duchenne Muscular Dystrophy and Severe Left Ventricular Dysfunction.

Duchenne muscular dystrophy (DMD) is characterized by myocardial fibrosis and left ventricular (LV) dysfunction. Implantable cardioverter defibrillator (ICD) use has not been characterized in this population but is considered for symptomatic patients with severe LV dysfunction (SLVD) receiving guideline-directed medical therapy (GDMT). We evaluated ICD utilization and efficacy in patients with DMD. Retrospective cohort study of DMD patients from 17 centers across North America between January 2, 2005 and December 31, 2015. ICD use and its effect on survival were evaluated in patients with SLVD defined as ejection fraction (EF) < 35% and/ or shortening fraction (SF) < 16% on final echocardiogram. SLVD was present in 57/436 (13.1%) patients, of which 12 (21.1%) died during the study period. Of these 12, (mean EF 20.9 ± 6.2% and SF 13.7 ± 7.2%), 8 received GDMT, 5 received steroids, and none received an ICD. ICDs were placed in 9/57 (15.8%) patients with SLVD (mean EF 31.2 ± 8.5% and SF 10.3 ± 4.9%) at a mean age of 20.4 ± 6.3 years; 8/9 received GDMT, 7 received steroids, and all were alive at study end; mean ICD duration was 36.1 ± 26.2 months. Nine ICDs were implanted at six different institutions, associated with two appropriate shocks for ventricular tachycardia in two patients, no inappropriate shocks, and one lead fracture. ICD use may be associated with improved survival and minimal complications in DMD cardiomyopathy with SLVD. However, inconsistent GDMT utilization may be a significant confounder. Future studies should define optimal indications for ICD implantation in patients with DMD cardiomyopathy.

Risk Factors for Cardiac and Non-cardiac Causes of Death in Males with Duchenne Muscular Dystrophy.

As survival and neuromuscular function in Duchenne muscular dystrophy (DMD) have improved with glucocorticoid (GC) therapy and ventilatory support, cardiac deaths are increasing. Little is known about risk factors for cardiac and non-cardiac causes of death in DMD. A multi-center retrospective cohort study of 408 males with DMD, followed from January 1, 2005 to December 31, 2015, was conducted to identify risk factors for death. Those dying of cardiac causes were compared to those dying of non-cardiac causes and to those alive at study end. There were 29 (7.1%) deaths at a median age of 19.5 (IQR: 16.9-24.6) years; 8 (27.6%) cardiac, and 21 non-cardiac. Those living were younger [14.9 (IQR: 11.0-19.1) years] than those dying of cardiac [18 (IQR 15.5-24) years, p = 0.03] and non-cardiac [19 (IQR: 16.5-23) years, p = 0.002] causes. GC use was lower for those dying of cardiac causes compared to those living [2/8 (25%) vs. 304/378 (80.4%), p = 0.001]. Last ejection fraction prior to death/study end was lower for those dying of cardiac causes compared to those living (37.5% ± 12.8 vs. 54.5% ± 10.8, p = 0.01) but not compared to those dying of non-cardiac causes (37.5% ± 12.8 vs. 41.2% ± 19.3, p = 0.58). In a large DMD cohort, approximately 30% of deaths were cardiac. Lack of GC use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Further work is needed to ensure guideline adherence and to define optimal management of systolic dysfunction in males with DMD with hopes of extending survival.

Biventricular Impella use in pediatric patients with severe graft dysfunction from acute rejection after heart transplantation.

Rejection with severe hemodynamic compromise is a significant source of morbidity and mortality for pediatric heart transplant patients. Traditionally, treatment for these patients includes inotropes and escalation to extracorporeal membrane oxygenation (ECMO) when necessary. There is increasing interest in using percutaneous ventricular assistive devices in the pediatric population as a less invasive alternative to ECMO. We report the largest case series to date of biventricular support using percutaneous Impella devices. Retrospective case series was performed by chart review. Hemodynamics, left ventricular ejection fraction (LVEF), and indices of end organ function were collected before and after Impella placement. A 14-year-old male, 18-year-old male, and 19-year-old female, all status post heart transplant, presented with severely decreased biventricular function due to presumed clinical rejection, requiring maximal inotropic support without improvement. In all the three cases, simultaneous Impella CP and RP devices were placed percutaneously. Prior to implantation, LVEFs were 40%, 23%, and 25%, respectively. Hemodynamics measured invasively prior to device placement showed elevated filling pressures. Adverse events while on support included bleeding, hemolysis, and right femoral arterial dissection during implantation. All patients were successfully weaned from the devices and survived to discharge. The average time of right-sided support and total support was 11 days and 13 days, respectively. After device removal, right-sided pressures and echocardiographic measurements showed improvement in all patients. Bilateral Impella configuration (BiPella) is a viable option for temporary mechanical circulatory support in pediatric patients with significant graft dysfunction.