MILESTONE: More Than 1,200 Children Bridged to Heart Transplantation with Mechanical Circulatory Support.

2022

577-583

2022 Apr 01

1538-943X

<p>Pediatric mechanical circulatory support (MCS) has been successfully used to bridge numerous children to transplantation who otherwise would have been unlikely to survive on the waitlist and, in many cases, make them better transplant candidates. The purpose of this study was to analyze what the pediatric heart failure community has achieved over the last 15 years in reaching 1,200 cases of bridging children to heart transplantation. The United Network for Organ Sharing database was used to identify MCS patients ages 0-18 at the time of listing for heart transplantation between 2005 and 2019, divided into three eras: first (2005-2009), second (2010-2014), and third (2015-2019). From 2005 to 2019, 1,289 pediatric cases were identified. More patients were successfully bridged to transplantation with MCS in the third-era (28%) [vs. first-era (16%), second-era (24%), p ≤ 0.004]. The proportion of discharges on ventricular assist device has increased as well from 3% to 22% (p &lt; 0.001). Post-transplant survival was significantly better in the third era (1-year survival: 96%; 3-year survival: 89%) compared to the two previous eras (p = 0.006). On MCS, renal dysfunction, ventilator dependence, inotrope use, and functional status improved from the time of listing to transplantation (p &lt; 0.01). Hepatic dysfunction (p &lt; 0.001), renal dysfunction (p = 0.004), congenital heart disease (p = 0.023), and infant age (p = 0.002) were risk factors for post-transplant mortality. Over the last 15 years, pediatric MCS has become an accepted and increasingly used strategy for bridging children to transplantation. MCS therapy is associated with improved end-organ function at the time of transplantation, perhaps contributing to the increasing post-transplantation survival of patients bridged with MCS.</p>

10.1097/MAT.0000000000001635

ASAIO J

35349524

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

2020

2020 Oct 08

1552-6259

<p><strong>BACKGROUND: </strong>Pedimacs, an originally NIH-sponsored U.S. database, provides a platform to understand the population of children supported with VADs during this time of increasing numbers, new devices, expanding indications, and improved outcomes.</p>

<p><strong>METHODS: </strong>Between 9/19/12-12/31/19, 44 hospitals implanted 1031 devices in 856 patients under 19 years-of-age.</p>

<p><strong>RESULTS: </strong>Overall, diagnosis was cardiomyopathy in 497(58%), congenital heart disease(CHD) in 216(25%), myocarditis in 85(10%), and other in 58(7%). Positive outcome (alive on device or bridge to transplantation/recovery) occurred in 82% at 6-months. The patient cohort for implantable continuous flow(IC) pumps (n=365)[age:13.2+/-3.9yrs., 18% INTERMACS profile-1, 23% intubated at implant, 16% with CHD] was significantly different from the paracorporeal continuous flow(PC) pump cohort (n=212)[age:3.6+/-4.9yrs, 46% INTERMACS profile-1, 81% intubated, 42% CHD] and the paracorporeal pulsatile(PP) pump cohort (n=230)[age:2.7 +/-3.5yrs, 31% INTERMACS profile-1, 76% intubated, 26% CHD]. Consistent with their cohort composition, positive outcomes at 6 months based on device type were IC-92%, PC-68%, and PP-81%. The incidence of cerebrovascular accidents(CVA) in the IC, PC, and PP cohorts is 7%, 14% and 15%, respectively.</p>

<p><strong>CONCLUSIONS: </strong>IC VADs, the most common VAD-type placed in children, are associated with improved outcomes compared to PP/PC devices, though PP/PC devices are limited to supporting our most challenging patients. Noteworthy, the incidence of CVA for pediatric VADs has significantly decreased and is now 11% overall. This report demonstrates again that although often attributed to age, size, or device type, much of the burden in mortality and adverse events is correlated to the patient's overall state at VAD implantation.</p>

10.1016/j.athoracsur.2020.09.003

Ann Thorac Surg

33039359

Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support.

2019

2019 Nov 20

1538-943X

<p>Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged &lt;19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.</p>

10.1097/MAT.0000000000001093

ASAIO J.

31789654

Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support.

2020

939-945

2020 Aug

1538-943X

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.

10.1097/MAT.0000000000001093

ASAIO J.

32740356

Epidemiology and Outcomes of Acute Decompensated Heart Failure in Children.

2020

e006101

2020 Apr

1941-3297

<p><strong>BACKGROUND: </strong>Acute decompensated heart failure (ADHF) is a highly morbid condition among adults. Little is known about outcomes in children with ADHF. We analyzed the Pediatric Cardiac Critical Care Consortium registry to determine the epidemiology, contemporary treatments, and predictors of mortality in critically ill children with ADHF.</p>

<p><strong>METHODS: </strong>Cardiac intensive care unit (CICU) patients ≤18 years of age meeting Pediatric Cardiac Critical Care Consortium criteria for ADHF were included. ADHF was defined as systolic or diastolic dysfunction requiring continuous vasoactive or diuretic infusion, respiratory support, or mechanical circulatory support. Demographics, diagnosis, therapies, complications, and mortality are described for the cohort. Predictors of CICU mortality were identified using logistic regression.</p>

<p><strong>RESULTS: </strong>Among 26 294 consecutive admissions (23 centers), 1494 (6%) met criteria for analysis. Median age was 0.93 years (interquartile range, 0.1-9.3 years). Patients with congenital heart disease (CHD) comprised 57% of the cohort. Common therapies included the following: vasoactive infusions (88%), central venous catheters (86%), mechanical ventilation (59%), and high flow nasal cannula (46%). Common complications were arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis (3%). Median length of CICU stay was 7.9 days (interquartile range, 3-18 days) and the CICU readmission rate was 22%. Overall, CICU mortality was 15% although higher for patients with CHD versus non-CHD (19% versus 11%; &lt;0.001). Independent risk factors associated with CICU mortality included age &lt;30 days, CHD, vasoactive infusions, ventricular tachycardia, mechanical ventilation, sepsis, pulmonary hypertension, extracorporeal membrane oxygenation, and cardiac arrest.</p>

<p><strong>CONCLUSIONS: </strong>ADHF in children is characterized by comorbidities, high mortality rates, and frequent readmission, especially among patients with CHD. Opportunities exist to determine best practices around appropriate use of mechanical support, cardiac arrest prevention, and optimal heart transplantation candidacy to improve outcomes for these patients.</p>

10.1161/CIRCHEARTFAILURE.119.006101

Circ Heart Fail

32301336

Third Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: Pre-Implant Characteristics and Outcomes.

2019

2019 Feb 25

1552-6259

<p><strong>BACKGROUND: </strong>The influence of ventricular assist device (VAD) use in the care of children with end-stage heart failure is growing rapidly through increasing numbers, new devices, expanding indications, and improving outcomes. Pedimacs, a NIH-sponsored U.S. database, provides a platform to understand this emerging population.</p>

<p><strong>METHODS: </strong>Between 9/19/12-12/31/17, 30 hospitals implanted 508 devices in 423 patients under 19 years-of-age. This past year was one of evolution for the Database as its management was transitioned to the Society of Thoracic Surgery, therefore data from institutions not under contract by August 1 2018 was not included in this report.</p>

<p><strong>RESULTS: </strong>Of the 423 patients, the diagnosis was cardiomyopathy in 261 (62%), myocarditis in 48 (11%), other in 28 (7%) and congenital heart disease in 86 (20%) with 52 of these patients having single ventricle physiology. The two most common support strategies included LVAD-342 (81%) and BiVAD-64 (15%). Positive Outcome (alive on device or bridge to transplantation/recovery) was 80% at 6-months (overall mortality of 20%). The patient cohort for implantable continuous flow (IC) pumps (n=197) [age at implant 13.4+/-3.8yrs., 19% INTERMACS profile-1, 21% intubated at implant and 12% with CHD] was significantly different from the paracorporeal continuous flow (PC) pump cohort (n=79) [age 3.9+/-5.2yrs, 49% INTERMACS profile-1, 86% intubated at implant, and 38% with CHD] and the paracorporeal pulsatile (PP) pump cohort (n=121) [age 3.3+/-3.9yrs, 41% INTERMACS profile-1, 77 % intubated at implant, and 21% with CHD]. Consistent with their cohort composition, device type positive outcomes at 6 months were PC-63%, PP-77% and IC-92%. Using Parametric Hazard Modeling, an early hazard for death was associated with INTERMACS profile-1, BiVAD, percutaneous devices, PC devices, small volume institutions, low age and low weight, while a constant hazard was associated with intubation and liver dysfunction at time of implant.</p>

<p><strong>CONCLUSIONS: </strong>IC VADs are the most common VAD type placed in children. The positive outcomes for the IC VADs are &gt;90% at 6 months, which may represent our field's maturation in both patient selection and timing of implantation. Currently the PP/PC devices are limited to supporting our most challenging patients, those less than 20kg, and those with CHD. The introduction of new devices and our communities' commitment to shared learning and improvement will lead to more pediatric lives saved by VAD support, and will also focus on improving the quality of life of children supported with VADs.</p>

10.1016/j.athoracsur.2019.01.038

Ann. Thorac. Surg.

30817920

Outcomes of children implanted with ventricular assist devices in the United States: First analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).

2016

578-84

2016 May

1557-3117

<p><strong>BACKGROUND: </strong>Use of mechanical circulatory support in children has increased as more options have become available. A national account of the use of mechanical support in children and adolescents is essential to understanding outcomes, refining patient selection and improving quality of care.</p>

<p><strong>METHODS: </strong>The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Heart, Lung, and Blood Institute-supported nationwide registry for temporary and durable ventricular assist device (VAD) use in patients &lt;19 years of age. Between the launch in September 2012 and June 2015, 37 hospitals in the USA have enrolled patients. This first report of data from PediMACS analyzed pre-implant patient characteristics, survival using competing outcomes, and adverse events.</p>

<p><strong>RESULTS: </strong>Two hundred pediatric patients underwent 222 durable VAD implants. Patients' characteristics and outcomes of children supported with a temporary device (n = 41) were not analyzed in this report. The etiology of heart disease included 146 (73%) patients with cardiomyopathy and 35 (18%) with congenital heart disease. Thirty patients (15%) transitioned from extracorporeal membrane oxygenation (ECMO) and 76 (38%) had previous cardiac surgery. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 (27%) or Level 2 (56%) at implant, with 13% at Level 3. Of the 200 patients supported with a durable device, 91 (46%) were supported with a pulsatile-flow device and 109 (55%) with a continuous-flow (CF) device. Patient age at first implant included 30 patients (15%) &lt;1 year of age, 37 (19%) 1 to 5 years, 32 (16%) 6 to 10 years and 101 (51%) 10 to 18 years. Patients were supported with left ventricular assist device alone in 161 (81%), biventricular ventricular assist device in 29 (15%), right ventricular assist device in 4 (2.0%) and total artificial heart in 6 (3%), together comprising 783 months of follow-up. The 200 patients receiving primary durable devices had an actuarial survival of 81% at 6 months. Competing risk analysis at 6 months revealed that 58% of patients had been transplanted, 28% were alive on support, 14% had died and 0.6% recovered. In the overall cohort, there were 28 deaths. Reported serious adverse events included infection (n = 78), bleeding (n = 68), device malfunction (n = 79) and neurologic dysfunction (n = 52).</p>

<p><strong>CONCLUSIONS: </strong>PediMACS constitutes the largest single data repository with detailed information of pediatric patients implanted with VADs. The first PediMACS report reveals favorable outcomes despite the varying patient characteristics and pump types. However, the rate of adverse events remains high. With further data collection, analysis of patient risk factors critical to improving outcomes will be possible.</p>

10.1016/j.healun.2016.01.1227

J. Heart Lung Transplant.

27009673

Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: A report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).

2016

585-90

2016 May

1557-3117

<p><strong>BACKGROUND: </strong>Continuous-flow (CF) ventricular assist devices (VADs) have largely replaced pulsatile-flow VADs in adult patients. However, there are few data on CF VADs among pediatric patients. In this study we aimed to describe the overall use, patients' characteristics and outcomes of CF VADs in this population.</p>

<p><strong>METHODS: </strong>The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a national registry for U.S. Food and Drug Adminstration (FDA)-approved VADs in patients &lt;19 years of age. Patients undergoing placement of durable CF VADs between September 2012 and June 2015 were included and outcomes were compared with those of adults from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).</p>

<p><strong>RESULTS: </strong>CF VADs were implanted in 109 patients at 35 hospitals. The median age at implantation was 15 years (2.8 to 18.9 years) and median weight was 62 kg (range 16 to 141 kg). The underlying disease was cardiomyopathy in 89 (82%) patients. The INTERMACS level at time of implant was Level 1 in 20 (19%), Level 2 in 64 (61%) and Levels 3 to 7 in 21 (20%) patients. Most were implanted as LVADs (n = 102, 94%). Median duration of support was 2.3 months (range &lt;1 day to 28 months). Serious adverse event rates were low, including neurologic dysfunction (early event rate 4.1 per 100 patient-months with 2 late events). Competing outcomes analysis at 6 months post-implant indicated 61% transplanted, 31% alive with device in place and 8% death before transplant. These outcomes compared favorably with the 3,894 adults supported with CF VADs as a bridge to transplant.</p>

<p><strong>CONCLUSIONS: </strong>CF VADs are commonly utilized in older children and adolescents, with excellent survival rates. Further study is needed to understand impact of patient and device characteristics on outcomes in pediatric patients.</p>

10.1016/j.healun.2016.01.1228

J. Heart Lung Transplant.

27056612

Favorable Waitlist and Posttransplant Outcomes in Children and Adolescent Patients Supported With Durable Continuous-Flow Ventricular Assist Devices.

2016

2352-9

2016 Aug

1600-6143

<p>Pediatric centers are implanting durable adult continuous-flow ventricular assist devices (CFVADs) in children who are smaller than the industry-recommended size. Waitlist and posttransplant outcomes data in pediatric patients supported with CFVADs as a bridge to transplant are limited. We analyzed the United Network of Organ Sharing and Organ Procurement and Transplantation Network registry to identify patients aged ≤18 years with a CFVAD at the time of listing or transplantation. Patients were stratified by body surface area (BSA; &gt;1.5 vs. ≤1.5 m(2) ) at time of listing. We identified 138 patients with a durable CFVAD during the listing period (100 with BSA &gt;1.5 m(2) , 38 with BSA ≤1.5 m(2) ). Patients with BSA ≤1.5 m(2) were more likely to have a noncardiomyopathy diagnosis (18% vs. 4%, p = 0.007) and to be implanted with a centrifugal-flow rather than an axial-flow device (74% vs. 30%, p = 0.001). There was no difference in failure-free waitlist survival between BSA groups (p = 0.99) among patients with a CFVAD at listing. Posttransplantation survival was 100% and 88% at 1 and 5 years, respectively, for the entire cohort and did not differ by BSA group (p = 0.99). Consequently, waitlist and posttransplant outcomes are favorable for pediatric CFVAD recipients. Small patients (≤1.5 m(2) ) had pre- and posttransplant outcomes similar to those of larger patients that met the industry-recommended size for implantation.</p>

10.1111/ajt.13745

Am. J. Transplant.

26841727

Second annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) report: Pre-implant characteristics and outcomes.

2018

38-45

2018 Jan

1557-3117

<p><strong>BACKGROUND: </strong>Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute-sponsored North American database, provides a platform to understand this emerging population.</p>

<p><strong>METHODS: </strong>Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs.</p>

<p><strong>RESULTS: </strong>Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3-10.0) years for paracorporeal continuous-flow pumps (n = 60), 1.7 (0.4-5.3) years for paracorporeal pulsatile pumps (n = 105), and 15.0 (11.3-16.9) years for implantable continuous-flow pumps (n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high.</p>

<p><strong>CONCLUSIONS: </strong>Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.</p>

10.1016/j.healun.2017.06.017

28965736