Authors: Angela Lorts (1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Christina VanderPluym (2Boston Children’s Hospital, Boston, MA), Iki Adachi (3Texas Children’s Hospital, Houston, TX), Tanya Perry (1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Peta M A Alexander (2Boston Children’s Hospital, Boston, MA), Christopher S Almond (4Stanford University School of Medicine, Palo Alto, CA), Scott R Auerbach (5University of Colorado Denver Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, CO), Ryan P Barbaro (6C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI), Sonya Bhavsar (7Abiomed, J&J, Danvers, MA), Kevin Bourque (8Abbott, Burlington, MA), Jennifer Conway (9Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada), Lara A Danziger-Isakov (1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Ryan R Davies (10University of Texas Southwestern Medical Center, Children’s Health, Dallas, TX), Pirooz Eghtesady (11Washington University, St. Louis Children’s Hospital, St. Louis, MO), Yasutaka Hirata (12Department of Cardiac Surgery, The University of Tokyo Hospital, Tokyo, Japan), Rebecca N Ichord (13Children’s Hospital of Philadelphia, Philadelphia, PA), Robert L Kormos (14Global Medical Affairs Heart Failure, Abbott Laboratories, Austin, TX), Robert Kroslowitz (15Berlin Heart Inc, The Woodlands, TX), Mitchell Krucoff (16Department of Cardiology, Duke University Medical Center, Durham, NC), Jodie Lantz (10University of Texas Southwestern Medical Center, Children’s Health, Dallas, TX), Mary Mehegan (11Washington University, St. Louis Children’s Hospital, St. Louis, MO), Roxana Mehran (17Icahn School of Medicine at Mount Sinai, New York, NY), David L S Morales (1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Jenna Murray (4Stanford University School of Medicine, Palo Alto, CA), Robert A Niebler (18Herma Heart Institute, Children’s Hospital of Wisconsin, Milwaukee, WI), Matthew J O’Connor (13Children’s Hospital of Philadelphia, Philadelphia, PA), Francis D Pagani (19Department of Cardiac Surgery, University of Michigan, Ann Arbor, MI), David M Peng (6C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI), Joseph W Rossano (13Children’s Hospital of Philadelphia, Philadelphia, PA), Ernest Spitzer (20Cardialysis, Rotterdam, the Netherlands; Rotterdam, the Netherlands), Marie E Steiner (21Divisions of Hematology/Oncology and Critical Care, University of Minnesota, Minneapolis, MN), David L. Sutcliffe (22Children’s Mercy Hospital – Kansas City, Kansas City, MO), J Michael Taylor (1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Chet R Villa (1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Peter D Wearden (23Department of Cardiovascular Services, Nemours Children’s Health, Florida, Orlando, FL), David Rosenthal (4Stanford University School of Medicine, Palo Alto, CA)
Categories: Article, Pediatric, Ventricular Assist Device, Adult Congenital Heart, Adverse Event Definitions, ACTION
Source: ASAIO journal (American Society for Artificial Internal Organs : 1992)
Authors: Angela Lorts, Christina VanderPluym, Iki Adachi, Tanya Perry, Peta M A Alexander, Christopher S Almond, Scott R Auerbach, Ryan P Barbaro, Sonya Bhavsar, Kevin Bourque, Jennifer Conway, Lara A Danziger-Isakov, Ryan R Davies, Pirooz Eghtesady, Yasutaka Hirata, Rebecca N Ichord, Robert L Kormos, Robert Kroslowitz, Mitchell Krucoff, Jodie Lantz, Mary Mehegan, Roxana Mehran, David L S Morales, Jenna Murray, Robert A Niebler, Matthew J O’Connor, Francis D Pagani, David M Peng, Joseph W Rossano, Ernest Spitzer, Marie E Steiner, David L. Sutcliffe, J Michael Taylor, Chet R Villa, Peter D Wearden, David Rosenthal
Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries and regulatory evaluation.
Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussion were used as a modified Delphi process.
Nineteen AE types were identified and defined, including 7 new event types and 6 event types that were deleted and will no longer be collected, achieving consensus.
ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD.
Implantable Ventricular Assist Devices (VADs) have been used in short- and long-term applications in adults, and primarily as bridge to transplant in children.^1–4^ Early in device development, adverse event (AE) definitions for clinical trials were agreed upon between the individual device manufacturer and United States Food and Drug Administration (FDA), making comparison among devices problematic. In 2003, the International Society for Heart and Lung Transplantation (ISHLT) developed the earliest VAD registry, followed by the Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) in 2005.^5,6^ These registries provided a foundation for developing consistent adult AE definitions, most recently updated in 2020.^7^
A first set of AE definitions for pediatric VAD use defined for the Pedimacs part of Intermacs in 2016^8^ were modified for use in the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) VAD registry in 2018^9^ but new devices and management strategies in pediatric VAD therapy provide impetus for an update.
ACTION and the Academic Research Consortium (ARC) convened a series of meetings with key stakeholders in this field, including the FDA, pediatric VAD support clinicians (cardiothoracic surgery, cardiology, intensive care, neurology, hematology, and infectious disease nurses and physicians), and industry representatives.
The ARC promotes informed, collaborative discussion to develop and disseminate consensus definitions in targeted medical device fields for the public domain. ACTION is a learning network focused on improving outcomes for children with heart failure, including those with VADs.^10^ One component is the ACTION VAD registry (ACT-VAD), which has enrolled more than 1,600 patients from 48 sites. ACTION registry data adjudication exposed gaps and unclarity, prompting AE definition modifications.
The definitions apply to children with either acquired or congenital heart disease and adults with congenital heart disease (ACHD) supported with implantable and percutaneous ventricular assist devices. Accordingly, references made to pediatric VAD include ACHD patients. Those treated with Extracorporeal Membrane Oxygenation (ECMO), addressed in a separate process, are excluded.
A series of online meetings (one in-person) were conducted between December 2022 and May 2023. All ACTION registry events defined historically from June 2018 to December 2022 were reviewed and discussed with a subset of authors, who drafted modified AE definitions based upon clinical practice and registry adjudication experience. ACTION-ARC iterated these until consensus was achieved singly for each definition and overall.
AE definitions infrequently or never utilized, often pertinent to adult VAD therapy (e.g., myocardial infarction) were identified and eliminated, favoring user-friendliness of data collection in pediatric VAD care over comprehensiveness. Efforts were exerted to ensure compatibility with prior AE definitions wherever possible.
Conversely, important aspects of VAD therapy specific to children or ACHD VAD patients not well captured in prior Pedimacs-ACTION definitions led to creation of new ACTION-ARC AE definitions. (Supplemental Table 1)
Finally, AE severity, relatedness, and resolution, not typically captured in registries, do offer value in clinical trials, a target application for AE definitions. Therefore, ACTION-ARC definitions now include these factors. For severity grades, we used the framework employed by the National Cancer Institute’s Common Terminology Criteria for Adverse Events.^11^
The definition of serious adverse event (SAE) was retained without alteration.
Presented here are the ACTION-ARC consensus pediatric VAD definitions. New additions are shown in Table 1, with comparison to past Pedimacs-ACTION definition shown in Supplemental Table 1. These changes reflect growing experience with VADs and expanded understanding of the unique anatomical and physiologic challenges of VAD in children.
An AE is any untoward medical occurrence in a patient administered a pharmaceutical/therapeutic product, irrespective of whether there is a causal relationship between the occurrence and the therapy.
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, or requires medical or surgical intervention to prevent these consequences. SAEs are a subset of AEs.
Each AE will be graded for seriousness (Table 2), if applicable. Specifics will be defined for each AE below and in Supplementary Table 1. The most severe condition realized during the event should determine the grade assigned.
Each adverse event can be categorized in a case report as either device/procedure-related or patient/treatment-related (Table 3).
Definitions of each AE with grades are presented below and in Supplemental Table 2.
Arrhythmia is an abnormal cardiac rhythm identified at any time after completing the index procedure. Types include atrial (excludes sinus tachycardia), accelerated junctional, and ventricular.
Bleeding is defined as an episode of internal or external bleeding, identified at any time during VAD support after completing the index procedure. Anemia resulting from blood draws does not qualify. Bleed locations include gastrointestinal, nasal/oral, pleural/mediastinal, pericardial, pulmonary, genitourinary, cannula/driveline/percutaneous site, retroperitoneal, and other.
Chylothorax is defined as a pleural effusion with any of the following triglyceride level > 110mg/ml, serum triglyceride concentration < pleural triglyceride concentration, or lymphocyte % count > 80% in the pleural fluid, identified at any time after completing the index procedure.^12^
Device malfunction means the device is not functioning to the manufacturer’s specifications, even if due to user error or human factors (e.g. non-FDA approved accessories leading to overheating or damage), at any time during or after the index procedure. If the device is not yet implanted it is a manufacturer complaint, not an AE.
Each event will have an associated location, type, and grade. Locations of device malfunction include pump, oxygenator, power (e.g., IKUS, C2 Driver, Mobile Driver), accessories (e.g., Flow Probe, Batteries, Monitor), tubing/connectors, and other. Types are (1) mechanical failure- mechanical fault in any component (e.g. controller overheating); (2) structural failure- structural component integrity loss (e.g. membrane or cannula rupture); (3) device or component dysfunction- device not working as expected (e.g. battery not charging); or (4) none- device functioning properly but exchanged due to concern. Of note, a paracorporeal pump or device component replacement unrelated to thrombus will be classified as a device malfunction (e.g. valve or membrane issue). If the exchange is due to pump thrombus with no other malfunction, it will meet the pump thrombus AE definition.
Feeding intolerance occurs when the patient is not taking adequate (per defined individualized patient goal in judgement of treating team) daily caloric demands enterally, identified at any time after 10 days of completing the index procedure. If feeding intolerance occurs in association with a prior GI anatomic abnormality judged to explain the feeding intolerance, this should not be recorded as an AE.
Fontan venous failure is either (1) worsening or ongoing clinical evidence of high venous pressure (e.g. effusions, ascites, lymphatic dysfunction) in the setting of inadequate delivery of preload to the SVAD (calculated CO < 50% expected, unresponsive to pump parameter changes) > 10 days after the index operation; (2) transition to ECMO for right sided failure at any time; or (3) implantation of right sided “Fontan” VAD at any time. If only medical management is required, criteria can be met any time after 10 days of completing the index procedure. These criteria may be identified at any time after the index operation, if right sided VAD or ECMO is needed.
Hemolysis is the presence of any of the following on 2 consecutive, separate lab (1) plasma free Hgb > 50 mg/dl with free-flowing lab draw; (2) LDH > 3x above the upper limit of normal for the implanting center, in the absence of an alternative explanation for the elevation (e.g. infection, hepatic or pulmonary dysfunction, red cell transfusion/transfusion reaction); attribution of the reason for LDH elevation is a judgement by the treating provider; or (3) moderate or greater hemolyzed cells on direct visualization of smear (unrelated to hemolyzed blood products administration).
Hepatic dysfunction is the presence of at least two of the following, on 2 consecutive, separate lab (1) total bilirubin > 3x the upper limit of normal at the implanting center or if elevated prior to implant, 3x baseline (last lab draw before the index operation); (2) coagulopathy (INR >3 and not attributable to antithrombotic therapy, dilution, or Vitamin K deficiency); (3) AST and/or ALT > 3x the upper limit of normal at the implanting center (not attributable to hemolysis, myositis, rhabdomyolysis) or if elevated prior to implant 3x baseline (last lab draw before the index operation); and (4) hepatic encephalopathy, diagnosed by neurologist.
Inadequate hemodynamics is insufficient systemic perfusion and/or ongoing systemic or pulmonary venous congestion, without the presence of device malfunction or pump thrombus, persisting either beyond 10 days from the initial device implantation or resulting in death before 10 days (deemed by the treating provider to be due to inadequate VAD support), after implantation of any combination of VAD (LVAD, RVAD, BIVAD, TAH, or SVAD). The definition requires (1) Ongoing treatment with any vasoactive infusion (excluding any other explanation for the vasoactive medication), including milrinone, and new onset or lack of improvement in pre-existing end-organ dysfunction by 10 days after the index operation. End-organ dysfunction is defined by AE definitions grade 3 and higher, with at least two of the following end-organ AEs respiratory, hepatic, renal, or feeding intolerance; or (2) a failed trial, after 10 days post index operation, of weaning off vasoactive medication even if restarting the vasoactive drug resolved the end-organ dysfunction. This AE should not be utilized if criteria are met for right heart dysfunction (see definition of right heart dysfunction).
Each event will have an associated etiology (attributed by the treating provider): (1) device patient mismatch; device is not providing adequate hemodynamic support for the needs of the patient (e.g. low cardiac output, elevated systemic or venous pressures), but is functioning properly, including submaximal settings set by team for any reason; or (2) implantation/technical issue; technical issue leads to impaired device function (e.g. cannula obstruction by ventricular trabeculation, or intracorporeal outflow graft obstruction).
Types of infections have been defined as (1) Superficial driveline/cannula or peripheral cannulation site infection; blood culture must be negative (if done) with presence of either purulence from the driveline/cannula/percutaneous site with or without positive culture OR pain, erythema, or induration at driveline/cannula/percutaneous site; (2) deep percutaneous driveline/cannula or peripheral cannulation site infection; must meet the criteria for superficial driveline infection and in addition have at least two of the following fluid collection at driveline/cannula/percutaneous site with or without positive culture, imaging study consistent with deep infection (e.g. fluid collection or findings consistent with infection along the path of the lead), or signs or symptoms such as fever, leukocytosis, tachycardia, or systemic inflammatory response; (3) device-specific bloodstream positive blood culture associated with signs and symptoms of systemic inflammatory response and one of the deep percutaneous driveline/cannula or peripheral cannulation site infection, positive blood culture from the device circuit, persistently positive blood culture with the same organism >72 hours apart, OR radiographic or echocardiographic evidence of vegetation or thrombus of the intravascular aspect of the device component; and (4) sternal wound infection with extension into the mediastinum; an infection that involves the external components of the pump (e.g. cannulas for paracorporeal devices or external housing for intracorporeal devices) must have *all of the * positive culture from the tissue or fluid collection surrounding the external surface of the pump or cannula, AND signs and symptoms of infection such as fever, leukocytosis, tachycardia, or other signs of systemic inflammatory response.
Non-device related infection is characterized by an infectious episode that does not meet the criteria for device related infection, identified at any time after completing the index procedure. Each event will have an associated type of infection and grade.
Types of non-device related infections (1) viral upper/lower respiratory infection; (2) viral gastroenteritis; (3) sternal wound infection without extension into mediastinum; involves the superficial mediastinal or thoracotomy wound involving the skin, subcutaneous tissue and muscle at surgical site; (4) pneumonia; characteristic radiographic abnormalities and clinical findings; (5) urinary tract infection; clinical suspicion and positive culture; or (6) other.
Necrotizing enterocolitis is diagnosed if both of the following criteria are (1) intestinal dilation, pneumatosis intestinalis, pneumoperitoneum or portal gas on abdominal imaging; and (2) two or more of the temperature instability, apnea, bradycardia, grossly bloody stool, thrombocytopenia or DIC deemed by the treating team to be abdominal in origin, and abdominal distension with or without tenderness.^13^
NEC may be identified at any time after completing the index procedure. Each event will have an associated grade.
Overt neurological event occurs when any of the following (1) neurological exam findings are discovered and are associated with abnormal neuroimaging or pathology; (2) neurological exam findings are present for >24 hours (documented in medical record by a neurologist) but neuroimaging and/or pathology is negative; or (3) neurological exam findings are present for >24 hours (documented in medical record by a neurologist) but neuroimaging is unable to be obtained. Of note, in pediatrics, signs and symptoms may be non-localizing. If there is discordance between the neuroimaging and exam findings, this will be regarded as a single event (e.g. if the patient has a left sided weakness but the imaging shows an infarct distribution that does not correlate). Covert neurological event occurs when neurological exam findings are not present, but injury is detected by abnormal neuroimaging or pathology. This includes incidental findings on surveillance imaging.
Types of Neurological Events (1) ischemic Stroke; ischemic stroke or hemorrhagic conversion from an initial ischemic stroke; (2) intracerebral hemorrhage (blood in the brain or spinal cord); may be intraventricular, parenchymal, or spinal cord; (3) extra-axial Hemorrhage (blood around the brain or spinal cord); may be epidural, subdural or subarachnoid; (3) undefined Type; an overt injury but no neuroimaging obtained or negative; (4) hypoxic ischemic encephalopathy; new encephalopathy attributed to hypoxia or cerebral hypoperfusion, with supporting findings such as diffuse encephalopathy without focal neurologic exam findings or pathology and/or neuroimaging in a non-vascular distribution; (5) encephalopathy (other); non-focal neurological exam findings that may be associated with many patient-associated factors, must have a neurology consultation and documentation in medical record (e.g. Fontan with Fontan Associated Liver Disease (FALD) that leads to encephalopathy post procedure); and (6) neuropathy; neuropathy due to a mechanical complication of a transcatheter placed VAD, including femoral, sciatic, or brachial injury.
To assess stroke severity, the Pediatric Cerebral Performance Category (PCPC) scores will be used.^14^ The PCPC can be measured retrospectively from medical chart review from baseline (prior to event) and at a defined time (e.g. discharge). Scoring of the PCPC is summarized in Table 4. Severity of stroke sequelae is assessed by calculating the difference from the baseline score and the score at hospital discharge. This change indicates the severity of the sequelae as (1) no change from no change in PCPC; (2) moderate 1 point increase in PCPC; (3) severe 2 or more-point increase in PCPC; or (4) PCPC 6 or brain death.
Pump thrombus is the presence of clinically significant thrombus within any component of the VAD system, including internal and external components, and tubing/connectors if applicable, identified at any time during VAD support after completing the index procedure. Each event will have an associated type, device component(s), and grade.
Pump thrombus includes two types. The first type is paracorporeal/transcatheter device and components. Pump thrombus AE criteria will be met if a component or pump exchange is performed with the reason for exchange being related to thrombus/fibrin formation, documented in the medical record by the treating provider. Multiple device components can be exchanged during one procedure and count as one AE. Of note, paracorporeal device exchange will be categorized as pump thrombus if the pump is exchanged due to thrombus/fibrin, but the pump is functioning appropriately. If the device is not functioning appropriately, the exchange will qualify as a device malfunction AE.
The second pump thrombus type is intracorporeal devices. Pump thrombus AE criteria will be met if reason for exchange is secondary to two or more of the (1) unexpected device function or parameter changes outside of normal variability attributed to thrombus by the treating provider, (2) signs of inadequate cardiovascular support or an embolic event that is attributed to thrombus by the treating provider, (3) hemolysis that is attributed to thrombus in the device by the treating provider, and (4) confirmed thrombus in an intracorporeal device, by direct visualization after explant and/or by non-invasive imaging. Multiple AE definitions may be met (e.g. if there is hemolysis leading to concern for pump thrombus and pump exchange, the AE criteria for hemolysis may be met as well).
Device Component(s) may include any of the pump, tubing, connectors, or cannula.
Renal dysfunction is an abnormality of either of the laboratory values listed as follows, with the abnormality present on 2 consecutive, separate lab creatinine or GFR calculated by either Cystatin C or modified Schwartz or CKiD, and can be identified at any time after completing the index procedure.^15^ Each event will have an associated grade and chronicity. Acute renal dysfunction is defined as <90 days in duration, while chronic renal dysfunction persists for at least 90 days.
*Baseline = last lab draw, before the index operation
Respiratory dysfunction is an impairment of respiratory function, unrelated to a diagnostic or therapeutic procedure, necessitating the use of new positive pressure ventilation (non-invasive or invasive) or escalation of MCS (e.g. ECMO, oxygenator) after completing the index operation. This must be identified >10 days after completing the index procedure unless the patient needs ECMO for respiratory failure, an oxygenator, or tracheostomy, which will qualify as a respiratory AE at any time following the index procedure. Each event will have an associated grade.
Right heart dysfunction is defined as one finding from both the hemodynamics and imaging categories as follows, >72 hours after the index operation, without the presence of device malfunction or thrombus. (1) Hemodynamics: right sided or systemic venous filling pressure elevated above 14 mmHg for >24 hours OR clinical evidence of high central venous pressure (e.g. effusions, ascites, hepatomegaly) in the setting of inadequate delivery of preload to the LVAD (calculated CO that is <50% expected, not responsive to pump parameter changes). (2) Imaging: > moderate/severe tricuspid regurgitation, OR > moderately/severely reduced right ventricular systolic function, documented in medical record. Alternatively, criteria can be met by one of the following events at any time after the index procedure, in the absence of device malfunction or pump transition to ECMO (for right sided dysfunction) or implantation of an RVAD.
These criteria are met any time after the index procedure, if RVAD or ECMO is needed. If only medical management is required, criteria can be met any time > 10 days after completing the index procedure. Each event will have an associated grade.
Vascular access site injury is defined as the development of any injury related to the percutaneous or surgical access to a blood vessel used for percutaneous VAD support. This AE pertains only to devices inserted through the percutaneous route. Do not use this AE definition to describe vascular injuries unrelated to cannulation. This AE may be identified at any time after leaving the index procedure OR/catheterization laboratory.
Each event will have an associated type and grade. Types of vascular injury include cardiac or caval perforation, pneumothorax from penetrating injury, pseudo-aneurysm, arteriovenous fistula, vessel thrombosis, vessel dissection, vessel stenosis, cannulation site bleeding and limb hypoperfusion/ischemia. Peripheral neuropathy is categorized as a neurological AE.
Vasoplegia is the presence of an abnormally low systemic vascular resistance as deemed by treating provider, not otherwise explained by sepsis or medication toxicity. In addition to low systemic vascular resistance, one additional finding must be met within 72 hours after the index procedure, in the presence of a properly functioning VAD. These additional criteria include either (1) severe hypotension for age, with an elevated or normal device flow (CI > 2.4 L/min/m^2^) directly measured or calculated by device and without alternate cause (e.g. bleeding, sepsis, right heart dysfunction, anaphylaxis, anatomic issues) OR (2) end-organ hypoperfusion and new end-organ dysfunction (as defined by the AE definitions grade 3 and higher). Criteria may be identified within 72 hours of completing the index procedure. Each event will have an associated grade.
AE definitions presented here reflect consensus among experts representing diverse interests and perspectives in this field. They are freely available for use in clinical registries and trials with appropriate attribution.
These definitions reflect current pediatric VAD care, including the growing use of VADs in univentricular heart disease, the expanded use of percutaneous VADs, and the new patient-device interactions and nuances in AE analysis by pediatric clinicians with VAD patients. A new addition to each AE definition is a severity grade. Where relevant, AE relatedness to device, procedure, patient, or treatment is considered.
AE definitions from the prior system rarely or never utilized have been removed in interests of minimizing data collection burden and critically missing AEs have been added, acknowledging the importance of data collection efficiency, particularly in the context of clinical registries.
In order to make the definitions as broadly applicable as possible, we removed time-based exclusions that were previously used in Pedimacs and ACTION registries for some AEs that occur very frequently and transiently after implantation. This applies to hemolysis, hepatic dysfunction, renal dysfunction AEs which previously were not applicable within the first 72 hours. Individual data collection settings may have different needs, and in some cases the time windows may still serve a useful purpose. They may be implemented at the discretion of the investigators.
We acknowledge the seminal importantance of clinician contributors to Pedimacs and ACTION registries, and it is our expectation and hope that pediatric VAD support growth and experience with these new AE definitions leads to future refinement and succession by revision(s). We hope these definitions will be widely utilized without restriction, promoting consistency. We have prepared a standard set of case report forms for data entry, which will be available by license only. For additional information, please Info@Actionlearningnetwork.org.