Robert A. Niebler

Berlin Heart EXCOR Pediatric Ventricular Assist Device for Bridge to Heart Transplantation in US Children

Background— Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection. Methods and Results— This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1–435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death. Conclusions— Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

Antithrombin Replacement During Extracorporeal Membrane Oxygenation

Heparin remains the predominant anticoagulant during extracorporeal membrane oxygenation (ECMO). Heparin acts by potentiating the anticoagulant effect of antithrombin (ATIII). Acquired ATIII deficiency, common in pediatric patients requiring ECMO, may result in ineffective anticoagulation with heparin. ATIII replacement may result in increased bleeding. Our objective is to determine ATIIIs effect on anticoagulation and blood loss during ECMO. A retrospective chart review was performed of all patients at Childrens Hospital of Wisconsin who received ATIII while supported on ECMO in 2009. ATIII activity levels, heparin drip rate, and activated clotting times (ACT) were compared before, 4, 8, and 24 h after ATIII administration. Chest tube output and packed red blood cell (pRBC) transfusion volume were compared from 24 h before ATIII administration to 24 h after. Twenty-eight patients received ATIII as a bolus dose during the course of 31 separate times on ECMO support. The median age of these patients was 0.3 years (range 1 day-19.5 years). ATIII activity increased significantly at 8 and 24 h after administration. No significant difference was noted in heparin drip rate, ACT levels, chest tube output, or pRBC transfusion volume. ATIII administration resulted in higher ATIII activity levels for 24 h without a significant effect on heparin dose, ACT, or measures of bleeding.

Activated recombinant factor VII for refractory bleeding during extracorporeal membrane oxygenation.

Objective: To determine the frequency of adverse events with the use of activated recombinant factor VII during extracorporeal membrane oxygenation support and to quantify the effect on bleeding parameters. Design: Retrospective case series from January 1999 to August 2006. Setting: Pediatric intensive care unit at a tertiary academic childrens hospital. Patients: Seventeen patients received a total of 26 doses of activated recombinant factor VII while supported on extracorporeal membrane oxygenation or within 3 hrs of initiation of extracorporeal membrane oxygenation support from February 2003 to August 2006, and 23 historical controls from January 1999 to December 2002 with bleeding complications reported to the Extracorporeal Life Support Organization database while supported on extracorporeal membrane oxygenation before the use of activated recombinant factor VII. Interventions: None. Measurements and Main Results: No significant difference in the rate of thromboembolic complications, extracorporeal membrane oxygenation circuit failures, or mortality was found between the patients and historical controls. No trend toward increased survival was found, and a significant number of circuit complications was seen in both groups. In patients treated with activated recombinant factor VII, a significant reduction in chest tube output and blood product transfusion rates was seen within 5 hrs of activated recombinant factor VII administration. Conclusion: Activated recombinant factor VII administration during extracorporeal membrane oxygenation support was associated with a decrease in bleeding severity (indicated by chest tube output and blood product transfusion rates) and was not associated with an increased rate of thromboembolic complications.

Use of a HeartWare Ventricular Assist Device in a Patient With Failed Fontan Circulation

We present a successful case of the use of a HeartWare ventricular assist device as a bridge to transplantation in an 11-year-old with a hypoplastic left heart and failed Fontan circulation.

Thromboelastography in the assessment of bleeding following surgery for congenital heart disease.

Background: Perioperative bleeding is common in pediatric cardiac surgery patients. Traditional laboratory tests do not adequately characterize coagulation derangements in patients with bleeding. We sought to establish preoperative thromboelastography parameters in children prior to cardiopulmonary bypass, to compare thromboelastography assessment with standard coagulation parameters postoperatively, and to assess thromboelastography in children with significant hemorrhage. Methods: Sixty patients requiring cardiopulmonary bypass were enrolled in a prospective observational study of perioperative thromboelastography. Thromboelastography measures were obtained preoperatively, intraoperatively after protamine administration, upon admit to the intensive care unit, and when patients were treated for bleeding. Thromboelastography measures were not used for clinical care. Postoperative thromboelastography measurements were compared with the standard coagulation parameters. Intraoperative thromboelastography, postoperative thromboelastography, and clinical outcomes were compared among patients who did and did not have significant postoperative bleeding. Results: Preoperative thromboelastography parameters were similar to other published normal values for pediatric patients. Transfusion recommendations based on thromboelastography measurements were significantly different from those based on the standard coagulation testing. Thromboelastography measures after initial protamine administration were significantly different in patients with postoperative bleeding. This difference was not present upon arrival to the intensive care unit. Patients with significant bleeding tended to cease bleeding when clinical interventions were in agreement with recommendations based on thromboelastography. Conclusions: Pediatric patients with significant postoperative bleeding after surgery are more likely to have abnormal thromboelastography early after cessation of cardiopulmonary bypass. Thromboelastography illustrates derangements in the coagulation system and may aid in the treatment of postoperative bleeding.

Ventricular Assist Device in Single-Ventricle Heart Disease and a Superior Cavopulmonary Anastomosis

Our objective is to describe the use of a ventricular assist device (VAD) in single-ventricle patients with circulatory failure following superior cavopulmonary anastomosis (SCPA). We performed a retrospective chart review of all single-ventricle patients supported with a VAD following SCPA. Implantation techniques, physiologic parameters while supported, medical and surgical interventions postimplant, and outcomes were reviewed. Four patients were supported with an EXCOR Pediatric (Berlin Heart Inc., The Woodlands, TX, USA) following SCPA for a median duration of 10.5 days (range 9-312 days). Selective excision of trabeculae and chords facilitated apical cannulation in all patients without inflow obstruction. There were two pump exchanges in the one patient supported for 312 days. Two patients were evaluated by cardiac catheterization while supported. Three of four patients were successfully bridged to transplantation. One patient died while supported. All patients had significant bleeding at the time of transplantation, and one required posttransplant extracorporeal membrane oxygenation with subsequent full recovery. VAD support can provide a successful bridge to transplantation in patients with single-ventricle circulation following SCPA. A thorough understanding of the challenges encountered during this support is necessary for successful outcomes.

Bleeding and thrombotic emergencies in pediatric cardiac intensive care: unchecked balances.

Children in the cardiac intensive care unit (CICU) with congenital or acquired heart disease are at risk for hematologic complications, both hemorrhage and thrombosis. The overall incidence of hematologic complications in the CICU is unknown, but risk factors and target groups have been identified where the essential physiologic balance between bleeding and clotting has been disrupted. Although the best management of life-threatening bleeding and clotting is prevention, the cardiac intensivist is often faced with managing life-threatening hematologic events involving patients from within the unit or those who present from outside. Part I of this review deals with the propensity of children with congenital and acquired heart disease to complications of both bleeding and clotting, and includes discussions of perioperative bleeding, thromboses in single-ventricle patients, clotting of Blalock-Taussig shunts and thrombotic complications of mechanical valves. Part II deals with the subject of stroke in children with heart disease. Part III reviews monitoring the effectiveness of anticoagulation and thrombolysis in the CICU. Currently available diagnostics modalities, medications and management strategies are reviewed and future directions discussed.

HeartWare Ventricular Assist Device Implantation in Patients With Fontan Physiology

We aim to describe the clinical course of a series of patients with hypoplastic left heart syndrome and refractory systolic heart failure supported with a HeartWare ventricular assist device (HVAD) following Fontan palliation. This is a retrospective review of three consecutive patients supported with a HVAD following Fontan palliation through February 2016. Data include patient characteristics, operative variables, postimplantation hemodynamic/device parameters, event outcomes, and duration of HVAD support. Patient ages were 11.7, 13.5, and 17.5 years, respectively, at the time of HVAD implant. The duration of HVAD support was 148, 272, and 271 days, respectively, of which 86, 222, and 211 were outpatient days. Inflow cannula position was the morphologic right ventricle with depth adjustment and manipulation of the tricuspid subvalvar apparatus to ensure good inflow. Echocardiographic, hemodynamic, and noninvasive oximetric monitoring resulted in high RPM settings for all patients. Despite various complications, all patients were successfully transplanted and discharged home alive. We present three patients bridged to transplantation using the HVAD following Fontan palliation. We demonstrate potential for durable support with transition to outpatient care while awaiting heart transplantation in a subset of patients status post Fontan surgery.

Mechanical Circulatory Support of the Fontan Patient

Because of the inadequacies inherent to a circulation supported by a single ventricle, many Fontan patients will experience failure of their circulation. To date, there is no medical regimen that reliably and consistently restores circulatory function in these patients. Because of the shortage of donor organs and the fact that many of these patients present with features that either preclude or render heart transplantation a high risk, there is an intense need to better understand how mechanical circulatory support (MCS) may benefit these patients. In this report, we share our experience of successful MCS and transplantation of three patients. Our experience and that of others is very encouraging, but also preliminary. In general, a systemic ventricular assist device, with or without a Fontan fenestration, is a reasonable consideration for a patient presenting with predominantly systolic dysfunction. A pulmonary/systemic venous assist device may be sufficient for the patient with preserved systolic function and failure of the systemic venous/lymphatic system; however, this remains speculative. The more comprehensive approach of a total artificial heart or bilateral support is attractive in theory, but beset by the need for a more complex operation. In all scenarios, early referral, before organ failure, is paramount to successful MCS.

A Pilot Study of Antithrombin Replacement Prior to Cardiopulmonary Bypass in Neonates

Neonates have low levels of antithrombin. Inadequate anticoagulation during cardiopulmonary bypass (CPB) due to low antithrombin activity may result in a poor preservation of the coagulation system during bypass. We hypothesize that antithrombin replacement to neonates prior to CPB will preserve the hemostatic system and result in less postoperative bleeding. A randomized, double-blinded, placebo-controlled pilot study of antithrombin replacement to neonates prior to CPB was conducted. Preoperative antithrombin levels determined the dose of recombinant antithrombin or placebo to be given. Antithrombin levels were measured following the dosing of the antithrombin/placebo, after initiation of bypass, near the completion of bypass, and upon intensive care unit admission. Eight subjects were enrolled. No subject had safety concerns. Mediastinal exploration occurred in two antithrombin subjects and one placebo subject. Antithrombin activity levels were significantly higher in the treated group following drug administration; levels continued to be higher than preoperatively but not different from the placebo group at all other time points. Total heparin administration was less in the antithrombin group; measurements of blood loss were similar in both groups. A single dose of recombinant antithrombin did not maintain 100% activity levels throughout the entire operation. Although no safety concerns were identified in this pilot study, a larger trial is necessary to determine clinical efficacy.