Melody Valve in Aortic Position to Facilitate Mechanical Circulatory Support as a Bridge to Cardiac Transplantation.

We report a patient with congenital heart disease and end stage heart failure after interventions for congenital heart disease resulting in aortic regurgitation that could not be treated with mechanical support to bridge to transplantation. We used a Melody valve (Medtronic Inc, Minneapolis, MN) in aortic position to achieve aortic competence to allow use of a left ventricular assist device to bridge the patient successfully to cardiac transplantation.

Antithrombotic therapy in pediatric ventricular assist devices: Multicenter survey of the European EXCOR Pediatric Investigator Group.

OBJECTIVES: Mechanical circulatory support for pediatric heart failure patients with the Berlin Heart EXCOR ventricular assist system is the only approved and established bridging strategy for recovery or heart transplantation. In recent years, the burden of thromboembolic events has led to modifications of the recommended antithrombotic therapy. Therefore, we aimed to assess modifications of antithrombotic practice among the European EXCOR Pediatric Investigator Group members. METHODS: We sent a questionnaire assessing seven aspects of antithrombotic therapy to 18 European hospitals using the EXCOR device for children. Returned questionnaires were analyzed and identified antithrombotic strategies were descriptively compared to "Edmonton protocol" recommendations developed for the US EXCOR pediatric approval study. RESULTS: Analysis of 18 received surveys revealed substantial deviations from the Edmonton protocol, including earlier start of heparin therapy at 6-12 h postoperatively and in 50% of surveyed centers, monitoring of heparin effectiveness with aPTT assay, administering vitamin K antagonists before 12 months of age. About 39% of centers use higher international normalized ratio targets, and platelet inhibition is changed in 56% including the use of clopidogrel instead of dipyridamole. Significant inter-center variability with multiple deviations from the Edmonton protocol was discovered with only one center following the Edmonton protocol completely. CONCLUSION: Current antithrombotic practice among European EXCOR users representing the treatment of more than 600 pediatric patients has changed over time with a trend toward a more aggressive therapy. There is a need for systematic evidence-based evaluation and harmonization of developmentally adjusted antithrombotic management practices in prospective studies toward revised recommendations.

Closing the gap in paediatric ventricular assist device therapy with the Berlin Heart EXCOR® 15-ml pump.

OBJECTIVES: The Berlin Heart EXCOR ® (EXCOR) paediatric ventricular assist device is used worldwide for mechanical support of infants and small children with end-stage heart failure. A clinically important gap between the smallest EXCOR blood pump (10 ml) and the next larger size (25 ml) limited the choice of pump size in patients with a body surface area (BSA) between 0.33 and 0.5 m 2 . We present the first clinical experience from the early product surveillance (EPS) of the new EXCOR 15-ml blood pump. METHODS: After CE and U.S. Food and Drug Administration approval in January 2013, 20 patients with a mean age of 1.6 years (range 0.5-3.5 years) and a mean BSA of 0.45 m 2 (range 0.33-0.59 m 2 ) were enrolled in the EPS. The main diagnosis was idiopathic cardiomyopathy in 13 patients; the majority ( n = 16) of children were in INTERMACS level 1 or 2. Data from high-volume paediatric transplant centres were collected prospectively for a defined follow-up period of 60 days after device implantation. RESULTS: Mean time on the EXCOR 15-ml blood pump was 43 days; the survival rate was 100% at the end of the EPS period. Seven patients underwent a heart transplant from the device; 2 children were weaned; and 11 patients remained on support. Infection of cannula exit sites occurred in 3 patients. Two patients had minor thromboembolic strokes but made a complete neurological recovery. CONCLUSIONS: The new EXCOR 15-ml blood pump demonstrated optimal ventricular assist device support of children with a BSA of 0.33-0.5 m 2 .

Right ventricular dysfunction in children supported with pulsatile ventricular assist devices.

OBJECTIVES: To describe the incidence and severity of right ventricular dysfunction (RVD) in pediatric ventricular assist device (VAD) recipients and to identify the preoperative characteristics associated with RVD and their effect on outcomes. METHODS: Children bridged to transplantation from 2004 to 2011 were included. RVD was defined as the use of a left VAD (LVAD) with an elevated central venous pressure of >16 mm Hg with inotropic therapy and/or inhaled nitric oxide for >96 hours or biventricular assist (BiVAD). RESULTS: A total of 57 children (median age, 2.97 years; range 35 days to 15.8 years) were supported. Of the 57, 43 (75%) had an LVAD, and of those, 10 developed RVD. The remaining 14 (25%) required BiVAD. Thus, RVD occurred in 24 of 57 patients (42%). Preoperative variables such as younger age (P = .01), use of extracorporeal mechanical support (P = .006), and elevated urea (P = .03), creatinine (P = .02), and bilirubin (P = .001) were associated with RVD. Multiple logistic regression analysis indicated that elevated urea and extracorporeal mechanical support (odds ratio, 26.4; 95% confidence interval, 2.3-307.3; and odds ratio, 27.8; 95% confidence interval, 2.5-312.3, respectively) were risk factors for BiVAD. The patients who developed RVD on LVAD had a complicated postoperative course but excellent survival (100%), comparable to those with preserved right ventricular function (91%). The survival for those requiring BiVAD was reduced (71%). CONCLUSIONS: RVD occurred in approximately 40% of pediatric VAD recipients and affects their peri-implantation morbidity and bridging outcomes. Preoperative extracorporeal membrane oxygenation and elevated urea were risk factors for BiVAD. Additional studies of the management of RVD in children after VAD implantation are warranted.

A longer waiting game: bridging children to heart transplant with the Berlin Heart EXCOR device--the United Kingdom experience.

BACKGROUND: Mechanical circulatory support (MCS) is used to support children with end-stage heart failure to heart transplant. METHODS: This was a retrospective cohort study of 7 years' experience with the Berlin Heart (BH) EXCOR (Berlin Heart AG, Berlin Germany) paracorporeal ventricular assist device (VAD) in 2 United Kingdom (UK) pediatric heart transplant centers and the effect of this program on the UK pediatric heart transplant service. RESULTS: Of 102 children who received BH support, 84% survived to transplant or BH explant and 81% survived to discharge. Neither age nor duration of support influenced outcome. Stroke, ongoing requirement for ventilation while on BH, and diagnosis other than dilated cardiomyopathy were the only independent mortality risk factors. Children who weighed < 20 kg had significantly (p = 0.03) longer support times than bigger children. The number of children treated with a BH increased over time (p = 0.01). Currently > 50% of pediatric heart transplants are bridged with a BH; however, pediatric transplants per year have not increased significantly (p = 0.07) CONCLUSIONS: BH use in the UK has allowed significant increases in the number of children with end-stage heart failure who can be successfully bridged to transplant and the length of time they can be supported. The total number of transplants has not increased.

Successful mechanical circulatory support for 251 days in a child with intermittent severe neutropenia due to Barth syndrome.

Barth syndrome is an X-linked recessive disorder that is characterized by cardiomyopathy, variable neutropenia, skeletal myopathy, growth delay, and organic aciduria. The cardiac involvement typically results in a high risk of severe heart failure in infancy or early childhood. While Berlin Heart EXCOR is widely accepted as ventricular assistance in pediatric patients with end-stage cardiac failure, infections remain a frequent and potentially severe complication. Therefore, the extended use of the device in the setting of intermittent or severe neutropenia is challenging. We present the case of a three-yr child with Barth syndrome who was bridged successfully to transplant with a Berlin Heart EXCOR assist device for eight months (251 days) without major infectious complication, despite several episodes of severe neutropenia. This case demonstrates that prolonged mechanical circulatory support for a patient with neutropenia is feasible without important morbidity, with careful monitoring and a multidisciplinary approach. G-CSF provides an excellent support in managing neutropenia.

Mechanical bridging to orthotopic heart transplantation in children weighing less than 10 kg: feasibility and limitations.

OBJECTIVE: Infants and young children are considered the most difficult group to bridge to orthotopic heart transplantation (OHT) and data regarding outcomes are scarce. METHODS: We reviewed our patients ≤ 10 kg with those who were bridged to OHT using ventricular assist device (VAD) Berlin Heart (BH) Excor ± extracorporeal membrane oxygenation (ECMO) between 2004 and 2009. RESULTS: Eleven children ≤ 10 kg with end-stage heart failure (cardiomyopathy or myocarditis) were treated with VAD as bridge to OHT: the median weight was 8.0 (range 3.9-10.0 kg)kg and median age was 12.3 (range 1.2-33.9 months) months. Five (45%) required ECMO support pre-BH and six were on mechanical ventilation and inotropes. In 9/11 (82%), the support mode was left ventricular assist device (L-VAD) (all alive): one of two patients needing Bi-VAD support died. On BH, the median support time was 27 days and time to extubation was 8 days. Two out of 11 (18%) suffered strokes confirmed on brain imaging; both recovered and one underwent resection of infarcted small bowel. Ten out of 11 (91%) were transplanted, one remains in hospital and nine are at home in good health. When compared to patients >10 kg bridged with BH (n = 15), the mortality (p = 0.51) and rates of neurological complications (p = 0.54) were similar. Post-transplant recovery (ventilation times and time to home discharge) was similar between the bridged children ≤ 10 kg and non-bridged children ≤ 10 kg who underwent OHT. CONCLUSIONS: Mechanical bridging to transplantation is clinically feasible in children ≤ 10 kg, achieving excellent outcomes. Judicious use of VADs in smaller children will optimise the use of donor organs; however, the effect on overall OHT waiting times, if mechanical bridging was extended to a large number of small children, is unknown.

Impact of rapid leukodepletion on the outcome of severe clinical pertussis in young infants.

OBJECTIVES: Bordetella pertussis is a common, underrecognized, and vaccine-preventable cause of critical illness with a high mortality in infants worldwide. Patients with severe cases present with extreme leukocytosis and develop refractory hypoxemia and pulmonary hypertension that is unresponsive to maximal intensive care. This may reflect a hyperviscosity syndrome from the raised white blood cell (WBC) count. Case reports suggest improved outcomes with exchange transfusion to reduce the WBC count. Our objective was to quantify possible benefits of aggressive leukodepletion. METHODS: We, as a regional PICU and extracorporeal membrane oxygenation referral center, adopted a strategy of aggressive leukodepletion in January 2005. The impact of this strategy on crude and case mix-adjusted survival of all infants who were critically ill with B pertussis were compared with control subjects from January 2001 to December 2004 and Extracorporeal Life Support Organisation registry data. RESULTS: Nineteen infants (7 [37%] boys) received intensive care for B pertussis from 2001 to 2009. Admission WBC counts were equivalent in 2 time periods: 2001-2004 (mean: 52,000/µL) and 2005-2009 (mean: 75,000/µL). In 2001-2004, 5 (55%) of 9 patients survived the ICU. Between 2005 and 2009, 9 (90%) of 10 patients survived. When case-mix adjustment for age, WBC count, and extracorporeal membrane oxygenation referral were considered, the 2001-2004 predicted survival (4.4 [49%] of 9.0) was equivalent to the observed mortality (4.0 [44%] of 9.0). Between 2005 and 2009, observed mortality (1.0 [10%] of 10.0) was significantly better than predicted (4.7 [47%] of 10.0). CONCLUSIONS: Leukodepletion should be considered in critically ill infants with B pertussis and leukocytosis.

Extracorporeal membrane oxygenation and term neonatal respiratory failure deaths in the United Kingdom compared with the United States: 1999 to 2005.

OBJECTIVE: To compare national neonatal extracorporeal membrane oxygenation data and deaths from primary respiratory disorders of term neonates between the United Kingdom and the United States from 1999 to 2005. DESIGN: Cross-sectional study. SETTING: National data sets from the United Kingdom and the United States. PATIENTS: Neonatal extracorporeal membrane oxygenation patients submitted to the Extracorporeal Life Support Organization Registry and national birth and death registrations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Meconium aspiration syndrome was the most common indication for extracorporeal membrane oxygenation in the United Kingdom: 50.6% vs. 25.8% in the United States (p < .001). Congenital diaphragmatic hernia was most common indication for extracorporeal membrane oxygenation in the United States: 30.7% vs. 15.4% in the United Kingdom (p < .001).Extracorporeal membrane oxygenation use was greater in the United States than the United Kingdom: rate ratio, 1.81 (95%, confidence interval, 1.64, 2.00). The extracorporeal membrane oxygenation rate decreased over time in the United States (p < .001) but was unchanged for all diagnoses in the United Kingdom (p = .49). The rates of extracorporeal membrane oxygenation use for meconium aspiration syndrome were equivalent in both countries: rate ratio, 0.92 (95% confidence interval, 0.80, 1.07) but greater in the United States for congenital diaphragmatic hernia: rate ratio, 3.60, (95% confidence interval, 2.82, 4.66) and persistent pulmonary hypertension newborn: rate ratio, 4.67 (95% confidence interval, 3.33, 6.74).National neonatal death rates included nonextracorporeal membrane oxygenation + extracorporeal membrane oxygenation death. Meconium aspiration syndrome deaths were equivalent overall between the two countries: rate ratio, 0.99 (95% confidence interval, 0.77, 1.29), but decreased in the United States (p < .001) although not in the United Kingdom (p = .17). Congenital diaphragmatic hernia deaths were more prevalent in the United Kingdom than in the United States: rate ratio, 1.57 (95% confidence interval, 1.34, 1.84). CONCLUSIONS: Extracorporeal membrane oxygenation is used more often in the United States: clinicians seem less willing to offer extracorporeal membrane oxygenation for persistent pulmonary hypertension of the newborn and congenital diaphragmatic hernia in the United Kingdom. In contrast to the United States, no reduction in either extracorporeal membrane oxygenation use or death due to meconium aspiration syndrome was observed in the United Kingdom. Early transfer to a tertiary center is recommended for term neonates with respiratory failure.

Subcutaneous low molecular weight heparin for management of anticoagulation in infants on excor ventricular assist device.

Anticoagulation in infants and children on a ventricular assist device presents particular challenges. Unfractionated heparin has poor bioavailability; it can be difficult to achieve a stable anticoagulant effect; and, in the long-term, there is a risk of osteopenia. Long-term warfarin can be difficult to manage in infants on formula milk with vitamin K supplementation. We review our recent experience with subcutaneous low molecular weight heparin. Two patients received a left ventricular assist device (Excor, Berlin Heart AG) as a bridge to transplantation. Initial anticoagulation consisted of unfractionated heparin infusion beginning 6 hours after implantation to maintain an activated partial thromboplastin time of 70 seconds, checked every 4 to 6 hours. Platelet count (aim >80,000/microl) and thromboelastography were assessed daily. Antithrombin required substitution to maintain levels >70 IU/dl. To optimize anticoagulation, both infants were switched to subcutaneous low molecular weight heparin twice daily aiming for an anti-Xa activity between 0.5 and 1.0 IU/ml. Aspirin was added on day 4, checking platelet aggregation every 2 to 4 days, aiming at arachidonic acid stimulated aggregation 10% to 30% of baseline, collagen 100% of baseline. Dipyridamole was added once stability was reached if platelets count exceeded 150,000/microl. There were no clinical thromboembolic or bleeding events. Both patients had successful transplantation.

Sequential use of extracorporeal membrane oxygenation and the Berlin Heart Left Ventricular Assist Device for 106-day bridge to transplant in a two-year-old child.

We describe a 2 year-old girl with end-stage dilated cardiomyopathy in whom extracorporeal membrane oxygenation (ECMO) was used for mechanical cardiac assistance. After 4 weeks, ECMO-related complications necessitated change to a Berlin Heart Left Ventricular Assist Device (LVAD), and she received a successful cardiac transplant after a total of 106 days on mechanical cardiac support.

A wet-primed extracorporeal membrane oxygenation circuit with hollow-fiber membrane oxygenator maintains adequate function for use during cardiopulmonary resuscitation after 2 weeks on standby.

OBJECTIVE: To assess the durability of wet-preprimed extracorporeal membrane oxygenation (ECMO) circuits for potential use in resuscitation after a 2-wk period of storage. DESIGN: Experimental laboratory study. SETTING: Tertiary care pediatric cardiac intensive care unit. SUBJECTS: None. INTERVENTIONS AND MEASUREMENTS: 14 ECMO circuits (polyvinyl chloride and super-Tygon tubing with hollow-fiber oxygenator, Medos Hilite 800LT) were primed with crystalloid under sterile conditions and stored for 0 (control, n = 4), 7 (n = 5) and 14 (n = 5) days and maintained at 8 degrees C on pump at 10 rpm and gas flow at 0.2 L/min. Daily samples were inspected for plasticizers by means of high-performance liquid chromatography and for microorganisms by culture and polymerase chain reaction techniques. After storage, the oxygenators were primed with red blood cells (hemoglobin, 12 g/dL) and tested in vitro with a deoxygenator according to Association for Advancement of Medical Instrumentation standards. Oxygen and CO(2) transfer rates were calculated by standard formulae at maximum blood flow (800 mL/min) and maximum sweep gas flow (1.6 L/min). MAIN RESULTS: Oxygen transfer was linearly related to venous oxygen saturation, increasing by 11 mL/min for each 10% decrease in venous oxygen saturation. Estimated oxygen transfer at venous oxygen saturation of 60% was 45.8 mL/min (95% confidence interval [CI], 43.5-48.1) for controls, 51.0 mL/min (95% CI, 48.9-53.2) for 7-day oxygenators, and 49.0 mL/min (95% CI, 47.8-50.1) for 14-day oxygenators. CO(2) transfer declined to 29.2 mL/min at 14 days of storage, a mean fall of 11.5 mL/min (95% CI, 4.2-18.7) in comparison with 7-day storage. All circuits were free from microbes/microbial DNA. Plasticizer levels fell below the lower limit of detection (0.003 microg/mL) at 7 and 14 days. CONCLUSIONS: A wet-preprimed ECMO circuit with hollow-fiber membrane oxygenator can be stored for up to 2 wks with adequately preserved function if prepared appropriately. These data may improve safe access to rapid-response ECMO support.

Plasticizer di(2-ethylhexyl)phthalate (DEHP) release in wet-primed extracorporeal membrane oxygenation (ECMO) circuits.

A wet-primed ready-to-use extracorporeal membrane oxygenation (ECMO) circuit is used in some centres for rapid deployment of ECMO during cardiopulmonary resuscitation. Yet, the potential release of plasticizer di(2-ethylhexyl)phthalate (DEHP) from the polyvinyl chloride tubing in the circuit during storage is a concern. In this study, a high performance liquid chromatography method was used to determine the concentration of DEHP in the priming solution (Plasmalyte) from an ECMO circuit stored for up to 14 days at 8 degrees C. No accumulation of DEHP in the circulating fluid was detected. The results provide important information for centres where ECMO circuits are kept wet-primed prior to clinical use.