Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study.

OBJECTIVES: Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited. DESIGN: Retrospective cohort study. SETTING: Single tertiary-quaternary referral center. PATIENTS: All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange. CONCLUSIONS: Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

Population Pharmacokinetics of Vancomycin in the Pediatric Ventricular Assist Device Population.

OBJECTIVES: Determine the pharmacokinetic disposition of vancomycin in the pediatric ventricular assist device population. DESIGN: A retrospective, population pharmacokinetic study. SETTING: Large, quaternary care children's hospital. PATIENTS: Less than 19 years old initiated on vancomycin while undergoing ventricular assist device therapy from 2011 to 2018 in our institution. INTERVENTIONS: Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM (Icon, PLC, Dublin, Ireland). Simulation was performed to identify a vancomycin dosing strategy that resulted in a trough concentration less than 15 mg/L and an area under the curve0-24:minimum inhibitory concentration ratio of greater than 400. MEASUREMENTS AND MAIN RESULTS: A total of 69 patients (male 50.7%, median age 7.1 years [interquartile range, 2.4-11.9]) met study criteria (HeartWare [Framingham, MA] = 37, Berlin Heart [Berlin, Germany] = 22, Impella [Abiomed, Danvers, MA] = 4, RotaFlow [Maquet, Hirrlingen, Germany] right ventricular assist device = 3, HeartMate II [Abbott Laboratories, Abbott Park, IL] = 2, Berlin Heart biventricular assist device = 1). Patients received a median of 21 doses (interquartile range, 13-44 doses) of IV vancomycin (14.8 ± 1.8 mg/kg/dose) along with vancomycin as an intrathoracic irrigation (n = 48; 69.6%). The mean serum concentration was 12.2 ± 5.2 mg/L at 11.2 ± 6.9 hours after a dose. A one-compartment pharmacokinetic model best fit the data with allometric scaling on clearance and volume of distribution. Clearance was characterized by total body weight and serum creatinine, and volume of distribution was characterized by total body weight. Simulation identified doses greater than 15 mg/kg/dose with extended intervals were necessary to achieve endpoints. CONCLUSIONS: Vancomycin dosing in pediatric ventricular assist device patients should be altered in comparison to nonventricular assist device patients and should be accompanied with frequent serum concentration monitoring.

Readmissions for Heart Failure in Children.

OBJECTIVE: To assess the frequency of inpatient 30-day readmission for heart failure in children with cardiomyopathy discharged after an admission for heart failure and the impact of discharge pharmacotherapy on readmissions. STUDY DESIGN: The Pediatric Health Information System Database was queried for patients ≤18 years of age with an International Classification of Diseases, Ninth Revision code for heart failure (428.xx) or cardiomyopathy (425.xx) discharged from 2004 to 2013. Patients were excluded if they had congenital heart disease, expired on the initial admission, or underwent cardiac surgery. Patient admission characteristics were documented and discharge medications were captured. Frequency of 30-day readmission for heart failure was identified, and mixed effects multivariable logistic regression analysis was performed to determine factors significant for readmission. RESULTS: A total of 2386 patients met study criteria (52.1% male, median age 8.1 years [IQR 1.2-14.6 years]). Vasoactive medications were used in 70.3% of patients on initial admission, the most common of which was milrinone (62.8%). Angiotensin converting enzyme inhibitors and beta-blockers were given at discharge to 67.4% and 35.9%, respectively. Frequency of 30-day readmission for heart failure was 12.9%. Duration of milrinone or beta-blocker use at discharge and institutional heart failure patient volume were associated with a greater odds of 30-day readmission, whereas mechanical ventilation on initial admission was associated with decreased odds of readmission. CONCLUSIONS: Pediatric patients with cardiomyopathy and heart failure have a high frequency of heart failure-related 30-day readmission. Outpatient pharmacotherapy at discharge does not appear to influence readmission.

Prevalence of Anemia and Iron Deficiency in Pediatric Patients on Ventricular Assist Devices.

The prevalence and characteristics of anemia and iron deficiency in children supported by a ventricular assist device (VAD) are unknown. Patients <21 years of age on durable VAD support for ≥7 days at Texas Children's Hospital from 2006 to 2015 were retrospectively reviewed. Red blood cell (RBC) and iron deficiency indices in pulsatile VAD (P-VAD) and continuous-flow VAD (CF-VAD) were evaluated. Anemia, iron deficiency, and iron therapy regimens were identified. Seventy-six VAD implants in 74 patients were included: 45 P-VAD and 31 CF-VAD. Overall, 48% (36/75) of patients were anemic at VAD implant, with 67% of CF-VAD and 34% of P-VAD affected. Iron deficiency was seen in 52% (39/75) of patients at implant (similar in both groups). At explant, 71% (53/75) had anemia (similar in both groups). No patients had microcytosis. Iron supplementation was given to 20 patients, with four receiving target replacement therapy (2-6 mg/kg/d × 90 days). Red blood cell transfusion volumes were higher for P-VAD versus CF-VAD. We concluded that anemia and iron deficiency are common in pediatric VAD patients. Pulsatile VAD patients tend to develop anemia over the course of VAD support. Lack of microcytosis, likely masked by high RBC transfusions, suggests that specific iron studies are necessary to identify iron deficiency.

Incidence, Severity, and Association With Adverse Outcome of Hyponatremia in Children Hospitalized With Heart Failure.

Hyponatremia is a common finding in adults hospitalized with heart failure (HF) and is associated with longer hospital stays and increased mortality. The significance of hyponatremia in children with HF is not known. We sought to determine the incidence of hyponatremia and association with clinical outcome in children hospitalized with HF. Admission and inpatient serum sodium concentrations were analyzed in 141 consecutive children hospitalized with acute decompensated HF. Inclusion criteria include patients (age, birth to 21 years) with biventricular hearts who were hospitalized for HF from January 2007 to December 2012. The primary composite end point was death, cardiac transplantation, or the use of mechanical circulatory support (MCS) during hospitalization. Data for 141 patients were included in the analysis. The cohort included 48 patients (34%) with preexisting HF. Mean serum sodium at admission was 136 ± 4 mmol/L (range 124 to 150 mmol/L). Hyponatremia (serum sodium <135 mmol/L) was present in 45 patients (32%) at admission. Seventy-one patients (75%) with normal serum sodium concentrations at admission subsequently developed acquired hyponatremia during their hospitalization. Hyponatremia persisted at discharge in 17 of 66 patients (26%). Fifty-eight patients (41%) reached the composite end point during hospitalization (death, n = 15; cardiac transplantation, n = 27; MCS, n = 46). Hyponatremia at admission was independently associated with death, cardiac transplantation, or the use of MCS during hospitalization (odds ratio 3.1, p = 0.02). In conclusion, hyponatremia occurs commonly in children hospitalized with acute decompensated HF and is associated with increased risk of in-hospital mortality, cardiac transplantation, and need for MCS.