Lindsay J. May

Outpatient Outcomes of Pediatric Patients with Left Ventricular Assist Devices.

Outpatient experience of children supported with continuous-flow ventricular assist devices (CF-VAD) is limited. We reviewed our experience with children discharged with CF-VAD support. All pediatric patients <18 years old with CF-VADs implanted at our institution were included. Discharge criteria included a stable medication regimen, completion of a VAD education program and standardized rehabilitation plan, and presence of a caregiver. Hospital readmissions (excluding scheduled admissions) were reviewed. Adverse events were defined by Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria. Of 17 patients with CF-VADs, 8 (47%) were discharged from the hospital (1 HeartWare ventricular assist device (Heartware Inc., Framingham, MA), 7 HeartMate II (Thoratec Corp, Pleasanton, CA)). Median age was 15.3 (range 9.6–17.1) years and weight was 50.6 (33.6–141) kg. Device strategies were destination therapy (DT; n = 4) and bridge to transplant (n = 4). Patients spent a median 49 (26–107) days hospitalized postimplant and had 2 (1–5) hospital readmissions. Total support duration was 3,154 patient-days, with 2,413 as outpatient. Most frequent adverse events were device malfunction and arrhythmias. There was one death because of pump thrombosis and no bleeding or stroke events. Overall adverse event rate was 15.22 per 100 patient-months. Early experience suggests that children with CF-VADs can be safely discharged. Device malfunction and arrhythmia were the most common adverse events but were recognized quickly with structured outpatient surveillance.

HLA desensitization with bortezomib in a highly sensitized pediatric patient

The proteasome inhibitor bortezomib has been used with variable success in the treatment of AMR following heart transplant. There is limited experience with this agent as a pretransplant desensitizing therapy. We report a case of successful HLA desensitization with a bortezomib‐based protocol prior to successful heart transplantation. A nine‐yr‐old boy with dilated cardiomyopathy, not initially sensitized to HLA (cPRA of zero), required three days of ECMO, followed by implantation of a Heartmate II LVAD. Within six wk, the patient developed de novo class I IgG and C1q complement‐fixing HLA antibodies with a cPRA of 100%. Two doses of IVIG (2 g/kg) failed to reduce antibody levels, although two courses of a novel desensitization protocol consisting of rituximab (375 mg/m2), bortezomib (1.3 mg/m2 × 5 doses), and plasmapheresis reduced his cPRA to 0% and 87% by the C1q and IgG assays, respectively. He underwent heart transplantation nearly two months later. The patient is now >one yr post‐transplant, is free of both AMR and ACR, and has no detectable donor‐specific antibodies by IgG or C1q. Proteasome inhibition with bortezomib and plasmapheresis may be an effective therapy for HLA desensitization pretransplant.

A novel pediatric treatment intensity score: development and feasibility in heart failure patients with ventricular assist devices

BACKGROUND The evolution of pharmacologic therapies and mechanical support including ventricular assist devices (VADs) has broadened the scope of care available to children with advanced heart failure. At the present time, there are only limited means of quantifying disease severity or the concomitant morbidity for this population. This study describes the development of a novel pediatric treatment intensity score (TIS), designed to quantify the burden of illness and clinical trajectory in children on VAD support. METHODS There were 5 clinical domains assessed: nutrition, respiratory support, activity level, cardiovascular medications, and care environment. A scale was developed through expert consensus. Higher scores indicate greater morbidity as reflected by intensity of medical management. To evaluate feasibility and face validity, the TIS was applied retrospectively to a subset of pediatric inpatients with VADs. The Bland-Altman method was used to assess limits of agreement. RESULTS The study comprised 39 patients with 42 implantations. Bland-Altman interobserver and intraobserver comparisons showed good agreement (mean differences in scores of 0.02, limits of agreement ±0.12). Trends in TIS were concordant with the overall clinical impression of improvement. Scores remained ≥0.6 preceding VAD implantation and peaked at 0.71 3 days after VAD implantation. CONCLUSIONS We describe a pediatric VAD scoring tool, to assess global patient morbidity and clinical recovery. We demonstrate feasibility of using this TIS in a test population of inpatients on VAD support.

Haemodynamic profiles of children with end-stage heart failure

Aims To evaluate associations between haemodynamic profiles and symptoms, end-organ function and outcome in children listed for heart transplantation. Methods and results Children <18 years listed for heart transplant between 1993 and 2013 with cardiac catheterization data [pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac index (CI)] in the Pediatric Heart Transplant Study database were included. Outcomes were New York Heart Association (NYHA)/Ross classification, renal and hepatic dysfunction, and death or clinical deterioration while on waitlist. Among 1059 children analysed, median age was 6.9 years and 46% had dilated cardiomyopathy. Overall, 58% had congestion (PCWP >15 mmHg), 28% had severe congestion (PCWP >22 mmHg), and 22% low cardiac output (CI < 2.2 L/min/m2). Twenty-one per cent met the primary outcome of death (9%) or clinical deterioration (12%). In multivariable analysis, worse NYHA/Ross classification was associated with increased PCWP [odds ratio (OR) 1.03, 95% confidence interval (95% CI) 1.01-1.07, P = 0.01], renal dysfunction with increased RAP (OR 1.04, 95% CI 1.01-1.08, P = 0.007), and hepatic dysfunction with both increased PCWP (OR 1.03, 95% CI 1.01-1.06, P < 0.001) and increased RAP (OR 1.09, 95% CI 1.06-1.12, P < 0.001). There were no associations with low output. Death or clinical deterioration was associated with severe congestion (OR 1.6, 95% CI 1.2-2.2, P = 0.002), but not with CI alone. However, children with both low output and severe congestion were at highest risk (OR 1.9, 95% CI 1.1-3.5, P = 0.03). Conclusion Congestion is more common than low cardiac output in children with end-stage heart failure and correlates with NYHA/Ross classification and end-organ dysfunction. Children with both congestion and low output have the highest risk of death or clinical deterioration.

Electrocardiographic repolarization abnormalities and increased risk of life-threatening arrhythmias in children with dilated cardiomyopathy

BACKGROUND Life-threatening arrhythmia events (LTEs) occur in ~5% of children with dilated cardiomyopathy (DCM). While prolonged QRS duration has been shown to be associated with LTEs, electrocardiographic (ECG) repolarization findings have not been examined. OBJECTIVE We sought to determine the associations between ECG repolarization abnormalities and LTEs in children with DCM. METHODS A single-center retrospective review of children with DCM was performed. LTEs were defined as documented ventricular tachycardia or fibrillation requiring medical intervention. Three pediatric cardiologists, blinded to clinical events, evaluated ECGs obtained at the time of initial referral. Kaplan-Meier survival and Cox proportional hazards analyses were used to evaluate time to LTEs. RESULTS A total of 137 patients (mean age 7.8 ± 6.7 years; 75(55%) male patients) with DCM (mean ejection fraction 35% ± 16%) were included; 67 patients (49%) had a corrected JT (JTc) interval of ≥340 ms, 72 (53%) had a corrected QT (QTc) interval of ≥450 ms, and 41 (30%) had abnormal T waves. LTEs occurred in 15 patients at a median of 12 months (interquartile range 3-36 months) after the initial ECG. Patients with LTEs had a longer JTc interval (371 ± 77 ms vs 342 ± 41 ms; P = .02) and a longer QTc interval (488 ± 96 ms vs 453 ± 44 ms; P = .01). In survival analysis, a JTc interval of ≥390 ms (hazard ratio [HR] 4.07; 95% confidence interval [CI] 1.12-14.83; P = .03), a QTc interval of ≥510 ms (HR 6.95; 95% CI 1.53-31.49; P = .01), abnormal T-wave inversion (HR 11.62; 95% CI 2.75-49.00; P = .001), and ST-segment depression (HR 6.91; 95% CI 1.25-38.27; P = .03) were associated with an increased risk of LTEs, even after adjusting for QRS duration and amiodarone use. CONCLUSION Repolarization abnormalities are common in children with DCM. Certain ECG repolarization abnormalities, such as significantly prolonged JTc and QTc intervals, may be useful in identifying patients at risk of LTEs.

Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure

BACKGROUND Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children. METHODS Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2)). RESULTS The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001). CONCLUSIONS Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure.

Group visits in the pediatric heart transplant outpatient clinic

The “GVM” has emerged as an alternative to traditional individualized appointments in the ambulatory care setting. We hypothesized that group visits could successfully be utilized in a PHtx clinic. Seven patients, ages 1–18 yr old, and their families participated in a total of 11 group visits in lieu of individualized appointments. Patients were divided into two groups based on whether they were greater or less than one yr post‐transplant. Patient/provider satisfaction, medication adherence, and content retention were ascertained via questionnaires and free‐response tests. Total clinic throughput time, including per‐patient clinic utilization time, was compared to historical data. Six of seven patients completed the study with one dropout. Overall satisfaction ratings were 3.98 of 4 with all patients reporting that they would “strongly recommend” group visits to others. Health information retention tests demonstrated improvement between pre‐ and post‐tests in eight of nine (89%) of the group visits. Overall clinic utilization decreased by nearly 50% while providing 70 min of face‐to‐face time with the provider. Medication adherence neared 100% for all patients. The GVM can be successfully applied to the PHtx population with high patient and provider satisfaction, more face‐to‐face time, excellent content retention, and greatly improved clinic efficiency.

RELIABILITY OF ECHOCARDIOGRAPHIC MEASUREMENTS OF LEFT VENTRICULAR SYSTOLIC FUNCTION IN POTENTIAL PEDIATRIC HEART TRANSPLANT DONORS

BACKGROUND Echocardiogram reports, but not images, are usually available for the evaluation of potential donor hearts. To assess the reliability of local reports of potential pediatric heart donors, we compared echocardiographic measurements of left ventricular (LV) systolic function between local hospitals and a central echocardiography laboratory. METHODS We identified all potential donors aged <18 years managed by the California Transplant Donor Network from 2009 to 2013. Echocardiograms and reports were obtained from local hospitals. All studies were reviewed in a central laboratory by an experienced pediatric cardiologist blinded to local reports. Local and central measurements of fractional shortening (FS) were compared using the Bland-Altman method (mean difference ± 2 standard deviations). LV function was categorized based on FS as normal or mild, moderately, or severely depressed. RESULTS There were 70 studies from 59 donors with local and central measurements of FS. The mean difference between local and central FS was 3.9 ± 9.0. The limits of agreement ranged from -14.2 to 22. Twenty-five studies had discordant measurements of LV function, with 17 discordant by 1 category and 8 by 2 or more categories. Of 55 studies categorized as normal by local measurement, 6 were moderately to severely depressed by central review. Of 15 studies categorized as depressed by local measurement, 3 were normal by central review. CONCLUSIONS Local and central measurements of LV systolic function were discordant in 36% of studies. Given such discordance, efforts to obtain and view actual echocardiographic images should be part of the standard evaluation of potential pediatric heart donors.