Justin Yeh

Outcomes of Children Following a First Hospitalization for Dilated Cardiomyopathy

Background—We hypothesized that children with dilated cardiomyopathy who require hospital admission are at increased risk for death or transplantation during their first hospitalization and in the first year that follows. We also assessed the value of routine data collected during that time to predict death or the need for transplantation prior to discharge and within 1 year of admission. Methods and Results—We conducted a retrospective review of 83 pediatric patients with dilated cardiomyopathy whose initial hospitalization fell between 2004 and 2009. The mean age at hospitalization was 7 years. The majority of patients demonstrated moderate or severe left ventricular dysfunction on initial echocardiogram (80%) and/or the need for intravenous inotropes within 7 days of hospital admission (69%). Five patients (6%) died, and 15 (18%) were transplanted in the initial hospitalization. At 1 year, 11/71 (15%) had died, and 27/71 (38%) were transplanted. The overall freedom from death, transplantation, or rehospitalization at 1 year following admission was 21%. Fractional shortening, left ventricular ejection fraction, serum cholesterol, uric acid, mixed venous saturation, and atrial filling pressures were all predictive of death or transplantation during the initial hospitalization. Left ventricular ejection fraction was predictive of death or transplantation at 1 year. Conclusions—The first hospitalization for dilated cardiomyopathy marks a period of high risk for clinical decline, end stage heart failure, and the need for cardiac transplantation. Echocardiographic function and hemodynamic and serum measurements may aid in predicting outcomes. Despite medical management, most patients will be rehospitalized and/or require cardiac transplantation within 1 year of admission.

Ventricular assist devices in a contemporary pediatric cohort: Morbidity, functional recovery, and survival

BACKGROUND Limited availability of donor organs has led to the use of ventricular assist devices (VADs) to treat heart failure in pediatric patients, primarily as bridge to transplantation. How effective VAD therapy is in promoting functional recovery in children is currently not known. METHODS We report morbidity and mortality as defined by the Interagency Registry for Mechanically Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of the Treatment Intensity Score to assess functional status for 50 VAD patients supported at a single pediatric program from 2004 to 2013. RESULTS In this cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first 7 days of support compared with the subsequent support period. Functional status, as measured by the Treatment Intensity Score, improved with duration of support. Successful bridge to transplantation was associated with fewer adverse events during support and greater improvement in the Treatment Intensity Score during the period of support. CONCLUSIONS Overall survival in this cohort is excellent. The risk of serious adverse events decreases over the first month of support. However, a clinically significant risk of morbidity and mortality persists for the duration of pediatric VAD support. Measures of functional status improve with duration of support and are associated with survival to transplantation.

Use of the Impella 5.0 as a bridge from ECMO to implantation of the HeartMate II left ventricular assist device in a pediatric patient

A 10-yr-old previously healthy boy presented in cardiogenic shock after collapsing at school was subsequently diagnosed with a dilated cardiomyopathy at an outside hospital. Within hours following transfer to our cardiovascular intensive care unit (CVICU), the patient quickly decompensated, necessitating emergent V-A ECMO cannulation. Social service issues initially precluded listing for cardiac transplantation. On hospital day no. 14, an Impella 5.0 device was surgically implanted via the right femoral artery leading to successful weaning from ECMO (Fig. 1). The Impella required replacement 10 days after implantation because of mechanical failure. On hospital day no. 27, the Impella was removed and a HeartMate II LVAD was implanted for long-term management (Fig. 2). The procedure was complicated by pericardial tamponade requiring emergent chest exploration and evacuation of a large pericardial hematoma. The patient was extubated on hospital day no. 56 and weaned off all inotropic infusions. Demonstrating consistently appropriate hemodynamics, the patient was discharged from the CVICU to the acute care floor, and on hospital day no. 139, the patient was transferred to another institution closer to his father s home for continuing care. After further rehabilitation, the patient was listed for and subsequently underwent successful cardiac transplantation. Ventricular assist devices are used with increasing frequency in children for the treatment of cardiogenic shock (INTERMACS indication 1) or progressive decline, while on inotropic support (INTERMACS indication 2) (1). A recent report of 99 patients in the Pediatric Heart Transplant Study database reported 77% patients surviving to transplantation and 5% being successfully weaned from support (2). Fig. 1. The Impella 5.0 is seen in long axis on transesophageal echocardiogram. Fig. 2. The HeartMate II (LV apical cannula) is seen in four-chamber view on transthoracic echocardiogram. Pediatr Transplantation 2012: 16: 205–206 2011 John Wiley & Sons A/S.

Successful bridge to transplant with a continuous flow ventricular assist device in a single ventricle patient with an aortopulmonary shunt.

Ventricular assist devices are frequently used to bridge pediatric patients to cardiac transplantation; however, experience in single ventricle patients with aortopulmonary shunts remains limited. This case report addresses the challenge of balancing pulmonary and systemic circulation with a focus on the role of continuous versus pulsatile ventricular assist device support.

HeartWare HVAD for Biventricular Support in Children and Adolescents: The Stanford Experience.

Despite increasing use of mechanical circulatory support in children, experience with biventricular device implantation remains limited. We describe our experience using the HeartWare HVAD to provide biventricular support to three patients and compare these patients with five patients supported with HeartWare left ventricular assist device (LVAD). At the end of the study period, all three biventricular assist device (BiVAD) patients had been transplanted and were alive. LVAD patients were out of bed and ambulating a median of 10.5 days postimplantation. The BiVAD patients were out of bed a median of 31 days postimplantation. Pediatric patients with both left ventricular and biventricular heart failure can be successfully bridged to transplantation with the HeartWare HVAD. Rapid improvement in functional status following HVAD implantation for isolated left ventricular support is seen. Patients supported with BiVAD also demonstrate functional recovery, albeit more modestly. In the absence of infection, systemic inflammatory response raises concern for inadequate support.

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.

Orthotopic heart transplantation in two infants with histiocytoid cardiomyopathy and left ventricular non-compaction

HC is a rare cause of congestive heart failure that typically presents with malignant ventricular arrhythmias in infants, often requiring urgent intervention. Successful heart transplantation in a patient with HC has only been reported once (J Heart Lung Transplant 2004: 23: 902). The combination of HC with concurrent LVNC has only been described three times (Int J Legal Med 2009: 123: 47; Hum Pathol 2005: 36: 403; Pediatr Dev Pathol 2012: 15: 397). We report two rare cases of HC with LVNC in two infants presenting with cardiogenic shock, one requiring ECMO support who was successfully bridged to orthotopic heart transplantation with a Berlin Heart LVAD.

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.