Seth A. Hollander

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.

Intermediate-term outcomes after combined heart-liver transplantation in children with a univentricular heart.

For patients with end-stage hepatic failure secondary to failing hemodynamics, combined heart-liver transplant (H-LT) remains the only option for long-term survival. We report a series of three pediatric patients who successfully underwent orthotopic H-LT for failed single-ventricle palliation. All three patients are currently living, now two, three, and five years post-transplant, and remain completely free of cardiac cellular allograft rejection despite reduced immunosuppression protocols. One patient, however, did develop acute antibody-mediated rejection in the immediate post-transplant period, suggesting that this protective effect may be less effective in attenuating humoral mechanisms of rejection.

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.

An inpatient rehabilitation program utilizing standardized care pathways after paracorporeal ventricular assist device placement in children

BACKGROUND Structured rehabilitation programs in adults after ventricular assist device (VAD) placement result in improvements in physical function and exercise capacity, and have been shown to improve survival and accelerate post-transplant recovery. The objective of this study was to determine the safety and feasibility of an acute inpatient rehabilitation program for children utilizing standardized, age-appropriate, family-centered care pathways after paracorporeal VAD placement in both the ICU and acute-care inpatient settings. METHODS Between November 12, 2010 and March 15, 2013, 17 patients were referred to therapy after VAD implantation, 14 of whom were medically stable enough to participate. Beginning in the ICU, a structured physical and occupational therapy program was implemented utilizing novel age-appropriate, standardized care pathways for infants (age <1 year) and children (age 1 to 12 years). The infant and child pathways consisted of 8 and 10 goals, respectively. Retrospective review was conducted to ascertain the number of phases achieved per patient. Adverse events, defined as bleeding, physiologic instability, stroke, or device disruption during therapy, were also analyzed. RESULTS The median age was 1.1 (range 0.5 to 14.4) years in the 14 patients considered medically stable enough to participate in rehabilitation. Nine of them were female. Eight patients participated in the infant standardized care pathway (SCP) and 6 participated in the child SCP. Seven patients were on biventricular support. Twelve patients were transplanted and survived. Two patients died while awaiting transplantation. There were 1,473 total days on the VAD (range 40 to 229 days). The median time to extubation was 2 days (range 1 to 8) and the median ICU stay was 6.5 days (range 3 to 152). Eleven patients achieved all goals of the SCP, including all of the patients in the child group. For the infant group, 5 patients achieved all goals of the SCP (range 5 to 8), and all but 1 patient achieved at least 7 goals of the SCP. There were no adverse events related to therapy. CONCLUSIONS Standardized, family-centered inpatient rehabilitation care paths are safe for infants and children after paracorporeal device placement. Structured rehabilitation goals can be achieved by the majority of pediatric patients during VAD support. Early mobilization and inpatient rehabilitation in this cohort promotes normalization of function while awaiting cardiac 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.

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.

Abdominal complaints as a common first presentation of heart failure in adolescents with dilated cardiomyopathy

OBJECTIVE We hypothesized that isolated gastrointestinal complaints (abdominal pain, nausea, anorexia, weight loss), in the absence of other symptoms, were a common mode of initial presentation in children with congestive heart failure (CHF). STUDY DESIGN Ninety-eight patients younger than 18 years hospitalized with dilated cardiomyopathy at a single institution between January 1, 2000, and December 31, 2009, were included. Retrospective review of their presenting complaints was recorded and analyzed according to 3 age groups: 0 to 1 year (infants), 1 to 10 years (children), and 11 to 18 years (adolescents) of age. RESULTS Respiratory symptoms were common in all age groups (range, 56%-63%). Gastrointestinal complaints were also common in all age groups (42%, 28%, and 65%, respectively) and were more frequent than respiratory complaints in adolescents. Adolescents were likely to present with abdominal pain as their only complaint (10/43, 23%). Chest pain, syncope, or cardiac arrest occurred rarely. CONCLUSIONS Abdominal complaints are a common component of the presenting symptom complex of CHF in pediatric dilated cardiomyopathy in all age groups. In adolescents, abdominal complaints occur more frequently than respiratory complaints and often in the absence of any other symptoms. Unlike CHF in adults, chest pain, arrhythmia, or cardiac arrest occurs rarely at presentation in pediatric patients. Recognition of the different presenting symptoms of heart failure in children by primary providers is crucial to ensuring prompt diagnosis and timely initiation of therapy.

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.

Electrical and mechanical dyssynchrony in pediatric pulmonary hypertension

BACKGROUND Electrical and mechanical dyssynchrony are often seen in patients with left ventricular failure. In pediatric pulmonary hypertension (PH), right ventricular failure predominates; however, the prevalence of electrical and/or mechanical dyssynchrony in these patients is unknown. We examined the prevalence of electrical and mechanical dyssynchrony in pediatric PH patients. METHODS Medical records (including, functional status, electrocardiograms and echocardiograms) of pediatric PH patients were reviewed. QRS duration z-scores were calculated to determine electrical dyssynchrony. Echo vector velocity imaging was used to calculate the mechanical dyssynchrony index (DI). RESULTS Seventy-seven PH patients (idiopathic pulmonary arterial hypertension [IPAH]: n = 26; congenital heart disease: n = 41; other: n = 10) were studied. Electrical dyssynchrony was seen in 84% (p < 0.01 vs historic controls), with a mean z-score of 4.3 (95% CI 3.5 to 5.1). There was no difference between those with IPAH, z = 3.6 (95% CI 2.5 to 4.6), and those without, z = 4.7 (95% CI 3.6 to 5.8). Mechanical dyssynchrony was seen in 76% of patients (mean DI = 66 ± 47 vs 18 ± 8 milliseconds in historic controls, p < 0.01) in both IPAH and non-IPAH patients. Post-operative congenital heart disease patients had the largest dyssynchrony index. No correlation was found among electrical or mechanical dyssynchrony, hemodynamics or disease severity. CONCLUSIONS Significant electrical and mechanical dyssynchrony is present in pediatric PH patients, regardless of etiology. The overall effect of electrical and mechanical dyssynchrony on outcomes in this patient population is still unknown. Select patients may benefit from resynchronization therapy.