Robert D.B. Jaquiss

Prospective Trial of a Pediatric Ventricular Assist Device

BACKGROUND Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited. METHODS We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO). RESULTS For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%). CONCLUSIONS Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).

Home surveillance program prevents interstage mortality after the Norwood procedure

OBJECTIVE To determine whether early identification of physiologic variances associated with interstage death would reduce mortality, we developed a home surveillance program. METHODS Patients discharged before initiation of home surveillance (group A, n = 63) were compared with patients discharged with an infant scale and pulse oximeter (group B, n = 24). Parents maintained a daily log of weight and arterial oxygen saturation according to pulse oximetry and were instructed to contact their physician in case of an arterial oxygen saturation less than 70% according to pulse oximetry, an acute weight loss of more than 30 g in 24 hours, or failure to gain at least 20 g during a 3-day period. RESULTS Interstage mortality among infants surviving to discharge was 15.8% (n = 9/57) in group A and 0% (n = 0/24) in group B (P =.039). Surveillance criteria were breached for 13 of 24 group B patients: 12 patients with decreased arterial oxygen saturation according to pulse oximetry with or without poor weight gain and 1 patient with poor weight gain alone. These 13 patients underwent bidirectional superior cavopulmonary connection (stage 2 palliation) at an earlier age, 3.7 +/- 1.1 months of age versus 5.2 +/- 2.0 months for patients with an uncomplicated interstage course (P =.028). A growth curve was generated and showed reduced growth velocity between 4 and 5 months of age, with a plateau in growth beyond 5 months of age. CONCLUSION Daily home surveillance of arterial oxygen saturation according to pulse oximetry and weight selected patients at increased risk of interstage death, permitting timely intervention, primarily with early stage 2 palliation, and was associated with improved interstage survival. Diminished growth identified 4 to 5 months after the Norwood procedure brings into question the value of delaying stage 2 palliation beyond 5 months of age.

Bridging children of all sizes to cardiac transplantation: The initial multicenter North American experience with the Berlin Heart EXCOR ventricular assist device

BACKGROUND Beginning in 2000 and accelerating in 2004, the Berlin Heart EXCOR (Berlin Heart Inc Woodlands, TX) became the first pediatric-specific ventricular assist device (VAD) applied throughout North America for children of all sizes. This retrospective study analyzed the initial Berlin Heart EXCOR pediatric experience as a bridge to transplantation. METHODS Between June 2000 and May 2007, 97 EXCOR VADs were implanted in North America at 29 different institutions. The analysis is limited to 73 patients (75%) from 17 institutions, for which retrospective data were available. RESULTS Median age and weight at VAD implant were 2.1 years (range, 12 days-17.8 years) and 11 kg (range, 3-87.6 kg), respectively. The primary diagnoses were dilated cardiomyopathy in 42 (58%), congenital heart disease in 19 (26%), myocarditis in 7 (10%), and other cardiomyopathies in 5 (7%). Pre-implant clinical condition was critical cardiogenic shock in 38 (52%), progressive decline in 33 (45%), or other in 2 (3%). Extracorporeal membrane oxygenation was used as a bridge to EXCOR in 22 patients (30%). Device selection was left VAD (LVAD) in 42 (57%) and biventricular assist devices (BiVAD) in 31 (43%). The EXCOR bridged 51 patients (70%) to transplant and 5 (7%) to recovery. Mortality on the EXCOR was 23% (n = 17) overall, including 35% (11 of 31) in BiVAD vs 14% (6 of 42) in LVAD patients (p = 0.003). Multivariate analysis showed younger age and BiVAD support were significant risk factors for death while on the EXCOR. CONCLUSIONS This limited but large preliminary North American experience with the Berlin Heart EXCOR VAD as a bridge to cardiac transplantation for children of all ages and sizes points to the feasibility of this approach. The prospective investigational device evaluation trial presently underway will further characterize the safety and efficacy of the EXCOR as a bridge to pediatric cardiac transplantation.

Prospective echocardiographic diagnosis and surgical repair of anomalous origin of a coronary artery from the opposite sinus with an interarterial course

OBJECTIVES In this study, we sought to describe the mode of presentation, anatomic features, diagnostic techniques, and surgical outcome in a group of patients with anomalous origin of a coronary artery from the opposite sinus with an interarterial course between the great arteries (AOCA). BACKGROUND Anomalous origin of a coronary artery from the opposite sinus with an interarterial course is associated with myocardial ischemia and sudden cardiac death, particularly in adolescents and young adults. METHODS The cardiology database at Childrens Hospital of Wisconsin was reviewed to identify all patients diagnosed with AOCA. RESULTS From September 1997 to August 2002, 10 patients were identified with AOCA; all were children/adolescents (age range, 3 months to 20 years; weight range, 4.7 to 72 kg), and nine were diagnosed prospectively by transthoracic echocardiography (TTE). Symptoms of cardiac ischemia initiated investigation in 4/10 patients at a mean age of 16 +/- 2.8 years; the other six had TTE for suspected congenital heart disease/musculoskeletal chest pain. The left coronary artery originated from the right sinus in six patients, and the right coronary artery originated from the left sinus in four patients. An intramural course of the AOCA within the anterior aortic wall was found in 9/10 patients and was reliably identified by TTE; the other patient had an intramyocardial course of the anomalous coronary. Surgical repair was performed in 8/10 patients at a mean age of 13 +/- 4.7 years. Unroofing of the intramural portion of the AOCA to relocate the ostia in the appropriate sinus was successfully performed in seven patients. All patients status post unroofing were asymptomatic with patent coronary flow by Doppler and normal exercise treadmill testing at a median follow-up interval of 1.5 years. CONCLUSIONS Anomalous origin of a coronary artery from the opposite sinus with an interarterial course is frequently characterized by an intramural course, which can be prospectively identified by TTE. Unroofing the intramural segment without bypass grafting can reliably repair the intramural form of AOCA.

The use of the Berlin heart EXCOR in patients with functional single ventricle

INTRODUCTION The frequency and successful use of pediatric ventricular assist devices (VADs) as a bridge to cardiac transplantation have been steadily increasing since 2003, but the experience in patients with complex congenital heart disease has not been well described. Using a large prospectively collected dataset of children supported with the Berlin Heart EXCOR VAD, we have reviewed the experience in children with single ventricular anatomy or physiology (SV), and compared the results with those supported with biventricular circulation (BV) over the same time period. METHODS The EXCOR Investigational Device Exemption study database was retrospectively reviewed. VAD implants under the primary cohort and compassionate use cohort between May 2007 and December 2011 were included in this review. RESULTS Twenty-six of 281 patients supported with a VAD were SV. The most common diagnosis was hypoplastic left heart syndrome (15 of 26). Nine patients were supported after neonatal palliative surgery (Blalock-Taussig shunt or Sano), 12 after a superior cavopulmonary connection (SCPC), and 5 after total cavopulmonary connection (TCPC). Two patients received biventricular assist devices, 1 after stage I surgery and 1 after stage II. SV patients were supported for a median time of 10.5 days (range, 1-363 days) versus 39 days (range, 0-435 days) for BV (P = .01). The ability to be bridged to transplant or recovery in SV patients is lower than for BV patients (11 of 26 [42.3%] vs 185 of 255 [72.5%]; P = .001). Three of 5 patients with TCPC were successfully bridged to transplant and were supported with 1 VAD. Seven of 12 patients with SCPC were bridged to transplant, and only 1 of 9 patients supported after a stage I procedure survived. CONCLUSIONS The EXCOR Pediatric VAD can provide a bridge to transplant for children with SV anatomy or physiology, albeit less successfully than in children with BV. In this small series, results are better in patients with SCPC and TCPC. VAD support for patients with shunted sources of pulmonary blood flow should be applied with caution.

Association of Center Volume With Mortality and Complications in Pediatric Heart Surgery

OBJECTIVE: Previous analyses have suggested center volume is associated with outcome in children undergoing heart surgery. However, data are limited regarding potential mediating factors, including the relationship of center volume with postoperative complications and mortality in those who suffer a complication. We examined this association in a large multicenter cohort. METHODS: Children 0 to 18 years undergoing heart surgery at centers participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2006–2009) were included. In multivariable analysis, we evaluated outcomes associated with annual center volume, adjusting for patient factors and surgical risk category. RESULTS: A total of 35 776 patients (68 centers) were included. Overall, 40.6% of patients had ≥1 complication, and the in-hospital mortality rate was 3.9%. The mortality rate in those patients with a complication was 9.0%. In multivariable analysis, lower center volume was significantly associated with higher in-hospital mortality. There was no association of center volume with the rate of postoperative complications, but lower center volume was significantly associated with higher mortality in those with a complication (P = .03 when volume examined as a continuous variable; odds ratio in centers with <150 vs >350 cases per year = 1.59 [95% confidence interval: 1.16–2.18]). This association was most prominent in the higher surgical risk categories. CONCLUSIONS: These data suggest that the higher mortality observed at lower volume centers in children undergoing heart surgery may be related to a higher rate of mortality in those with postoperative complications, rather than a higher rate of complications alone.

Bridge to Cardiac Transplant in Children: Berlin Heart versus Extracorporeal Membrane Oxygenation

BACKGROUND For small children requiring mechanical circulatory support as a bridge to transplantation (BTT), extracorporeal membrane oxygenation (ECMO) has been the only option until the recent introduction of the Berlin Heart EXCOR ventricular assist device (Berlin Heart AG, Berlin, Germany). We reviewed our recent experience with these two technologies with particular focus on early outcomes. METHODS Data for 55 consecutive children undergoing BTT between 2001 and 2008 were abstracted from an institutional database. The analysis excluded 13 patients because EXCOR was not used for acute postcardiotomy BTT. Patients were divided into ECMO (n = 21) and EXCOR groups (n = 21). Specific end points included survival to transplant, overall survival, and bridge to recovery. Incidences of adverse events and the duration of support were determined. RESULTS Groups were similar in weight, age, and etiologies of heart failure. Likewise, the incidences of stroke and multisystem organ failure were similar. Survival to transplant, recovery, or continued support was 57% in ECMO and 86% in EXCOR (p = 0.040). EXCOR patients had overall significantly better survival (p = 0.049). Two ECMO patients and 1 EXOR patient were bridged to recovery. The mean duration of support was 15 +/- 12 days in the ECMO group and 42 +/- 43 days in the EXCOR group (p < 0.001). CONCLUSIONS In children requiring BTT, EXCOR provided substantially longer support times than ECMO, without significant increase in the rates of stroke or multisystem organ failure. Survival to transplant and long-term survival was higher with EXCOR.

Preliminary single center North American experience with the Berlin Heart pediatric EXCOR device.

For children requiring mechanical circulatory support as a bridge to cardiac transplantation in North America, options previously were limited to extracorporeal membrane oxygenation (ECMO) or centrifugal pump ventricular assist, both of which were suitable for only very short term application and were associated with significant complications and limitations. The Berlin Heart EXCOR ventricular assist device (VAD) was recently introduced into practice in North America to address this deficiency. We report a preliminary single center experience with the EXCOR in 17 children, 13 who received only a left-sided pump and four who required biventricular support. Before EXCOR placement, six patients were on ECMO, and one was on a centrifugal VAD. Eleven children were bridged to transplantation, one was bridged to recovery, and one remains on support. Three children died during support and one died after explantation. There was one late death nearly 2 years after transplant. Complications included stroke in seven patients, two of which were ultimately fatal. Five patients required re-operations for bleeding or evacuation of hematoma. Despite a disappointing rate of neurologic morbidity, our preliminary experience with the EXCOR has been very encouraging.

Perioperative Methylprednisolone and Outcome in Neonates Undergoing Heart Surgery

BACKGROUND: Recent studies have called into question the benefit of perioperative corticosteroids in children undergoing heart surgery, but have been limited by the lack of placebo control, limited power, and grouping of various steroid regimens together in analysis. We evaluated outcomes across methylprednisolone regimens versus no steroids in a large cohort of neonates. METHODS: Clinical data from the Society of Thoracic Surgeons Database were linked to medication data from the Pediatric Health Information Systems Database for neonates (≤30 days) undergoing heart surgery (2004–2008) at 25 participating centers. Multivariable analysis adjusting for patient and center characteristics, surgical risk category, and within-center clustering was used to evaluate the association of methylprednisolone regimen with outcome. RESULTS: A total of 3180 neonates were included: 22% received methylprednisolone on both the day before and day of surgery, 12% on the day before surgery only, and 28% on the day of surgery only; 38% did not receive any perioperative steroids. In multivariable analysis, there was no significant mortality or length-of-stay benefit associated with any methylprednisolone regimen versus no steroids, and no difference in postoperative infection. In subgroup analysis by surgical-risk group, there was a significant association of methylprednisolone with infection consistent across all regimens (overall odds ratio 2.6, 95% confidence interval 1.3–5.2) in the lower-surgical-risk group. CONCLUSIONS: This multicenter observational analysis did not find any benefit associated with methylprednisolone in neonates undergoing heart surgery and suggested increased infection in certain subgroups. These data reinforce the need for a large randomized trial in this population.

Berlin Heart EXCOR Pediatric ventricular assist device Investigational Device Exemption study: Study design and rationale

BACKGROUND Currently, there are no Food and Drug Administration-approved devices available that can provide long-term mechanical circulatory support to smaller children with severe heart failure as a bridge to heart transplant (HT). In recent years, the Berlin Heart EXCOR Pediatric ventricular assist device (VAD) has emerged as a potential treatment option. Systematic data on the safety and efficacy of the EXCOR are limited. METHODS The Investigational Device Exemption (IDE) clinical study is designed to evaluate the safety and probable benefit of the EXCOR to support regulatory review of the device under the Humanitarian Device Exemption regulation. The study design and rationale are reviewed in light of the well-described challenges inherent in small population studies. RESULTS The Berlin Heart EXCOR IDE clinical study is a prospective, multicenter, single-arm, clinical cohort study. Children aged 0 to 16 years with severe heart failure (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2) due to 2-ventricle heart disease and actively listed for HT comprise the primary study cohort. The control population is a propensity-matched retrospective cohort of children supported with extracorporeal membrane oxygenation, the only bridge device available to smaller children before the EXCOR. The primary efficacy end point is survival to heart transplantation or recovery. The primary safety end point is the incidence of serious adverse events as defined by pediatric Interagency Registry for Mechanically Assisted Circulatory Support criteria. The study will enroll a total of 48 subjects in 2 cohorts based on body surface area (cohort 1 <0.7 m(2), cohort 2 0.7-1.5 m(2)) and is powered to show safety superiority to a prespecified performance goal of 0.25 serious adverse events per day of support. Children ineligible for the primary cohort will still have access to the device in a third compassionate-use cohort where adverse event data will be collected for additional safety characterization of the device. CONCLUSION The Berlin Heart IDE clinical study will be the first bridge-to-HT VAD study designed exclusively for children. It is anticipated that the study will provide important information on the safety and efficacy of the Berlin Heart EXCOR Pediatric in children while providing valuable lessons into the design and conduct of future VAD studies in children.