Post-transplant outcomes of children bridged to transplant with the Berlin Heart EXCOR Pediatric ventricular assist device.

BACKGROUND: Recent data suggest that Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device improves waiting list survival for pediatric heart transplant candidates. Little is known about their post-transplant outcomes. The aim of this analysis was to determine whether there was a difference in early survival for children bridged to transplant with EXCOR versus status 1A pediatric heart transplant patients not transplanted with ventricular assist device support. METHODS AND RESULTS: Pediatric heart transplant patients (n=106) bridged to transplantation with EXCOR were compared with a similarly aged cohort (n=1021) within the Organ Procurement and Transplant Network (OPTN) database (both cohorts from May 2007 to December 2010). In the EXCOR group, 12-month post-transplant survival (88.7%) was similar to OPTN patients listed status 1A who were not on ventricular assist device support at transplant (89.3%; P=0.85) and significantly better than 12-month survival in OPTN patients on extracorporeal membrane oxygenation at transplant (60.3%; P<0.001). Rejection (50%) was a significantly (P=0.005) higher cause of 12-month post-transplant mortality in the EXCOR compared with the OPTN group. Death after transplant was also higher in EXCOR patients with congenital heart disease compared with those with cardiomyopathy (26.1% versus 7.2%; P=0.02). Post-transplant survival was similar in EXCOR patients with ≥1 serious adverse event during ventricular assist device support as those without an event during support. CONCLUSIONS: The 12-month post-transplant survival with EXCOR is comparable with overall pediatric heart transplant survival and superior to survival after extracorporeal membrane oxygenation. Neither adverse events during support nor factors associated with mortality during support influence post-transplant survival. Rejection was a significantly greater cause of post-transplant mortality in EXCOR than in OPTN patients.

Maternal ß-hemolytic streptococcal pharyngeal exposure and colonization in pregnancy.

OBJECTIVES: To report the pharyngeal colonization rate of ß-hemolytic streptococci and changes in the value of antistreptolysin O (ASO) and anti-DNase B serology titers during pregnancy. METHODS: Healthy pregnant women were recruited and blood was drawn in each trimester. The upper limit of normal (ULN) values for ASO and anti-DNase B was calculated for each trimester. Throat swabs were collected for culture and positive cultures were further assessed for the identification of serogroup of the isolated ß-hemolytic streptococcus. RESULTS: Out of a total of 126 pregnant women, 34.1% had positive throat cultures. Group C and group G strains were isolated in 18.2% of throat cultures while group F was detected in 13.5% of cases. The rate of colonization with GAS was 1.6%. There was an overall drop in ASO titer during pregnancy while anti-DNase B titers remained relatively unchanged. ULN values of 164(IU), 157(IU), and 156(IU) were calculated for ASO at the first, second, and third trimesters, respectively. Based on the ULN values, 28.6% of patients had recent streptococcal exposure. CONCLUSIONS: These results show that pregnant women act as a reservoir for spreading potentially immunogenic (groups C and G) and disease producing (group F) virulent strains of streptococci.

Routine Collection of Patient-Reported Outcomes in Thoracic Surgery: A Quality Improvement Study.

BACKGROUND: Patient-reported outcomes are critical for delivering high-quality surgical care, yet they are seldom collected in routine clinical practice. The objective of this quality improvement study was to improve routine patient-reported outcomes collection in a thoracic surgery clinic. METHODS: Thoracic surgery patients at a single academic institution were prospectively monitored from April 2019 to March 2020. The National Institutes of Health-validated Patient-Reported Outcomes Measurement Information System (PROMIS) was used. Using a Model for Improvement design and through multidisciplinary participant observation, we performed multiple plan-do-study-act cycles, an iterative, 4-stage model for rapidly testing interventions, to improve routine collection reliability. RESULTS: During the study period, 2315 patient visits occurred. The baseline PROMIS assessment collection rate was 53%. After convening a multidisciplinary stakeholder team, the key drivers for PROMIS collection were having engaged staff, engaged patients, adequate technological capacity, and adequate time for survey completion, including when to complete the survey during the patient visits. Regular meetings between stakeholders were initiated to promote these key drivers. Several plan-do-study-act cycles were then used to test different interventions, resulting in several positive system shifts, as demonstrated on a statistical process control chart. Adherence to survey collection reached 91% of office visits by approximately 7 months, a 72% relative improvement, which was sustained. CONCLUSIONS: Routine collection of patient-reported outcomes, such as PROMIS, are critical for improving thoracic surgical care. Our study shows that reliably collecting these data is possible in a clinical setting with minimal additional hospital resources.

Biventricular assist devices as a bridge to heart transplantation in small children.

BACKGROUND: Experience with the use of biventricular assist device (BiVAD) support to bridge small children to heart transplantation is limited. METHODS AND RESULTS: We used BIVAD support (Berlin EXCOR) in 9 pediatric heart transplant candidates from 4/05 to 7/07. The median patient age was 1.7 years (12 days to 17 years). The median patient weight was 9.4 kg (3 to 38 kg). All children were supported with multiple intravenous inotropes+/-mechanical ventilation (6) or ECMO (3) before BiVAD implantation. All had significant right ventricular dysfunction. The median pulmonary vascular resistance index (Rpi) was 6.0 WU/m(2). Eight patients were successfully bridged to heart transplantation after a median duration of BiVAD support of 35 days (1 to 77 days). One death occurred after 10 days of support from perioperative renal failure in a 3 kg infant. Five patients required at least 1 blood pump change. One patient had a driveline infection requiring treatment. There were no acute neurological complications, no thromboembolic events, and no bleeding complications. In 2 patients with Rpi >10 WU/m(2) unresponsive to pulmonary vasodilator therapy, Rpi dropped to 1.4 and 4.6 WU/m(2), after 33 and 41 days of support, respectively. All 8 survivors underwent successful heart transplantation. Of 5 patients supported >30 days, 3 developed an extremely elevated (>90%) panel reactive antibody by ELISA that was not confirmed by other methods; none had a positive donor-specific retrospective crossmatch. There was 1 episode of rejection (with hemodynamic compromise) in the 8 transplanted patients. Rpi was normal (<3 WU/m(2)) without pulmonary vasodilators in all patients within 3 months after transplant. There have been no deaths after transplant with a median follow-up of 19 months. CONCLUSIONS: BiVAD support can effectively be used in small children as a bridge to heart transplantation and can be accomplished with low mortality and morbidity. BiVAD support may offer an additional means to reverse extremely elevated pulmonary vascular resistance. Surveillance for HLA antibody sensitization during BiVAD support may be complicated by the development of non-HLA antibodies which may not reflect true HLA presensitization.

Improved waitlist and transplant outcomes for pediatric lung transplantation after implementation of the lung allocation score.

BACKGROUND: Although the lung allocation score (LAS) has not been considered valid for lung allocation to children, several additional policy changes for pediatric lung allocation have been adopted since its implementation. We compared changes in waitlist and transplant outcomes for pediatric and adult lung transplant candidates since LAS implementation. METHODS: The United Network for Organ Sharing database was reviewed for all lung transplant listings during the period 1995 to June 2014. Outcomes were analyzed based on date of listing (pre-LAS vs post-LAS) and candidate age at listing (adults >18 years, adolescents 12 to 17 years, children 0 to 11 years). RESULTS: Of the 39,962 total listings, 2,096 (5%) were for pediatric candidates. Median waiting time decreased after LAS implementation for all age groups (adults: 379 vs 83 days; adolescents: 414 vs 104 days; children: 211 vs 109 days; p < 0.001). The proportion of candidates reaching transplant increased after LAS (adults: 52.6% vs 71.6%, p < 0.001; adolescents: 40.3% vs 61.6%, p < 0.001; children: 42.4% vs 50.9%, p = 0.014), whereas deaths on the waitlist decreased (adults: 28.0% vs 14.4%, p < 0.001; adolescents: 33.1% vs 20.9%, p < 0.001; children: 32.2% vs 25.0%; p = 0.025), despite more critically ill candidates in all groups. Median recipient survival increased after LAS for adults and children (adults: 5.1 vs 5.5 years, p < 0.001; children: 6.5 vs 7.6 years, p = 0.047), but not for adolescents (3.6 vs 4.3 years, p = 0.295). CONCLUSIONS: Improvements in waiting time, mortality and post-transplant survival have occurred in children after LAS implementation. Continued refinement of urgency-based allocation to children and broader sharing of pediatric donor lungs may help to maximize these benefits.

Outcomes and Trends of Ventricular Assist Device Selection in Children with End-Stage Heart Failure.

We aimed to examine trends in ventricular assist device (VAD) selection, continuous flow devices (CFD) versus pulsatile flow devices (PFD), and their associated outcomes in children eligible for both device types. To accomplish this, the United Network for Organ Sharing database was reviewed for pediatric patients listed for heart transplant (HT) from January 2007 to June 2014. Patients were included if a durable VAD was present at wait listing or when removed from the waiting list and who met size eligibility for a CFD (BSA > 1.0 m). In total, 253 patients met inclusion criteria, 144 (57%) CFD and 109 (43%) PFD. Device type varied significantly based on year with CFD increasing from 11% in 2007 to 88% in 2014 (p < 0.01). PFD patients were younger, had a lower BSA, and an increased rate of extracorporeal membrane oxygenation and biventricular assist device support at listing. Survival to transplant or recovery was similar for CFDs and PFDs (96 vs. 94%; p = 0.57), as was the post-HT survival, 95% for both device types. Despite PFD patients having more risk factors for a poor outcome, survival was similar between device types. Even so, there is a dramatic trend toward CFD utilization in patients who are large enough to support one.

Improved survival after heart transplant for failed Fontan patients with preserved ventricular function.

BACKGROUND: Patients with a failing Fontan continue to have decreased survival after heart transplant (HT), particularly those with preserved ventricular function (PVF) compared with impaired ventricular function (IVF). In this study we evaluated the effect of institutional changes on post-HT outcomes. METHODS: Data were retrospectively collected for all Fontan patients who underwent HT. Mode of failure was defined by the last echocardiogram before HT, with mild or no dysfunction considered PVF and moderate or severe considered IVF. Outcomes were compared between early era (EE, 1995 to 2008) and current era (CE, 2009 to 2014). Management changes in the CE included volume load reduction with aortopulmonary collateral (APC) embolization, advanced cardiothoracic imaging, higher goal donor/recipient weight ratio and aggressive monitoring for post-HT vasoplegia. RESULTS: A total of 47 patients were included: 27 in the EE (13 PVF, 14 IVF) and 20 in the CE (12 PVF, 8 IVF). Groups were similar pre-HT, except for more PLE in PVF patients. More patients underwent APC embolization in the CE (80% vs 28%, p < 0.01). There was no difference in donor/recipient weight ratio between eras. There was a trend toward higher primary graft failure for PVF in the EE (77% vs 36%, p = 0.05) but not the CE (42% vs 75%, p = 0.20). Overall, 1-year survival improved in the CE (90%) from the EE (63%) (p = 0.05), mainly due to increased survival for PVF (82 vs 38%, p = 0.04). CONCLUSIONS: Post-HT survival for failing Fontan patients has improved, particularly for PVF. In the CE, our Fontan patients had a 1-year post-HT survival similar to other indications.

Adverse events in children implanted with ventricular assist devices in the United States: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).

BACKGROUND: Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are <19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions. RESULTS: This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 81% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population. CONCLUSIONS: In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar.

Pediatric Quality of Life while Supported with a Ventricular Assist Device.

OBJECTIVE: Ventricular assist devices (VADs) have emerged as an important treatment option for bridging pediatric patients with heart failure to transplant. VADs have shown improved survival; however, the pediatric quality of life (QoL) while on VAD support is unknown. We aimed to evaluate the QoL of our pediatric patients while supported with a VAD. DESIGN: In this prospective study, pediatric patients who underwent VAD placement, and their parents, were administered a generic Pediatric Quality of Life Inventory (PedsQL) 4.0 pre-VAD implant, when feasible, after the acute postoperative period, and then periodically until heart transplant or death. Their final scores while on support were compared with three previously reported groups: healthy controls, outpatients with severe heart disease, and children after heart transplant. RESULTS: From January 2008 to July 2014, 13 pediatric patients required VAD support greater than 2 weeks and completed a PedsQL. The mean age at implant was 10.0 ± 4.2 years and median duration of support was 1.6 (0.5-19.7) months. Eleven (85%) patients survived to transplant with one (8%) patient remaining alive on support. The median duration of support prior to their final PedsQL was 1.4 (0.5-11.4) months. Patients self-reported significantly (P < .05) lower total and physical QoL scores when compared with all three comparison groups. Self-reported psychosocial QoL scores were significantly lower than healthy controls only. Parent proxy-reported scores were significantly lower than all three comparison groups for all three categories (P < .05). CONCLUSIONS: A large deficit exists in the total QoL of pediatric patients supported by a VAD compared with outpatient management of severe heart disease or postheart transplant patients; however, VAD patients do represent a group with more severe heart failure. Improvements in QoL must be made, as time spent with a VAD will likely continue to increase.

Early Biventricular Assist Device Use in Children: A Single-Center Review of 31 Patients.

Biventricular assist device (BiVAD) support is considered a risk factor for worse outcomes compared with left ventricular assist device (LVAD) alone for children with end-stage heart failure. It remains unclear whether this is because of the morbidity associated with a second device or the underlying disease severity. We aimed to show that early BiVAD support can result in good survival by analyzing our prospectively collected database for all pediatric patients who underwent BiVAD implantation. From 2005 to 2009, BiVADs were used exclusively. From 2010 to 2014, LVAD alone was considered, maintaining a low threshold for BiVAD support. All BiVADs were pulsatile devices. Thirty-one patients with median age of 3.5 years received BiVAD support. Diagnoses included dilated cardiomyopathy in 17 (55%), myocarditis in 6 (19%), and congenital heart disease in 3 (10%). Survival to transplant was achieved in 27 (87%) with a median duration of 41 days (interquartile range, 15-69). Adverse event rates (per 100 days of support) were bleeding at 0.52, infection at 1.17, and central nervous system dysfunction at 0.78. Of those who survived to transplant, 26 (96%) remain alive with a median follow-up of 55 months. These results show that BiVAD support can bridge patients to transplant with excellent long-term survival.

Continuous Flow Device Support in Children Using the HeartWare HVAD: 1,000 Days of Lessons Learned From a Single Center Experience.

The purpose of this study is to provide a single center experience with a continuous flow device in adolescents with end-stage heart failure. A retrospective single center analysis of patients aged 18 years or younger implanted with HVAD (HeartWare Inc, Framingham, MA) between October 2012 and March 2014 was performed. Demographics, preimplant and postimplant clinical data, survival, and adverse events (AEs) were recorded. A matched group of adults based on diagnosis, body surface area (BSA), and time period were used for outcome comparisons. Six adolescents with dilated cardiomyopathy were implanted with the HVAD. Median age and BSA were 13.4 years and 1.45 m2, respectively. All were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile-1 or profile-2. Median days on device were 108 with total patient-days on device of 1,017. Four adolescents were discharged home on device all in New York Heart Association 1. Five underwent transplantation with 100% survival. There were 18 AEs with one AE per 170 days on device. Compared with the adult cohort (n = 5), there was no difference in 1 year survival (p = 0.32). HVAD support in adolescents is highly successful as a bridge to transplantation. It provides early rehabilitation and improvement in quality of life. Morbidity is not negligible but appears comparable with that seen in adults.

Lung transplant is a viable treatment option for patients with congenital and acquired pulmonary vein stenosis.

BACKGROUND: Congenital pulmonary vein stenosis (PVS) is associated with high mortality because surgical repair is usually not feasible or is ineffective. In addition, acquired PVS after repair of congenital heart disease is a potential complication that occurs in 5% to 10% of patients and carries a poor prognosis. Lung transplantation has been proposed as a viable option. However, long-term outcomes after lung transplant in these patients remain unknown. METHODS: This was a retrospective review of prospectively maintained database. RESULTS: Between 1990 and 2010, 20 patients (12 girls, 8 boys) with PVS underwent transplantation. Of these, 8 had acquired stenosis from prior repair for total anomalous pulmonary venous return and 1 from atrioventricular canal repair. The median waiting time was 26 days. The mean age at transplant was 1.1 ± 0.89 years, and 16 of the 20 patients were white. All patients received bilateral lung transplants on cardiopulmonary bypass. Four patients (20%) were receiving extracorporeal membrane oxygenation (ECMO) support before transplant, and 3 (15%) required ECMO after transplant due to graft dysfunction. The mean intensive care unit stay was 33.5 ± 29.1 days, and the mean hospital stay was 58.7 ± 43.5 days. The 30-day mortality was 10%. ECMO support in the peri-operative period was the main predictor of 30-day and 1-year mortality (hazard ratio, 3.6; p = 0.01). The overall 5-year survival of the entire cohort was 59.8% (67.3% congenital vs 50.7% acquired). The predominant cause of long-term mortality was bronchiolitis obliterans. The 5-year bronchiolitis obliterans-free survival was 48% (57.2% congenital vs 41% acquired). CONCLUSION: Lung transplant is a viable treatment option for PVS, particularly for patients with diffuse disease or failed surgical correction.

Trends in the indications and survival in pediatric heart transplants: a 24-year single-center experience in 307 patients.

BACKGROUND: Heart transplantation is the only viable treatment for children with end-stage heart failure due to congenital heart disease (CHD) or cardiomyopathy. This study reviewed the trends in the indications for transplant and survival after transplant during the past 24 years. METHODS: A retrospective review was performed of the 307 heart transplants performed at our center since 1986. To analyze the trends in the indications for transplant as well as operative death and late-survival, the data were divided into three periods in 8-year increments: 1986 to 1993 (50 patients), 1994 to 2001 (116 patients), and 2002 to 2009 (141 patients). RESULTS: The indications for transplantation were 39% cardiomyopathy, 57% CHD, and 4% retransplant. Of the 173 with CHD, 139 (80%) had single-ventricle (SV) anomalies. In the CHD group, transplantation for failed SV palliation, including Fontan procedure, became the predominant indication in the last 8-year interval of our program. Survival after transplant was the best in patients with cardiomyopathy and the worst in patients with failed palliations for SV anomalies, including failed Fontan procedures. CONCLUSIONS: Transplantation for heart failure related to failed SV palliation has become the most common indication for patients with CHD. The high-risk nature of these transplants will have significant implications for heart transplant programs as more infants with SV anomalies survive palliative procedures performed during infancy.

Extracorporeal membrane oxygenation in pediatric lung transplantation.

OBJECTIVE: Effectiveness of preoperative and postoperative extracorporeal membrane oxygenation support in pediatric lung transplantation was studied. METHODS: Institutional database of pediatric lung transplants from 1990 to 2008 was reviewed. RESULTS: Three hundred forty-four patients underwent lung transplants in the study period. Thirty-three of 344 patients (9.6%) required perioperative extracorporeal membrane oxygenation support. Fifteen patients (median, age 1.3 years; range, 0.2-18 years) required 16 pretransplant extracorporeal membrane oxygenation runs. Indications were respiratory failure (8/16, 50%), severe pulmonary hypertension (5/16, 31%), and cardiopulmonary collapse (3/16, 19%). Four of these patients (27%) also required postoperative support. Six (40%) were weaned before lung transplant. Six (40%) survived to hospital discharge. Survival to discharge was higher among patients weaned before lung transplant (4/6, 66% vs 2/9, 22%). Twenty-two patients (median age, 9.4 years; range, 0.2-21 years) underwent 24 extracorporeal membrane oxygenation runs after lung transplant. Indications for postoperative support were primary graft dysfunction (18/24, 75%), pneumonia (4/24, 16%), and others (2/24, 9%). Median time between lung transplant and institution of extracorporeal membrane oxygenation was 32 hours (range, 0-1084 hours); median duration of support was 141 hours (range, 48-505 hours). Five of these patients (23%) survived to hospital discharge. Among nonsurvivors, causes of death were intractable respiratory failure (12/17, 70%) and infectious complications (4/17, 24%). CONCLUSIONS: Need for perioperative extracorporeal membrane oxygenation support is associated with significant morbidity and mortality among pediatric patients receiving lung transplants. A subset of patients who can be weaned from support preoperatively have greater likelihood of survival.