Christina VanderPluym

Impact of medication non-adherence on survival after pediatric heart transplantation in the USA

BACKGROUND Medication non-adherence (NA) can result in life-threatening illness in children after solid-organ transplantation. Little is known about the incidence, risk factors and outcomes of NA in large numbers of pediatric heart transplant (HT) recipients. METHODS Organ Procurement Transplant Network (OPTN) data were used to identify all children <18 years of age in the U.S.A. who underwent HT from October 1999 to January 2007. Cox proportional hazards analysis was used to identify risk factors for NA and the effect on graft survival. RESULTS Of 2,070 pediatric heart transplants performed the median age at transplant was 6 years (interquartile range [IQR] 0 to 13 years); 40% had congenital heart disease (CHD), 7% were re-transplants, 42% were non-white and 43% had Medicaid insurance. Overall, 186 (9%) children had a report of NA at a median age of 15 years with more than two-thirds of NA episodes occurring after 12 years of age. Factors independently associated with NA were: adolescent age at transplant (hazard ratio [HR] 7.0, 95% confidence interval [CI] 4.1 to 12, compared with infants); black race (HR 2.3, 95% CI 1.7 to 3.3, compared with white); Medicaid insurance (HR 2.0, 95% CI 1.5 to 2.7, compared with non-Medicaid insurance); and ventilator or ventricular assist device (VAD) support at transplant. The risk of mortality conditional upon report of NA was 26% at 1 year and 33% at 2 years. CONCLUSIONS Medication NA is an important problem in pediatric HT recipients and is associated with high mortality. Adolescent age, black race, Medicaid insurance and invasive hemodynamic support at transplant were associated with NA, whereas time on the wait list and gender were not. Targeted interventions among at-risk populations may be warranted.

Outpatient management of intra-corporeal left ventricular assist device system in children: a multi-center experience.

Little is known about the outcomes of children supported on intracorporeal left ventricular assist device (HVAD), and the feasibility of outpatient management. All centers with pediatric patients discharged from the hospital on the device were identified using company database. A total of 14 centers were contacted, with 9 centers, contributing data retrospectively. From 2011 to 2013, 12 pediatric patients (7 females), mean aged 11.9 ± 2.3 years (range 8–15), mean weight 43 ± 19 kg (range 18–81), mean body surface area 1.3 ± 0.3 m2 (range 0.76–1.96) were identified. Diagnosis included: dilated cardiomyopathy (CMP) (n = 5), noncompaction CMP (n = 4), toxic CMP (n = 2) and viral CMP (n = 1). Indications for support were permanent support (n = 1), bridge to recovery (n = 1) and bridge to transplantation (n = 10). Prior to HVAD implantation, all patients received intravenous inotropes and two patients were on temporary mechanical support. Overall mortality was 0%. Mean duration of inpatient and outpatient support were 56 (range: 19–95 days) and 290 days (range: 42–790), respectively. Mean readmission rate was 0.02 per patient month (2.1 per patient). No adverse events involving emergency department occurred. Eight children resumed local schooling. Home discharge of children supported on HVAD is feasible and safe. School integration can be achieved. There is wide center variability to discharge practice for children.

A multicenter study of the HeartWare ventricular assist device in small children

A multicenter study of the HeartWare ventricular assist device in small children Oliver Miera, MD, Richard Kirk, MD, Holger Buchholz, MD, Katharina R.L. Schmitt, MD, Christina VanderPluym, MD, Ivan M. Rebeyka, MD, Neil Wrightson, MD, Felix Berger, MD, Massimo Griselli, MD, and Jennifer Conway, MD From the Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany; Department of Pediatric Cardiology, Freeman Hospital, Newcastle Upon Tyne, UK; Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada; and the Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts, USA

Advanced Therapies for Congenital Heart Disease: Ventricular Assist Devices and Heart Transplantation

Improvement in pre-, peri-, and postoperative management of congenital heart disease (CHD) has significantly increased long-term survival in children with CHD. However, there is a subset of patients with CHD who are either poor candidates for surgical palliation or in whom surgical intervention has failed and require advanced cardiac support. Heart transplant (HT) as a therapy for CHD has undergone tremendous evolution. Though transplantation remains the standard of care to improve survival and quality of life when conventional medical and surgical therapies have failed, it remains limited by the scarcity and unpredictability of donor organ availability. As such, the use of ventricular assist devices (VADs) as a bridge to transplant is gaining increasing popularity. Because of improvement in device technology, and reduced rate of VAD-related complications, the use of these devices is expanding to smaller children and more complex congenital anatomy. Challenges with VAD support and HT in the congenital heart population will be addressed in this review with focus on: (1) reasons for VAD implantation; (2) VAD support in Fontan circulation; (3) challenges with human leukocyte antigen (HLA) sensitization in HT; and (4) effect of VAD support on HT in CHD.

Ventricular assist devices in children: progress with an orphan device application.

Pediatric mechanical circulatory support (MCS) has advanced tremendously over the last decade, with momentum building in the development and implantation of durable ventricular assist devices (VADs) in smaller children with increasingly complex anatomy. Despite these advancements, VAD support for children continues to lag behind support options for adults. The most obvious disparity is the limited number of devices suitable for children for both short- and long-term support. Thus, there has been burgeoning interest in developing devices specifically tailored to suit the unique needs of children. From a design perspective, pediatric VADs differ significantly from adult devices: they are required to support a wide range of patient sizes (from newborn to adolescence), to allow for the increased circulatory demand commensurate with growth, and to accommodate the anatomic and physiological heterogeneity of congenital heart disease. Beyond the challenges of designing and developing pediatric VADs, there are multiple barriers to the clinical evaluation of these devices because of the small number of children who require this level of support. Therefore, it is considered infeasible to test device safety and effectiveness through large randomized, controlled trials like the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH),1 a large adult study. Additionally, industry is disincentivized to invest the necessary resources in the research and development of pediatric-specific medical devices with applicability to such a narrow market population.2 In the United States, the Food and Drug Administration (FDA) is tasked with the responsibility of ensuring that medical devices marketed in the United States have met the requirements establishing the safety and effectiveness for use in humans to treat a specific condition. Many pediatric-specific medical devices, including VADs, fall under the category of a humanitarian use device.3 Humanitarian use devices are devices that are used to treat or diagnose …

Now how do we get them home? Outpatient care of pediatric patients on mechanical circulatory support.

The last five yr have been monumental for the pediatric heart failure community. In the US, the most notable has been the FDA approval of the first pediatric specific device (Berlin Heart EXCOR®; Berlin Heart, Inc., Berlin, Germany). Subsequently, the field of heart failure has gained a great deal of knowledge regarding the nuances of MCS in children. Despite FDA approval in the US, the Berlin EXCOR® is only currently indicated for in‐hospital use. Due to the limitations with discharge and the positive in‐ hospital experiences with the Berlin EXCOR®, there has been an increased interest in the implantation of adult durable devices into children. While many institutions have focused their intial efforts on the first phase of care within the hospital, they are now ready to tackle the challenge of how to safely transition children to the community setting.

Outcomes following implantation of mechanical circulatory support in adults with congenital heart disease: An analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)

BACKGROUND Adults with congenital heart disease represent an expanding and unique population of patients with heart failure (HF) in whom the use of mechanical circulatory support (MCS) has not been characterized. We sought to describe overall use, patient characteristics, and outcomes of MCS in adult congenital heart disease (ACHD). METHODS All patients entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between June 23, 2006, and December 31, 2015, were included. Patients with ACHD were identified using pre-operative data and stratified by ventricular morphology. Mortality was compared between ACHD and non-ACHD patients, and multivariate analysis was performed to identify predictors of death after device implantation. RESULTS Of 16,182 patients, 126 with ACHD stratified as follows: systemic morphologic left ventricle (n = 63), systemic morphologic right ventricle (n = 45), and single ventricle (n = 17). ACHD patients were younger (42 years ± 14 vs 56 years ± 13; p < 0.0001) and were more likely to undergo device implantation as bridge to transplant (45% vs 29%; p < 0.0001). A higher proportion of ACHD patients had biventricular assist device (BiVAD)/total artificial heart (TAH) support compared with non-ACHD patients (21% vs 7%; p < 0.0001). More ACHD patients on BiVAD/TAH support were INTERMACS profile 1 compared with patients on systemic left ventricular assist device (LVAD) support (35% vs 15%; p = 0.002). ACHD and non-ACHD patients with LVADs had similar survival; survival was worse for patients on BIVAD/TAH support. BiVAD/TAH support was the only variable independently associated with mortality (early phase hazard ratio 4.4; 95% confidence interval, 1.8-11.1; p = 0.001). For ACHD patients receiving MCS, ventricular morphology was not associated with mortality. CONCLUSIONS ACHD patients with LVADs have survival similar to non-ACHD patients. Mortality is higher for patients requiring BiVAD/TAH support, potentially owing to higher INTERMACS profile. These outcomes suggest a promising role for LVAD support in ACHD patients as part of the armamentarium of therapies for advanced HF.

Second annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) report: Pre-implant characteristics and outcomes

BACKGROUND Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute-sponsored North American database, provides a platform to understand this emerging population. METHODS Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs. RESULTS Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3-10.0) years for paracorporeal continuous-flow pumps (n = 60), 1.7 (0.4-5.3) years for paracorporeal pulsatile pumps (n = 105), and 15.0 (11.3-16.9) years for implantable continuous-flow pumps (n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high. CONCLUSIONS Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.

Survival in patients removed from the heart transplant waiting list before receiving a transplant

BACKGROUND Little is known about the outcomes in patients who are removed from the heart transplant (HT) waiting list before receiving a transplant. We sought to analyze outcomes in such patients in the United States (U.S.) in the current era. METHODS All patients aged ≥ 18 years old listed for a primary HT in the U.S. between July 2004 and September 2010 were identified. Outcomes in those removed from the list by March 2011 (survival, relisting, HT) were examined using time-to-event analyses. RESULTS Of 15,061 patients listed for primary HT, 10,168 (68%) received a HT, 1,393 (9%) died on the waiting list, and 1,871(12%) were removed before receiving HT. Of patients removed from the list, 560 (30%) were removed due to clinical improvement, 692 (37%) due to deterioration, and 619 (33%) due to other reasons. After removal, 30-day and 1-year survival were 99.6% and 94%, respectively, in patients removed due to improvement and 44% and 26%, respectively, in patients removed due to deterioration. Multivariable predictors of death after removal were removal due to clinical deterioration, hypertrophic or restrictive cardiomyopathy, United Network of Organ Sharing status 1A/1B at listing, and renal dysfunction. Only 27 patients (4.8%) among those removed due to improvement, 21 (3.0%) removed due to deterioration, and 46 (7.4%) removed due to other reasons were relisted. CONCLUSIONS One in 8 patients listed for HT in the U.S. are removed from the waiting list before receiving HT. The indication for removal (clinical deterioration vs improvement) is the strongest independent predictor of survival after removal from the list.

Safety and Efficacy of Warfarin Therapy in Kawasaki Disease

Objective To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. Study design We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5. Results In 9 patients (5 male), median age 14.4 years (range 7.1–22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3–13.3 years). Goal INR was 2.0–3.0 (n = 6) or 2.5–3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%‐85%), and median percentage of INRs in range was 68% (52%‐87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient‐years (95% CI 0.9–12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients. Conclusions Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two‐thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.