Hepatorenal dysfunction assessment with the Model for End-Stage Liver Disease Excluding INR score predicts worse survival after heart transplant in pediatric Fontan patients.

BACKGROUND: Fontan physiology results in multiorgan dysfunction, most notably affecting the liver and kidney. We evaluated the utility of Model for End-Stage Liver Disease Excluding INR (MELD-XI) score, a score evaluating the function of both liver and kidney to identify Fontan patients at increased risk for morbidity and mortality post-heart transplant. METHODS: The Pediatric Heart Transplant Society database was queried to identify Fontan patients listed for heart transplant between January 2005 and December 2018. MELD-XI scores were calculated at listing and heart transplant. A multivariable analysis was conducted to identify risk factors for post-heart transplant mortality. Demographic, clinical characteristics, and survival differences were evaluated and compared between the high and low MELD-XI score cohorts. The impact of changing MELD-XI scores during the waitlist period on post-heart transplant outcomes was also evaluated. RESULTS: Of 565 Fontan patients who underwent transplantation, 524 (93%) had calculable MELD-XI scores at the time of heart transplant: 421 calculable at listing and 392 calculable at listing and at heart transplant. On multivariable analysis, only MELD-XI score (squared) (hazard ratio, 1.007), history of protein-losing enteropathy (hazard ratio, 2.1), and ventricular assist device use at transplant (hazard ratio, 3.4) were risk factors for early phase post-heart transplant mortality. Patients with high MELD-XI scores at heart transplant had inferior survival post-heart transplant (P = .02); those in the high MELD-XI score cohort at wait listing and heart transplant tend to have the worst post-heart transplant survival; however, this was not significant (P = .42). CONCLUSIONS: The MELD-XI, an easily calculated score, serves as a valuable aid in identifying pediatric Fontan patients at increased risk for post-heart transplant mortality.

STS INTERMACS Database: The Key to Conduct Single-Arm Trials in Advanced Heart Failure Patients.

BACKGROUND: Safe introduction of novel mechanical circulatory support (MCS) devices into clinical practice is a challenging process. Single-arm trials using a control arm from existing database is an effective alternative that could be applied for regulatory approval. This study analyzes the capability of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database to establish objective performance criteria and select patient population that could be used for future single-arm MCS trials. METHODS: Patients with INTERMACS profiles IM1-2 and IM3-5, who underwent implantation of isolated left ventricular assist devices between 2014 and 2017, were included. Both cohorts were further stratified into shock and nonshock groups using surrogate markers of shock (extracorporeal membrane oxygenation, temporary ventricular assist device, vasopressor infusions). Survival, transplantation rates, adverse events, 6-minute walk test, and quality-of-life measures were obtained for all 4 groups at 6 and 12 months. RESULTS: Total of 7907 patients were divided into IM1-2 (n = 3909), IM3-5 (n = 3998), shock (n = 3469), and nonshock (n = 3040) groups. Recategorization occurred in 11% of patients from the IM3-5 group into the shock group. Overall, patients in the shock group had similar outcomes to the IM1-2 group (1-year survival: 86% vs 85%; P = .74). Patients in the nonshock group also had similar outcomes to the IM3-5 (1-year survival: 90% vs 90%; P = .43). CONCLUSIONS: The INTERMACS database can successfully establish objective performance criteria and concurrent control group for single-arm trials that could be used to support regulatory approval of new, less invasive MCS. INTERMACS data allow reliable comparisons of outcomes and adverse events.

Concordance of Treatment Effect: An Analysis of The Society of Thoracic Surgeons Intermacs Database.

BACKGROUND: The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations. METHODS: Patients (≥19 years of age) enrolled into STS Intermacs between August 2017 and June 2019 were stratified by device type (continuous flow, centrifugal left ventricular assist device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by 3 statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis). RESULTS: Of 4448 patients, 2012 (45.2%) received the CF-HL and 2436 (54.8%) received the CF-FML. One-year survival for the CF-FML was 88% vs 79% for the CF-HL (overall P < .001), with a hazard ratio for mortality of 3.18 for the CF-HL (P < .0001) after risk adjustment. With propensity score matching (n = 1400 each cohort), 1-year survival was 87% for the CF-FML vs 80% for the CF-HL, with a hazard ratio of 3.20 for mortality with the CF-HL (P < .0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving the CF-HL was associated with a hazard ratio of 3.11 (P < .0001). CONCLUSIONS: Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of the CF-FML vs CF-HL.

Quantifying the impact from stroke during support with continuous flow ventricular assist devices: An STS INTERMACS analysis.

INTRODUCTION: Adverse events, especially strokes, during the implantation of continuous flow durable left ventricular assist devices (LVADs) remain the major barriers to greater application among patients with ambulatory advanced heart failure. METHODS: Between June 2014 and June 2017, a total of 9,489 patients in the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support database received 10,285 continuous flow LVADs, with follow-up through June 2018. RESULTS: During the follow-up period, 1,515 (16%) patients suffered 1 or more strokes, with a nearly equal frequency of ischemic and hemorrhagic etiology. The risk of stroke was about 4% in the first month, 9% during the first 6 months, and 14% in the first year. By multivariable hazard function analysis, the major risk factors identified in the early phase were LVAD centrifugal flow device and concomitant cardiac surgery, whereas in the constant phase (longer term), a history of repeated non-compliance was most associated with a stroke event. Using a modulated renewal model, the occurrence of an ischemic and especially a hemorrhagic stroke dominated as risk factors for subsequent mortality. Six-month survival after an ischemic stroke was 70%, and after a hemorrhagic stroke, it was <50%. Disabling stroke as judged by Modified Rankin Score was associated with significantly worse survival at 1 and 2 years compared with strokes with mild or no early disability. CONCLUSIONS: This study confirms the 20% incidence of stroke over the first 2 years with axial flow and hybrid (magnetic and hydrodynamic) levitated centrifugal flow pumps. This study suggests a major increase in 1- and 2-year mortality among those with an initial disabling vs non-disabling stroke. To better understand the impact of strokes after implantation and the effect of prevention and intervention strategies, we need more complete Modified Rankin Scores and quality of life data during the stroke recovery period.

Characteristics, risks, and outcomes of post-transplant lymphoproliferative disease >3 years after pediatric heart transplant: A multicenter analysis.

Post-transplant lymphoproliferative disorder (PTLD) is a significant complication after pediatric heart transplantation (HT), occurring in 5%-15% of patients within 3 years. Data >3 years from HT are limited. We sought to describe the prevalence, risk factors, and outcomes of PTLD occurring late (>3 years) after pediatric HT in the Pediatric Heart Transplant Study from 1993 to 2010. Among 3844 primary HT patients, 110 (3%) developed late, nonrecurrent PTLD. The hazard rate for late PTLD was constant at 0.01 events/year out to 20 years after HT. Risk factors for late PTLD were younger age at HT (HR 1.06, P = 0.003) and Epstein-Barr virus (EBV) naivety (HR 1.65, P = 0.02). Survival after late PTLD was 86% and 68% at 1 and 5 years, with nonwhite race (HR 2.27, P = 0.03) and earlier year of HT (HR 1.03, P = 0.04) independently associated with mortality. Acute rejection and infection were both common after late PTLD, occurring in 26% and 34% of patients. The constant late hazard and contribution of EBV to late PTLD suggest that vigilance for development of PTLD, including for EBV conversion, should persist indefinitely after pediatric HT. The reasons for elevated risk of death for nonwhites after late PTLD are unclear and warrant further investigation.

Linkage of Medicare Records to the Interagency Registry of Mechanically Assisted Circulatory Support.

BACKGROUND: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a United States registry for adults receiving durable United States Food and Drug Administration-approved mechanical circulatory support devices (MCSDs). We merged INTERMACS records with Medicare claims to investigate the uncertainty of penetrance of Medicare beneficiaries within INTERMACS. METHODS: INTERMACS records and Medicare claims (January 1, 2008, through December 31, 2013) from the Centers for Medicare and Medicaid (CMS) were linked using a deterministic matching methodology. RESULTS: There was annual growth of CMS and INTERMACS centers performing durable MCSD implants among adults from 2008 through 2013 (54% and 87% increase, respectively). The number of CMS centers outnumbered INTERMACS centers throughout all years, with the 68% to 88% of CMS centers being represented in INTERMACS. Although annual patient volume was greatest for INTERMACS, the absolute number of patients significantly increased annually across both data sets from 2008 through 2013 (149% increase in CMS; 268% increase in INTERMACS). As a proportion of all INTERMACS registrants, Medicare beneficiary representation grew from 30% in 2008 to a high of 48% in 2010 and remained stable thereafter. Representation within INTERMACS of MCSDs implanted in Medicare beneficiaries more than doubled, from 36% in 2008 to 77% in 2013. CONCLUSIONS: Using a merged data set of MCSDs implanted between 2008 and 2013, we report that the vast majority of CMS centers and Medicare beneficiaries receiving MCSDs are increasingly captured in INTERMACS. Accordingly, contemporary studies in INTERMACS are relevant and generalizable to the Medicare population.

Biventricular Support With Intracorporeal, Continuous Flow, Centrifugal Ventricular Assist Devices.

BACKGROUND: The incidence of right ventricular dysfunction requiring right ventricular assist device after left ventricular assist device placement has been reported between 10% to 30%. The mortality rate is higher compared with patients who require left ventricular assist device only; the most effective and safest biventricular assist device remains unknown. We aimed to determine the survival outcomes and frequency of adverse events in patients with two durable, intracorporeal, continuous flow centrifugal pumps for support. METHODS: Between November 2012 and June 2015, 38 patients were identified from INTERMACS received durable, intracorporeal continuous flow centrifugal pumps for biventricular support. Pediatric patients were excluded. Mean age was 47 years, and 74% of patients were male. The common primary diagnoses in this cohort were dilated myopathy, idiopathic (37%) and ischemic (16%). RESULTS: Nineteen participating centers implanted devices in 38 patients; 11 patients died with device in place, 9 patients received a heart transplant, and 18 were alive on support with the right ventricular assist device in place. Survival outcomes were 68% at 6 months and 62% at 12 months. The left ventricular assist device was placed in the left ventricle apex in 91% of cases, and in 9%, the location was not specified. The right ventricular assist device was placed in the right ventricle in 50%, right atrium in 37%, and not specified in 13%. The adverse events included infection 50%, bleeding 44%, respiratory failure 31.6%, and malfunction 26.3%; neurologic dysfunction 26.3%; renal dysfunction 18.4%; and arrhythmia 18.4%. CONCLUSIONS: The use of durable, intracorporeal, continuous flow centrifugal pumps for management of advanced biventricular heart failure is associated with high morbidity and mortality. Further investigation of this device configuration is warranted.

Early Right Ventricular Assist Device Use in Patients Undergoing Continuous-Flow Left Ventricular Assist Device Implantation: Incidence and Risk Factors From the Interagency Registry for Mechanically Assisted Circulatory Support.

BACKGROUND: To investigate preimplant risk factors associated with early right ventricular assist device (RVAD) use in patients undergoing continuous-flow left ventricular assist device (LVAD) surgery. METHODS AND RESULTS: Patients in the Interagency Registry for Mechanically Assisted Circulatory Support who underwent primary continuous-flow-LVAD surgery were examined for concurrent or subsequent RVAD implantation within 14 days of LVAD. Risk factors for RVAD implantation and the combined end point of RVAD or death within 14 days of LVAD were assessed with stepwise logistic regression. We compared survival between patients with and without RVAD using Kaplan-Meier method and Cox proportional hazards modeling. Of 9976 patients undergoing continuous-flow-LVAD implantation, 386 patients (3.9%) required an RVAD within 14 days of LVAD surgery. Preimplant characteristics associated with RVAD use included interagency registry for mechanically assisted circulatory support patient profiles 1 and 2, the need for preoperative extracorporeal membrane oxygenation or renal replacement therapy, severe preimplant tricuspid regurgitation, history of cardiac surgery, and concomitant procedures other than tricuspid valve repair at the time of LVAD. Hemodynamic determinants included elevated right atrial pressure, reduced pulmonary artery pulse pressure, and reduced stroke volume. The final model demonstrated good performance for both RVAD implant (area under the curve, 0.78) and the combined end point of RVAD or death within 14 days (area under the curve, 0.73). Compared with patients receiving an isolated LVAD, patients requiring RVAD had decreased 1- and 6-month survival: 78.1% versus 95.8% and 63.6% versus 87.9%, respectively (P<0.0001 for both). CONCLUSIONS: The need for RVAD implantation after LVAD is associated with indices of global illness severity, markers of end-organ dysfunction, and profiles of hemodynamic instability.

Bacterial infections after pediatric heart transplantation: Epidemiology, risk factors and outcomes.

BACKGROUND: Bacterial infections represent a major cause of morbidity and mortality in heart transplant recipients. However, data describing the epidemiology and outcomes of these infections in children are limited. METHODS: We analyzed the Pediatric Heart Transplant Study database of patients transplanted between 1993 and 2014 to determine the etiologies, risk factors and outcomes of children with bacterial infections post-heart transplantation. RESULTS: Of 4,458 primary transplants in the database, there were 4,815 infections that required hospitalization or intravenous therapy, 2,047 (42.51%) of which were bacterial. The risk of bacterial infection was highest in the first month post-transplant, and the bloodstream was the most common site (24.82%). In the early post-transplant period (<30 days post-transplant), coagulase-negative staphylococci were the most common pathogens (16.97%), followed by Enterobacter sp (11.99%) and Pseudomonas sp (11.62%). In the late post-transplant period, community-acquired pathogens Streptococcus pneumoniae (6.27%) and Haemophilus influenzae (2.82%) were also commonly identified. Patients' characteristics independently associated with acquisition of bacterial infection included younger age (p < 0.0001) and ventilator (p < 0.0001) or extracorporeal membrane oxygenation (p = 0.03) use at time of transplant. Overall mortality post-bacterial infection was 33.78%, and previous cardiac surgery (p < 0.001) and multiple sites of infection (p = 0.004) were independent predictors of death. CONCLUSIONS: Bacteria were the most common causes of severe infections in pediatric heart transplant recipients and were associated with high mortality rates. The risk of acquiring a bacterial infection was highest in the first month post-transplant, and a large proportion of the infections were caused by multidrug-resistant pathogens.

Fontan Patient Survival After Pediatric Heart Transplantation Has Improved in the Current Era.

BACKGROUND: Historically, patients with a prior Fontan procedure for complex congenital heart disease (CHD) have been considered at higher risk for death after heart transplant (HT) compared with other HT transplant candidates. With the overall trend of improved survival of pediatric HT recipients, it is unclear of Fontan patient post-HT survival has also improved in the current era. METHODS: Data from the Pediatric Heart Transplant Study database for Fontan patients who underwent HT was compared between the early era (1993 to 2006, n = 150) and late era (2007 to 2014, n = 252). Post-HT survival and pre-HT characteristics were compared among eras and also with non-Fontan CHD patients. RESULTS: At time of HT, Fontan patients in the late era were more likely to require inotropic support, have protein-losing enteropathy, have failure to thrive, and be further from time of Fontan, although less likely to be on ventilator support. Only ventilator support and earlier year of HT were significant risk factors for death in the multivariate analysis. Post-HT Fontan patient survival significantly improved from the early to late era (p = 0.02), particularly in the early phase, with 1-year survival of 77% in the early era and 89% in the late era. Late era non-Fontan CHD patient 1-year post-HT survival was similar to Fontan patients at 92%. CONCLUSIONS: Survival of Fontan patients after HT has significantly improved in the current era. Currently, expected post-HT survival for Fontan patients is on par with other CHD patients. Fontan patients should not be excluded from consideration for HT solely on a history of Fontan.

Use of sirolimus in pediatric heart transplant patients: A multi-institutional study from the Pediatric Heart Transplant Study Group.

BACKGROUND: Proliferation signal inhibitors, such as sirolimus, are increasingly used in solid-organ transplantation. However, limited data exist on sirolimus-treated pediatric patients. We aimed to describe sirolimus use in pediatric heart transplant patients and test the hypothesis that sirolimus use is associated with improved outcomes. METHODS: A retrospective review and propensity-matched analysis of the Pediatric Heart Transplant Study database was performed on patients undergoing primary heart transplantation from 2004 to 2013 with at least 1 year of follow-up comparing patients treated vs not treated with sirolimus at 1 year after transplant. The primary outcome of interest was patient survival, with secondary outcomes including cardiac allograft vasculopathy, rejection, malignancy, and renal insufficiency. RESULTS: Between 2004 and 2013, 2,531 patients underwent transplantation. At least 1 year of follow-up was available for 2,080 patients, of whom 144 (7%) were on sirolimus at 1 year post-transplant. Sirolimus-treated and non-treated patients had similar survival in the overall cohorts and in the propensity-matched analysis. The secondary outcomes measures were also similar, including a composite end point of all outcome measures. There was a trend toward increased time to cardiac allograft vasculopathy (p = 0.09) and decreased time to infection (p = 0.05) among sirolimus-treated patients in the overall cohort (p = 0.19) but not in the propensity-matched cohort (p = 0.17). CONCLUSIONS: Sirolimus was used in less than 10% of patients at 1 year post-transplant. Overall outcomes of sirolimus treated and non-treated patients were similar with respect to survival and major transplant adverse events. Further study of sirolimus in pediatric heart transplant patients is needed.

A multi-institutional evaluation of antibody-mediated rejection utilizing the Pediatric Heart Transplant Study database: Incidence, therapies and outcomes.

BACKGROUND: Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT. METHODS: We queried the PHTS database for patients <18 years of age undergoing primary HT between January 2010 and December 2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production. Biopsy data, treatment strategies and survival were analyzed. RESULTS: An episode of AMR was identified in 179 of 1,596 (11%) HT recipients and in 246 of 705 (35%) rejection episodes. AMR was diagnosed by biopsy in 182 of 246 episodes and by immunotherapy in 64 of 179 episodes. Mixed rejection was identified in 179. Freedom from AMR was 88% and 82% at 1 and 3 years, respectively. AMR therapies included intravenous immunoglobulin (IVIg) (58%), plasmapheresis (40%), rituximab (40%), bortezomib (11%) and eculizumab (0.4%). The most commonly used combination therapies included IVIg/plasmapheresis/rituximab (13%). Thirty-three patients (16%) died after developing AMR. Patient and graft survival were lower for the AMR+ group. One- and 3-year survival after initial AMR diagnosis was 88% and 77%, respectively. CONCLUSIONS: In his study we report the largest experience of AMR in pediatric HT recipients. AMR was common and often occurred concurrently with acute cellular rejection. There is wide variability in the treatment of AMR. Short-term patient and graft outcomes were worse for those with treated AMR.

Limited Utility of Tricuspid Valve Repair at the Time of Left Ventricular Assist Device Implantation.

BACKGROUND: The optimal management of tricuspid regurgitation (TR) in patients undergoing left ventricular assist device (LVAD) implantation is controversial. This study was undertaken to determine the impact of tricuspid valve repair (TVR) at the time of LVAD implantation on survival. METHODS: The Interagency Registry for Mechanically Assisted Circulatory Support was used to analyze the outcomes of patients undergoing LVAD implantation as destination therapy with or without concomitant TVR. RESULTS: Among 2,527 patients undergoing implant of a continuous flow LVAD as destination therapy during the study period, 989 (39%) had moderate or severe TR. The management of TR was not uniform among these patients. Patients with moderate and severe TR underwent TVR in 16.7% and 35.3% of cases, respectively. Moderate and severe TR at the time of LVAD implantation were associated with poorer survival over the entire follow-up period (p = 0.009). Interestingly, TVR at the time of LVAD implantation did not confer improved survival, even among patients with preimplant moderate or severe TR. A potential explanation for this finding is that patients with preimplant moderate or severe TR who underwent LVAD implant with concomitant TVR commonly experienced recurrent, late TR (21% to 27%). CONCLUSIONS: Tricuspid valve repair is performed commonly at the time of LVAD implant despite the fact that it does not confer a clear survival benefit. For many patients, LVAD implant alone relieves preimplant TR as effectively as LVAD implant with TVR. Further study is necessary to determine what factors lead to recurrence of late TR in LVAD patients both with and without TVR.

Age and gender differences and factors related to change in health-related quality of life from before to 6 months after left ventricular assist device implantation: Findings from Interagency Registry for Mechanically Assisted Circulatory Support.

BACKGROUND: Gaps in the literature exist regarding health-related quality of life (HRQOL) early after left ventricular assist device (LVAD) surgery. The purposes of our study were to describe HRQOL over time, by age and gender, and identify risk factors for poor HRQOL early after LVAD implant. METHODS: Patients (n = 7,353) from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database received a continuous-flow LVAD as a primary implant at 133 United States hospitals. Of these, 5,640 patients had pre-LVAD HRQOL data, 3,353 patients had 6-month post-LVAD HRQOL data, and 2,748 patients had data at both times. HRQOL was measured using the EQ-5D-3L (Euro-Qol) instrument. Data were collected pre-implant and 3 and 6 months post-operatively. Statistical analyses included chi-square test, t-test, Pearson correlation coefficients, and multiple regression analysis. RESULTS: Overall HRQOL and dimensions of HRQOL improved from before to 6 months after device implant when examined by age and gender. However, younger patients and women reported significantly more problems regarding all dimensions before implant and significantly more problems regarding pain/discomfort and anxiety/depression at 3 and 6 months after implant. An increase in overall HRQOL from before to 6 months after implant was related to pre-implant INTERMACS Level 1. Factors related to a decrease in HRQOL from before to 6 months after implant were listed for heart transplant before surgery, comorbidities, better preoperative HRQOL, adverse events within 6 months after implant, bridge to transplant moderately likely and unlikely, and New York Heart Association Functional Classification IV at 6 months after LVAD (R(2) = 41%). CONCLUSIONS: Overall HRQOL and dimensions of HRQOL improve in sub-groups of patients from before to 6 months after surgery, although differences in improvement exist. Adverse events are risk factors for decreased HRQOL across time and support the ongoing need to improve device technology with the aim of reducing adverse events.

Outcomes of children implanted with ventricular assist devices in the United States: First analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).

BACKGROUND: Use of mechanical circulatory support in children has increased as more options have become available. A national account of the use of mechanical support in children and adolescents is essential to understanding outcomes, refining patient selection and improving quality of care. METHODS: The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Heart, Lung, and Blood Institute-supported nationwide registry for temporary and durable ventricular assist device (VAD) use in patients <19 years of age. Between the launch in September 2012 and June 2015, 37 hospitals in the USA have enrolled patients. This first report of data from PediMACS analyzed pre-implant patient characteristics, survival using competing outcomes, and adverse events. RESULTS: Two hundred pediatric patients underwent 222 durable VAD implants. Patients' characteristics and outcomes of children supported with a temporary device (n = 41) were not analyzed in this report. The etiology of heart disease included 146 (73%) patients with cardiomyopathy and 35 (18%) with congenital heart disease. Thirty patients (15%) transitioned from extracorporeal membrane oxygenation (ECMO) and 76 (38%) had previous cardiac surgery. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 (27%) or Level 2 (56%) at implant, with 13% at Level 3. Of the 200 patients supported with a durable device, 91 (46%) were supported with a pulsatile-flow device and 109 (55%) with a continuous-flow (CF) device. Patient age at first implant included 30 patients (15%) <1 year of age, 37 (19%) 1 to 5 years, 32 (16%) 6 to 10 years and 101 (51%) 10 to 18 years. Patients were supported with left ventricular assist device alone in 161 (81%), biventricular ventricular assist device in 29 (15%), right ventricular assist device in 4 (2.0%) and total artificial heart in 6 (3%), together comprising 783 months of follow-up. The 200 patients receiving primary durable devices had an actuarial survival of 81% at 6 months. Competing risk analysis at 6 months revealed that 58% of patients had been transplanted, 28% were alive on support, 14% had died and 0.6% recovered. In the overall cohort, there were 28 deaths. Reported serious adverse events included infection (n = 78), bleeding (n = 68), device malfunction (n = 79) and neurologic dysfunction (n = 52). CONCLUSIONS: PediMACS constitutes the largest single data repository with detailed information of pediatric patients implanted with VADs. The first PediMACS report reveals favorable outcomes despite the varying patient characteristics and pump types. However, the rate of adverse events remains high. With further data collection, analysis of patient risk factors critical to improving outcomes will be possible.

Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents.

BACKGROUND: Although used routinely, the pleiotropic benefits of statins remain understudied in children after heart transplantation. We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD). METHODS: This study was a retrospective review of 964 pediatric (ages 5 to 18 years) heart transplant recipients in the multicenter Pediatric Heart Transplant Study registry from 2001 to 2012. Patients were excluded if they were undergoing re-transplantation, survived <1 year post-transplant, or had missing data regarding statin use. The effects of statins beyond the first year were estimated by Kaplan-Meier and Cox regression multivariable analysis for freedom from PTLD, rejection requiring treatment, any severity of CAV, and survival. RESULTS: Statin use was variable among participating centers with only 30% to 35% of patients ≥10 years of age started on a statin at <1 year post-transplant. After the first year post-transplant, statin-treated children (average age at transplant 13.24 ± 3.29 years) had significantly earlier rejection (HR 1.42, 95% CI 1.11 to 1.82, p = 0.006) compared with untreated children (transplanted at 12 ± 3.64 years) after adjusting for conventional risk factors for rejection. Freedom from PTLD, CAV and overall survival up to 5 years post-transplant were not affected by statin use, although the number of events was small. CONCLUSIONS: Statin therapy did not confer a survival benefit and was not associated with delayed onset of PTLD or CAV. Early (<1 year post-transplant) statin therapy was associated with increased later frequency of rejection. These findings suggest that a prospective trial evaluating statin therapy in pediatric heart transplant recipients is warranted.

Predictors of hospital length of stay after implantation of a left ventricular assist device: an analysis of the INTERMACS registry.

BACKGROUND: Few studies have reported on hospital length of stay (LOS) after left ventricular assist device (LVAD) implantation. The purpose of this study was to determine pre- and peri-operative predictors of hospital LOS after LVAD implantation. METHODS: We analyzed adult primary continuous-flow LVAD patients implanted between June 23, 2006 and December 31, 2010 at 105 institutions from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Retrospective analyses included measures of central tendency, frequencies, correlations and stepwise multivariable regression modeling (p ≤ 0.05). Independent variables included demographic characteristics, pre-implant clinical and behavioral variables and concomitant surgery. RESULTS: Characteristics of the patients (n = 2,200) included: mean age 54.6 ± 12.6 years; 79% male; 69% white; 57% INTERMACS Profile 1 or 2; 37% diabetic; 21% with history of coronary artery bypass graft (CABG); 7% with history of valve surgery; and 37% with concomitant surgery. Median hospital LOS (implant to discharge) was 20 days. Significant predictors of an increased hospital LOS included demographic characteristics (older age and non-white), pre-implant clinical variables (history of CABG or valve surgery, diabetes, ascites, INTERMACS Profiles 1 and 2, low albumin, high blood urea nitrogen, high right atrial pressure) and concomitant surgery, explaining 12% variance (F = 22.65, p<0.001). CONCLUSIONS: Demographic characteristics, pre-implant variables and concomitant surgery partially explained hospital LOS after continuous-flow LVAD implant. These variables have implications regarding selection of patients for mechanical circulatory support.

Overall quality of life improves to similar levels after mechanical circulatory support regardless of severity of heart failure before implantation.

BACKGROUND: The severity of pre-implantation heart failure may affect post-implantation health-related quality of life (HRQOL). The purpose of our study was to examine differences in HRQOL from before mechanical circulatory support (MCS) through 1 year after surgery by Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patient profiles. METHODS: Data from 1,559 adults with advanced heart failure who received primary continuous-flow pumps between June 23, 2006, and March 31, 2010, and were enrolled in INTERMACS were analyzed. HRQOL data were collected using the EQ-5D-3L survey before implantation and at 3, 6, and 12 months after implantation. Statistical analyses included chi-square and t-tests, using all available data for each time period. Paired t-tests and sensitivity analyses were also conducted. RESULTS: HRQOL was poor before MCS implantation among patients with INTERMACS profiles 1 to 7 and significantly improved after MCS implantation for all profiles. Stratified by INTERMACS profile, problems within each of the 5 dimensions of HRQOL (i.e., mobility, self-care, usual activities, pain, and anxiety/depression) generally decreased from before to after implantation. By 6 months after implantation, patients with all INTERMACS profiles reported similar frequencies of problems for all HRQOL dimensions. Paired t-tests and sensitivity analyses supported almost all of our findings. CONCLUSIONS: HRQOL is poor among advanced heart failure patients with INTERMACS profiles 1 to 7 before MCS implantation and improves to similar levels for patients who remained on MCS 1 year after surgery. Patients have problems in HRQOL dimensions before and after MCS; however, the frequency of reporting problems decreases for all dimensions within most profiles across time.

Increased need for right ventricular support in patients with chemotherapy-induced cardiomyopathy undergoing mechanical circulatory support: outcomes from the INTERMACS Registry (Interagency Registry for Mechanically Assisted Circulatory Support).

OBJECTIVES: The aim of this study was to investigate the use of durable mechanical circulatory support (MCS) in patients with chemotherapy-induced cardiomyopathy (CCMP) and determine their outcomes and survival in comparison to that of other patients with end-stage heart failure treated similarly. BACKGROUND: Patients with end-stage heart failure as a result of CCMP from anthracyclines are often precluded from heart transplantation because of a history of cancer. In such patients, durable MCS may offer an important chance for life prolongation. Yet, there are no data to support the use of MCS in this increasingly prevalent group of patients. METHODS: We searched 3,812 MCS patients from June 2006 through March 2011 in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database for the diagnosis of CCMP. We compared characteristics, outcomes, and survival between CCMP patients and patients with nonischemic cardiomyopathy and ischemic cardiomyopathy. RESULTS: Compared with patients with nonischemic cardiomyopathy and ischemic cardiomyopathy, patients with CCMP were overwhelmingly female (72% vs. 24% vs. 13%, p = 0.001), had MCS more often implanted as destination therapy (33% vs. 14% vs. 22%, p = 0.03), required more right ventricular assist device support (19% vs. 11% vs. 6%, p = 0.006), and had a higher risk of bleeding (p = 0001). Survival of CCMP patients was similar to that of other groups. CONCLUSIONS: CCMP patients treated with MCS have survival similar to other MCS patients despite more frequent need for right ventricular assist device support and increased bleeding risk.

Variations in institutional staffing and clinical practice are predictive of center-specific 1-year survival post-transplant.

BACKGROUND: The accuracy of various risk models to predict early post-transplant mortality is limited by the type, quality, and era of the data collected. Most models incorporate a large number of recipient-derived and donor-derived variables; however, other factors related to specific institutional practices likely influence early mortality. The goal of this study was to determine if the addition of institutional practice variables would improve the predictive accuracy of a recipient/donor risk model in a modern cohort of heart transplant recipients. METHODS: Between 1999 and 2007, 3,591 primary heart transplants were performed at the 26 institutions participating in the Cardiac Transplant Research Database. Multivariable regression analysis in the hazard domain was used to identify recipient, donor, and institutional practice variables that were predictive of 1-year mortality. The derived model was used to predict institutional outcomes and compare them with observed outcomes first without and then with the inclusion of the institutional practice variables. RESULTS: Eleven individual plus 2 interaction recipient variables and 2 individual plus 2 interaction donor variables were predictive of increased mortality. The addition of institutional practice variables to the model identified 4 variables associated with decreased mortality: greater number of transplant cardiologists, a thoracic surgery fellowship, a surgery or cardiology attending taking donor call, and routine surveillance for antibody-mediated rejection. By using a p-value > 0.10 as a robust measure of similarity, the addition of institutional practice variables increased the number of institutions with similar predicted vs. observed mortality from 18 of 26 institutions (69%) to 26 of 26 (100%), demonstrating improved predictive accuracy of the model. CONCLUSIONS: Multiple recipient and donor variables influence early survival but do not fully explain the difference in predicted and observed outcomes at the institutional level. Variations in staffing and clinical practice contribute to risk, and the addition of these variables to our risk model improved predictive accuracy.