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.

Cardiovascular Disease Events and Mortality After Myocardial Infarction Among Black and White Adults: REGARDS Study.

BACKGROUND: Despite improvements in prognosis following myocardial infarction (MI), racial disparities persist. The objective of this study was to examine disparities between Black and White adults in cardiovascular disease (CVD), coronary heart disease, stroke, heart failure (HF), and mortality after MI and characteristics that may explain the disparities. METHODS: This prospective cohort study included 1122 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants with incident MI between 2003 and 2016. We followed participants for subsequent CVD events (MI, stroke, HF hospitalization, or death from CVD; n=431), coronary heart disease events (MI or death from coronary heart disease; (n=277), stroke (n=68), HF events (HF hospitalization or death from HF; n=191), and all-cause mortality (n=527; 3-year median follow-up after MI). RESULTS: Among 1122 participants with incident MI, 37.5% were Black participants, 45.4% were women, and mean age was 73.2 (SD, 9.5) years. The unadjusted hazard ratio for CVD events comparing Black to White participants was 1.42 (95% CI, 1.17-1.71). Adjusting for sociodemographic characteristics did not attenuate the association (1.41 [95% CI, 1.14-1.73]), but further adjusting for pre-MI health status (1.25 [95% CI, 1.00-1.56]) and characteristics of the MI (1.01 [95% CI, 0.80-1.27]) resulted in substantial attenuation. Similar patterns were observed for the other outcomes, although the number of strokes was small. CONCLUSIONS: Black individuals had a higher risk of CVD events and mortality after MI than White individuals. The disparities were explained by health status before MI and characteristics of the MI. These findings suggest that both primordial prevention of risk factors and improved acute treatment strategies are needed to reduce disparities in post-MI outcomes.

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.

Outcomes with ambulatory advanced heart failure from the Medical Arm of Mechanically Assisted Circulatory Support (MedaMACS) Registry.

BACKGROUND: The outlook for ambulatory patients with advanced heart failure (HF) and the appropriate timing for left ventricular assist device (LVAD) or transplant remain uncertain. The aim of this study was to better understand disease trajectory and rates of progression to subsequent LVAD therapy and transplant in ambulatory advanced HF. METHODS: Patients with advanced HF who were New York Heart Association (NYHA) Class III or IV and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 4 to 7, despite optimal medical therapy (without inotropic therapy), were enrolled across 11 centers and followed for the end-points of survival, transplantation, LVAD placement, and health-related quality of life. A secondary intention-to-treat survival analysis compared outcomes for MedaMACS patients with a matched group of Profile 4 to 7 patients with LVADs from the INTERMACS registry. RESULTS: Between May 2013 and October 2015, 161 patients were enrolled with INTERMACS Profiles 4 (12%), 5 (32%), 6 (49%), and 7 (7%). By 2 years after enrollment, 75 (47%) patients had reached a primary end-point with 39 (24%) deaths, 17 (11%) undergoing LVAD implantation, and 19 (12%) receiving a transplant. Compared with 1,753 patients with Profiles 4 to 7 receiving LVAD therapy, there was no overall difference in intention-to-treat survival between medical and LVAD therapy, but survival with LVAD therapy was superior to medical therapy among Profile 4 and 5 patients (p = 0.0092). Baseline health-related quality of life was lower among patients receiving a LVAD than those enrolled on continuing oral medical therapy, but increased after 1 year for survivors in both cohorts. CONCLUSIONS: Ambulatory patients with advanced HF are at high risk for poor outcomes, with only 53% alive on medical therapy after 2 years of follow-up. Survival was similar for medical and LVAD therapy in the overall cohort, which included the lower severity Profiles 6 and 7, but survival was better with LVAD therapy among patients in Profiles 4 and 5. Given the poor outcomes in this group of advanced HF patients, timely consideration of transplant and LVAD is of critical importance.

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.

Ventricular Assist Device Support as a Bridge to Transplantation in Pediatric Patients.

BACKGROUND: Pediatric ventricular assist device (VAD) use has evolved dramatically over the last 2 decades. OBJECTIVES: This study sought to describe the evolution of VAD support to heart transplantation (HTx) in children in a large international multicenter cohort. METHODS: Using data from the Pediatric Heart Transplant Study, comparisons were made between children (<18 years) supported to HTx (January 1, 1993 to December 31, 2015) with VAD or extracorporeal membrane oxygenation (ECMO) to VAD support. RESULTS: Of 7,135 listed patients, 5,145 underwent HTx; 995 (19.3%) were supported by a VAD (113 with congenital heart disease [CHD]). Patients with a VAD as their first device (n = 821) were older, larger, and more likely to have cardiomyopathy (80%) than patients transitioned from ECMO to VAD (n = 164). In the VAD-only cohort, 79% underwent HTx and 14% died, compared with 69% and 24% in the ECMO-to-VAD cohort, respectively. Patients with cardiomyopathy achieved HTx 84% of the time, with a 9% waitlist mortality rate compared with 55% and 36%, respectively, for CHD. Among VAD-treated patients, 79% were age >10 years in the earliest era, a percentage decreasing to 34% more recently, though neonates still represent <1%. Overall, survival at 2 and 20 years showed no difference between VAD and no support (2 years: 75% vs. 80%; 20 years: 55% vs. 54%). Post-HTx outcomes were better for durable versus temporary VADs (p < 0.01) and for continuous versus pulsatile VADs (p < 0.01) from 2005 onward; timing of VAD had no impact on post-HTx survival (p = 0.65). CONCLUSIONS: For one-quarter of a century, major advances have occurred in mechanical support technology for children, thereby expanding the capability to bridge to HTx without compromising post-HTx outcomes. Significant challenges remain, especially for neonates and patients with CHD, but ongoing innovation portends improved methods of support during the next decade.

Association Between Thiopurine S-Methyltransferase (TPMT) Genetic Variants and Infection in Pediatric Heart Transplant Recipients Treated With Azathioprine: A Multi-Institutional Analysis.

OBJECTIVES: Bone marrow suppression is a common adverse effect of the immunosuppressive drug azathioprine. Polymorphisms in the gene encoding thiopurine S-methyltransferase (TPMT) can alter the metabolism of azathioprine, resulting in marrow toxicity and life-threatening infection. In a multicenter cohort of pediatric heart transplant (HT) recipients, we determined the frequency of TPMT genetic variation and assessed whether azathioprine-treated recipients with TPMT variants were at increased risk of infection. METHODS: We genotyped TPMT in 264 pediatric HT recipients for the presence of the TPMT*2, TPMT*3A, and TPMT*3C variant alleles. Data on infection episodes and azathioprine use were collected as part of each patient's participation in the Pediatric Heart Transplant Study. We performed unadjusted Kaplan-Meier analyses comparing infection outcomes between groups. RESULTS: TPMT variants were identified in 26 pediatric HT recipients (10%): *3A (n = 17), *3C (n = 8), and *2 (n = 1). Among those with a variant allele, *3C was most prevalent in black patients (4 of 5) and *3A most prevalent among white and Hispanic patients (16 of 20). Among 175 recipients (66%) who received azathioprine as part of the initial immunosuppressive regimen, we found no difference in the number of infections at 1 year after HT (0.7 ± 1.3; range, 0-6 versus 0.5 ± 0.9; range, 0-3; p = 0.60) or in freedom from infection and bacterial infection between non-variant and variant carriers. There was 1 infection-related death in each group. CONCLUSIONS: In this multicenter cohort of pediatric HT recipients, the prevalence of TPMT variants was similar across racial/ethnic groups to what has been previously reported in non-pediatric HT populations. We found no association between variant alleles and infection in the first year after HT. Because clinically detected cytopenia could have prompted dose adjustment or cessation, we recommend future studies assess the relationship of genotype to leukopenia/neutropenia in the pediatric transplantation population.

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.

Concomitant mitral valve procedures in patients undergoing implantation of continuous-flow left ventricular assist devices: An INTERMACS database analysis.

BACKGROUND: Management of existing mitral valve (MV) disease in patients undergoing left ventricular assist device (LVAD) implantation remains controversial. METHODS: Among continuous-flow LVAD patients with moderate to severe mitral regurgitation entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database between April 2008 and March 2014 (n = 4,930), outcomes were compared between patients who underwent MV repair (MVr, n = 252), MV replacement (MVR, n = 11) and no MV procedure (no MVP, n = 4,667). Impact on survival was analyzed by stratified actuarial and hazard function multivariable methodology. Post-operative functional capacity and quality of life were assessed. RESULTS: Patients who underwent MVPs had higher pre-operative pulmonary vascular resistance (3.6 ± 2.9 vs 2.9 ± 2.6 Wood units; p = 0.0006) and higher pulmonary artery systolic pressures (55.1 ± 13.8 vs 51.5 ± 14.0 mm Hg; p = 0.0003). Two-year survival was 76% for patients with concomitant MVr, 57% for those with MVR and 71% for those with no MVP (p = 0.15). By multivariable analysis, neither MVr nor MVR affected early or late survival. Although improvements in post-operative functional status as evaluated by 6-minute walk distances were comparable across groups, visual analog score assessments of quality of life suggested a benefit of concomitant MVPs at 1-year post-implant (79.00 ± 1.73 vs 74.45 ± 0.51; p = 0.03), with fewer re-admissions observed for MVP patients (p < 0.0001). CONCLUSIONS: Concomitant MVPs are not associated with increased survival overall. However, MVPs are associated with benefits in terms of reduced hospital re-admission and improved quality of life in select patients.

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.

Risk stratification to determine the impact of induction therapy on survival, rejection and adverse events after pediatric heart transplant: A multi-institutional study.

BACKGROUND: Induction therapy is increasingly being used in pediatric heart transplantation. General versus risk-adapted use remains controversial. We aimed to determine the impact of induction therapy on outcomes after stratifying patients by diagnosis and risk. METHODS: The Pediatric Heart Transplant Study (PHTS) database was used to identify patients (age ≤18 years) who underwent transplantation between January 1, 2001 and December 31, 2014. Patients were excluded if they survived <48 hours or received multiple induction agents. Patients were stratified using a multivariable model to predict 1-year mortality. Patients within the top 25% risk of predicted mortality were defined as high risk (HR) and the bottom 75% as low risk (LR). RESULTS: Of the 2,860 patients studied, 1,370 received anti-lymphocyte antibody (ALA), 707 received an interleukin-2 receptor antagonist (IL-2RA) and 783 received no induction (NI) therapy. Overall, patients with NI had lower survival (p < 0.01); however, multivariable analysis did not demonstrate an association with graft loss. Freedom from rejection was greater among LR congenital heart disease (CHD) and all cardiomyopathy (CMP) patients who received induction therapy (p < 0.01, for both), as confirmed in a multivariable analysis for CMP patients. Frequency of graft vasculopathy was higher in LR CMP patients who received NI. Freedom from infection was lower with IL-2RA in the LR groups. CONCLUSIONS: Pediatric heart transplant survival has improved in the recent era, in concert with increased use of induction therapy. Although induction therapy is associated with decreased rejection, it was not found to directly influence survival on multivariable analysis. Lower risk patients may benefit the most from induction therapy, particularly IL-2RA, which may be correlated with decreased infection and rejection in this cohort.

Causes and Consequences of Missing Health-Related Quality of Life Assessments in Patients Who Undergo Mechanical Circulatory Support Implantation: Insights From INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support).

BACKGROUND: Missing health-related quality of life (HRQOL) data in longitudinal studies can reduce precision and power and bias results. Using INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support), we sought to identify factors associated with missing HRQOL data, examine the impact of these factors on estimated HRQOL assuming missing at random missingness, and perform sensitivity analyses to examine missing not at random (MNAR) missingness because of illness severity. METHODS AND RESULTS: INTERMACS patients (n=3248) with a preimplantation profile of 1 (critical cardiogenic shock) or 2 (progressive decline) were assessed with the EQ-5D-3L visual analog scale and Kansas City Cardiomyopathy Questionnaire-12 summary scores pre-implantation and 3 months postoperatively. Mean and median observed and missing at random-imputed HRQOL scores were calculated, followed by sensitivity analyses. Independent factors associated with HRQOL scores and missing HRQOL assessments were determined using multivariable regression. Independent factors associated with preimplantation and 3-month HRQOL scores, and with the likelihood of missing HRQOL assessments, revealed few correlates of HRQOL and missing assessments (R2 range, 4.7%-11.9%). For patients with INTERMACS profiles 1 and 2 and INTERMACS profile 1 alone, missing at random-imputed mean and median HRQOL scores were similar to observed scores, before and 3 months after implantation, whereas MNAR-imputed mean scores were lower (≥5 points) at baseline but not at 3 months. CONCLUSIONS: We recommend use of sensitivity analyses using an MNAR imputation strategy for longitudinal studies when missingness is attributable to illness severity. Conduct of MNAR sensitivity analyses may be less critical after mechanical circulatory support implant, when there are likely fewer MNAR data.

Outcomes of Restrictive and Hypertrophic Cardiomyopathies After LVAD: An INTERMACS Analysis.

BACKGROUND: Patients with restrictive (RCM) and hypertrophic (HCM) cardiomyopathies are felt to be a difficult population to treat with left ventricular assist device (LVAD) therapy. Scarce data exist on outcomes of continuous-flow (CF) LVAD support in these challenging patient cohorts. METHODS: The Interagency Registry for Mechanically Assisted Circulatory Support Registry was queried for all patients with RCM (n = 94) and HCM (n = 104) who underwent CF LVAD implantation between March 2008 and March 2014. Survival, adverse event rates, baseline demographics, echocardiography parameters, and competing outcomes were compared with patients with dilated cardiomyopathy (DCM) (n = 8749). RESULTS: Left ventricular size was smaller and baseline EF was higher in RCM and HCM compared with DCM patients. Nonetheless, these parameters were not completely normal in the RCM and HCM groups, suggesting that most of these patients exhibited features of a DCM and represented a mixed phenotype. In these specific patient populations, survival up to 4 years was not different among the 3 groups (log rank 0.25) and competing outcomes at 1 year were similar. In the subgroup of patients with very small ventricles (ie, < 5.0 cm), survival was far inferior. Finally, overall rates of right ventricular assist device requirement, hemolysis, pump dysfunction, and cardiac arrhythmias were similar among the 3 groups. CONCLUSION: Relatively few patients with HCM and RCM undergo CF LVAD implantation, and most that do display some features of a DCM. Overall survival and adverse event profiles of these patients were similar to traditional DCM patients; however, in those with very small ventricles, survival was inferior.

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.

Eighth annual INTERMACS report: Special focus on framing the impact of adverse events.

BACKGROUND: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database now includes >20,000 patients from >180 hospitals. METHODS: The eighth annual report of INTERMACS updates the first decade of patient enrollment. RESULTS: In the current era, >95% of implants are continuous flow devices. Overall survival continues to remain >80% at 1 year and 70% at 2 years. Review of major adverse events shows minimal advantage for patients with ambulatory heart failure pre-implant. Stroke, major infection, and continued inotrope requirement during the first 3 months have a major effect on subsequent survival. CONCLUSIONS: Greater application of durable devices to patients with ambulatory heart failure will mandate more effective neutralization or prevention of major adverse events.

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.