Reduced incidence of cardiac rejection in multi-organ transplants: A propensity matched study.

2023

e15019

05/2023

1399-0012

BACKGROUND: Rejection remains a primary cause of graft loss after heart transplant (HT). Recognizing the immunomodulation of multi-organ transplant can enhance our understanding of the mechanisms of cardiac rejection.

METHODS: This retrospective cohort study identified patients from the UNOS database with isolated heart (H, N = 37 433), heart-kidney (HKi, N = 1516), heart-liver (HLi, N = 286), and heart-lung (HLu, N = 408) transplants from 2004 to 2019. Propensity score matching reduced baseline differences between groups. Outcomes included risk of rejection prior to transplant hospital discharge and within 1 year, and mortality within 1 year of transplant.

RESULTS: In the propensity score matched data, the relative risk of being treated for rejection prior to transplant hospital discharge was 61% lower for HKi (RR .39, 95% CI .29, .53) and 87% lower for HLi (RR .13, 95% CI .05, .37) compared to H. Similarly, the probability of being treated for rejection in the first year after transplant remained lower in HKi (RR .45, 95% CI .35, .57) and HLi (RR .13, 95% CI .06, .28) compared to H. The 1-year survival analysis revealed an equivalent risk of death in HKi (HR .84, 95% CI .68, 1.03) and HLi (HR 1.41, 95% CI .83, 2.41) compared to H, while HLu had a higher risk of death in the first year after transplant (HR 1.65, 95% CI 1.17, 2.33).

CONCLUSIONS: Recipients of HKi and HLi experience a reduced risk of rejection when compared to H, but an equivalent risk of 1 yr mortality. These findings have important implications for the future of HT medicine.

10.1111/ctr.15019

Clin Transplant

37212365

Temporal trends in primary payers in pediatric heart transplant and association with long-term survival.

2023

e14484

05/2023

1399-3046

BACKGROUND: Pediatric heart transplantation (HT) is resource intensive. In adults, there has been an increase in the proportion of HTs funded by public insurance, with post-HT outcomes inferior to those funded by private sources. Trends in the funding of pediatric HT and outcomes in children have not been described.

METHODS: We queried the United Network for Organ Sharing (UNOS) database for children (<18 years) listed for and undergoing HT between 2004 and 2021. We identified the primary payer at listing, HT, 1 year, and 1-5 years following HT. Trends were analyzed using generalized logit models. Multivariable-extended Cox regression models were used to test the relationship between insurance type at the time of transplant and time to death or re-transplant.

RESULTS: There were 6382 pediatric patients who underwent transplants and had either public or private insurance at the time of transplant. The percentage of patients with public insurance at the time of HT increased over time. Public insurance at the time of HT was associated with an increased risk of death or re-transplant beyond 2 months after HT (adjusted HR at 6 months = 1.43, 95% CI: 1.13-1.81, p = .003; adjusted HR at 9 months = 1.67, 95% CI: 1.17-2.37, p = .004).

CONCLUSION: There has been a statistically significant trend toward increasing public insurance for children awaiting, at the time of, and after HT. Black patients and those with public insurance at HT have worse long-term outcomes. This study highlights ongoing disparities in pediatric HT and the need to focus efforts on achieving equitable outcomes.

10.1111/petr.14484

Pediatr Transplant

36751006

Association of Donors With US Public Health Service Risk Criteria and Outcomes After Adult vs Pediatric Cardiac Transplant.

2022

1121-1127

11/2022

2380-6591

Importance: The United Network for Organ Sharing (UNOS) evaluates donor risk for acute transmission of HIV, hepatitis B, or hepatitis C based on US Public Health Services (PHS)-specific criteria. However, recent data regarding use and outcomes of those donors with PHS risk criteria among pediatric and adult heart transplant recipients are lacking.

Objective: To compare use and outcomes of graft from donors with PHS risk criteria vs those with a standard-risk donor (SRD) in children vs adults in a contemporary cohort.

Design, Setting, and Participants: This cohort was a nationwide analysis of heart transplants in the US that used data from the UNOS database. Participants were children (<18 years old) and adults (≥18 years old) who received a heart transplant from January 1, 2010, to December 31, 2021.

Exposures: UNOS-defined donor risk status.

Main Outcomes and Measures: Trend analysis compared changes in PHS risk criteria use among children and adults. Patient survival was analyzed using Kaplan-Meier curves with log rank and Cox proportional hazards to compare PHS risk-criteria outcomes vs SRD-criteria outcomes in children and adult heart transplant recipients. Additional analysis was performed among adults who received a PHS-risk criteria graft that was previously declined for pediatric recipients.

Results: Of 5115 pediatric transplant recipients (donor without PHS risk median [IQR] age, 5 [0-13] years and donor with PHS risk median [IQR] age, 8 [0-14] years) and 30 289 adult heart transplant recipients (donor without PHS risk median [IQR] age, 56 [46-63] years and donor with PHS risk median [IQR] age, 57 [47-63] years), PHS risk criteria comprised 8% in children vs 25% in adults. PHS criteria are being increasingly used over the past decade with the proportion of recipients transplanted with PHS risk-criteria donors being approximately 3 times greater among adult recipients than children recipients. Pediatric recipients of a PHS risk-criteria donor had greater pretransplant ventilatory support, whereas adult recipients of a PHS risk-criteria donor had greater pretransplant extracorporeal membrane oxygenation use. Patient survival was similar between pediatric recipients of PHS risk-criteria grafts vs SRD-criteria grafts and slightly higher among adult recipients of PHS risk-criteria grafts vs SRD-criteria grafts. The 1778 adult recipients who received a PHS criteria-risk donor that was previously declined for pediatric recipients had similar patient survival recipients compared with SRD-criteria donors (HR, 0.92; 95% CI, 0.81-1.03; P = .18).

Conclusions and Relevance: In the current era, a 3-fold greater proportion of adult recipients receive a PHS risk-criteria graft compared with children despite similar posttransplant patient survival. The ongoing organ donor shortage underscores the need for consideration of PHS risk criteria where these donors remain underused.

10.1001/jamacardio.2022.3070

JAMA Cardiol

36129691

Sex Differences in Left Ventricular Assist Device-related Emergency Department Encounters in the United States.

2022

1445-1455

05/2022

1532-8414

BACKGROUND: There is a paucity of data regarding sex differences in the profiles and outcomes of ambulatory patients on left ventricular assist device (LVAD) support who present to the emergency department (ED).

METHODS AND RESULTS: We performed a retrospective analysis of 57,200 LVAD-related ED patient encounters from the 2010 to 2018 Nationwide Emergency Department Sample. International Classification of Diseases Clinical Modification, Ninth Revision and Tenth Revision, codes identified patients aged 18 years or older with LVADs and associated primary and comorbidity diagnoses. Clinical characteristics and outcomes were stratified by sex and compared. Multivariable logistic regression was used to evaluate predictors of hospital admission and death. Female patient encounters comprised 27.2% of ED visits and occurred at younger ages and more frequently with obesity and depression (all P < .01). There were no sex differences in presentation for device complication, stroke, infection, or heart failure (all P > .05); however, female patient encounters were more often respiratory- and genitourinary or gynecological related (both P < .01). After adjustment for age group, diabetes, depression, and hypertension, male patient encounters had a 38% increased odds of hospital admission (95% confidence interval 1.20-1.58), but there was no sex difference in the adjusted odds of death (odds ratio 1.11, 95% confidence interval 0.86-1.45).

CONCLUSIONS: Patient encounters of females on LVAD support have significantly different comorbidities and outcomes compared with males. Further inquiry into these sex differences is imperative to improve long-term outcomes.

10.1016/j.cardfail.2022.05.005

J Card Fail

35644307

Pediatric Device Trials are the Ideal way to Bring Devices to Market.

2022

231-234

2022 Mar

2150-136X

10.1177/21501351221075572

World J Pediatr Congenit Heart Surg

35238711

Safety and Feasibility of Exercise Rehabilitation in Children with Ventricular Assist Devices.

2022

2022 Feb 08

1432-1971

<p>Children with advanced heart failure may require ventricular assist devices (VAD) while awaiting heart transplantation. Currently, no data exist regarding the safety of exercise rehabilitation (ER) in children on VAD support. The purpose of this study was to determine the safety and feasibility of ER in children on VAD support awaiting heart transplantation. Eligible patients underwent VAD placement between 1998 and 2019; both inpatient and outpatient participants were included. After VAD implantation and when ambulatory, patients were enrolled in ER. Exercise sessions were scheduled three times a week and consisted of aerobic and musculoskeletal conditioning. A total of 29 patients (59% male, mean age 14 ± 3.2&nbsp;years) were included with a median VAD duration of 120 ± 109&nbsp;days. Cardiac diagnoses included cardiomyopathy (81%) and congenital heart disease (19%). VAD type included pulsatile (59%) and continuous-flow devices (41%). Eight hundred and sixty-four (85%) ER sessions were successfully completed and began at a mean of 49&nbsp;days (range 19-108) after VAD implant. No adverse events, including episodes of hypotension, significant complex arrhythmia, or VAD malfunction occurred during exercise testing or ER, and no sessions were discontinued prematurely. Pediatric patients on VAD support can safely participate in ER with relatively high compliance, and sessions can be implemented early after VAD implantation. Given the safety profile, ER in pediatric VAD recipients, which is a modifiable pre-transplant risk factor that may improve functional capacity, warrants further study as a potential modality to improve post-transplant outcomes.</p>

10.1007/s00246-022-02819-x

Pediatr Cardiol

35137274

Novel Risk Model to Predict Emergency Department Associated Mortality for Patients Supported With a Ventricular Assist Device: The Emergency Department-Ventricular Assist Device Risk Score.

2022

e020942

2022 Jan 13

2047-9980

<p><strong>Background</strong> The past decade has seen tremendous growth in patients with ambulatory ventricular assist devices. We sought to identify patients that present to the emergency department (ED) at the highest risk of death. <strong>Methods and Results</strong> This retrospective analysis of ED encounters from the Nationwide Emergency Department Sample includes 2010 to 2017. Using a random sampling of patient encounters, 80% were assigned to development and 20% to validation cohorts. A risk model was derived from independent predictors of mortality. Each patient encounter was assigned to 1 of 3 groups based on risk score. A total of 44&nbsp;042 ED ventricular assist device patient encounters were included. The majority of patients were male (73.6%), &lt;65&nbsp;years old (60.1%), and 29% presented with bleeding, stroke, or device complication. Independent predictors of mortality during the ED visit or subsequent admission included age ≥65&nbsp;years (odds ratio [OR], 1.8; 95% CI, 1.3-4.6), primary diagnoses (stroke [OR, 19.4; 95% CI, 13.1-28.8], device complication [OR, 10.1; 95% CI, 6.5-16.7], cardiac [OR, 4.0; 95% CI, 2.7-6.1], infection [OR, 5.8; 95% CI, 3.5-8.9]), and blood transfusion (OR, 2.6; 95% CI, 1.8-4.0), whereas history of hypertension was protective (OR, 0.69; 95% CI, 0.5-0.9). The risk score predicted mortality areas under the curve of 0.78 and 0.71 for development and validation. Encounters in the highest risk score strata had a 16-fold higher mortality compared with the lowest risk group (15.8% versus 1.0%). <strong>Conclusions</strong> We present a novel risk score and its validation for predicting mortality of patients with ED ventricular assist devices, a high-risk, and growing, population.</p>

10.1161/JAHA.121.020942

J Am Heart Assoc

35023355

Impact of Age on Emergency Resource Utilization and Outcomes in Pediatric and Young Adult Patients Supported with a Ventricular Assist Device.

2021

2021 Nov 03

1538-943X

<p>There are minimal data describing outcomes in ambulatory pediatric and young adult ventricular assist device (VAD)-supported patient populations. We performed a retrospective analysis of encounter-level data from 2006 to 2017 Nationwide Emergency Department Sample (NEDS) to compare emergency department (ED) resource utilization and outcomes for pediatric (≤18 years, n = 494) to young adult (19-29 years, n = 2,074) VAD-supported patient encounters. Pediatric encounters were more likely to have a history of congenital heart disease (11.3% vs. 4.8%). However, Pediatric encounters had lower admission/transfer rates (37.8% vs. 57.8%) and median charges ($3,334 (IQR $1,473-$19,818) vs. $13,673 ($3,331-$45,884)) (all p &lt; 0.05). Multivariable logistic regression modeling revealed that age itself was not a predictor of admission, instead high acuity primary diagnoses and medical complexity were: (adjusted odds ratio; 95% confidence intervals): cardiac (3.0; 1.6-5.4), infection (3.4; 1.7-6.5), bleeding (3.9; 1.7-8.8), device complication (7.2; 2.7-18.9), and ≥1 chronic comorbidity (4.1; 2.5-6.7). In this largest study to date describing ED resource use and outcomes for pediatric and young adult VAD-supported patients, we found that, rather than age, high acuity presentations and comorbidities were primary drivers of clinical outcomes. Thus, reducing morbidity in this population should target comorbidities and early recognition of VAD-related complications.</p>

10.1097/MAT.0000000000001603

ASAIO J

34743138

Prevalent Pharmacotherapy of United States Fontan Survivors: A study utilizing data from the MarketScan Commercial and Medicaid Claims Databases.

2021

2021 Sep 25

1097-6744

<p><strong>BACKGROUND: </strong>Survivors of Fontan palliation are at life-long risk of thrombosis, arrhythmia, and circulatory failure. To our knowledge, no studies have evaluated current United States pharmaceutical prescription practice in this population.</p>

<p><strong>METHODS: </strong>A retrospective observational study evaluating the prevalent use of prescription medications in children and adolescents with hypoplastic left heart syndrome or tricuspid atresia after Fontan completion (identified using ICD9/10 codes) was performed using data contained in the MarketScan® Commercial and Medicaid databases for the years 2013 through 2018. Cardiac pharmaceuticals were divided by class. Anticoagulant agents other than platelet inhibitors, which are not uniformly a prescription medication, were also studied. Associations between increasing age and the likelihood of a filled prescription for each class of drug were evaluated. Annualized retail costs of pharmaceutical regimens were calculated.</p>

<p><strong>RESULTS: </strong>A cohort of 4056 subjects [median age 12 years (IQR: 8-16), 61% male, 60% commercial insurance] was identified. Of the cohort, 50% received no prescription medications. Angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (38%), diuretics (15%), and mineralocorticoid receptor antagonists (8%) were prescribed with the highest frequency. Pulmonary vasodilators were received by 6% of subjects. Older age was associated with increased likelihood of filled prescriptions for anticoagulants (p=0.008), antiarrhythmic agents, digoxin, ACEi/ARB, and beta blockers (each p&lt;0.0001), but also lower likelihood of filled prescriptions for pulmonary vasodilators, conventional diuretics (both p&lt;0.0001), and mineralocorticoid receptor antagonists (p=0.02).</p>

<p><strong>CONCLUSION: </strong>Pharmaceuticals typically used to treat heart failure and pulmonary hypertension are the most commonly prescribed medications following Fontan palliation. While the likelihood of treatment with a particular class of medication is associated with the age of the patient, determining the optimal regimen for individual patients and the population at large is an important knowledge gap for future research.</p>

10.1016/j.ahj.2021.09.012

Am Heart J

34582777

The influence of mechanical Circulatory support on post-transplant outcomes in pediatric patients: A multicenter study from the International Society for Heart and Lung Transplantation (ISHLT) Registry.

2021

2021 Jun 11

1557-3117

<p><strong>BACKGROUND: </strong>Mechanical circulatory support (MCS) is increasingly being used as a bridge to transplant in pediatric patients. We compare outcomes in pediatric patients bridged to transplant with MCS from an international cohort.</p>

<p><strong>METHODS: </strong>This retrospective cohort study of heart-transplant patients reported to the International Society for Heart and Lung Transplantation (ISHLT) registry from 2005-2017 includes 5,095 patients &lt;18 years. Pretransplant MCS exposure and anatomic diagnosis were derived. Outcomes included mortality, renal failure, and stroke.</p>

<p><strong>RESULTS: </strong>26% of patients received MCS prior to transplant: 240 (4.7%) on extracorporeal membrane oxygenation (ECMO), 1,030 (20.2%) on ventricular assist device (VAD), and 54 (1%) both. 29% of patients were &lt;1 year, and 43.8% had congenital heart disease (CHD). After adjusting for clinical characteristics, compared to no-MCS and VAD, ECMO had higher mortality during their transplant hospitalization [OR 3.97 &amp; 2.55; 95% CI 2.43-6.49 &amp; 1.42-4.60] while VAD mortality was similar [OR 1.55; CI 0.99-2.45]. Outcomes of ECMO+VAD were similar to ECMO alone, including increased mortality during transplant hospitalization compared to no-MCS [OR 4.74; CI 1.81-12.36]. Patients with CHD on ECMO had increased 1 year, and 10 year mortality [HR 2.36; CI 1.65-3.39], [HR 1.82; CI 1.33-2.49]; there was no difference in survival in dilated cardiomyopathy (DCM) patients based on pretransplant MCS status.</p>

<p><strong>CONCLUSION: </strong>Survival in CHD and DCM is similar in patients with no MCS or VAD prior to transplant, while pretransplant ECMO use is strongly associated with mortality after transplant particularly in children with CHD. In children with DCM, long term survival was equivalent regardless of MCS status.</p>

10.1016/j.healun.2021.06.003

J Heart Lung Transplant

34253457