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

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy.

2020

2020 May 18

1524-4539

<p>Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric HCM to guide SCD prevention strategies. In an international multi-center observational cohort study, phenotype-positive patients with isolated HCM &lt;18 years at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of SCD events at 5-year follow-up: SCD, resuscitated sudden cardiac arrest (SCA), and aborted SCD, i.e. appropriate shock following primary prevention ICD. Competing risk models with cause-specific hazard regression were used to identify and quantify clinical and genetic factors associated with SCD. The cause-specific regression model was implemented using boosting, and tuned with ten repeated four-fold cross-validations. The final model was fitted using all data with the tuned hyperparameter value that maximizes the c-statistic, and its performance was characterized using c-statistic for competing risk models. The final model was validated in an independent external cohort (SHaRe, n=285). Overall, 572 patients met eligibility criteria with 2855 patient-years of follow-up. The 5-year cumulative proportion of SCD events was 9.1% (14 SCD, 25 resuscitated SCA, 14 aborted SCD). Risk predictors included age at diagnosis, documented non-sustained ventricular tachycardia, unexplained syncope, septal diameter z-score, LV posterior wall diameter z-score, LA diameter z-score, peak LV outflow tract (LVOT) gradient, and presence of a pathogenic variant. Unlike adults, LVOT gradient had an inverse association, and family history of SCD had no association with SCD. Clinical and clinical/genetic models were developed to predict 5-year freedom from SCD. Both models adequately discriminated patients with and without SCD events with a c-statistic of 0.75 and 0.76 respectively and demonstrated good agreement between predicted and observed events in the primary and validation cohorts (validation c-statistic 0.71 and 0.72 respectively). Our study provides a validated SCD risk prediction model with over 70% prediction accuracy and incorporates risk factors that are unique to pediatric HCM. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision-making for ICD insertion. URL: https://clinicaltrials.gov Unique Identifier: NCT04036799.</p>

10.1161/CIRCULATIONAHA.120.047235

Circulation

32418493

Cardiac Biomarkers in Pediatric Cardiomyopathy: Study Design and Recruitment Results from the Pediatric Cardiomyopathy Registry.

2019

1-10

2019 Jun

1058-9813

<p><strong>Background: </strong>Cardiomyopathies are a rare cause of pediatric heart disease, but they are one of the leading causes of heart failure admissions, sudden death, and need for heart transplant in childhood. Reports from the Pediatric Cardiomyopathy Registry (PCMR) have shown that almost 40% of children presenting with symptomatic cardiomyopathy either die or undergo heart transplant within 2 years of presentation. Little is known regarding circulating biomarkers as predictors of outcome in pediatric cardiomyopathy.</p>

<p><strong>Study Design: </strong>The Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) study is a multi-center prospective study conducted by the PCMR investigators to identify serum biomarkers for predicting outcome in children with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Patients less than 21 years of age with either DCM or HCM were eligible. Those with DCM were enrolled into cohorts based on time from cardiomyopathy diagnosis: categorized as new onset or chronic. Clinical endpoints included sudden death and progressive heart failure.</p>

<p><strong>Results: </strong>There were 288 children diagnosed at a mean age of 7.2±6.3 years who enrolled in the PCM Biomarkers Study at a median time from diagnosis to enrollment of 1.9 years. There were 80 children enrolled in the new onset DCM cohort, defined as diagnosis at or 12 months prior to enrollment. The median age at diagnosis for the new onset DCM was 1.7 years and median time from diagnosis to enrollment was 0.1 years. There were 141 children enrolled with either chronic DCM or chronic HCM, defined as children ≥2 years from diagnosis to enrollment. Among children with chronic cardiomyopathy, median age at diagnosis was 3.4 years and median time from diagnosis to enrollment was 4.8 years.</p>

<p><strong>Conclusion: </strong>The PCM Biomarkers study is evaluating the predictive value of serum biomarkers to aid in the prognosis and management of children with DCM and HCM. The results will provide valuable information where data are lacking in children.</p>

<p><strong>Clinical Trial Registration NCT01873976: </strong>https://clinicaltrials.gov/ct2/show/NCT01873976?term=PCM+Biomarker&amp;…;

10.1016/j.ppedcard.2019.02.004

Prog. Pediatr. Cardiol.

31745384

No Obesity Paradox in Pediatric Patients With Dilated Cardiomyopathy.

2018

222-230

2018 Mar

2213-1787

<p><strong>OBJECTIVES: </strong>This study aimed to examine the role of nutrition in pediatric dilated cardiomyopathy (DCM).</p>

<p><strong>BACKGROUND: </strong>In adults with DCM, malnutrition is associated with mortality, whereas obesity is associated with survival.</p>

<p><strong>METHODS: </strong>The National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry was used to identify patients with DCM and categorized by anthropometric measurements: malnourished (MN) (body mass index [BMI]&nbsp;&lt;5% for&nbsp;≥2 years or weight-for-length&nbsp;&lt;5% for&nbsp;&lt;2 years), obesity (BMI &gt;95% for age&nbsp;≥2 years or weight-for-length &gt;95% for&nbsp;&lt;2 years), or normal bodyweight (NB). Of 904 patients with DCM, 23.7% (214) were MN, 13.3% (120) were obese, and 63.1% (570) were NB.</p>

<p><strong>RESULTS: </strong>Obese patients were older (9.0 vs. 5.7 years for NB; p&nbsp;&lt; 0.001) and more likely to have a family history of DCM (36.1% vs. 23.5% for NB; p&nbsp;= 0.023). MN patients were younger (2.7 years vs. 5.7 years for NB; p&nbsp;&lt; 0.001) and more likely to have heart failure (79.9% vs. 69.7% for NB; p&nbsp;= 0.012), cardiac dimension z-scores &gt;2, and higher ventricular mass compared with NB. In multivariable analysis, MN was associated with increased risk of death (hazard&nbsp;ratio [HR]: 2.06; 95% confidence interval [CI]: 1.66 to 3.65; p&nbsp;&lt; 0.001); whereas obesity was not (HR: 1.49; 95% CI: 0.72 to 3.08). Competing outcomes analysis demonstrated increased risk of mortality for MN compared with NB (p&nbsp;=&nbsp;0.03), but no difference in transplant rate (p&nbsp;= 0.159).</p>

<p><strong>CONCLUSIONS: </strong>Malnutrition is associated with increased mortality and other unfavorable echocardiographic and clinical&nbsp;outcomes compared with those of NB. The same effect of obesity on survival was not observed. Further studies are needed investigating the long-term impact of abnormal anthropometric measurements on outcomes in pediatric DCM. (Pediatric&nbsp;Cardiomyopathy Registry; NCT00005391).</p>

10.1016/j.jchf.2017.11.015

JACC Heart Fail

29428438