Cardiac allograft vasculopathy in pediatric heart transplant recipients does early-onset portend a worse prognosis?

PURPOSE: We sought to evaluate the association between timing of cardiac allograft vasculopathy (CAV) occurrence post-heart transplant (HT) with graft survival and progression of CAV severity in pediatric HT recipients. METHODS: Data from the Pediatric Heart Transplant Society for pediatric (<18 years old) HT recipients between 1993-2019 with available angiographic data were obtained (N = 5,075). The timing of CAV diagnosis (<3; 3-<5; 5-<10; and ≥10 years post-HT) and severity of disease at each assessment (CAV 1-3) was determined. Associations between CAV timing, graft survival, and CAV progression were evaluated using Kaplan-Meier survival curves, multivariable COX proportional hazard regression analyses, and competing risk analyses. RESULTS: Over a median follow-up period of 4.1 (IQR 1.3-8.3) years, CAV was identified in 17% (885/5,075), 28% (252/885) of which were early-onset CAV. Compared with late onset CAV ≥10 years post-HT, patients with early CAV were older at the time of transplant (8.3 ± 6.2 vs. 3.8 ± 4.8 years, p < .0001). While the five-year graft-survival in the ≥10-year group (79.2%, p = 0.03) was significantly higher than the <3, 3-<5, and 5-<10 years post-HT groups (65.0%-67%) (p = 0.03), overall post-CAV graft survival was not significantly different across the CAV time-points. CAV disease progression did not vary with CAV timing post-HT, with an overall five-year freedom from CAV ≥2 of 75.4% (73.1%-77.6%). CONCLUSION: Later onset CAV (≥10-years post-HT) was associated with improved five-year graft survival compared with CAV onset at earlier time-points, but similar and poor long-term outcomes. CAV timing post-HT was not associated with progression of CAV disease severity.

Fetal Unguarded Mitral Valve Orifice, Aortic Atresia, and Severe Left Heart Enlargement.

Unguarded mitral valve orifice is a rare disease with only 7 described cases in the literature. We describe the first known case of unguarded mitral valve orifice with normal segmental cardiac anatomy, severe left ventricular dilatation and dysfunction, aortic atresia, and atrial flutter. (Level of Difficulty: Advanced.).

Cardiomyopathy in limb girdle muscular dystrophy R9, FKRP related.

INTRODUCTION: Reported frequencies of cardiomyopathy in limb girdle muscular dystrophy R9 (LGMDR9) vary. We describe the frequency and age at onset of cardiomyopathy in an LDMDR9 cohort. METHODS: Echocardiograms from 56 subjects (157 echocardiograms) with LGMDR9 were retrospectively reviewed. The cumulative probability of having an abnormal echocardiogram as a function of age was assessed by survival analysis for interval-censored data by genotype. Correlations between cardiac and clinical function were evaluated. RESULTS: Twenty-five (45%) participants had cardiomyopathy. The median age at first abnormal echocardiogram for subjects homozygous for the c.826C>A variant was 54.2 y compared to 18.1 y for all other fukutin-related protein (FKRP) genotypes (P < .0001). There was a weak correlation between ejection fraction and 10-Meter Walk Test speed (r = 0.25), but no correlation with forced vital capacity (r = 0.08). DISCUSSION: Cardiomyopathy is prevalent among those with LGMDR9 and occurs later in subjects homozygous for the c.826C>A mutation. These data will help to guide surveillance and management.

Fontan-associated protein-losing enteropathy and post‒heart transplant outcomes: A multicenter study.

BACKGROUND: The influence of Fontan-associated protein-losing enteropathy's (PLE) severity, duration, and treatment on heart transplant (HTx) outcomes is unknown. We hypothesized that long-standing PLE and PLE requiring more intensive therapy are associated with increased post-HTx mortality. METHODS: This 12-center, retrospective cohort study of post-Fontan patients with PLE referred for HTx from 2003 to 2015 involved collection of demographic, medical, surgical, and catheterization data, as well as PLE-specific data, including duration of disease, intensity/details of treatment, hospitalizations, and complications. Factors associated with waitlist and post-HTx outcomes and PLE resolution were sought. RESULTS: Eighty patients (median of 5 per center) were referred for HTx evaluation. Of 68 patients listed for HTx, 8 were removed due to deterioration, 4 died waiting, and 4 remain listed. In 52 patients undergoing HTx, post-HTx 1-month survival was 92% and 1-year survival was 83%. PLE-specific factors, including duration of PLE pre-HTx, pre-HTx hospitalizations, need for/frequency of albumin replacement, PLE therapies, and growth parameters had no association with post-HTx mortality. Immunosuppressant regimen was associated with mortality; standard mycophenolate mofetil immunotherapy was used in 95% of survivors compared with only 44% of non-survivors (p = 0.03). Rejection (53%) and infection (42%) post-HTx were common, but not associated with PLE-specific factors. PLE resolved completely in all but 1 HTx survivor at a median of 1 month (interquartile range 1 to 3 months); resolution was not affected by PLE-specific factors. CONCLUSIONS: PLE severity, duration, and treatment do not influence post-HTx outcome, but immunosuppressive regimen may have an impact on survival. PLE resolves in nearly all survivors.

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.