Erin L. Albers

Predictors of myocardial recovery in pediatric tachycardia-induced cardiomyopathy

BACKGROUND Tachycardia-induced cardiomyopathy (TIC) carries significant risk of morbidity and mortality, although full recovery is possible. Little is known about the myocardial recovery pattern. OBJECTIVE The purpose of this study was to determine the time course and predictors of myocardial recovery in pediatric TIC. METHODS An international multicenter study of pediatric TIC was conducted. Children ≤18 years with incessant tachyarrhythmia, cardiac dysfunction (left ventricular ejection fraction [LVEF] <50%), and left ventricular (LV) dilation (left ventricular end-diastolic dimension [LVEDD] z-score ≥2) were included. Children with congenital heart disease or suspected primary cardiomyopathy were excluded. Primary end-points were time to LV systolic functional recovery (LVEF ≥55%) and normal LV size (LVEDD z-score <2). RESULTS Eighty-one children from 17 centers met inclusion criteria: median age 4.0 years (range 0.0-17.5 years) and baseline LVEF 28% (interquartile range 19-39). The most common arrhythmias were ectopic atrial tachycardia (59%), permanent junctional reciprocating tachycardia (23%), and ventricular tachycardia (7%). Thirteen required extracorporeal membrane oxygenation (n = 11) or ventricular assist device (n = 2) support. Median time to recovery was 51 days for LVEF and 71 days for LVEDD. Two (4%) underwent heart transplantation, and 1 died (1%). Multivariate predictors of LV systolic functional recovery were age (hazard ratio [HR] 0.61, P = .040), standardized tachycardia rate (HR 1.16, P = .015), mechanical circulatory support (HR 2.61, P = .044), and LVEF (HR 1.33 per 10% increase, p=0.005). For normalization of LV size, only baseline LVEDD (HR 0.86, P = .008) was predictive. CONCLUSION Pediatric TIC resolves in a predictable fashion. Factors associated with faster recovery include younger age, higher presenting heart rate, use of mechanical circulatory support, and higher LVEF, whereas only smaller baseline LV size predicts reverse remodeling. This knowledge may be useful for clinical evaluation and follow-up of affected children.

HLA molecular epitope mismatching and long-term graft loss in pediatric heart transplant recipients

BACKGROUND Although evidence links HLA allele mismatching to worse outcomes in pediatric heart transplantation, no studies to our knowledge have applied the quantification of structural HLA differences between donor and recipient to risk evaluation. We examine the association between molecular-level HLA mismatching and long-term graft loss in pediatric recipients of heart transplants. METHODS HLA Matchmaker was used to quantify the number of mismatched class-specific HLA eplets among 4,851 heart transplant recipients ≤18 years of age in the Scientific Registry of Transplant Recipients (1987-2012). Survival analysis was used to compare long-term probabilities of graft loss by number of eplet mismatches and allele mismatches stratified by eplet mismatches. RESULTS Recipients with 10 to 20 or >20 class I (HLA-A and HLA-B) eplet mismatches experienced increased long-term graft loss compared with recipients with <10 class I eplet mismatches (adjusted hazard ratio = 1.23 [95% confidence interval = 1.06-1.42], adjusted hazard ratio = 1.27 [95% confidence interval = 1.08-1.50], respectively). Recipients with 2 to 4 class I allele mismatches had increased long-term graft loss compared with recipients with 0 to 1 class I allele mismatches. Neither class II (HLA-DR) eplet mismatching nor class II allele mismatching was associated with graft loss. On stratification by allele and structural eplet mismatching, only recipients with 2 to 4 class I allele mismatches and ≥10 class I eplet mismatches had an increased probability of graft loss compared with recipients with 0 to 1 class I allele mismatches (adjusted hazard ratio = 1.42 [95% confidence interval = 1.09-1.57]). CONCLUSIONS Molecular-level HLA mismatching may aid in identifying recipients at increased risk of long-term graft loss who could benefit from intensified post-transplant surveillance and management.

Feasibility and interpretation of global longitudinal strain imaging in pediatric heart transplant recipients

Evaluation of myocardial mechanics after heart transplant is important in monitoring allograft function and identifying rejection. Speckle tracking global longitudinal strain (GLS) may be more sensitive to early regional changes from rejection. This study aimed to determine feasibility of GLS in pediatric hearts during surveillance echocardiograms, compare their GLS to published norms (−18% to −22%), and assess association of GLS with other indices of graft function. Retrospective review of transplant echocardiograms from 2013 to 2014. Philips QLAB was used for post‐acquisition GLS analysis. Multiple linear regression was used to assess the association of GLS with echocardiographic/catheterization indices, and B‐type natriuretic peptide (BNP). Forty‐seven patients (84 studies) were included. Calculation of GLS was feasible in 82 studies (97%) with inter‐ and intra‐observer variability of 0.71 and 0.69. Patients (n=9) with rejection had GLS of −16.4% (SD=3.5%) compared to those without [−16.8% (SD=3.7%)]. GLS worsened linearly with increasing Ln(BNP) (P=<.001), left ventricular volume in diastole (P=<.001), septal a’ wave (P=<.001), and pulmonary capillary wedge pressure (P=<.001). Speckle tracking‐based GLS is feasible and reproducible in pediatric heart recipients and is reduced at baseline. The role of GLS and BNP in detecting early systolic dysfunction warrants further investigation.

Posterior reversible encephalopathy syndrome after pediatric heart transplantation: Increased risk for children with preexisting Glenn/Fontan physiology

Identification of risk factors for PRES after organ transplant can improve early detection and avoid permanent neurological injury. High calcineurin‐inhibitor levels and hypertension are recognized risk factors for PRES in adult transplant recipients. Limited data exist regarding PRES after pediatric HTx, with studies limited to case reports. We performed a retrospective review of 128 pediatric HTx recipients to identify risk factors for PRES. Seven of 128 (5.5%) recipients developed PRES at a median of 10 days (5–57) after HTx. The median age of recipients with PRES was 10.0 yr (5.7–19.0), compared to 1.4 yr (0.0–19.8) for recipients without PRES (p = 0.010). Fewer than half of recipients with PRES had elevated post‐transplant calcineurin‐inhibitor levels (n = 3) and/or preceding severe hypertension (n = 3). Four of seven who developed PRES (57%) had pretransplant Glenn or Fontan physiology (G/F). G/F was a significant risk factor for PRES (RR 4.99, 95% CI: 1.19–21.0, p = 0.036). Two recipients (29%), both with severe PRES, had residual neurological symptoms. In summary, PRES occurred in 5.5% of pediatric HTx recipients and presented early after HTx. All recipients with PRES were > 5 yr. Patients with pretransplant G/F were at increased risk, a risks factor not previously described.

Myocarditis masquerading as acute coronary syndrome: diagnostic role of cardiac MRI

Background Myocarditis presenting as isolated acute chest pain with elevated troponins but normal systolic function by echocardiogram is rare in previously healthy children. Diagnosis is challenging in this situation with significant drawbacks even for the gold standard endomyocardial biopsy. Our study aim is to evaluate the diagnostic role of cardiac MRI in comparison with echocardiography in these patients.

Diastolic pressure indices offer a novel approach to predicting risk of graft loss after pediatric heart transplant

PH is a risk factor for GL after HTx. However, traditional parameters are not reliable predictors of risk in children. We hypothesized that DPI (dPAP and DPG) are predictive of GL in pediatric HTx recipients. The UNOS/SRTR database was reviewed to identify pediatric HTx recipients (age <18 years) between 1994 and 2013. Recipients with pretransplant hemodynamic data were grouped by diagnosis (CMP or CHD), and the groups were analyzed separately. Bivariate Cox regression analysis examined the association between hemodynamic variables and GL. DPI showed the strongest association with early GL in recipients with CMP (dPAP: HR = 1.25 [1.09‐1.42]; DPG: 1.24 [1.11‐1.38]). Among CHD recipients, DPI were associated with early GL in those with preexisting PH (dPAP: HR = 1.16 [1.01‐1.33]; DPG: HR = 1.10 [1.00‐1.21]). No cutoff values for “high‐risk” DPI were identified, but a continuous relationship between higher DPI and risk of early GL was observed. DPI are associated with early GL in select pediatric HTx recipients. Our findings suggest that DPI should be considered as part of routine hemodynamic assessment for pediatric HTx candidates.

Novel findings of left ventricular non-compaction cardiomyopathy, microform cleft lip and poor vision in patient with SMC1A-associated Cornelia de Lange syndrome

Relatively few patients with Cornelia de Lange syndrome (CdLS) due to SMC1A mutation have been reported, limiting understanding of the full extent of the phenotype. Compared to children with classic NIPBL‐associated CdLS, patients with SMC1A‐associated CdLS have a milder physical phenotype with prominent intellectual disability, high rate of cleft palate and absence of limb reductions. We present a patient with SMC1A‐associated CdLS who had typical features including developmental delay, seizure disorder, feeding difficulties, hirsutism, and cleft palate. She also was found to have three novel features: (i) left ventricular non‐compaction (LVNC) cardiomyopathy; (ii) microform cleft lip; and (iii) severe hyperopia and astigmatism. These features have implications regarding potential insight into the pathogenesis of the disorder, screening, and medical management. Hypertrophic cardiomyopathy has previously been reported in SMC1A‐associated CdLS, but to our knowledge this is the first reported child with LVNC. Previous reports have included children with isolated clefts of the palate without involvement of the lip. When cleft palate alone is associated with a disorder, the underlying pathophysiology for clefting is sometimes secondary due to mechanical blocking of the fusion of the palatal shelves with the developing tongue. The presence of microform cleft lip in this patient suggests that the pathophysiology of clefting in SMC1A is primary rather than secondary. Few studies report ophthalmologic findings specific to SMC1A. Based on these findings, LVNC cardiomyopathy and cleft lip should be considered features of SMC1A‐associated CdLS. All patients should receive echocardiogram and undergo thorough ophthalmologic evaluation as part of routine CdLS care.

GLOBAL LONGITUDINAL ECHOCARDIOGRAPHIC STRAIN IMAGING IN PEDIATRIC HEART TRANSPLANT RECIPIENTS

Evaluation of myocardial mechanics in heart transplant is important in monitoring allograft function and identifying acute rejection. Speckle tracking based global longitudinal strain (GLS) detects global and regional abnormalities and may detect rejection. This study aimed to compare GLS to other