Left atrial deformation predicts pulmonary capillary wedge pressure in pediatric heart transplant recipients.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) is an important indicator in pediatric heart transplant patients, but commonly used noninvasive surrogates, such as ratio of early diastolic mitral inflow velocity to annular velocity (E/E'), have limitations in this population. This study aimed to evaluate the relation of left atrial (LA) peak systolic strain and distensibility with PCWP in pediatric heart transplant recipients. METHODS: Consecutive pediatric heart transplant patients were enrolled at time of cardiac catheterization, with echocardiogram immediately afterward. E/E' ratio at the lateral and medial mitral annulus, peak LA systolic longitudinal strain by speckle tracking, and LA distensibility were measured from echocardiograms and compared to invasively measured PCWP. RESULTS: In 38 patients (11.1 ± 5.8 years old), PCWP correlated with peak LA systolic strain (r = -0.44, P = 0.01) and LA distensibility (r= -0.43, P = 0.02), but not with E/E'. On receiver operating characteristics analysis, LA strain had a higher area under the curve than LA distensibility (0.846 vs. 0.606). LA strain <18.9% had sensitivity 62% and specificity 95%, with likelihood ratio 12.3 for PCWP ≥12. However, LA strain had lower intra-observer and inter-observer reproducibility than distensibility (intra-class correlation coefficients 0.89 and 0.75 vs. 0.93 and 0.90). CONCLUSIONS: Peak LA systolic strain and LA distensibility may be more useful surrogates of left ventricular filling pressure than E/E' in the pediatric heart transplant population, with greater reproducibility of LA distensibility. Longitudinal studies are needed to evaluate which parameters track changes in PCWP and clinical outcome.

Outcomes of third heart transplants in pediatric and young adult patients: analysis of the United Network for Organ Sharing database.

BACKGROUND: Repeat heart transplantation (re-HTx) is standard practice in many pediatric centers. There are limited data available on outcomes of third HTx after failure of a second graft. We sought to compare outcomes of third HTx in pediatric and young adult patients with outcomes of second HTx in comparable recipients. METHODS: All recipients of a third HTx in whom the primary HTx occurred before 21 years of age were identified in the United Network for Organ Sharing database (1985 to 2011) and matched 1:3 with a control group of second HTx patients by age, era and re-HTx indication. Outcomes including survival, rejection and cardiac allograft vasculopathy (CAV) were compared between groups. RESULTS: There was no difference between third HTx patients (n = 27) and control second HTx patients (n = 79) with respect to survival (76% vs 80% at 1 year, 62% vs 58% at 5 years and 53% vs 34% at 10 years, p = 0.75), early (<1 year from HTx) rejection (33.3% vs 44.3%, p = 0.32) or CAV (14.8% vs 30.4%, p = 0.11). Factors associated with non-survival in third HTx patients included mechanical ventilation at listing or HTx, extracorporeal membrane oxygenation support at listing or HTx, and elevated serum bilirubin at HTx. CONCLUSIONS: Outcomes among recipients of a third HTx are similar to those with a second HTx in matched patients, with no difference in short- or long-term survival and comparable rates of early rejection and CAV. Although the occurrence of a third HTx remains relatively rare in the USA, consideration of a third HTx appears reasonable in appropriately selected patients.

Association of pediatric heart transplant coronary vasculopathy with abnormal hemodynamic measures.

OBJECTIVE: Transplant coronary artery disease (TCAD) is the limiting factor to long-term cardiac allograft survival; however, presymptomatic diagnosis remains challenging. To that concern, we evaluated the association of abnormal catheter-derived filling pressures with TCAD in pediatric heart transplant (HTx) recipients. DESIGN, PATIENTS, OUTCOME MEASURES: Data from 52 presymptomatic pediatric HTx patients were analyzed. Catheter-derived right ventricular end-diastolic pressure (RVEDP) and pulmonary capillary wedge pressure (PCWP) were recorded. Biopsies were collected to verify the absence of rejection. RESULTS: TCAD was diagnosed an average of 8.3 years post-HTx in 20 (38%) patients, six of whom died and four of whom underwent retransplantation. Catheter-derived pressure measurements showed that RVEDP was elevated in TCAD compared with non-TCAD patients (9.5 ± 6.0 vs. 5.4 ± 4.7; P= .005), as was the PCWP (12.9 ± 5.7 vs. 9.1 ± 5.7; P= .012). Results from logistic regression analysis showed RVEDP > 10 mm Hg or PCWP > 12 mm Hg was associated with TCAD (OR = 5.2; P= .010). CONCLUSIONS: In this series, elevated ventricular filling pressures measured during routine surveillance catheterizations were associated with angiographic TCAD. Recognizing the association between elevated RVEDP/PCWP and TCAD may prompt earlier diagnosis and treatment of this potentially lethal process.

Infection and malignancy after pediatric heart transplantation: the role of induction therapy.

BACKGROUND: Variable rates of malignancy and early infection have previously been reported in heart transplant (HTx) recipients who received induction therapy. This study hypothesized that induced pediatric patients would have an increased risk of these events compared with non-induced patients. METHODS: Data from a prospective, multicenter event-driven registry of outcomes after HTx listing in patients aged < 18 years was used to analyze risks of infection and malignancy and their association with induction between January 1993 and December 2007. RESULTS: Of 2,374 patients, 1,258 (53%) received induction and more frequently from 1999 to 2008 compared with 1993 to 1998 (70.8% vs 57.5%, p < 0.001). At HTx, induced patients were more likely to have congenital heart disease (56.9% vs 48.1%, p < 0.001) but no more likely to be positive for Epstein-Barr virus (50.3% vs 51.4%, p = 0.67). Post-transplant lymphoproliferative disease (PTLD) was the most common malignancy (n = 92) within 5 years of HTx. Patients who received induction had a lower risk for PTLD (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.84; p = 0.009) and early fungal infections (HR, 0.60; 91% CI, 0.40-0.91; p = 0.016). Among induction agents used, OKT3 was associated with lowest freedom from PTLD and fungal/cytomegalovirus infection. CONCLUSIONS: Induction use has increased since 1999 and has not been associated with an increased risk of malignancy (predominantly PTLD) or overall infection. Because these adverse events occurred with higher rates in non-induced patients, it is likely that induction alone is not the primary risk determinant for PTLD and infection.

Lack of correlation between MMF dose and MPA level in pediatric and young adult cardiac transplant patients: does the MPA level matter?

To determine the correlation between mycophenolate mofetil (MMF) dose and mycophenolic acid (MPA) level as well as its impact on rejection among young cardiac transplant recipients (OHT), trough concentrations of MPA and its metabolite, mycophenolic acid glucuronide (MPAG), were measured following MMF doses of 1200 mg/m2/d (max 3000 mg/d). Corresponding endomyocardial biopsy (EMB) grades and calcineurin inhibitor levels were recorded with simultaneous MPA/MPAG levels. Correlation coefficients were derived between MMF dose and MPA/MPAG levels. Contingency analysis evaluated the relation between MPA level and EMB score. Twenty-six patients (median age 15.4 years) had 120 MPA/MPAG levels measured. Average MMF dose was 1208.8 mg/m2/d with median MPA and MPAG concentrations: 2.1 (therapeutic: 1.0-3.5 microg/mL) and 48 microg/mL (reference range: 35-100 microg/mL), respectively. Only 50% of patients consistently achieved therapeutic levels with standard dosing. No correlation was found between MMF dose and MPA/MPAG levels. In the presence of therapeutic calcineurin inhibition, EMB grade > or = 2 occurred more with MPA concentrations < 2.5 microg/mL (p = 0.01). In young OHT patients, MMF dose does not correlate with MPA/MPAG levels, and standard MMF dosing fails to consistently achieve 'therapeutic' MPA concentrations. An MPA trough level < 2.5 microg/mL was more frequently associated with EMB grade > or = 2. Concentration rather than dose-driven management is a more prudent strategy when using MMF.