Changes in myocardial function and hemodynamics after ligation of the ductus arteriosus in preterm infants.

Background Rejection is a major cause of morbidity and mortality after pediatric heart transplantation (HTx). Survival after pediatric HTx has improved over time, but whether there has been an era-related improvement in the occurrence of allograft rejection is unknown. Methods The Pediatric Heart Transplant Study (PHTS) database was queried for patients who underwent HTx from January 1993 to December 2005 to determine the incidence of rejection and identify factors associated with the first episode of rejection in the first year after HTx. Results Data were reviewed in 1,852 patients from 36 centers. The incidence of rejection declined over 13 years at a rate of −2.58 ± 0.41 ( p p p p p = 0.046). Increased risk of rejection was associated with positive donor-specific crossmatch (OR, 1.85; 95% CI, 1.18–2.88; p = 0.007) and older recipient age (OR, 1.05; 95% CI, 1.02–1.07; p Conclusions Although the overall incidence and prevalence of rejection has substantially decreased over time in pediatric HTx recipients in the first year after HTx, the rate of rejection with hemodynamic compromise or death from rejection remains unchanged.

Decline in rejection in the first year after pediatric cardiac transplantation: a multi-institutional study

Despite modern immunosuppressive regimes, acute rejection remains a leading cause of morbidity and mortality in heart transplant recipients. Clinical features are unreliable, and therefore, screening is performed in order to detect rejection, and hence, augment immunosuppressive therapy, at an early stage, with the aim of reducing short- and long-term sequelae. Histological analysis of right ventricular myocardial tissue obtained at endomyocardial biopsy remains the 'gold standard' surveillance technique; however 'biopsy-negative' rejection occurs in up to 20% of patients, the procedure is associated with uncommon but potentially serious complications and it is expensive. Non-invasive screening would, conceivably, be safer, more tolerable and cheaper, and could potentially allow more comprehensive monitoring. The evidence for non-invasive methods of diagnosing acute rejection, including assessment of myocardial deformation, myocardial tissue characterisation, electrophysiological monitoring, visualisation of cellular and molecular components of rejection and peripheral monitoring of immune activation, is reviewed.

https://heart.bmj.com/content/heartjnl/99/7/445.full.pdf

Non-invasive approaches for the diagnosis of acute cardiac allograft rejection

Background Diagnosing and monitoring acute cellular rejection (ACR) is a major objective in the surveillance of heart-transplanted patients. The aim of this study was to evaluate the value of global longitudinal strain (GLS), measured by two-dimensional speckle-tracking echocardiography, as a noninvasive tool for graft function monitoring in relation to ACR. Methods The study population consisted of all heart-transplanted patients who underwent biopsy and corresponding echocardiography at one institution from 2011 to 2013 ( n  = 64). ACR was classified according to the International Society of Heart and Lung Transplantation (0R–3R). Changes in graft function were serially evaluated before, during, and in the resolving period after ACR. Results No sign of rejection was seen in 268 biopsies (52.7%), minimal rejection (1R) in 202 biopsies (39.7%), and moderate rejection (2R) in 39 biopsies (7.7%); no patients had severe (3R) rejection. A significant difference in GLS was observed comparing the groups with 0R (−15.5%; 95% confidence interval, −16.2% to −14.2%), 1R (−15.3%; 95% confidence interval, −16.0% to −14.6%), and 2R (−13.8%; 95% confidence interval, −14.6% to −12.9%) rejection ( P 2 years) after transplantation. In the serial assessment, GLS was decreasing significantly at the time of moderate 2R rejection and improved significantly in the resolving period. The traditional diastolic Doppler parameters, E-wave deceleration time and isovolumetric relaxation time, were unaffected by rejections, whereas the E/A and E/e′ ratios were significantly higher in the 2R group ( P  = .004 and P  = .01) compared with the 0R and 1R groups. Conclusions GLS is significantly reduced during moderate (2R) ACR and improves significantly in the resolving period. The present results provide encouraging evidence to consider the routine use of GLS as a marker of graft function involvement during ACR.

Changes in Longitudinal Myocardial Deformation during Acute Cardiac Rejection: The Clinical Role of Two-Dimensional Speckle-Tracking Echocardiography

Background— Allograft dysfunction is a common finding early after heart transplant (HT). We sought to assess the recovery of left (LV) and right ventricular (RV) function during the first year after HT in children and young adults using pulsed-wave tissue Doppler imaging.

Methods and Results— We analyzed serially performed echocardiography in 44 pediatric HT recipients (median age: 7.3 years at HT) who remained rejection-free during the first year post-transplant. Age-based normative values for systolic ( S ′), early-diastolic ( E ′), and late-diastolic ( A ′) velocities obtained using pulsed-wave tissue Doppler imaging in 380 healthy children were used to transform patient data into z scores. Pulsed-wave tissue Doppler imaging studies ≤10 days post-HT demonstrated biventricular systolic and diastolic dysfunction with most prominent impairment in RV systolic function ( S ′ z score −2.7±0.8), RV early-diastolic filling ( E ′ z score −2.3±1.1), and LV early-diastolic filling ( E ′ z score −2.3±1.1). LV systolic function ( S ′ z score) and late-diastolic filling ( A ′ z score) improved to normal in 11 to 30 days, LV early-diastolic filling ( E ′ z score) in 4 to 6 months, and RV early-diastolic filling in 6 to 9 months ( P <0.001 for all on longitudinal analysis). However, RV systolic function (RV S ′ z score −1.2±1.1) remained impaired 1-year post-transplant. Analysis of serial cardiac catheterization studies showed that RV and LV filling pressures were elevated early post-HT and declined gradually during the first year post-transplant.

Conclusions— Pediatric HT recipients have biventricular dysfunction using pulsed-wave tissue Doppler imaging early after HT with most significant impairment in RV systolic function and RV and LV early-diastolic filling. Although other aspects of LV and RV function normalize in 6 to 9 months, RV systolic function remains abnormal 1 year-post-transplant.

Cardiac allograft function during the first year after transplantation in rejection-free children and young adults.

Background To date, cardiac catheterization and endomyocardial biopsy have been considered the "gold standard" for rejection surveillance after heart transplantation. Factors such as patient size (i.e., infant transplantation), loss of vascular access after repeated catheterizations, and anesthesia requirements all present unique problems and risks related to pediatric rejection surveillance. Therefore, additional methods to monitor for rejection in a non-invasive, reliable and frequent manner have been sought. We studied the utility of echocardiographic measurement of the left ventricular myocardial performance index (LVMPI), a reproducible measure of combined systolic and diastolic performance, in pediatric heart transplant recipients as a method of identifying acute rejection. Methods Two-dimensional/Doppler echocardiographic studies ( n = 36) were performed on 21 cardiac transplant patients (ages 6.2 to 21.9 years) at the time of endomyocardial biopsy. The LVMPI, the sum of the isovolumic contraction time and isovolumic relaxation time divided by aortic ejection time, was determined at each study, as well as other echocardiographic measures of systolic and diastolic function. Patients were grouped by concurrent histologic rejection grade and the results compared between groups. Results Significant differences in LVMPI ( p n = 23) and those with moderate to severe rejection (Grade 3; n = 5), as well as between those with no rejection and those with focal moderate (Grade 2; n = 8) rejection ( p n = 7). No significant differences were noted between groups for left ventricular ejection fraction or shortening fraction, percent septal or posterior wall thickening, left ventricular mass index or mitral valve deceleration time. In addition, for those individual patients with multiple studies, the LVMPI consistently increased with higher rejection grades and decreased after therapy. Conclusions In this series, increased LVMPI correlated with biopsy-proven rejection, and frequent serial assessments using this technique may provide a relatively sensitive non-invasive means of rejection surveillance after pediatric cardiac transplantation. False positive results may be encountered, likely due to alterations in diastolic function that have been previously observed in transplant recipients.

Debra Pruett

Papers

Increased myocardial performance index correlates with biopsy-proven rejection in pediatric heart transplant recipients.