Doppler tissue imaging in children following cardiac transplantation: a comparison to catheter derived hemodynamics

Previous studies have demonstrated a correlation between E:E(a) and ventricular filling pressure in adults after heart transplantation. We sought to determine if E:E(a) correlates with filling pressure after heart transplantation in children. A prospective analysis of children who have undergone heart transplantation was performed. Inflow and myocardial velocities were recorded and compared to catheter-derived filling pressures and rejection status. We performed 61 studies in 49 subjects. No correlation was found between septal E:E(a) and PCWP (r=0.14, p=0.28); or between lateral tricuspid E:E(a) and mean RAp (r=0.04, p=0.79). However, the mean PCWP was higher among subjects with elevated septal E:E(a) (>12) compared to normal E:E(a) (12.3±2.8mmHg vs. 10.1±2.9mmHg, p=0.02). Similarly, mean RAp was higher among subjects with an elevated lateral tricuspid E:E(a) (>10) compared to normal lateral tricuspid E:E(a) (7.7±2.1mmHg vs. 6.0±2.4mmHg, p=0.04). Elevated septal E:E(a) was also associated with high-grade cellular rejection (OR=17.3 [95% CI 1.4-221], p=0.028). In children following heart transplant, E:E(a) does not correlate well with the range of filling pressures seen after pediatric heart transplantation. However, a septal E:E(a)>12 is associated with elevated PCWP and high grade cellular rejection and a lateral tricuspid E:E(a)>10 is associated with elevated mean RAp.     

Serial measurements of exercise performance in pediatric heart transplant patients using stress echocardiography

Heart transplantation is an increasingly acceptable therapeutic option for children with end-stage and complex congenital heart disease. With advances in surgery, immunosuppression, and follow-up care, functional outcomes need to be evaluated. We report the results of serial exercise testing performed using stress echocardiography in a cohort of pediatric HTP. HTP (n = 7) exercised on a semi-recumbent ergometer to volitional fatigue. Echocardiography-Doppler measurements, HR, and blood pressure were taken at rest and during staged exercise. Results were compared with healthy CON (n = 12). HTP did significantly less work during exercise (940 vs. 1218 J/kg, p < 0.03). Their SVI (33 vs. 49 mL/m(2), p < 0.003), CI (5.16 vs. 9.25 L/min/m(2), p < 0.0005), and HR (162 vs. 185 bpm, p < 0.02) were lower at peak exercise. HTP had a lower SF at peak exercise (48% vs. 52%, p < 0.03) and an abnormal relationship between the MVCFc and σPS. During follow-up, hemodynamics and left ventricular function remained relatively constant in HTP. HTP are able to exercise safely; however, their exercise tolerance is reduced, and hemodynamics and contractility are diminished. Over time, their hemodynamics and left ventricular function have remained relatively constant.     

Left ventricular assist device to avoid heart–lung transplant in an adolescent with dilated cardiomyopathy and severely elevated pulmonary vascular resistance

Orthotopic heart transplantation remains the definitive treatment of choice for patients with end‐stage heart failure; however, elevated PVRI is a reported risk factor for mortality after heart transplant and, when severely elevated, is considered an absolute contraindication. Use of a ventricular assist device has been proposed as one treatment for reducing pulmonary vascular resistance index in potential heart transplant candidates refractory to medical vasodilator therapies. We report on a teenage patient with dilated cardiomyopathy and severely elevated PVRI, unresponsive to pulmonary vasodilator therapy, who underwent left ventricular assist device implantation to safely allow for aggressive pulmonary vasodilator therapy and to decrease PVRI. The resulting dramatic improvement in PVRI in a relatively short period of time allowed for successful heart transplantation, avoiding the need for heart–lung transplant.     

Decline in ventricular function as a result of general anesthesia in pediatric heart transplant recipients

Echocardiography is frequently performed under anesthesia during procedures such as cardiac catheterization with EMB in pediatric HTx recipients. Anesthetic agents may depress ventricular function, resulting in concern for rejection. The aim of this study was to compare ventricular function as measured by echocardiography before and during GA in 17 pediatric HTx recipients. Nearly all markers of ventricular systolic function were significantly decreased under GA, including EF (?4.2% ±1.2, P < .01) and RV FAC (?0.05 ± 0.02, P = .04). Subjects in the first post‐transplant year (n = 9) trended toward a more significant decrease in EF vs those beyond the first post‐transplant year (n = 8; ?6.0% ±1.2 vs ?2.1 ± 2.0, P = .1). This information quantifies a decline in biventricular function that should be expected in pediatric HTx recipients while under GA and can assist the transplant clinician in avoiding unnecessary treatment of transient GA‐induced ventricular dysfunction.     

Comparison of inhospital outcomes of pediatric heart transplantation between single ventricle congenital heart disease and cardiomyopathy

Data investigating the impact of household income and other factors on SV patient status‐post‐Fontan palliation after heart transplantation are lacking. We aim to evaluate factors affecting outcomes after OHT in this population. The PHIS database was interrogated for either SV or myocarditis/primary CM who were 4 years or older who underwent a single OHT. There were 1599 patients with a median age of 13.2 years (IQR: 9.3‐16.1). Total hospital costs were significantly higher in the SV group ($408 000 vs $294 000, P < 0.0001), but as median household income increased, the risk of inhospital mortality, post‐transplant LOS, and LOS‐adjusted total hospital costs all decreased. The risk of inhospital mortality increased 6.5% per 1 year of age increase at the time of transplant. Patients in the SV group had significantly more diagnoses than those in the CM group (21 vs 15, P < 0.0001) and had longer total hospital LOSs as a result of longer post‐transplant courses (25 days vs 15, P < 0.0001). Increased median household income and younger age are associated with decreased resource utilization and improved inhospital mortality in SV CHD patients who undergo OHT. In conclusion, earlier consideration of OHT in this population, coupled with improved selection criteria, may increase survival in this population.     

Refractory dilated cardiomyopathy associated with metastatic neuroblastoma

A 2‐year‐old African American male presented with heart failure and an abdominal mass. Computerized tomography (CT) scan revealed a 7 cm adrenal lesion, confirmed as poorly differentiated neuroblastoma (NB). CT and meta‐iodobenzoguanidine (MIBG) scans identified multiple metastases, but cardiac MIBG imaging was absent. Cardiac ejection fraction (EF) was 8% with 7% shortening fraction. The patient underwent six cycles of chemotherapy and investigational immunotherapy. Cardiac function improved to 26% EF. However, the tumor proved unresponsive to treatment. The patient died from stage IV congestive heart failure (CHF) and progressive NB. Autopsy confirmed dilated cardiomyopathy with endocardial fibroelastosis. Pediatr Blood Cancer. 2010;55:736–738. © 2010 Wiley‐Liss, Inc.     

Serial evaluation for myocardial performance in fetuses and neonates using a new Doppler index

BACKGROUND: Fetal echocardiography has been used for non-invasive evaluation of human fetal cardiac anatomy, function and hemodynamics. The Tei index, a new Doppler index known to be independent of both ventricular geometry and heart rate, has recently been applied to the evaluation of myocardial performance. METHODS: In the present study, the Tei index was prospectively and longitudinally determined in 50 normal fetuses, 35 fetuses with intrauterine growth retardation (IUGR), 30 fetuses of diabetic mothers (DM) and 20 normal infants. The Tei index of both left and right ventricles was calculated from a Doppler ventricular inflow and outflow trace using the following formula: Tei index = (ICT + IRT)/ET, where ICT is isovolumetric contraction time; IRT, isovolumetric relaxation time; and ET, ejection time). RESULTS: The Tei index of the left ventricle decreased linearly with advancing gestational age during 18-33 weeks and decreased acceleratively with increasing gestational age after 34 weeks. The index of the right ventricle decreased slightly and linearly with advancing gestational age during 18-41 weeks. In neonates, the Tci index of the left and right ventricle increased immediately and transitorily after birth and decreased and stabilized after 24 h of life. From 18 to 26 weeks of gestation, the Tei indices in fetuses with IUGR and of DM were not significantly different from controls. However, from 27 to 40 weeks of gestation, the Tei indices in both fetuses with IUGR and of DM were significantly greater than controls. CONCLUSIONS: This gradual decrease in the Tei index during gestation may represent the maturational or developmental alternation of myocardial performance in utero. Fetuses with IUGR and of DM may have abnormal myocardial performance in later gestation.     

Left ventricular myocardial performance index change for detection of acute cellular rejection in pediatric heart transplantation

EMB, the gold standard for diagnosis of ACR, poses unique risks in children. Limited cross‐sectional data have associated LV MPI with ACR. We hypothesize that a relative change in MPI from baseline without ACR to the time of ACR will better detect ACR than an absolute threshold LV MPI value. We identified 40 children with ACR ≥60 days post‐transplant matching them by age and time from transplantation to 40 children without ACR. There was a significant increase in LV MPI at time of ACR vs. baseline (0.59 ± 0.17 vs. 0.41 ± 0.11; p < 0.001). There was no difference in LV MPI between baseline and follow‐up (0.41 ± 0.11 vs. 0.42 ± 0.11; p = 0.65). An absolute increase in LV MPI of ≥0.47 had 82.5% sensitivity and 85% specificity for ACR, whereas an increase in LV MPI from baseline of ≥20.4% was 90% sensitive and 100% specific. Serial measurement of LV MPI appears to be a sensitive and specific marker of ACR. LV MPI shows good interobserver agreement and increases at the time of EMB‐proven ACR with subsequent resolution to baseline measurements upon EMB‐proven resolution of ACR. Future studies in larger, prospective cohorts should be undertaken to validate these findings.     

扩张型心肌病的心功能变化:多普勒组织显像的敏感性与可靠性

探讨扩张型心肌病（DCM）的心功能变化,比较多普勒组织显像（DTI）与传统心功能指标的敏感性及可靠性。方法对25例DCM患儿分别测量其心腔大小、EPSS（Epoint－septalseparation）、左室心肌重量指数（LVMI）、二大瓣血流E峰及A峰、左室射血分数（LVEF）、每搏指数（SI）及DTI测量其二尖瓣环收缩期及舒张早期运动速度（MVR－SV、MVR－DeV）,在室后壁心内膜收缩期及舒张期运动速度（LVPW－EnSV、LVPW－EnDV）,并设正常对照组143名。结果DCM患儿心脏收缩及舒张功能均显著下降,心肌运动速度显著降低．MVR－DeV与LVMI、EPSS是显著负相关（r=-0．84,-0．83P＜0．01）,与LVEF、SI是显著正相关（r=0．844,0．77P＜0．01）,同时其敏感性显著高于LVEF及SI（P＜0．05）;DTI测量心肌的舒张功能其敏感性、可靠性均高于二失瓣血流E峰与A峰,而E／A敏感性最差,且多数DCM呈假性正常,MVR－DeV与E峰、A峰及E／A均无显著直线相关性（P均＞0．05）,与病情一致。结论DCM的收缩及舒张功能均显著下降,DTI指标较传统心功能指标更敏感而可靠。     

扩张型心肌病患儿心率变异改变及与心脏结构和功能的相关性

目的 研究扩张型心肌病(DCM)患儿的心率变异(HRV)改变及其与心脏结构和功能的相关性.方法 对36例DCM患儿和30例健康儿童分别进行24 h心率变异分析,得出连续平均正常RR间期标准差(SDNN)、每5 min正常R-R间期平均值的标准差(SDANN)、每5 min正常RR间期标准差的平均值(SDNN index)、相邻RR间期≥50ms的百分数(PNN50)、相邻RR间期差的均方根(rMSSD)、总功率(TP)、低频成份(LF)、高频成分(HF)及LF/HF等指标.行常规超声心动图检查,取得左房舒张末期前后径(LAED)、左室舒张末期前后径(LVED)、左室射血分数(LVEF)、短轴缩短率(INFS)、二尖瓣峰值速度比值(E/A)等指标.对两组的上述指标进行比较,并分析DCM患儿的心率变异性与心脏结构和功能的相关性.结果 对照组男孩的SDNN、SDANN,SDNN index、rMSSD、PNN50、TP均高于女孩.DCM组男女的HRV差异无统计学意义,与对照组比较,DCM组的LF/HF显著升高,其余HRV指标明显下降;与对照组相比,DCM组的LAED和LVED显著增大,LVEF、LVFS及二尖瓣E/A均显著降低;DCM患儿的SDNN与LAED呈负相关关系,与LVEF、LVFS和E/A呈正相关关系(P均<0.05),其余HRV指标与心脏大小和功能无相关性.结论 DCM患儿存在明显的自主神经平衡失调,DCM患儿HRV的性别差异消失,均表现为迷走神经张力减退、交感神经相对激活.DCM患儿HRV中部分指标的改变与房室腔扩大和心功能下降有一定的相关性,部分HRV指标相对独立,将HRV指标与超声测量指标结合起来能更好地指导临床.     

Outcome of heart transplantation in pediatric cancer survivors

The aim of this study is to evaluate the outcome of heart transplantation in children surviving malignancies. Pediatric heart transplant recipients were identified using the UNOS database. Follow‐up data including survival and rate of malignancy were analyzed. A total of 7169 children received heart transplants between 1987 and 2011. Of these, 107 (1.5%) survived previous malignancy treatment (group I) and 7062 (98.5%) did not have prior malignancy (group II). Survival after transplant was 92.5%, 90.6%, 80.3%, and 65% at three months, one, five, and 10 yr in group I, similar to the rate in group II (90.1%, 84.4%, 73.8%, and 57.7%). Survival after transplantation was similar between group I and children who underwent OHT secondary to cardiomyopathy in group II. The rate of post‐OHT malignancy in group I was higher than that in group II (14/107(13%) vs. 386/7062 (5.4%), p = 0.001). Children who developed malignancy in group I had similar survival as children who developed malignancy in group II. Post‐transplant survival is similar in children with and without pretransplant malignancy in spite of higher rate of malignancy in children with pretransplant malignancy. OHT appears to be a reasonable treatment option in children who develop end‐stage heart disease after malignancy treatment.     

Changes in left ventricular strain parameters following pediatric heart transplantation

STE is increasingly utilized to assess strain in a variety of pathologies. Strain measurements have demonstrated utility following HT x and may aid in the detection of rejection and CAV . Strain parameters have not been well defined in the pediatric HT x population. This study aimed to describe strain in pediatric HT x recipients compared to controls and assess changes over time. All pediatric HT x recipients with available echocardiograms (2004‐2015) without rejection or CAV were identified. Longitudinal and circumferential strain was measured at <1 month, 1 year, 3 years, and 5 years post‐transplant and compared to controls. A total of 218 echocardiograms were analyzed in 79 HT x recipients. At <1 month post‐transplant, there was a significant decrement in longitudinal strain (GLS ?14.6 vs ?19.2, P  < .001) with concurrent augmentation of circumferential strain (GCS ?27.3 vs ?24.3, P  = .005). By 1 year post‐HT x, all strain parameters normalized and were not significantly different from the control population. In the absence of graft complications, strain parameters did not change up to 5 years post‐transplant. Abnormal longitudinal strain parameters are present in the early post‐HT x period with a compensatory increase in circumferential strain. These changes normalize by 1 year post‐transplant and do not change over time in the absence of graft complications.     

First reported use of the heartware HVAD in the US as bridge to transplant in an adolescent

D’Alessandro D, Forest SJ, Lamour J, Hsu D, Weinstein S, Goldstein D. First reported use of the heartware HVAD in the US as bridge to transplant in an adolescent. Abstract: Limited options exist for mechanical circulatory support as a bridge to transplantation in pediatric patients with advanced heart failure. This is particularly true when it comes to intracorporeal technologies. We describe the first reported experience with the use of the HVAD in the US as a successful bridge to transplantation in a 13‐yr‐old patient.     

Histopathological aspects of cardiac biopsy in pediatric patients with dilated cardiomyopathy

Background: Dilated cardiomyopathy (DCM) is a heart muscle disease with cardiac dysfunction and a heterogenous disorder. This disease may show various histopathological aspects of the myocardium, but little is known about these in children. Methods: Histopathological findings of endomyocardial biopsy from 20 pediatric patients with DCM were analyzed and compared with those in adult patients. Results: Advanced histopathology, including myocytolysis and/or fragmentation of muscle bundles, was frequently observed in patients with poor prognosis. Patchy fibrosis was predominantly demonstrated in the pediatric patients, whereas perivascular fibrosis was mostly observed in the older adults. The myocarditic index, assessed in terms of the findings of fibrosis, size variation of myocytes, disarrangement of muscle bundles and mononuclear cell infiltration was higher in the pediatric patients than in the older adults (P < 0.05). Bizarre myocardial hypertrophy with disorganization, which tends to be frequently demonstrated in hypertrophic cardiomyopathy, was revealed in 30% of the pediatric patients, whereas it was disclosed in none of the older adult patients (P < 0.05). Conclusion: These results suggest that the major pathogenetic factors of DCM in children may be different from those in adults.     

Histology of the explanted hearts of children transplanted for dilated cardiomyopathy

There is little information as to the histology of the explanted hearts of children transplanted for presumed dilated cardiomyopathy. We therefore aimed to describe the histology of these explants. Thirty-six children [mean age 7.4 years (range 0.1-17)] transplanted for dilated cardiomyopathy were identified. Based on histological examination of the explanted hearts patients were classified into three groups: severe inflammation, mild to moderate inflammation, and minimal or no inflammation. Cell death/damage and fibrosis were also scored. Duration of symptoms and degree of support at transplant were ascertained from the case notes. Two patients had severe confluent inflammation, nine mild or moderate focal inflammation, and 25 minimal or no inflammation. The degree of inflammation and fibrosis did not correlate with the interval between presentation and transplant (p = 0.37 and p = 0.78). Patients requiring inotropes or ventricular assist had a shorter time interval between presentation and transplant (p = 0.017) although these levels of support were not associated with the degree of inflammation or fibrosis (p = 0.90 and 0.5). We conclude that the explanted hearts of one-third of children transplanted for presumed cardiomyopathy have some degree of inflammation. Histological findings are not associated with symptom duration or support required.     

Heart transplantation in infants with idiopathic hypertrophic cardiomyopathy

Abstract:  Whereas it is well known that idiopathic HCM can present in newborns and infants, little information is available on HT in this very young age group. We report a series of 17 infants with idiopathic HCM, including two neonates with rapidly progressive severe HF for whom HT was necessary. When HF manifests in a newborn/infant with idiopathic HCM and extreme cavity size reduction, the possibility of a rapidly progressive clinical course should be anticipated and HT may become the only available therapeutic solution.     

Vasoactive–inotropic score after pediatric heart transplant: A marker of adverse outcome

VIS, a quantitative index of pressor support, has been shown to be a predictor of morbidity and mortality in infants younger than six months who underwent CPB. Data on its prognostic utility following pediatric OHT are lacking. This study compared clinical outcomes in children with differential VIS after pediatric OHT. A retrospective cohort study of 51 consecutive heart transplants from 2004 to 2011 was performed at a pediatric tertiary care facility. Peak VIS was computed within initial 24 and 48 h after OHT and was weighted for peak dose and administration of any or all of six pressors. Patients with peak VIS ≥ 15 constituted high VIS group. Children who persistently required a higher magnitude of pressor support for the first 48 h after OHT, as reflected by high peak VIS, had significantly longer ICU stay (30.2 vs. 15.9 days, p = 0.01), pressor (11.4 vs. 6.8 days, p = 0.02) and ventilatory durations (12.4 vs. 5.9 days, p = 0.05), and higher rates of short‐term morbidities. Patients with longer CPB (213 vs. 153 min, p = 0.005) time have higher peak VIS. High peak VIS at 48 h is an effective, yet simple clinical marker for adverse outcomes in pediatric OHT recipients.     

实时三维超声心动图在小儿扩张型心肌病左心功能评价中的应用

目的探讨实时三维超声心动图(RT-3DE)技术在评估小儿扩张型心肌病(DCM)左心功能中的价值。方法以28例DCM患儿和20例正常儿童为研究对象,应用RT-3DE技术测定反映左室功能的指标如左室舒张末期容积(LVEDV)、收缩末期容积(LVESV)、左室容量(LVSV)和左室射血分数(LVEF),并与改良Ross标准及传统二维超声(2DE)测定指标进行比较。结果 RT-3DE评估的EF值与Ross评分值呈负相关(r=-0.97,P<0.001),与2DE相比虽有相关性,但不如前二者显著(r=-0.59,P<0.01);2DE所测LVEDV及LVESV小于RT-3DE,而EF值及SV两者差异无统计学意义;RT-3DE测定的LVEF值与2DE测定的EF有很好的相关性(r=0.68,P<0.001)。随访1年后,有6例患儿死亡,死亡组患儿EF值明显低于存活组(P<0.01)。结论 RT-3DE所测量的左心室心功能参数能够准确、客观地反映DCM患者的左心功能。