The complication rate of intravascular ultrasound (IVUS) in a multicenter pediatric heart transplant population: A study of the international pediatric IVUS consortium.

BACKGROUND: Our purpose was to determine the complication rate from intravascular ultrasound (IVUS) in a large, multicenter cohort of pediatric heart transplant (PHT) patients. METHODS: We retrospectively reviewed all PHT who underwent IVUS at 5 institutions (2006-2014). Rates of major and minor complications were calculated. All adverse events (AE) were graded from 1 to 5 using a previously published AE severity scale. RESULTS: There were 1380 catheterizations in 505 patients and 32 AE (2.3%); 9 major (0.6%) and 23 AE (1.7%). The major AE attributed to IVUS were all coronary artery vasospasm (7). Major and minor AE rates directly related to IVUS were 0.5% and 0.7%, respectively. Minor AE possibly attributable to IVUS included excessive fluoroscopy (3) and transient ST segment changes (7). Of AE related to IVUS, only 3 were of moderate severity. The rest were ≤ minor in severity. There were no reports of coronary artery dissection or death. CONCLUSION: Most AE during routine PHT coronary evaluation with IVUS were minor and not directly related to the use of IVUS. The number of coronary related AE was similar to a registry-based report of coronary angiography alone. Efforts to minimize IVUS-related complications should be focused on preventing coronary artery vasospasm.

Evolution of Biventricular Loading Condition in Pediatric LVAD Patient: A Prospective and Observational Study.

The aim of this study was to describe the echocardiographic trend of left ventricular (LV) and right ventricular (RV) function after implantation of a pulsatile flow left ventricular assist device (LVAD) in children. From 2013 to 2016, we prospectively evaluated 13 consecutive pediatric Berlin Heart EXCOR LVAD patients. Clinical and echocardiographic data were collected at baseline, within 24 h after implantation and monthly until LVAD explant. Median age and weight at the implantation was 8 (4-23) months and 5 (4.6-8.3) kg at the time of implantation, respectively. All were affected by dilated cardiomyopathy. Average LVAD support time was 226.2 ± 121.2 days. Nine (70%) were transplanted, 4 (30%) died. LV end-systolic and end-diastolic volumes were reduced until the follow up of two months (P = 0.019 and P = 0.001). A progressive increase in RV dimensions was observed. After 4 months of follow up, RV fractional area change worsening was statistically related with the deterioration of LV unloading (P = 0.0036). Four patients needed prolonged inotropic support for RV failure. Pulsatile LVAD in pediatrics is followed by an early and mid-term LV unloading, as expressed by a decrease in LV volumes and diameters at echocardiogram. The effects of unloading do not remain stable at long term follow up. RV function improved in the acute phase, but a progressive dilatation of RV was noted over time. In some patients, RV failure might lead to the need of an increase of inotropic support at long term follow up.

Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.

RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy.

Paroxysmal atrioventricular block after heart transplantation in children: an early sign of rejection?

In OHT recipients, pathologic evaluation of the heart during acute rejection can show involvement of both the conduction system and the myocardium. We here describe the cases of a 9-year-old male with DCM and a 13-year-old female with RCM, who developed third-degree PAVB associated with acute rejection 36 months and 24 months after OHT, respectively. We conclude that PAVB could be considered an early sign of acute rejection after OHT in children who exhibit post-transplantation presyncope or syncope.

Role of HLA in cardiothoracic transplantation.

In current clinical practice, transplant clinicians create collaborative working relationships with histocompatibility laboratory scientists to identify the risk of long-term graft failure, which may assist in establishing strategies for treatment and surveillance. Transplant immunology research also focuses on optimizing human leukocyte antibody tissue typing and defines the most effective test for detecting the presence of donor-specific antibodies. Although several studies have been conducted, data on pediatric heart transplant recipients are limited. Epitope load information may be utilized to identify donors with permissible human leukocyte antibody mismatches to increase transplant success. Although current guidelines do not consider human leukocyte antibody epitope-based matching tools, these guidelines could be useful for identifying recipients at a high risk of donor-specific antibody production, which would be appropriate for routine donor-specific antibody screening to initiate early interventions to prevent antibody-mediated rejection. Human leukocyte antibody matching at the epitope level offers an effective approach for identifying acceptable mismatches in sensitized patients and provides information about epitope loads. In the future, eplet matching may be used to define the best immunosuppressive therapy protocol for cardiothoracic organ transplantation. This report provides an overview of the role of human leukocyte antibodies in heart and lung transplantation.

Lymphomonocytic inflammatory infiltrate with numerous eosinophilic granulocytes in the interstitium in a surviving heart transplant recipient: a case report.

Findings of eosinophilic and lymphomonocytic inflammatory infiltrates in endomyocardial biopsies (EMBs) may help in myocardial disease diagnosis identification. Eosinophilic myocarditis (EM), a rare condition, is fatal if left untreated and has rarely been described in heart transplant recipients. An extensive work up is necessary to achieve an early etiological diagnosis; however, the underlying cause remains unexplained in nearly one-third of the patients. The cornerstone of treatment is corticosteroids, comprehensive therapy and heart failure management (including advanced mechanical support for fulminant myocarditis). We have described the case of a 17-year-old heart transplant recipient who presented with a cardiogenic shock. He was admitted to our intensive care unit and treated with inotropic drugs, such as milrinone, adrenaline, vasopressin, and levosimendan; the doses of these drugs were in accordance with our internal protocol. The patient underwent cardiac catheterization, coronarography, and right ventricular EMB. EMB revealed inflammatory lymphomonocytic and eosinophil granulocyte infiltrates; thus, steroid therapy was initiated, with complete recovery achieved after 15 days. Performing an early differential diagnosis among eosinophilic infiltration, acute cellular rejection (ACR), and possible chemotherapeutic damage is emerging as an important challenge. To our knowledge, this is the first reported case of a lymphomonocytic inflammatory infiltration with numerous eosinophilic granulocytes in the interstitium in a surviving heart transplant recipient.

Heart rate variability arterial hypertension in young heart-transplanted recipients: association progression of cardiac allograft vasculopathy?

Hypertension and reduced HRV are frequent in heart-transplanted recipients. We studied 26 young recipients to investigate the relationship between BP and HRV during simultaneous 24-h monitoring. Presence of CAV was considered. All HRV measures were significantly lower than normal values. Significant correlations were found between mean daytime systolic BP and the rMSSD (p = 0.04), and mean daytime DBP and SDANN for all 5-min segments (p = 0.03) and between rMSSD and mean nighttime DBP (p = 0.03). Four patients were hypertensive during daytime, seven had a reduced nocturnal fall and two had a nocturnal rise in BP. Eight patients showed severe CAV grade (grade IV) on the Stanford scale, 13 moderate (grade III) and five mild (grade I-II). After a follow-up time of 30 months, four of the 13 patients (30%) with CAV grade III showed an increase to grade IV and all showed abnormalities of both HRV and ABPM patterns. The relationship between HRV abnormalities and arterial hypertension and CAV should be further explored.

Panel reactive antibody monitoring in pediatric patients undergoing ventricle assist device as a bridge to heart transplantation.

We describe the incidence and patterns of anti-human leukocyte antigens antibody production in a pediatric population undergoing ventricular assist device (VAD) implantation. Serial panel reactive antibody was obtained prior to VAD implant, during VAD support, and after orthotopic heart transplantation (OHT). Seven children (median age 15 months) underwent VAD support as bridge to OHT. Posttransplant sensitization occurred in 42% of VAD patients and in 14% during VAD support.

Neurological complications during pulsatile ventricular assistance with the Berlin Heart EXCOR in children: incidence and risk factors.

The aim of this study is to describe the incidence of brain injury (BI) in children with end-stage cardiac failure who were supported with the Berlin Heart EXCOR ventricular assist device (VAD) as a bridge to heart transplantation. Between January 2002 and January 2012, all patients <18 years of age who underwent the implantation of the Berlin Heart EXCOR at Bambino Gesú Children's Hospital were included. A total of 25 patients were included in this study. Median age and weight at implantation were 22.4 months (range 3.6-154.2) and 10 kg (range 4.5-36), respectively. Diagnosis included cardiomyopathy (n = 20) and congenital heart disease (n = 5). Eleven patients received atrial cannulation. Nine patients underwent biventricular assist device support. Seven patients underwent extracorporeal membrane oxygenation before the implantation of the EXCOR VAD. Median duration of VAD support was 51 days (range 2-167). Nine patients had evidence of acute BI including intracranial hemorrhage (n = 5) and cerebral ischemia (n = 4). Freedom from BI at 30, 60, and 90 days from VAD implantation was 80.7, 69.9, and 43.3%, respectively. Weight <10 kg at implantation was significantly associated with BI. BI is a frequent complication among children supported with EXCOR VAD and is associated with lower weight at implantation. However, our data do not support the association between size and BI. Future prospective multicenter studies are warranted to further help understand the etiology and the impact of BI and to improve functional outcomes for children undergoing EXCOR VAD mechanical support.

Brain natriuretic peptide level in a small series of children and grown-ups with congenital heart defects with chronic cardiac failure.

The present study assessed the usefulness of brain natriuretic peptide in evaluating the cardiovascular status in children and grown-ups with congenital or acquired disease affected by chronic cardiac failure. Brain natriuretic peptide should be included in the risk stratification of children with dilated cardiomyopathy. In patients with congenital heart defects, it is useful to tailor the optimal medical strategy to individual patients.

Case report: Coronary allograft vasculopathy: an accurate reflection of the histopathological findings on cardiovascular magnetic resonance imaging.

Heart transplant recipients undergo extensive invasive and non-invasive postoperative screening to exclude complications, such as allograft rejection and vasculopathy. Cardiac magnetic resonance imaging is a non-invasive, non-irradiating, diagnostic tool for monitoring graft health and identifying possible tissue rejection or myocardial fibrosis. We describe the case of a 29-year-old female heart transplant recipient admitted to our care center with a worsening clinical condition. The patient underwent clinical evaluation, blood tests, including troponin I and N-terminal pro brain type natriuretic peptide, transthoracic echocardiography, invasive coronary angiography, and cardiovascular magnetic resonance imaging. Cardiovascular magnetic resonance imaging showed widespread sub-epicardial hyperintensity of the myocardial segments along the course of the coronary arteries. T2 mapping sequences showed an elevated value and the myocardial native T1 values and extracellular volume percentage were significantly increased. Late gadolinium enhancement demonstrated a diffuse sub-epicardial hypersignal along the lateral, free, and left ventricular walls. All the sequences evidenced widespread hyper-enhancement of epicardial fat along the course of the thickened main coronary artery walls. One month later, the recipient underwent re-transplantation due to progressive worsening of the clinical condition and refractoriness to intravenous medication. The anatomopathological findings of the explanted heart provided impressive visualization of structural and histopathological changes. These results could guide the tailoring of preventive therapeutic strategies and non-invasive monitoring of cardiac grafts.

Heart rate variability abnormalities in young patients with dilated cardiomyopathy.

Heart rate variability (HRV) has become the conventionally accepted term for describing variations in both instantaneous heart rate and R-R intervals. In the pediatric age group, HRV has been investigated in healthy children, diabetics, respiratory distress syndrome of the newborn, and sudden infant death syndrome. This study aimed to evaluate HRV in pediatric patients with dilated cardiomyopathy and to compare it with that of age-matched normal subjects. The study evaluated 21 patients with dilated cardiomyopathy: 11 females (mean age, 7 ± 4 years; range, 2-17 years) and 10 males (mean age, 10 ± 6 years; range, 2-18 years). Dilated cardiomyopathy (DCM) was diagnosed according to commonly accepted criteria after a noninvasive cardiologic examination, echocardiography, and 24-h Holter monitoring (MR45 and MR45-3 Oxford recorder). The patients were divided into six groups according to age, sex, and type of cardiomyopathy. Heart rate variability was recorded and analyzed in the time domain. The patients with DCM showed an abnormal HRV pattern. Particularly in the 5-6-year-old male patient group, the HRV values all were significantly increased (p = 0.05). In the 2-6-year-old female patient group, the mean cycle length, the standard deviation of all normal sinus R-R intervals during 24 h (SDNN), and the standard deviation of the average normal sinus R-R intervals for all 5-min segments (SDANN) were significantly increased (p = 0.05). The 13-18-year-old female patient group showed a significant reduction in SDNN and the mean of the standard deviation of all normal sinus R-R intervals for all 5-min segments (SDNNi) (p = 0.05). The modification of the HRV pattern in the time domain, partially age- and gender-dependent modification, may reflect an imbalance of the autonomic nervous system in children who show a delayed or reduced activity, such as pediatric patients with DCM.

Incidence of healthcare-associated infections in a pediatric population with an extracorporeal ventricular assist device.

During the last decade, ventricular assist devices (VADs) have become a precious tool to support children with end-stage heart failure. However, thromboembolic events, bleeding, and infections may have a considerable impact on outcome. We retrospectively analyzed the incidence of healthcare-associated infections (HAIs) in nine patients supported by EXCOR Pediatric (Berlin Heart [BH]) VAD in a pediatric cardiosurgical intensive care unit between January 1, 2009 and March 31, 2011 (27 months). Median age was 8 months (interquartile range [IQR] 6-11), median weight 7.5 kg (IQR 4.5-8.5). Seven patients were supported with a left VAD, two with a biventricular VAD (BiVAD). Six patients with a left VAD underwent heart transplant after 89 days (median, IQR 41-143) of support. One patient is still on the waiting list. All patients with BiVAD died after 12 days of assistance due to VAD malfunction. Sixteen HAIs were reported in five out of nine patients (56%). All infected patients were supported by a left VAD. When compared with noninfected patients, they had a longer mechanical support period (median 131 days, IQR 75-164, vs. 25 days, IQR 11-61, P = 0.03), a longer intensive care unit stay (median 159 days, IQR 85-188, vs. 48 days, IQR 17-87, P = 0.06) and a longer length of hospital stay (median 186 days, IQR 105-222, vs. 64 days, IQR 34-113, P = 0.06). Overall, nine mechanical devices were replaced for thromboembolic issues, most of them (67%) in patients with VAD-related infections. Overall, infection rate was 17.6 per 1000 patients days, 1.3 BH endocarditis per 1000 BH days, 4.0 surgical sites infections per 1000 BH days, 12.5 central line-associated blood stream infections per 1000 central venous catheter days, 5 catheter-associated urinary tract infections per 1000 urinary catheter days, and 13.5 ventilator-associated pneumonia cases per 1000 mechanical ventilation days. Overall, VAD-related infections were 5.4 per 1000 BH days. Of the 17 isolated pathogens, 53% were Gram-negative rods, with a prevalence of Pseudomonas aeruginosa (35.3%). Four bacteria were multidrug resistant (25%), three were carbapenem-resistant P. aeruginosa (50% of all isolated pseudomonads), and one was a methicillin-resistant S. aureus. VADs used as a bridge to cardiac transplantation are associated with a large number of HAIs. Patients with infected VADs were admitted for longer time in intensive care and in hospital with increased healthcare costs but with no impact on survival.

Extracorporeal membrane oxygenation and high-dose continuous veno-venous hemodiafiltration in a young child as a successful bridge to heart transplant for management of combined heart and kidney failure: a case report.

Combined heart and kidney transplant is an established treatment modality in patients with coexisting end-stage heart and kidney failure. However, there is scarce information on the optimal management of children that are listed for cardiac transplantation with mild to severe renal dysfunction. Herein we report the case of a young child who presented with life-threatening dilative cardiomyopathy and severe renal dysfunction, and who required urgent extracorporeal membrane oxygenation associated with continuous veno-venous hemodiafiltration and eventually underwent successful isolated heart transplantation followed by complete recovery of kidney function.

Heart transplantation in a child with LGMD2I presenting as isolated dilated cardiomyopathy.

Limb-girdle muscle dystrophy type 2I is associated with mutations in the gene encoding Fukutin-related protein. Clinical phenotypes are heterogeneous, ranging from isolated hyperCkemia to severe congenital muscular dystrophy. Affected patients frequently develop dilated cardiomyopathy, depending on evolution of their skeletal myopathy. We report on an 8 years-old boy presenting a severe dilated cardiomyopathy requiring heart transplantation. The child harbored a homozygous p.Leu276Ile mutation in Fukutin-related protein gene (FKRP). At the current age of 20 years, the patient shows persistent hyperCKemia but no clinical muscle weakness, CT scan showing very mild features of muscle involvement. Our findings add to the array of clinical presentations of FKRP mutations.

Takotsubo cardiomyopathy in a young adult with transplanted heart: what happened to denervation?

This manuscript describes the first report of takotsubo cardiomyopathy in a young heart transplant recipient following angry debate. Our patient is a 21-year-old woman with cardiac transplant performed owing to right ventricular failure in congenital heart disease. Positive echocardiography with typical asymmetry of regional function, positive enzymes, and negative biopsy and angiography met the criteria for the diagnosis of takotsubo cardiomyopathy. Patient was discharged after 1 week in good clinical conditions and fully recovered cardiac function. The development of takotsubo cardiomyopathy in transplanted heart suggests that re-innervation occurs, thus representing a target for catecholamine-induced cardiac dysfunction.

Cardiac dysfunction in children and young adults with heart transplantation: A comprehensive echocardiography study.

BACKGROUND: Transplanted heart dysfunction is a serious life-threatening condition in pediatric transplant recipients. Several studies have focused on echocardiographic detection of early signs of cardiac dysfunction in this population. We evaluated advanced echocardiographic indices of cardiac function in a large sample of children and young adults with heart transplants with apparently normal cardiac function. METHODS: The study included 60 patients with normal ejection fraction with transplantation performed at pediatric age between 1986 and 2014 and 60 healthy control subjects. All patients and control subjects underwent a complete transthoracic echocardiographic examination including tissue Doppler analysis, 2-dimensional speckle tracking, and 3-dimensional echocardiography. Two-dimensional speckle tracking analysis was used to obtain measures of left ventricular (LV) radial, circumferential, and longitudinal strain and to derive LV twist and torsion from basal and apical rotation. Three-dimensional echocardiography was used to measure LV volumes and ejection fraction and to evaluate LV systolic synchrony. RESULTS: No differences were observed between groups in LV volumes, left atrial diameters, LV ejection fraction, or right ventricular fractional area change. However, patients showed lower values of longitudinal systolic excursion of valvular planes at both the mitral and the tricuspid valve level as well as higher mitral E/E' ratio. Cardiac radial strain was similar between groups; a significant net reduction in both global left and right ventricular longitudinal strain and LV global circumferential strain could be observed between the 2 groups (all p < 0.05). In addition, reduced LV twist and torsion was found in patients compared with healthy control subjects (p < 0.01) mainly owing to a significant reduction in basal rotation (-2.4° vs -3.8°; p < 0.05). none of the control subjects demonstrated LV dyssynchrony, whereas systolic dyssynchrony was observed in 20% of heart transplant recipients. CONCLUSIONS: Even in the absence of signs of graft failure and in the presence of a normal ejection fraction, transplanted hearts show a significant reduction in biventricular function. Additional prognostic studies are needed to establish whether these abnormalities predict development of overt heart failure.

Transvenous cryothermal catheter ablation of re-entry circuit located near the atrioventricular junction in pediatric patients: efficacy, safety, and midterm follow-up.

OBJECTIVES: We investigated the safety and efficacy of cryoablation in the treatment of pediatric patients with accessory pathways (APs) located near the atrioventricular junction and with atrioventricular nodal re-entrant tachycardia (AVNRT). BACKGROUND: Few studies concern cryoablation in a significant number of pediatric patients involving treatment for supraventricular tachycardias (SVTs) with the reentry circuit located near the atrioventricular junction. METHODS: Twenty-six pediatric patients (age range: 5 to 20 years) were treated; 14 had AVNRT, 10 had Wolff-Parkinson-White syndrome, and 2 had re-entrant SVT due to a concealed AP. Electrophysiologic study was performed with diagnostic catheters, and cryoablations were performed with a 7-F 4-mm-tip catheter (Freezor, CryoCath Technologies Inc., Kirkland, Canada). Cryomapping, used to identify the tissue site for safe arrhythmia ablation, was performed at -30 degrees C for a maximum of 60 s. Cryoablations were from 4 to 8 min long at -75 degrees C. Acute end points were noninducibility of AVNRT by programmed atrial stimulation at baseline or during isoproterenol performed 30 min after procedure, as well as noninducibility and conduction block over the AP. The chronic end point was arrhythmia recurrence after intervention. RESULTS: No permanent cryo-related complications or adverse outcomes were reported. Twenty-four (92%) patients were acutely successful. During follow-up (range: 1 to 22 months), seven (29%) acutely successful pediatric patients experienced arrhythmia recurrence. CONCLUSIONS: Acute results demonstrate cryoablation of SVTs with the reentry circuit located near the atrioventricular junction to be safe and efficacious in pediatric patients. However, the etiology of recurrences reported after intervention need further investigation.

Lengthier cryoablation and a bonus cryoapplication is associated with improved efficacy for cryothermal catheter ablation of supraventricular tachycardias in children.

INTRODUCTION: Cryoablation is an effective treatment for children with supraventricular tachycardias (SVT). The present study documents the effect of two different cryoablation protocols on acute and chronic success rates. METHODS AND RESULTS: Fifty-three consecutive patients (age range, 5-20 years) were treated; patients 1 to 17 were treated by a standard ablation protocol and patients 18 to 53 were treated by a modified ablation protocol that required lengthier cryoablations plus delivery of a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention. Electrophysiological study (EPS) was performed with diagnostic catheters and cryoablations were performed with a 7FR 4 mm tip catheter (CryoCath Technologies). Acute endpoints for non-inducibility of atrioventricular nodal re-entrant tachycardia (AVNRT) by programmed atrial stimulation at baseline or during isoproterenol performed 30 min post procedure, as well as non-inducibility and conduction block over the accessory pathway (AP). The chronic endpoint was arrhythmia recurrence post intervention. No permanent cryo-related complications or adverse outcomes were reported. Acute success rates for patients 1 to 17 and 18 to 53 were 88 and 100%, respectively. The cumulative percentage of patients without arrhythmia recurrence at 12 month follow-up was significantly different at 73 and 90%, respectively. CONCLUSIONS: Lengthier cryoablation delivery, approximating 7 min per cryoablation, increases the acute success rate at intervention. Moreover, these lengthier cryoablation deliveries plus a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention may also significantly improve the chronic success rate, while also maintaining an excellent safety profile for cryoablation treatment of children with SVT such as AVNRT and AP located near the AV junction.