Sylvie Di Filippo

Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France.

BACKGROUND Limited data are available describing paediatric pulmonary arterial hypertension. AIMS To characterize the epidemiology, management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension, excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. METHODS In this multicentre study, children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class, 6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. RESULTS Fifty children were included with a mean age of 8.9 +/- 5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%), familial pulmonary arterial hypertension (10%), pulmonary arterial hypertension associated with, but not caused by, congenital heart disease (24%), pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up, the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status, 6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% CI 76, 96) and 82% (95% CI 71, 93), respectively. CONCLUSIONS In children, idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival.

Rabbit antithymocyte globulin as induction immunotherapy in pediatric heart transplantation.

Background. There is little published data on the use of antithymocyte globulins in children. This retrospective study describes the use of Thymoglobulin (Imtix, SangStat, Lyon, France) in pediatric cardiac transplantation over a 13-year period in a single center that adjusted the dose of Thymoglobulin according to platelet count monitoring and examines the short-term hematological effects as well as longer-term outcomes. Methods. Data for all children who received a heart transplant at the Hôpital Cardiologique at Lyon from 1984 to 2001 and who were given Thymoglobulin as part of their immunosuppressive protocol were extracted. The dose of Thymoglobulin given depended on baseline platelet count and was 2, 1.5, or 1 mg/kg per day over 5 days for the following platelet count groups: greater than 150,000/mm3 (normal group), 100 to 150,000/mm3 (mild thrombocytopenia group), and 50 to 100,000/mm3 (moderate thrombocytopenia group). Results. Thirty children of median age 14.2 years were given a median cumulative dose of Thymoglobulin of 8 mg/kg per patient; the moderate thrombocytopenia subgroup was given significantly less (6.4 mg/kg) (P =0.032). Immediate tolerability of Thymoglobulin was good, with no cases of first-dose syndrome, anaphylaxis, or serum sickness. The platelet count decreased at the start of therapy, but recovered after discontinuation, and did not give rise to clinical concern. Patients were followed up for a median of 6.3 years (7 days–15.5 years); actuarial survival was 90%, 86%, and 74.5%, respectively, at 1, 5, and 10 years. In the first year, 50% of patients suffered an episode of rejection. The overall incidence of infection in the month following transplantation was 40%. One lymphoma occurred at 5 months. Conclusions. The use of Thymoglobulin in pediatric heart-transplant patients as part of an immunosuppressive protocol, with dose adjustment according to platelet levels, has been shown to be effective in terms of rejection rate and patient survival and safe in terms of the incidence of infections and malignancy.

Non-invasive detection of coronary artery disease by dobutamine-stress echocardiography in children after heart transplantation

BACKGROUND Coronary vasculopathy is the main cause of cardiac graft failure. Because yearly coronary angiography is invasive in children, a non-invasive method for detecting graft vasculopathy is needed. The aim of this study was to test dobutamine-stress echocardiography in a pediatric population to determine its feasibility, safety and reliability in the detection of graft coronary artery disease. METHODS Eighteen patients, aged 2 days to 16.8 years at transplantation (mean 8.4 years), underwent 44 dobutamine-stress echocardiography (DSE) exams, at a follow-up of 1.1 to 11.8 years (mean 5.1 years). Selective coronary angiography was performed for comparison. Echocardiographic recordings were obtained in 4 standard views of the left ventricle and measurements carried out within the frames of a 16-segment model. Segmental scores of contractility were obtained for each segment and a total segmental contractility index was calculated at each stage. RESULTS All patients reached the maximum dose stage. Maximum heart rate was 57% to 90% of predicted maximum. Maximum systolic blood pressure reached 190 mmHg. Segmental scores were normal in 37 and abnormal in 7 cases. Echographic results were concordant with angiography in 82% and discordant in 18% of the cases (4 negative DSEs with minor angiographic lesions, 2 positive DSEs with normal angiography), but there was no significant angiographic lesion with normal DSE. CONCLUSIONS DSE is a safe and highly feasible non-invasive technique in transplanted children. A normal DSE study successfully predicts the absence of significant coronary artery disease in the post-transplant population.

The challenge of renal function in heart transplant children

Renal dysfunction may occur after pediatric heart transplantation and impacts on long-term prognosis. This study aims to review the incidence and mechanisms of chronic nephropathy following heart transplantation, and suggest therapeutic directions. The proportion of pediatric heart-transplant recipients with impaired renal function varies from 22 to 57%, and end-stage renal failure from 3 to 10%, depending on the method used for estimating the glomerular filtration rate. The pathophysiology of renal dysfunction is in part due to calcineurin inhibitor-induced renal vasoconstriction, through activation of the intrarenal renin-angiotensin system, TGF-β1 upregulation and TGF-β1 gene polymorphisms. Overproduction of angiotensin II, associated with angiotensin-converting-enzyme genotype, might be associated with poor prognosis and pharmacological factor gene polymorphisms, and may contribute to variation of calcineurine inhibitor exposure in the kidney. Strategies to prevent renal dysfunction include reducing calcineurine inhibitor exposure or delaying calcineurine inhibitor administration from the early post-transplant period. Calcium channel blockers and angiotensin-converting-enzyme inhibitors, blockade of angiotensin II, or anti-TGF-β1 antibodies might limit nephrotoxicity. No accurate marker can predict the potential of renal lesions to develop. Lowering calcineurine inhibitors levels with immunosuppressive agents that are either less nephrotoxic or non-nephrotoxic should be formally studied. Of high interest is the impact of genetic polymorphism on the development of renal dysfunction.

Prophylaxis of infective endocarditis in patients with congenital heart disease in the context of recent modified guidelines

Infective endocarditis (IE) is a life-threatening complication that may impair significantly the long-term prognosis of patients with cardiac disease. The profile of IE has changed over recent decades, with a decreasing prevalence of rheumatic fever and increasing survival of patients with congenital heart disease (CHDs). Given the high rates of morbidity and mortality, and based on previous experimental studies, antibiotic prevention of IE has long been recommended for at-risk groups. Serial revised guidelines for prophylaxis have been published over the years. The most recent recommendations differ dramatically from previous guidelines and provide new insights into the prophylaxis of IE. Emphasis is put on oral activities (particularly brushing teeth) as both buccal and skin hygiene may present the greatest threats for individuals at-risk of IE. Significant limitations in both at-risk patients and procedures result in a potential and substantial change in the practice of clinicians and raise concerns about the safety and reliability of these new recommendations for patients with CHD.

Extracoronary echocardiographic findings as predictors of coronary artery lesions in the initial phase of Kawasaki disease

Objective To describe the significance of pericardial effusion (PE), mitral regurgitation (MR) and impaired systolic function in predicting coronary artery lesions (CAL) at diagnosis and follow-up in Kawasaki disease (KD). Design Echocardiographic records on admission, at 1–3 weeks of illness, and at 6–8 weeks of illness were retrospectively retrieved in children with acute KD treated by intravenous immunoglobulins. Setting, patients The study included 194 consecutive children (113 male; median age 2.1 years) in a paediatric cardiology tertiary care centre, from 1988 to 2007. Results Overall, children with CAL (64/194) were more likely to have PE (OR=3.00, CI 1.34 to 6.72) and MR (OR=2.51, CI 1.22 to 5.16) at diagnosis; PE was the sole echocardiographic abnormality associated with CAL in multivariable analysis. These abnormalities were predictive of the presence of CAL at the first echocardiography in the acute phase of the disease only. MR, systolic dysfunction and PE were not associated with persistence of CAL in the convalescent phase. Male gender, CAL size and resistance to immunoglobulin treatment were independent factors predictive of the persistence of CAL. Conclusions Children with MR or PE should undergo careful assessment of coronary status at diagnosis. However, PE or MR at diagnosis is not predictive of persistent CAL at follow-up.

Subtle bacterial endocarditis due to Kingella kingae in an infant: a case report.

A 9-month-old infant presented with fever, dyspnoea, and a murmur. Echocardiography showed a mitral vegetation with significant regurgitation. Mitral valve plasty was performed on day 6, and was polymerase chain reaction positive for Kingella kingae. The cardiac outcome was favourable. This case illustrates a subtle presentation of K. kingae mitral valve infective endocarditis in a normal-cardaic infant, treated with early surgery, and the agent belonged to the HACEK (Haemophilus spp Actinobacillus actinomycetemcomitans, Capnocytophaga spp, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) group.

Surgical repair of a pseudocoarctation with cervical aortic arch complicated by multiple aneurysms of the aorta: a case report

Aortic pseudocoarctation is a rare congenital anomaly characterized by elongation and deformity of the aortic arch and is known to be associated with aneurysmal formation. Several studies unite to say it leads to a surgical sanction as soon as symptomatic or associated with aneurysms of the aortic arch. Our patient is a 12 years old boy, followed since birth for a little tight pseudocoarctation with a cervical aortic arch and transverse aortic arch hypoplasia. Close clinical and paraclinical monitoring including angioscans, showed the gradual enlargement of the superior mediastinum, in relation with the appearance of three aneurysms of the aortic arch. The intervention, performed by sternotomy, has consisted of the resection of the aneurysmal area and the interposition of a Dacron tube to repair the aortic arch and the reimplantation of the left subclavian artery into the left carotid artery. The postoperative course was uneventful. Management of pseudocoarctation associated with cervical aortic arch and aneurysms remains surgical. Close monitoring of patients with pseudocorctation, seems to be essential to avoid fatal complications such as aneurysmal rupture.

0524: Experience with foetal supraventricular arrhythmias

This study was to review experience and outcomes of supraventricular (SV) arrhythmias in fetus Methods: Cases were divided in groups: SVPB= premature SV beats, NSSVT= non-sustained SV tachycardia, SSVT= sustained SV tachycardia, and AF= atrial flutter. Heart failure (HF) was defined as foetal hydrops or isolated effusion (pericardial or pleural or ascitis). Outcome was favourable if arrhythmia resolved or stabilized until full-term birth, not-favourable if premature birth or foetal death occurred. Results 188 fetuses were included:89 in SVPB(47.3%), 31 in NSSVT(16.5%), 60 in SSVT(31.9%), 8 in AF(4.3%), aged at diagnosis 30.8±4.5weeks (no difference between groups). Foetus HR at diagnosis was 241±30bpm in SSVT vs 226±26 in AF. Antiarrhytmic therapy was administered in sustained tachycardia (83% of SSVT and 71% AF): 28 had 1 medication, 25: 2 medications, 2: 3 medications. Complication occurred in 29 cases, all in SSVT and AF (29 of 68= 43%): 18 hydrops, 5 ascitis, 4 pericarditis, 1 pleural effusion and 1 LVdysfunction+MR, was more frequent in SSVT (86%: hydrops in 30%) than AF (51%: no hydrops), p= 0.08. Fetal HF was associated with HR at diagnosis: 251±25bpm in hydrops vs 228±31bpm in nohydrops (p=0.025). Outcome was favourable in SVPB and NSSVT, in 45 of SSVT+AF (79%). Tachycardia resolved in 36, more frequently in SSVT (57%) than AF (25%). HR only decreased in 9cases. Premature birth occurred in 10, foetal death in 2. Outcome was not associated with HR or weeks of gestation at diagnosis. Defavourable outcome was more frequent in hydrops or isolated effusion (57%) than in uncomplicated cases (10%, p= 0.0002). Resolution occurred in 45% hydrops vs 66% of non-hydrops cases. Digoxine decreased from 79% of cases before 2000 to 33% after 2000, while flecaine increased from 14% to 48.5%. There was no relationship between therapy or number of medications and outcomes. Conclusion Fetal SSVT more frequently resolves but has worse outcome than AF, especially if HR at diagnosis is high and hydrops occurs. Larger scale prospective studies are needed to evaluate the efficacy of flecaine compared to digoxine therapy.

0532: Features and outcomes of acute myocarditis in children

This study was to assess features and outcomes of children with acute myocarditis. Methods Patients 10y). Results 72 patients were included (1983 to 2012), 30males, aged 4.1±5.1y (med1.5y): 43 in group I, 17 in II and 12 in III. Heart failure was present at onset in 57(78%): 8 cardiogenic shock (12%), 30 severeHF (44%) were more frequent in I (56%) and II (46%) than in III (17%, p in 3). Nine patients died (13%) within 2months post-diagnosis (2days to 8.6months), 1 was transplanted (3rdmonth), 19 have sequellae (27.5%), 40 recovered (58%), at FU= 5.5±5.6y. Inotrope was needed in 34(47%):51%, 59% and 16% of groups I, II and III respectively (p Download : Download full-size image Abstract 0254 - Figure: Increase in HMDP heart retention after 16months. Conclusion Acute myocarditis in children has favourable outcomes despite early mortality. Myocardial dysfunction and heart failure are less frequent in patients > 10years. Mechanical circulatory support lessens mortality. Myocardial contractility progressively improves within the first 6months after onset.