Benedicte Eyskens

Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS.

We report data on a group of 37 VCFS patients with specific reference to their intelligence, behaviour, and social competence. Fifty five percent of the children had a borderline to normal IQ. Mental retardation (defined as IQ < 70 or > -2 SD below the mean) was found in 45%. In the majority, the mental retardation was mild (38%) and only two patients had moderate mental retardation. Severe mental retardation seems to be rare in VCFS. The present study shows also that the incidence of mental retardation is much higher in the familial than the de novo group. Intelligence is not correlated with the presence or absence of a heart defect. Significantly higher verbal IQs than performance IQs (probably related to deficits in visuospatial-perceptual functioning) were found. Problems in social-emotional functioning and attention were also found. Further longitudinal studies are necessary to provide an accurate prognosis and appropriate intervention for VCFS children.

Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring

The authors report 1-year prospective data on eight patients with Friedreich ataxia. Idebenone did not halt the progression of ataxia. At the end of therapy, cardiac ultrasound demonstrated significant reduction of cardiac hypertrophy in six of eight patients. Cardiac strain and strain rate imaging showed that the reduction of hypertrophy is preceded by an early and linear improvement in cardiac function. Idebenone reduced erythrocyte protoporphyrin IX levels in five of six patients with elevated baseline levels; however, changes did not consistently relate to cardiac improvement.

The Fontan circulation: who controls cardiac output?

In a Fontan circuit the mechanisms involved in control of cardiac output at rest and during exercise differ significantly from normal. The classical model presumes an unlimited preload which is not available in the Fontan circuit. This review critically analyses the role of contractility, heart rate, and afterload and highlights the importance of pulmonary vascular resistance (PVR) in determining adequate preload and, therefore, cardiac output in these patients. A conceptual model of the determinants of cardiac output in Fontan patients is presented.

Quantification of regional right and left ventricular function by ultrasonic strain rate and strain indexes after surgical repair of tetralogy of fallot

The quantification of regional myocardial function in tetralogy of Fallot (TOF) by conventional M-mode and 2-dimensional echocardiography is difficult because of the complex right ventricular (RV) and altered left ventricular (LV) geometry. In 30 asymptomatic postoperative TOF patients (aged 4 to 16 years) with a low pressure in the right ventricle and with varying degrees of pulmonary regurgitation and in 30 aged-matched healthy children, the ultrasonic-derived regional deformation parameters peak systolic strain rate (SR) and systolic strain (epsilon) were acquired from ventricles and compared. In TOF RV free walls, SR, and epsilon were reduced in the basal, mid-, and apical segments and averaged -1.5 +/- 0.6 second(-1) for SR and -22 +/- 8% for epsilon, respectively (p <0.001 vs normals). Peak systolic SR of the basal RV free wall correlated significantly with the QRS duration of the electrocardiogram (r = 0.81, p <0.0001). Abnormalities in RV deformation were more marked in patients with transannular patches versus infundibular patches. In the septum there was a homogeneous reduction in SR and epsilon in the basal, mid-, and apical segments. These averaged -1.4 +/- 0.3 second(-1) for SR and -19 +/- 4% for epsilon, respectively (p <0.01 vs normals). Longitudinal SR and epsilon values of the 3 LV lateral wall segments (averaged SR = -1.6 +/- 0.4 second(-1), averaged epsilon = -20 +/- 5%; p <0.05 vs normals), and radial SR and epsilon of the LV posterior wall (SR = 3.3 +/- 0.9 second(-1); epsilon = 51 +/- 14%; p <0.05 vs normals) were significantly reduced. Thus, abnormalities in regional RV and LV systolic myocardial function in asymptomatic postoperative TOF patients were quantified by the deformation parameters SR and epsilon. RV deformation abnormalities are associated with electrical depolarization abnormalities.

Delineation of the Critical Deletion Region for Congenital Heart Defects, on Chromosome 8p23.1

Deletions in the distal region of chromosome 8p (del8p) are associated with congenital heart malformations. Other major manifestations include microcephaly, intrauterine growth retardation, mental retardation, and a characteristic hyperactive, impulsive behavior. We studied genotype-phenotype correlations in nine unrelated patients with a de novo del8p, by using the combination of classic cytogenetics, FISH, and the analysis of polymorphic DNA markers. With the exception of one large terminal deletion, all deletions were interstitial. In five patients, a commonly deleted region of approximately 6 Mb was present, with breakpoints clustering in the same regions. One patient without a heart defect or microcephaly but with mild mental retardation and characteristic behavior had a smaller deletion within this commonly deleted region. Two patients without a heart defect had a more proximal interstitial deletion that did not overlap with the commonly deleted region. Taken together, these data allowed us to define the critical deletion regions for the major features of a del8p.

Early Regional Myocardial Dysfunction in Young Patients With Duchenne Muscular Dystrophy

BACKGROUND In young patients (aged <12 years) with Duchenne muscular dystrophy (DMD), cardiac systolic function is generally described to be within the normal range. Recent studies have suggested the presence of subclinical dysfunction in these young patients using cardiac magnetic resonance imaging, tissue Doppler measurements, and myocardial velocity gradients. The aim of this study was to further assess regional myocardial function in a young group of patients with DMD using myocardial velocity and deformation imaging. METHODS Thirty-two patients with DMD (mean age, 7.9 years; range, 3-12 years) and 29 age-matched normal controls were studied with echocardiography. Standard echocardiographic measurements of left ventricular (LV) systolic and diastolic function were performed. Myocardial velocity and deformation data, including peak systolic and early and late diastolic myocardial velocities, peak systolic strain rate (SR), and peak systolic strain (epsilon), were calculated in the radial direction in the inferolateral LV wall and in the longitudinal direction in the interventricular septum, the LV anterolateral wall, and the right ventricular (RV) free wall. RESULTS Higher heart rates and increased LV end-systolic dimensions were seen in patients with DMD compared with controls. Significant decreases in radial and longitudinal peak systolic SR, peak systolic epsilon, and peak systolic and early diastolic myocardial velocities were found in the LV inferolateral and anterolateral walls in patients with DMD. No significant differences in longitudinal function could be found in the interventricular septum or in the RV free wall. CONCLUSION In young patients with DMD who have global normal systolic function, reductions in systolic deformation parameters as well as reduced early diastolic myocardial velocities can be detected in the anterolateral and inferolateral LV walls. The prognostic significance of these findings warrants further longitudinal follow-up.

Infective endocarditis of a transcatheter pulmonary valve in comparison with surgical implants

Background Melody valved stents (Medtronic Inc, Minneapolis, Minnesota, USA) have become a very competitive therapeutic option for pulmonary valve replacement in patients with congenital heart disease. After adequate prestenting of the right ventricular outflow tract (RVOT) Melody valved stents have a good medium term functional result but are exposed to infective endocarditis (IE). Patients and methods Retrospective study of tertiary centre Congenital Heart Disease database; to compare incidence of IE in three different types of valved conduits in RVOT: Melody valved stent, cryopreserved homograft (European Homograft Bank) and Contegra graft (Medtronic Inc). Results Between 1989 and 2013, 738 conduits were implanted in 677 patients. 107 Melody valved stents were implanted in 107 patients; IE occurred in 8 (7.5%) patients during a follow-up of 2.0 years (IQR 2.4 years, range 0.3–7.8 years). 577 Homografts were implanted in 517 patients; IE occurred in 14 patients (2.4%) during a median follow-up of 6.5 years (IQR 9.2 years; range 0.1–23.7 years). Finally, 54 Contegra grafts were implanted in 53 patients; 11 patients (20.4%) had IE during a follow-up of 8.8 years (IQR 7.7 years; range 0.2–3.5 years). Survival free of IE by Kaplan–Meier for homografts was 98.7% at 5 years and 97.3% at 10 years; for Contegra 87.8% at 5 years and 77.3% at 10 years and for Melody 84.9% at 5 years (log-rank test; p<0.001). Conclusions The Contegra conduit and Melody valved stents have a significantly higher incidence of IE than homografts. IE is a significant threat for long-term conduit function.

Array comparative genomic hybridization as a diagnostic tool for syndromic heart defects.

OBJECTIVES To investigate different aspects of the introduction of array comparative genomic hybridization (aCGH) in clinical practice. STUDY DESIGN A total 150 patients with a syndromic congenital heart defect (CHD) of unknown cause were analyzed with aCGH at 1-Mb resolution. Twenty-nine of these patients, with normal results on 1Mb aCGH, underwent re-analysis with 244-K oligo-microarray. With a logistic regression model, we assessed the predictive value of patient characteristics for causal imbalance detection. On the basis of our earlier experience and the literature, we constructed an algorithm to evaluate the causality of copy number variants. RESULTS With 1-Mb aCGH, we detected 43 structural variants not listed as clinically neutral polymorphisms, 26 of which were considered to be causal. A systematic comparison of the clinical features of these 26 patients to the remaining 124 patients revealed dysmorphism as the only feature with a significant predictive value for reaching a diagnosis with 1-Mb aCGH. With higher resolution analysis in 29 patients, 75 variants not listed as clinically neutral polymorphisms were detected, 2 of which were considered to be causal. CONCLUSIONS Molecular karyotyping yields an etiological diagnosis in at least 18% of patients with a syndromic CHD. Higher resolution evaluation results in an increasing number of variants of unknown significance.

Regional right and left ventricular function after the Senning operation: an ultrasonic study of strain rate and strain

BACKGROUND Systemic right ventricular dysfunction is a major concern in the follow-up of patients who underwent an atrial redirection procedure for transposition (concordant atrio-ventricular and discordant ventriculo-arterial connections). No good non-invasive method is currently available for quantifying right ventricular function. AIMS We have used ultrasonically based imaging of strain rate and strain to quantify regional deformation in the right ventricle after the Senning operation, comparing properties of regional deformation of the right ventricle with right ventricular ejection fraction as measured using magnetic resonance imaging. METHODS In 20 asymptomatic patients who had undergone the Senning procedure, we measured peak systolic strain rate and systolic strain values in the right ventricular free wall, the septum and the left ventricular lateral wall using colour Doppler myocardial imaging, comparing the data with findings obtained in 30 healthy subjects. Global right ventricular ejection fraction was assessed using magnetic resonance imaging. RESULTS Properties of deformation of the right ventricular free wall were reduced and homogeneous after the Senning procedure compared to normals, with significantly lower values for peak systolic strain rate and systolic strain (-1.1 +/- 0.4 vs. -2.5 +/- 0.9 s(-1); p < 0.05 and -16 +/- 7% vs. -38 +/- 13%; p < 0.05, respectively). There was a significant correlation between regional longitudinal right ventricular systolic strain values and right ventricular ejection fraction (r = -0.87, p < 0.001). In the septum, peak systolic strain rate was again reduced and homogeneous (-1.2 +/- 0.4 vs. -1.8 +/- 0.5 s(-1); p < 0.05 vs. normals). Also in the left ventricle, the lateral wall peak systolic strain rate and systolic strain values were reduced (-1.5 +/- 0.5 vs. -2.1 +/- 0.9 s(-1); p < 0.05 and -20 +/- 6% vs.-25 +/- 9%; p < 0.05, vs. normals, respectively). CONCLUSIONS Properties of regional longitudinal deformation of the systemic right ventricle are reduced after the Senning procedure compared to normal controls, and correlate well with global right ventricular performance. These findings suggest that ultrasonic strain rate and strain imaging could be used in the non-invasive follow-up of ventricular function in these patients.

New ultrasound methods to quantify regional myocardial function in children with heart disease

From a temporally resolved radio-frequency data set, a series of new developing indices of regional myocardial deformation can be measured. These may be important new data sets to quantify regional radial and long axis function of the left or right ventricle in children with acquired or congenital heart disease. Using color Doppler methodology unidimensional regional myocardial strain rates (SR) and natural strain (e) can now be calculated from local myocardial velocity data sets. Normal regional velocity, SR, and e values have already been determined in older children and should form the database for studies into acquired or congenital heart disease in this age group. Neonatal and infant values have yet to be determined. This article will present preliminary data on the potential clinical value of ultrasonic regional SR and e imaging in children and will discuss the close interrelation of these new regional function parameters with an alternative approach to quantification: the measurement of local cyclical changes in integrated backscatter levels.