Willem A. Helbing

Birth Prevalence of Congenital Heart Disease Worldwide: A Systematic Review and Meta-Analysis

Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies. CHD birth prevalence worldwide and over time is suggested to vary; however, a complete overview is missing. This systematic review included 114 papers, comprising a total study population of 24,091,867 live births with CHD identified in 164,396 individuals. Birth prevalence of total CHD and the 8 most common subtypes were pooled in 5-year time periods since 1930 and in continent and income groups since 1970 using the inverse variance method. Reported total CHD birth prevalence increased substantially over time, from 0.6 per 1,000 live births (95% confidence interval [CI]: 0.4 to 0.8) in 1930 to 1934 to 9.1 per 1,000 live births (95% CI: 9.0 to 9.2) after 1995. Over the last 15 years, stabilization occurred, corresponding to 1.35 million newborns with CHD every year. Significant geographical differences were found. Asia reported the highest CHD birth prevalence, with 9.3 per 1,000 live births (95% CI: 8.9 to 9.7), with relatively more pulmonary outflow obstructions and fewer left ventricular outflow tract obstructions. Reported total CHD birth prevalence in Europe was significantly higher than in North America (8.2 per 1,000 live births [95% CI: 8.1 to 8.3] vs. 6.9 per 1,000 live births [95% CI: 6.7 to 7.1]; p < 0.001). Access to health care is still limited in many parts of the world, as are diagnostic facilities, probably accounting for differences in reported birth prevalence between high- and low-income countries. Observed differences may also be of genetic, environmental, socioeconomical, or ethnic origin, and there needs to be further investigation to tailor the management of this global health problem.

Comparison of echocardiographic methods with magnetic resonance imaging for assessment of right ventricular function in children

Assessment of right ventricular (RV) function is clinically relevant in the follow-up of various forms of congenital heart disease. Agreement on the value of different echocardiographic approaches for this purpose is lacking. Magnetic resonance imaging (MRI) provides dimensionally accurate RV volumes and ejection fraction. Transthoracic 2-dimensional echocardiography from 3 different views and gradient-echo tomographic MRI were performed in 16 children with congenital heart disease and 17 age-matched healthy children. RV volumes and ejection fraction were calculated with 5 mono- and biplane area-length and multiple-slice echocardiographic methods. Adequate MRI and echocardiographic apical 4-chamber images could be obtained in all 33 children. The best correlation between MRI and echocardiographic volumes was with the biplane pyramidal approximation method. End-diastolic volume by MRI was 92 +/- 27 ml: systematic difference with echocardiography was +14 +/- 16 ml (r = 0.86). End-systolic volume by MRI was 33 +/- 13 ml: systematic difference with echocardiography was -4 +/- 7 ml (r = 0.82). Ejection fraction by MRI was 65 +/- 8%: systematic difference with echocardiography was +5 +/- 7% (r = 0.72), using monoplane ellipsoid approximation. For all echocardiographic methods, significant effects of RV geometry were noted. Echocardiographic mono- and biplane area-length and multiple-slice calculations demonstrated moderate correlation and significant systematic errors compared with MRI-derived RV volumes. Echocardiographic results were influenced by RV geometry. The relatively simple monoplane area-length method provides ejection fraction results acceptable for clinical practice; results are not improved by more complex biplane and/or multislice methods.

Right Ventricular Diastolic Function in Children With Pulmonary Regurgitation After Repair of Tetralogy of Fallot: Volumetric Evaluation by Magnetic Resonance Velocity Mapping

OBJECTIVES We sought to assess right ventricular diastolic function in young patients with corrected tetralogy of Fallot and pulmonary regurgitation. BACKGROUND Pulmonary regurgitation is an important problem in repair of tetralogy of Fallot. Its effects on right ventricular diastolic function in children are unknown. METHODS Nineteen children with repair of tetralogy of Fallot (mean age [+/- SD] 12 +/- 3 years, mean age at operation 1.5 +/- 1) and 12 healthy children were studied. Summation of magnetic resonance velocity mapping pulmonary and tricuspid volume flow curves provided right ventricular time-volume curves. Ventricular size was assessed with tomographic magnetic resonance imaging (MRI). Graded exercise testing was performed. RESULTS Systematic and random differences (mean +/- SD) of velocity mapping and Doppler tricuspid time to peak velocities (peak E: 1 +/- 26 ms, r = 0.43; peak A: 2 +/- 11 ms, r = 0.76), E/A ratio (0.04 +/- 0.5, r = 0.63) and duration of pulmonary regurgitation (20 +/- 35 ms, r = 0.74) were satisfactory. In 6 patients (group I), late diastolic forward pulmonary artery flow was absent; in 13 patients (group II), this flow contributed 1% to 14% to right ventricular stroke volume. Significant differences were increased deceleration time (315 +/- 91 vs. 168 +/- 28 ms, p < 0.001), decreased filling fraction (44 +/- 11 vs. 55 +/- 16%, p = 0.02) and increased peak early filling rate (378 +/- 124 vs. 286 +/- 112 ml/s, p = 0.018) between control subjects and group I, and increased deceleration time (230 +/- 40, p = 0.03) between control subjects and group II. Pulmonary regurgitation, ventricular size and ejection fraction did not differ significantly between patient groups. Exercise function was diminished with restrictive right ventricular physiology (p < 0.001, group II vs. control subjects). CONCLUSIONS Impaired relaxation and restriction to filling affect right ventricular function in children with repair of tetralogy of Fallot and pulmonary regurgitation. Restrictive right ventricular physiology is associated with decreased exercise function.

Quantification of right ventricular function with magnetic resonance imaging in children with normal hearts and with congenital heart disease.

In clinical treatment of children with congenital heart disease (CHD) assessment of right ventricular (RV) function is important. Available imaging techniques have been of limited value because of technical factors and the complex geometry of the right ventricle. To validate magnetic resonance (MR) imaging measurements of RV function in children, gradient echo MR imaging of both ventricles and MR flow mapping of great vessel and tricuspid flow was performed in 20 children with CHD affecting the right ventricle and in 22 healthy children ranging in age from 5 to 16 years. Close correlation between RV versus LV stroke volumes (r = 0.96) and RV stroke volume versus great artery (r = 0.97) or tricuspid flow (r = 0.97) was observed with small interobserver and intraobserver variability. Results of healthy children were end-diastolic volume: 70 +/- 9 ml/m2, end-systolic volume: 21 +/- 5 ml/m2, and ejection fraction: 70% +/- 4%. In the patient groups clinically important differences were noted. We conclude that MR imaging provides accurate noninvasive measurements of RV function in healthy children and patients with (operated) CHD.

Evaluating the systemic right ventricle by CMR: the importance of consistent and reproducible delineation of the cavity

BackgroundThe method used to delineate the boundary of the right ventricle (RV), relative to the trabeculations and papillary muscles in cardiovascular magnetic resonance (CMR) ventricular volume analysis, may matter more when these structures are hypertrophied than in individuals with normal cardiovascular anatomy. This study aimed to compare two methods of cavity delineation in patients with systemic RV.MethodsTwenty-nine patients (mean age 34.7 ± 12.4 years) with a systemic RV (12 with congenitally corrected transposition of the great arteries (ccTGA) and 17 with atrially switched (TGA) underwent CMR. We compared measurements of systemic RV volumes and function using two analysis protocols. The RV trabeculations and papillary muscles were either included in the calculated blood volume, the boundary drawn immediately within the apparently compacted myocardial layer, or they were manually outlined and excluded. RV stroke volume (SV) calculated using each method was compared with corresponding left ventricular (LV) SV. Additionally, we compared the differences in analysis time, and in intra- and inter-observer variability between the two methods. Paired samples t-test was used to test for differences in volumes, function and analysis time between the two methods. Differences in intra- and inter-observer reproducibility were tested using an extension of the Bland-Altman method.ResultsThe inclusion of trabeculations and papillary muscles in the ventricular volume resulted in higher values for systemic RV end diastolic volume (mean difference 28.7 ± 10.6 ml, p < 0.001) and for end systolic volume (mean difference 31.0 ± 11.5 ml, p < 0.001). Values for ejection fraction were significantly lower (mean difference -7.4 ± 3.9%, p < 0.001) if structures were included. LV SV did not differ significantly from RV SV for both analysis methods (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and showed better inter-observer reproducibility for ejection fraction (p < 0.01).ConclusionThe choice of method for systemic RV cavity delineation significantly affected volume measurements, given the CMR acquisition and analysis systems used. We recommend delineation outside the trabeculations for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible measurements.

Clinical value of real-time three-dimensional echocardiography for right ventricular quantification in congenital heart disease: validation with cardiac magnetic resonance imaging.

BACKGROUND The objective of this study was to test the feasibility, accuracy, and reproducibility of the assessment of right ventricular (RV) volumes and ejection fraction (EF) using real-time three-dimensional echocardiographic (RT3DE) imaging in patients with congenital heart disease (CHD), using cardiac magnetic resonance (CMR) as a reference. METHODS RT3DE data sets and short-axis cine CMR images were obtained in 62 consecutive patients (mean age, 26.9 +/- 10.4 years; 65% men) with various CHDs. RV volumetric quantification was done using semiautomated 3-dimensional border detection for RT3DE images and manual tracing of contours in multiple slices for CMR images. RESULTS Adequate RV RT3DE data sets could be analyzed in 50 of 62 patients (81%). The time needed for RV acquisition and analysis was less for RT3DE imaging than for CMR (P < .001). Compared with CMR, RT3DE imaging underestimated RV end-diastolic and end-systolic volumes and EF by 34 +/- 65 mL, 11 +/- 55 mL, and 4 +/- 13% (P < .05) with 95% limits of agreement of +/-131 mL, +/-109 mL, and +/-27%, as shown by Bland-Altman analyses, with highly significant correlations (r = 0.93, r = 0.91, and r = 0.74, respectively, P < .001). Interobserver variability was 1 +/- 15%, 6 +/- 17%, and 8 +/- 13% for end-diastolic and end-systolic volumes and EF, respectively. CONCLUSION In the majority of unselected patients with complex CHD, RT3DE imaging provides a fast and reproducible assessment of RV volumes and EF with fair to good accuracy compared with CMR reference data when using current commercially available hardware and software. Further studies are warranted to confirm our data in similar and other patient populations to establish its use in clinical practice.

Clinical Applications of Cardiac Magnetic Resonance Imaging After Repair of Tetralogy of Fallot

Abstract. In the past 15 years, cardiovascular magnetic resonance (MR) has evolved into an imaging technique that provides adequate, and in part unique, information on residual problems in the follow-up of patients operated for tetralogy of Fallot. Spin-echo or gradient-echo cine magnetic resonance imaging allow detailed assessment of intracardiac and large vessel anatomy, which is particularly helpful in Fallot patients with residual abnormalities of right ventricular outflow and/or pulmonary artery. Multisection gradient-echo cine MRI can be used to obtain accurate measurements of biventricular size, ejection fraction, and wall mass. This allows serial follow-up of biventricular function. MR velocity mapping is the only imaging technique available that provides practical quantification of pulmonary regurgitation volume. MR velocity mapping can also be used to quantify right ventricular diastolic function in the presence of pulmonary regurgitation.

Right ventricular quantification in clinical practice: two-dimensional vs. three-dimensional echocardiography compared with cardiac magnetic resonance imaging.

AIMS To establish the additional value of three-dimensional echocardiography (3D echo) for assessment of right ventricular (RV) size and function in patients with congenital heart disease (CHD) in everyday clinical practice, the accuracy and reproducibility of 3D echo were compared with conventional two-dimensional echocardiography (2D echo) and cardiac magnetic resonance (CMR) imaging as reference. METHODS AND RESULTS Patients with CHD and primarily affected right ventricles (n = 62), patients with CHD and primarily affected left ventricles (LV group, n = 27), and healthy controls (n = 31) were studied. 2D echo-, 3D echo- and CMR data sets were obtained. Moderate correlations were found between RV dimensions by 2D echo and CMR-derived RV end-diastolic volumes (r = 0.32-0.77). The correlations between RV volumes obtained by 3D echo and CMR imaging were better (r = 0.71-0.97) than the 2D echo-derived correlations (P < 0.001). Only the 2D echo-derived RV inlet diameter correlated better in healthy controls than in the RV group. Receiver operating characteristic curve analysis revealed that 3D echo-derived end-diastolic volume best identified RV dysfunction (sensitivity 95% and specificity 100%). The 3D echo-derived measurements were as reproducible as the 2D echo-derived measurements (n = 37, coefficients of variation ranging from 5 to 19%), with tricuspid annular plane systolic excursion being the most reproducible measurement (coefficient of variation of 6%). CONCLUSION 3D echo improved quantitative RV size and function assessment compared with 2D echo in patients as well as in healthy controls. Everyday clinical use of 3D echo for RV assessment can be reality with the currently available software and provides incremental benefit in assessment of the right ventricle.

Normal biventricular function, volumes, and mass in children aged 8 to 17 years

To assess normal values for biventricular function, volumes, and mass with current cardiovascular magnetic resonance (CMR) imaging sequences in children.

Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease

Objective  To investigate the inter‐relation between mother and infant homocysteine, folate and vitamin B12 status and the risk of a child with congenital heart disease (CHD).