Nynke J. Elzenga

Differential responses of the right ventricle to abnormal loading conditions in mice: pressure vs. volume load.

Right ventricular (RV) dysfunction is a major determinant of long‐term morbidity and mortality in congenital heart disease. The right ventricle (RV) is genetically different from the left ventricle (LV), but it is unknown as to whether this has consequences for the cellular responses to abnormal loading conditions. In the LV, calcineurin‐activation is a major determinant of pathological hypertrophy and an important target for therapeutic strategies. We studied the functional and molecular adaptation of the RV in mouse models of pressure and volume load, focusing on calcineurin‐activation.

Decision making for the surgical management of aortic coarctation associated with ventricular septal defect

Coarctation of the aorta and associated ventricular septal defect may be repaired simultaneously or by initial coarctation repair with or without banding of the pulmonary artery. The question is whether specific preoperative criteria can enable the surgeon to choose the optimal surgical management. Between 1980 and 1993, 80 infants younger than 3 months with coarctation and ventricular septal defect were treated surgically. In 64 infants (multistage group), simple coarctation repair was performed through a posterolateral approach, with concomitant banding of the pulmonary artery in 10 infants. Twenty ventricular septal defects were closed as a secondary procedure and four were closed as a tertiary procedure. Sixteen infants (single-stage group) underwent one-stage repair through an anterior midline approach. The total in-hospital mortality rate was 7.5%. Freedom from recoarctation after 5 years was 91.3% in the multistage group versus 60.0% in the single-stage group (p = 0.018). Freedom from secondary ventricular septal defect treatment in the multistage group after 5 years was 40.7%, versus 100% in the single-stage group (p = 0.016). Thirty-seven ventricular septal defects (47.8%) closed spontaneously. In particular, the preoperative left-to-right shunt and extension of the perimembranous VSD into the inlet or outlet were risk factors for the need for eventual surgical ventricular septal defect closure after initial coarctation repair. On the basis of these two risk factors, the probability of the need for eventual surgical treatment of ventricular septal defect after initial coarctation repair can be calculated. This policy offers a well-considered choice between single-stage and multistage repair, weighing the risk of secondary ventricular septal defect treatment versus the risk of recoarctation. Finally, the number of surgical procedures per infant will be as low as possible.

Echocardiography in pediatric pulmonary arterial hypertension: early study on assessing disease severity and predicting outcome

Background—The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH. Methods and Results—Forty-three consecutive children (median age, 8.0 years; range, 0.4–21.5) with idiopathic/hereditary PAH (n=25) or PAH associated with congenital heart disease (n=18) were enrolled in a prospective single-center observational study. Anatomic and right ventricular-functional variables were obtained by two-dimensional echocardiography and Doppler-echocardiography at presentation and at standardized follow-up and were correlated with measures of disease severity (World Health Organization functional class [WHO-FC], N-terminal-pro-B-type natriuretic peptide, hemodynamics) and lung-transplantation–free survival. Right atrial and right ventricular dimensions correlated with WHO-FC and hemodynamics (P<0.05), whereas left ventricular dimensions correlated with hemodynamics and survival (P<0.05). Right-to-left ventricular dimension ratiocorrelated with WHO-FC, hemodynamics and survival (P<0.05). Right ventricular ejection time correlated with hemodynamics and survival (P<0.05) and tended to correlate with WHO-FC (P=0.071). Tricuspid annular plane systolic excursion correlated with WHO-FC, mean right atrial pressure and survival (P<0.05). Conclusions—This early descriptive study shows that echocardiographic chararacteristics of both the right and the left heart correlate with disease severity and outcome in pediatric PAH, both at presentation and during the course of the disease. The preliminary data from this study support the potential value of echocardiography as a tool in guiding management in children with PAH.Background— The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH. Methods and Results— Forty-three consecutive children (median age, 8.0 years; range, 0.4–21.5) with idiopathic/hereditary PAH (n=25) or PAH associated with congenital heart disease (n=18) were enrolled in a prospective single-center observational study. Anatomic and right ventricular-functional variables were obtained by two-dimensional echocardiography and Doppler-echocardiography at presentation and at standardized follow-up and were correlated with measures of disease severity (World Health Organization functional class [WHO-FC], N-terminal-pro-B-type natriuretic peptide, hemodynamics) and lung-transplantation–free survival. Right atrial and right ventricular dimensions correlated with WHO-FC and hemodynamics ( P <0.05), whereas left ventricular dimensions correlated with hemodynamics and survival ( P <0.05). Right-to-left ventricular dimension ratiocorrelated with WHO-FC, hemodynamics and survival ( P <0.05). Right ventricular ejection time correlated with hemodynamics and survival ( P <0.05) and tended to correlate with WHO-FC ( P =0.071). Tricuspid annular plane systolic excursion correlated with WHO-FC, mean right atrial pressure and survival ( P <0.05). Conclusions— This early descriptive study shows that echocardiographic chararacteristics of both the right and the left heart correlate with disease severity and outcome in pediatric PAH, both at presentation and during the course of the disease. The preliminary data from this study support the potential value of echocardiography as a tool in guiding management in children with PAH.

The Effect of Additional Pulmonary Blood Flow on Timing of the Total Cavopulmonary Connection

BACKGROUND The staged Fontan procedure is used to palliate functionally univentricular hearts. The effect of additional pulmonary blood flow combined with a bidirectional cavopulmonary shunt in these patients remains a controversial subject. METHODS This retrospective study included all 82 patients with a unilateral or bilateral bidirectional cavopulmonary shunt at our institution between April 1990 and July 2010. Patients with hypoplastic left heart syndrome were excluded. Two groups, based on the presence (n=57) or absence (n=25) of additional pulmonary blood flow after the bidirectional cavopulmonary shunt, were compared. RESULTS Patients with a bidirectional cavopulmonary shunt combined with additional pulmonary blood flow had higher arterial oxygen saturations postoperatively (86% [interquartile range, 85% to 90%] vs 82% [80% to 85%]; p=0.001) and had a longer median interval before the total cavopulmonary connection (3.42 [2.43 to 4.89] years vs 2.90 [2.08 to 3.32] years; p=0.06). At the total cavopulmonary connection, they were older (4.59 [3.88 to 6.49] years vs 3.94 [3.10 to 4.57] years; p=0.03) and had a larger median body surface area (0.73 [0.65 to 0.87] m2 vs 0.68 [0.59 to 0.73] m2; p=0.04). CONCLUSIONS Patients with a bidirectional cavopulmonary shunt and additional pulmonary blood flow have a longer interval before the total cavopulmonary connection without evident untoward effects. This may theoretically be advantageous for the pulmonary artery growth needed for a successful Fontan circulation. Furthermore, postponement of the final Fontan may ensure the insertion of a larger extracardiac conduit to avoid prosthesis-patient mismatch.

The right auricle tunnel as intercaval tunnel in total cavopulmonary connection may prevent atrial flutter

OBJECTIVE Total cavopulmonary connection (TCPC) is a routine operation for palliation of children with cardiac anomalies in whom biventricular repair is impossible. The original technique consists of the creation of a semi-prosthetic intercaval tunnel. A substantial proportion of these patients develop atrial flutter. We developed a technique for creating an intercaval tunnel that uses the tissue of the right auricle as intercaval tunnel. This technique avoids suture lines in the neighbourhood of the blood supply of the sinus node and leaves the terminal crest free. Since atrial flutter frequently occurs after Mustard and Senning operations in which suture lines are similar as for creating the lateral tunnel in TCPC we postulated that our technique for creating the intercaval tunnel without prosthetic material might prevent atrial flutter. METHODS All the children that qualified for a TCPC were included. Whenever possible our operative technique was applied. In the other cases a semi-prosthetic conduit was used for creating the intercaval tunnel. Of 47 consecutive patients 30 (64%) had a tunnel of right auricle tissue, 12 (26%) had a tunnel of prosthetic material. Five patients did not need an intercaval tunnel and were omitted in this study. Only surviving patients were included in this study. Patients that needed more atrial surgery then necessary for TCPC were also omitted. Postoperative ECGs and Holter monitorings were studied. RESULTS Overall mortality was 7 of 47 patients (14.9% 70% CL 9.4-22.2%). There was no mortality due to rhythm disturbances. Atrial flutter occurred in 3 of 31 included patients (9.7, 70% CL 4.3-18.5%). In the right auricle group 1 of 22 patients (4.5, 70% CL 0.6-14.6%) had atrial flutter compared to 2 of 9 patients (22.2, 70% CL 7.5-45.0%) in the prosthesis group (P=0.13). CONCLUSION The use of the right auricular technique for creating the intercaval tunnel TCPC is applicable in the majority of patients qualifying for a TCPC. Mortality and morbidity are equal comparing the two techniques. However, markedly less atrial flutter occurs in the group where the right auricle was used as intercaval tunnel. Therefore, we recommend the use of our technique for total cavopulmonary connection.

Congenital Anorectal Malformation Severity Does Not Predict Severity of Congenital Heart Defects

OBJECTIVE To determine the prevalence of congenital heart defects (CHDs) in patients with mild or severe congenital anorectal malformations (CARMs), and whether all patients with CARM need pediatric cardiology screening. STUDY DESIGN We included 129 patients with CARM born between 2004 and 2013, and referred to University Medical Center Groningen. Recto-perineal and recto-vestibular fistulas were classified as mild CARMs, all others as severe. Significant patent foramen ovale, secundum atrial septal defect, and small ventricular septum defect were classified as minor CHDs, all others as major. RESULTS Of 129 patients with CARM, 67% had mild CARM, 33% severe CARM, and 17% were additionally diagnosed with CHD. CHDs were distributed equally in patients with mild or severe CARMs. Patients with multiple congenital abnormalities were more frequently diagnosed with CHD (n = 16, 36%) than patients without multiple congenital malformations (n = 5, 9%, P = .001). Patients with CARM diagnosed with CHD using pediatric cardiac echo screening were younger than 3 months of age at diagnosis. Earlier general pediatric examinations missed 7 (50%) children with mild and 4 (50%) with severe CHDs. CONCLUSIONS The severity of CARM could predict neither prevalence nor severity of CHD. More than one-half of CHDs were missed during the first physical examination. No new CHDs were found in patients older than 3 months of age at the time CARMs were diagnosed. We recommend screening all patients with CARM younger than 3 months of age for CHD at the time CARM is diagnosed. Preoperative echocardiography should be the rule in children younger than 3 months of age and with multiple congenital anomalies.

Quantification of Ventricular Volume Load in the Context of a Bidirectional Cavopulmonary Shunt: A Theoretical Treatise

BACKGROUND Functional univentricular hearts are currently palliated by a staged procedure of which the bidirectional cavopulmonary shunt is usually the second stage. In addition to this stage, a calibrated amount of additional pulmonary blood flow may be preserved to promote pulmonary artery growth and increase the length of the interval preceding the total cavopulmonary connection. However, additional pulmonary blood flow can be deleterious for ventricular functioning and development as it increases functional ventricular volume load. METHODS Using the Fick principle we devised a theoretic framework to estimate the ventricular volume loading caused by additional pulmonary and collateral aortopulmonary flow. To use this framework, blood samples need to be taken intraoperatively from the aorta, pulmonary veins, and inferior caval vein to determine oxygen saturations. The oxygen saturation samples have to be taken sequentially with and without additional pulmonary blood flow. RESULTS The objective of this paper is to provide a theoretic framework to estimate the ventricular volume loading caused by collateral aortopulmonary flow and additional pulmonary blood flow in the context of a bidirectional cavopulmonary shunt in the staged palliation of univentricular hemodynamics. The formulas have not yet systematically been applied in vivo. CONCLUSIONS The added volume loading of the ventricle caused by additional pulmonary blood flow can theoretically be estimated using the newly devised formulas so as to calibrate ventricular volume loading to a desired level intraoperatively.

Echocardiography in Pediatric Pulmonary Arterial HypertensionCLINICAL PERSPECTIVE

Background—The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH. Methods and Results—Forty-three consecutive children (median age, 8.0 years; range, 0.4–21.5) with idiopathic/hereditary PAH (n=25) or PAH associated with congenital heart disease (n=18) were enrolled in a prospective single-center observational study. Anatomic and right ventricular-functional variables were obtained by two-dimensional echocardiography and Doppler-echocardiography at presentation and at standardized follow-up and were correlated with measures of disease severity (World Health Organization functional class [WHO-FC], N-terminal-pro-B-type natriuretic peptide, hemodynamics) and lung-transplantation–free survival. Right atrial and right ventricular dimensions correlated with WHO-FC and hemodynamics (P<0.05), whereas left ventricular dimensions correlated with hemodynamics and survival (P<0.05). Right-to-left ventricular dimension ratiocorrelated with WHO-FC, hemodynamics and survival (P<0.05). Right ventricular ejection time correlated with hemodynamics and survival (P<0.05) and tended to correlate with WHO-FC (P=0.071). Tricuspid annular plane systolic excursion correlated with WHO-FC, mean right atrial pressure and survival (P<0.05). Conclusions—This early descriptive study shows that echocardiographic chararacteristics of both the right and the left heart correlate with disease severity and outcome in pediatric PAH, both at presentation and during the course of the disease. The preliminary data from this study support the potential value of echocardiography as a tool in guiding management in children with PAH.Background— The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH. Methods and Results— Forty-three consecutive children (median age, 8.0 years; range, 0.4–21.5) with idiopathic/hereditary PAH (n=25) or PAH associated with congenital heart disease (n=18) were enrolled in a prospective single-center observational study. Anatomic and right ventricular-functional variables were obtained by two-dimensional echocardiography and Doppler-echocardiography at presentation and at standardized follow-up and were correlated with measures of disease severity (World Health Organization functional class [WHO-FC], N-terminal-pro-B-type natriuretic peptide, hemodynamics) and lung-transplantation–free survival. Right atrial and right ventricular dimensions correlated with WHO-FC and hemodynamics ( P <0.05), whereas left ventricular dimensions correlated with hemodynamics and survival ( P <0.05). Right-to-left ventricular dimension ratiocorrelated with WHO-FC, hemodynamics and survival ( P <0.05). Right ventricular ejection time correlated with hemodynamics and survival ( P <0.05) and tended to correlate with WHO-FC ( P =0.071). Tricuspid annular plane systolic excursion correlated with WHO-FC, mean right atrial pressure and survival ( P <0.05). Conclusions— This early descriptive study shows that echocardiographic chararacteristics of both the right and the left heart correlate with disease severity and outcome in pediatric PAH, both at presentation and during the course of the disease. The preliminary data from this study support the potential value of echocardiography as a tool in guiding management in children with PAH.

Echocardiography in Pediatric Pulmonary Arterial HypertensionCLINICAL PERSPECTIVE: Early Study on Assessing Disease Severity and Predicting Outcome

Background—The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH. Methods and Results—Forty-three consecutive children (median age, 8.0 years; range, 0.4–21.5) with idiopathic/hereditary PAH (n=25) or PAH associated with congenital heart disease (n=18) were enrolled in a prospective single-center observational study. Anatomic and right ventricular-functional variables were obtained by two-dimensional echocardiography and Doppler-echocardiography at presentation and at standardized follow-up and were correlated with measures of disease severity (World Health Organization functional class [WHO-FC], N-terminal-pro-B-type natriuretic peptide, hemodynamics) and lung-transplantation–free survival. Right atrial and right ventricular dimensions correlated with WHO-FC and hemodynamics (P<0.05), whereas left ventricular dimensions correlated with hemodynamics and survival (P<0.05). Right-to-left ventricular dimension ratiocorrelated with WHO-FC, hemodynamics and survival (P<0.05). Right ventricular ejection time correlated with hemodynamics and survival (P<0.05) and tended to correlate with WHO-FC (P=0.071). Tricuspid annular plane systolic excursion correlated with WHO-FC, mean right atrial pressure and survival (P<0.05). Conclusions—This early descriptive study shows that echocardiographic chararacteristics of both the right and the left heart correlate with disease severity and outcome in pediatric PAH, both at presentation and during the course of the disease. The preliminary data from this study support the potential value of echocardiography as a tool in guiding management in children with PAH.Background— The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH. Methods and Results— Forty-three consecutive children (median age, 8.0 years; range, 0.4–21.5) with idiopathic/hereditary PAH (n=25) or PAH associated with congenital heart disease (n=18) were enrolled in a prospective single-center observational study. Anatomic and right ventricular-functional variables were obtained by two-dimensional echocardiography and Doppler-echocardiography at presentation and at standardized follow-up and were correlated with measures of disease severity (World Health Organization functional class [WHO-FC], N-terminal-pro-B-type natriuretic peptide, hemodynamics) and lung-transplantation–free survival. Right atrial and right ventricular dimensions correlated with WHO-FC and hemodynamics ( P <0.05), whereas left ventricular dimensions correlated with hemodynamics and survival ( P <0.05). Right-to-left ventricular dimension ratiocorrelated with WHO-FC, hemodynamics and survival ( P <0.05). Right ventricular ejection time correlated with hemodynamics and survival ( P <0.05) and tended to correlate with WHO-FC ( P =0.071). Tricuspid annular plane systolic excursion correlated with WHO-FC, mean right atrial pressure and survival ( P <0.05). Conclusions— This early descriptive study shows that echocardiographic chararacteristics of both the right and the left heart correlate with disease severity and outcome in pediatric PAH, both at presentation and during the course of the disease. The preliminary data from this study support the potential value of echocardiography as a tool in guiding management in children with PAH.