Katya De Groote

Reference Values for Echocardiographic Assessment of the Diameter of the Aortic Root and Ascending Aorta Spanning All Age Categories

Thoracic aortic dilatation requires accurate and timely detection to prevent progression to thoracic aortic aneurysm and aortic dissection. The detection of thoracic aortic dilatation necessitates the availability of cut-off values for normal aortic diameters. Tools to evaluate aortic dimension above the root are scarce and inconsistent regarding age groups. The aim of this study was to provide reference values for aortic root and ascending aortic diameters on the basis of transthoracic echocardiographic measurements in a large cohort of children and adults. Diameters at the level of the sinuses of Valsalva (SoV) and ascending aorta (AA) were assessed with transthoracic echocardiography in 849 subjects (453 females, age range 1 to 85 years, mean 40.1 ± 21.3 years) and measured according to published guidelines. Linear regression analysis was applied to create nomograms, as well as equations for upper limits of normal and z-scores. SoV and AA diameters were strongly correlated with age, body surface area (BSA), and weight (r = 0.67 to 0.79, p <0.001 for all). Male subjects had significantly larger aortic dimensions at all levels in adulthood, even after BSA correction (p ≤0.004 for all age intervals). Gender-, age-, and BSA-specific upper limits of normal and z-score equations were developed from a multivariate regression model, which strongly predicts SoV and AA diameters (adjusted R(2) for SoV = 0.84 and 0.67 and for AA = 0.82 and 0.74, for male and female subjects, respectively). In conclusion, this study provides widely applicable reference values for thoracic aortic dilatation screening purposes. Age, BSA, and gender must be taken into account when assessing an individual patient.

Assessment of a right-ventricular infundibulum-sparing approach in transatrial-transpulmonary repair of tetralogy of Fallot.

OBJECTIVE The study aimed to evaluate the outcome of transatrial-transpulmonary repair of tetralogy of Fallot in relation to a right-ventricular outflow tract (RVOT)-sparing surgery. METHODS Based on the surgical management of right-ventricular outflow tract obstruction (RVOTO) at repair of tetralogy of Fallot, 140 children were retrospectively divided into three groups: (1) pulmonary valve (PV)-sparing, (2) infundibulum-sparing and (3) extended trans-annular patch (TAP). Clinical and echocardiographic outcome was assessed with regards to three equally divided study time eras between January 1994 and June 2010. RESULTS Over a 15-year study period, median age decreased from 11 (2-101) to 5 (1-11) months (p<0.001), whereas type of RVOT repair changed significantly between the first and the last era (group 1: 18-40%, group 2: 25-40% vs group 3: 57-20% (p=0.002)). Mortality was 0%. Complications were mainly related to clinical restrictive RV physiology (27%) and arrhythmia (10%). This cardiac morbidity remained constant over the eras and was associated with younger age (p=0.04), increased postoperative right ventricle/left ventricle (RV/LV) pressure ratio (p=0.01) and type of RVOT repair at the cost of TAP (p=0.03). Median follow-up of 8 years (1-16 years) showed an overall freedom from RVOT re-operation of 84% and 73%, respectively at 5 and 10 years. Most re-operations were for residual/recurrent RVOTO (12%) occurring more frequently in the latter era: 16% versus 7% in era 1 (p=0.08). Late echocardiographic evaluation revealed a strong correlation between severity of pulmonary regurgitation and increased RV/LV size ratio, which was mainly determined by increased TAP length (p<0.001) and duration of follow-up (p=0.06). CONCLUSION In a 15-years experience with transatrial-transpulmonary correction of tetralogy of Fallot, a valve- and infundibulum-sparing approach has been advanced by lowering the age for elective repair. This change has been performed without compromising immediate clinical outcome, despite an increased early re-operation rate for residual obstruction. However, longer follow-up will disclose whether this approach is protective against progressive and late RV dysfunction.

Pleural effusions, water balance mediators and the influence of lisinopril after completion Fontan procedures

OBJECTIVE To investigate whether the duration of pleural drainage after Fontan completion operations can be influenced by postoperative lisinopril administration or can be related to water balance hormone levels. METHODS In a prospective trial 21 patients scheduled for total cavopulmonary connection were randomized into two groups, with group I receiving lisinopril postoperatively, and group II receiving no angiotensin converting enzyme inhibitor. Plasma levels of antidiuretic hormone, renin and aldosteron were analyzed preoperatively and at four-time points postoperatively. Groups were comparable for age, preoperative saturation and pulmonary pressure, cardiopulmonary bypass time, cross-clamp time and preoperative hormone levels. RESULTS Mean duration of pleural drainage was comparable for both groups (group I: 9.6+/-8 days vs group II: 10+/-7 days; p=0.78). The hormone profiles in each group changed significantly at 1 and 24h postoperatively compared to preoperative values (p<0.05), with no significant differences between the treatment groups. The duration of pleural drainage correlated significantly with hormone levels at 24h postoperatively, and with longer bypass times. At multivariate analysis only aldosteron and antidiuretic hormone level at 24h came out as factors reaching significance for prolonged pleural drainage. CONCLUSIONS The Fontan completion induces significant changes in the levels of antidiuretic hormone, aldosteron and renin. Prolonged drainage correlates significantly with elevated levels of aldosteron, renin and antidiuretic hormone postoperatively, and with longer bypass time, but is not influenced by lisinopril. The eventual adjunct therapy with aldosteron antagonists warrants further study.

Disease-specific outcome analysis of palliation with the modified Blalock-Taussig shunt.

Background: Albeit being a simple surgical procedure, adverse outcomes with the modified Blalock-Taussig shunt (MBTS) are commonly reported in generalizing terms, independent of the underlying heart disorder. Methods: From August 1995 to December 2013, a total of 150 children underwent an MBTS for tetralogy of Fallot (TOF; n = 44, 29%), pulmonary atresia with ventricular septal defect (PA/VSD; n = 28, 19%), pulmonary atresia with intact ventricular septum (PA/IVS; n = 17, 11%), transposition of the great arteries with ventricular septal defect (TGA/VSD) with pulmonary stenosis (PS; n = 12, 8%), Ebstein malformation (n = 2, 1%), and complex univentricular anomalies (n = 47, 31%). Outcome analysis focused on operative mortality and survival until shunt takedown, adjusted to the underlying disease. Results: In-hospital mortality was 8.7% (n = 13), and interstage mortality was 5.1% (n = 7), resulting in 86.1% survival to the next surgery. Hospital mortality was 14% in PA/VSD, 13% in univentricular heart, and 18% in PA/IVS, while no mortality was observed in TOF, TGA/VSD/PS, and Ebstein disease. A shunt-related complication was observed in 18% (n = 27) of the children, including acute thrombosis (n = 7, 5%), shunt stenosis (n = 3, 2%), overshunting (n = 7, 5%), and pulmonary artery stenosis (n = 10, 7%). Multivariate analysis of shunt-dependent time survival identified a shunt complication occurring in a univentricular circulation (hazard ratio [HR] 4.10, 95% confidence interval [CI] = 1.05-17.43, P = .01) and increased shunt size-to-weight ratio (HR 2.72, 95% CI = 0.80-9.18, P = .04) as risk factors. Shunt thrombosis was also a negative outcome predictor in PA/VSD, when requiring associated unifocalization (P = .05). Conclusion: This study shows that the outcome of palliation with the MBTS is importantly affected by the occurrence of a shunt-related complication, whose circulatory effect is even more dismal in single ventricle hearts. Since an increased shunt size-to-weight ratio additionally compromises the shunt-dependent survival, it emphasizes that the choice of the shunt with regard to size as well as surgical approach remains critical.

Arterial hypertension in Turner syndrome: a review of the literature and a practical approach for diagnosis and treatment.

Turner syndrome is a rare chromosomal disorder with complete or partial absence of one X chromosome that only occurs in women. Clinical presentation is variable, but congenital and acquired cardiovascular diseases are frequently associated diseases that add significantly to the increased morbidity and mortality in Turner syndrome patients. Arterial hypertension is reported in 13-58% of adult Turner syndrome patients and confers an increased risk for stroke and aortic dissection. Hypertension can be present from childhood on and is reported in one-quarter of the paediatric Turner syndrome patients. This article reviews the prevalence and cause of arterial hypertension in Turner syndrome and describes the relationship between blood pressure, aortic dilation and increased cardiovascular risk. We compare current treatment strategies and also propose an integrated practical approach for the diagnosis and treatment of hypertension in Turner syndrome applicable in daily practice.

Cardiovascular pathology in males and females with 45,X/46,XY mosaicism

Context The phenotype of 45,X/46,XY mosaicism is heterogeneous ranging from females with Turner syndrome (TS) to apparently normal males. Males with 45,X/46,XY frequently show stigmata typically associated with TS. We hypothesised that males with 45,X/46,XY have similar cardiovascular pathology as females with 45,X/46,XY. Objective To investigate cardiovascular abnormalities in 45,X/46,XY males and to compare them with 45,X/46,XY females. Design Patients with 45,X/46,XY mosaicism were selected from the Belgian Registry for Growth and Puberty problems and via the multidisciplinary clinic for disorders of sexual development. Patients Eighteen patients were included: 8 raised as females (F) and 10 as males (M). Intervention Complete cardiac examination with blood pressure measurement, ECG, echocardiography and MRI. Main Outcome Measurement Cardiac parameters were registered for both groups. In a second phase, clinical features and external masculinisation score (EMS) were retrospectively collected from the medical files. Results A structural heart defect was diagnosed before inclusion in 1 F with coarctation and 1 M with spontaneously closed VSD. A bicuspid aortic valve was found in 8 (3 F, 5 M). Dilation of the ascending aorta was present in 4 M and was severe in 2 young boys. QTc was prolonged in 3 F and 2 M. Conclusion Males with 45,X/46,XY mosaicism have similar cardiovascular pathology as 45,X/46,XY females. Dilation of the ascending aorta can be important, also in males. We advise cardiac screening and life-long monitoring in all males with 45,X/46,XY mosaicism according to the existing guidelines for Turner syndrome.

Univentricular heart and Fontan staging: analysis of factors impacting on body growth

OBJECTIVES The optimal timing of the Fontan staging for a univentricular heart and its impact on growth remains debateable. In a Fontan cohort, the influence of staged interventions and patient factors on somatic development was explored. METHODS We reviewed 64 total cavopulmonary connection (TCPC) patients treated since 1992. Serial anthropometric parameters recorded from birth to the latest follow-up (mean 12.5 ± 6.1 years) and at each intervention [neonatal surgery, bidirectional cavopulmonary anastomosis (BCPA), TCPC, catheter treatment] were converted to z-scores. The influence of saturation, heart failure treatment and surgery intervals on growth was determined. RESULTS The mean z-scores for weight and height changed significantly at each surgery up to the TCPC (-0.3 ± 1.2 and 0 ± 1 at birth, -1.3 ± 1.9 and -0.9 ± 1.7 at neonatal surgery, -2.1 ± 1.2 and -1.6 ± 1.3 at the BCPA, -1.2 ± 1.3 and -0.7 ± 1.4 at the TCPC for weight and height, respectively; P < 0.05 for each interval), with the largest decline before the BCPA, and the most marked improvement before the TCPC. Z-scores did not change significantly after the TCPC. Younger age at the BCPA had a positive influence on the weight z-score at the TCPC (P < 0.05); somatic growth at the latest follow-up (FU) was negatively influenced by heart failure treatment (P < 0.05). CONCLUSIONS Body growth is severely impaired in Fontan patients. A close interstage follow-up between the first surgery and the BCPA must be targeted at optimizing nutritional support to counter the important growth retardation occurring before the BCPA. The better catch-up growth at the TCPC when the BCPA is performed earlier in life supports the current trend to perform the BCPA at a younger age. Heart failure treatment after a Fontan completion is independently associated with decreased late somatic development.

Functional analysis of the anatomical right ventricular components: should assessment of right ventricular function after repair of tetralogy of Fallot be refined?

OBJECTIVE Follow-up after tetralogy of Fallot (ToF) repair is directed to detect timely right ventricular (RV) dysfunction by following pulmonary regurgitation and global RV size, with little attention for the effective contribution of regional RV dysfunction. This study investigates the contribution of regional RV dysfunction on exercise capacity after ToF repair. METHODS Forty-two patients were investigated with cardiac magnetic resonance imaging for regional RV dysfunction in relation to global RV function by functional quantification of the sinus and outflow part of the RV. The impact of regional and global RV dysfunction on clinical status was studied by exercise testing. RESULTS Global RV function was lower than sinus function (ejection fraction (EF) 52±12% vs 58±10%, P<0.001), attributable to the adverse influence of right ventricular outflow tract (RVOT) dysfunction (EF 34±17%). Percent predicted peak VO2 correlated better with the RV sinus ejection fraction compared with the global RV ejection fraction (r=0.51, P=0.001 vs r=0.44, P=0.004). Multivariate analysis revealed the EF of RV sinus (β=0.34, 95% CI 0.07-0.61, P=0.013) and the extent of RVOT akinesia (β=-0.28, 95% CI -0.50; -0.06, P=0.015) as significant determinants of exercise capacity. Impaired exercise performance occurred in 43% of the patients, and was independently determined by the type of repair (transventricular vs transatrial: OR 6.0, 95% CI 1.31-17.3, P=0.02) by associating greater sinus and RVOT dysfunction. CONCLUSION Functional analysis of the RV components shows that exercise capacity after repair of ToF is better predicted by systolic function of the RV sinus as the extent of RVOT dysfunction commonly leads to underestimation of global RV function. This method of differential quantification of regional RV function might be more appropriate than assessment of global RV function during the long-term follow-up of repaired ToF patients.

The fate of the aortic root after early repair of tetralogy of Fallot

OBJECTIVE Late aortic root dilatation is a growing concern in patients operated on for tetralogy of Fallot (ToF). This longitudinal follow-up study sought to evaluate the changes in the aortic root dimensions in relation to body growth, assuming that early repair of tetralogy of Fallot might prevent late aortic dilatation. METHODS A retrospective analysis of the aortic root dimensions was performed in 88 patients repaired early for tetralogy of Fallot by echocardiographic measurement of aortic annulus, sinus of Valsalva and sinotubular junction, adjusted for body surface area and expressed as z-scores. Mean age at repair was 9.7 + or - 7.4 months. Median age was 7.3 months (range 45 days-29 months). RESULTS At the time of repair, all root dimensions were enlarged: z-score of the annulus 3.32 + or - 1.66; sinus 3.54 + or - 1.49; sinotubular junction 2.74 + or - 1.19. Within a mean follow-up of 6.9 + or - 4.4 years, the mean z-scores of both annulus and sinotubular junction significantly decreased to normal size at 7 years postoperatively: z-score of annulus 0.95 + or - 0.7 (p=0.006), z-score of sinotubular junction 0.99 + or - 1.47 (p=0.006). The z-score of the aortic sinuses appeared to regress slower to 2.78 + or - 1.26 (p=0.262). The indexed sinus diameter however regressed significantly from a mean of 51.4 + or - 13.4 mmm(-2) at correction to 28.9 + or - 7.2 mmm(-2) (p=0.0001) at latest follow-up. Evolution of aortic root size after repair was independent of aortic arch side, sex, age at repair or previous shunt palliation. CONCLUSIONS The initially dilated aortic root in tetralogy of Fallot normalises in size at the level of the annulus and sinotubular junction within 7 years after early repair. This process seems delayed at the level of the aortic sinuses, although the indexed root diameter shows significant regression over time. These results suggest that early repair of ToF abrogates the enlargement of the aortic root, validating one aspect of the need for tetralogy correction at a young age.

Increased aortic stiffness in prepubertal girls with Turner syndrome

BACKGROUND Aortic dilation and dissection contribute highly to the increased mortality of Turner syndrome (TS) but the exact pathophysiology is not completely understood. DESIGN Prospective case - control study. METHODS 15 prepubertal TS girls (median age 10.64, IQ 8.31-11.04) with a tricuspid (TAV, n=9) or a bicuspid (BAV, n=6) aortic valve, and 31 sex-, age-, and height-matched healthy controls underwent a cardiac and vascular ultrasound to evaluate aortic dimensions and elastic properties of the aortic wall. RESULTS TS BAV had significantly larger ascending aortic diameters than controls for absolute diameter, 22.2±5.1mm vs. 18.6±1.9mm (p=0.014) and z-score 1.7±2.1 vs. 0.1±0.7 (p=0.008). Distensibility of the ascending aorta was lower in the TS than in controls (40.2×10-3kPa-1, IQ 31.3-56.2 vs. 62.9×10-3kPa-1, IQ 55.5-76.5, p=0.003), both for TS TAV (p=0.014) and BAV (p=0.005). Stiffness index was higher in TS than in controls (5.26, IQ 3.34-5.26 vs. 3.23, IQ 2.55-3.24, p=0.005), both for TS TAV (p=0.028) and TS BAV (p=0.006). Pulse wave velocity was not different between groups. There was no correlation between stiffness and z-score of the ascending aortic diameter. CONCLUSIONS In prepubertal TS girls, stiffness of the ascending aorta is increased in patients with a BAV and TAV while dilation of the ascending aorta is more frequent in BAV. This suggests an intrinsic aortic wall abnormality making all TS patients at increased risk for severe aortic complications although the risk is the highest for TS with BAV.