Coarctation of the aorta: Prenatal assessment, postnatal management and neonatal outcomes.

Coarctation of the aorta (Coa) is a potentially life threatening diagnosis. It occurs in 0.3 per 1000 live births and accounts for 6-8% of all infants with congenital heart defects. Neonates with severe Coa may be completely asymptomatic at birth, as the ductus arteriosus can provide flow to the lower body. Those who are not diagnosed prenatally may be diagnosed only after constriction of the ductus arteriosus, when they present in cardiogenic shock. This group has a higher risk for mortality and morbidity relative to those diagnosed prenatally. Despite the increasing practice of universal pulse oximetry screening, many cases with significant coarctation of the aorta still go undiagnosed in the newborn period. In this article, we present the pathophysiology, diagnosis, presentation, treatment and outcomes of Coa.

Long-segmental middle aortic coarctation: a rare case first diagnosed by transthoracic echocardiography.

BACKGROUND: Middle aortic coarctation (MAC), also known as middle aortic syndrome, is an atypical aortic coarctation characterized by narrowing of the distal thoracic aorta and proximal abdominal aorta. MAC is a rare disease commonly diagnosed by computed tomography angiography (CTA). In this paper, we present a case of long-segmental MAC first diagnosed by transthoracic echocardiography (TTE) and further evaluated by CTA. CASE PRESENTATION: A 14-year-old girl, with dyspnea and fatigue on exertion for 2 months and refractory hypertension for 6 months, was referred by the local clinic to our hospital. Physical examination showed blood pressure up to 176/100 mmHg measured in the arms despite dual antihypertensives, a marked pressure gradient between her arms and legs, and weak pulses in both dorsal pedes arteries. TTE revealed a segmental narrowing in the descending thoracic aorta below the level of the atrioventricular sulcus, with a calcified plaque in the stenotic region. Abdominal vascular ultrasound revealed the segmental narrowing extending to the descending abdominal aorta (5.7 mm in diameter) above the level of the superior mesenteric artery. Subsequently, CTA verified a long-segment narrowing in the descending aorta from the level of T8 to L2 vertebra, with a calcified plaque in the stenotic aorta, right renal artery involvement, and a rich network of collateral vessels between the pre-and post-stenotic region. The patient was referred for cardiovascular surgery in which a successful ascending aorta-abdominal aorta bypass was performed. CONCLUSIONS: Although MAC is usually diagnosed by CTA, it may also be first diagnosed by TTE in some patients whose longitudinal axis view of the thoracic descending aorta could be shown. Careful TTE scan can improve the diagnostic rate of MAC, especially for some hypertension patients whose marked pressure gradient between arms and legs was ignored by the physician.

Hemodynamics and Wall Shear Stress of Blood Vessels in Aortic Coarctation with Computational Fluid Dynamics Simulation.

The purpose of this study was to identify the characteristics of blood flow in aortic coarctation based on stenotic shape structure, stenosis rate, and the distribution of the wall load delivered into the blood vessels and to predict the impact on aneurysm formation and rupture of blood vessels by using a computational fluid dynamics modeling method. It was applied on the blood flow in abdominal aortic blood vessels in which stenosis occurred by using the commercial finite element software ADINA on fluid-solid interactions. The results of modeling, with an increasing stenosis rate and Reynolds number, showed the pressure drop was increased and the velocity was greatly changed. When the stenosis rate was the same, the pressure drop and the velocity change were larger in the stenosis with a symmetric structure than in the stenosis with an asymmetric one. Maximal changes in wall shear stress were observed in the area before stenosis and minimal changes were shown in stenosis areas. The minimal shear stress occurred at different locations depending on the stenosis shape models. With an increasing stenosis rate and Reynolds number, the maximal wall shear stress was increased and the minimal wall shear stress was decreased. Through such studies, it is thought that the characteristics of blood flow in the abdominal aorta where a stenosis is formed will be helpful in understanding the mechanism of growth of atherosclerosis and the occurrence and rupture of the abdominal aortic flow.

Right Heart Dysfunction in Adults With Coarctation of Aorta: Prevalence and Prognostic Implications.

BACKGROUND: Chronic elevation of left heart filling pressure causes pulmonary vascular remodeling, pulmonary hypertension, and right heart dysfunction. Although diastolic dysfunction is relatively common in patients with coarctation of aorta, there are limited data about the prevalence and prognostic implications of pulmonary hypertension and right heart dysfunction in this population. The purpose of the study was to assess right heart function and hemodynamics in patients with coarctation of aorta and to determine the relationship between right heart indices and cardiovascular events defined as heart failure hospitalization, heart transplant, or cardiovascular death. METHODS: Right heart structure, function, and hemodynamics were assessed with these indices: right atrial volume, right atrial pressure, right atrial reservoir strain, right ventricular global longitudinal strain, right ventricular end-diastolic area, right ventricular systolic pressure, and tricuspid regurgitation severity. Right heart hemodynamic score, range 0 to 5, was generated based on the correlation between the right heart indices and cardiovascular events, using half of the cohort (derivation cohort, n=411), and then tested on the validation cohort (n=410). The goodness of fit and discrimination power was compared using C statistics and risk score. RESULTS: The median follow-up in the derivation cohort was 8.2 (4.0-11.1) years, and 59 (14%) patients had cardiovascular events during this period. Right heart hemodynamic score was independently associated with cardiovascular events (hazard ratio, 1.64 [95% CI, 1.38-2.17]) for every unit increase in right heart hemodynamic score after adjustment for clinical and echocardiographic indices (C statistic, 0.718 [95% CI, 0.682-0.746]). The right heart hemodynamic score was also independently associated with cardiovascular events in the validation cohort (C statistic, 0.711 [95% CI, 0.679-0.741]). The C statistic difference (0.007 [95% CI, 0.014-0.022]) and risk score (0.86 [95% CI, 0.54-1.17]) suggest a good model fit. CONCLUSIONS: The current study underscores the prognostic importance of right heart dysfunction in patients with coarctation of aorta and suggests that right heart indices should be used for risks stratification in this population.

Effects of Uncertainty of Outlet Boundary Conditions in a Patient-Specific Case of Aortic Coarctation.

Computational Fluid Dynamics (CFD) simulations of blood flow are widely used to compute a variety of hemodynamic indicators such as velocity, time-varying wall shear stress, pressure drop, and energy losses. One of the major advances of this approach is that it is non-invasive. The accuracy of the cardiovascular simulations depends directly on the level of certainty on input parameters due to the modelling assumptions or computational settings. Physiologically suitable boundary conditions at the inlet and outlet of the computational domain are needed to perform a patient-specific CFD analysis. These conditions are often affected by uncertainties, whose impact can be quantified through a stochastic approach. A methodology based on a full propagation of the uncertainty from clinical data to model results is proposed here. It was possible to estimate the confidence associated with model predictions, differently than by deterministic simulations. We evaluated the effect of using three-element Windkessel models as the outflow boundary conditions of a patient-specific aortic coarctation model. A parameter was introduced to calibrate the resistances of the Windkessel model at the outlets. The generalized Polynomial Chaos method was adopted to perform the stochastic analysis, starting from a few deterministic simulations. Our results show that the uncertainty of the input parameter gave a remarkable variability on the volume flow rate waveform at the systolic peak simulating the conditions before the treatment. The same uncertain parameter had a slighter effect on other quantities of interest, such as the pressure gradient. Furthermore, the results highlight that the fine-tuning of Windkessel resistances is not necessary to simulate the post-stenting scenario.

Persistent Hypertension and Left Ventricular Hypertrophy After Repair of Native Coarctation of Aorta in Adults.

[Figure: see text].

Coarctation of aorta is associated with left ventricular stiffness, left atrial dysfunction and pulmonary hypertension.

BACKGROUND: Brachial systolic blood pressure (BP) is the most commonly used metric for monitoring hypertension. However, recent studies suggest that brachial systolic BP underestimates left ventricle (LV) systolic load in patients with coarctation of aorta (COA). Since brachial systolic BP is used as a surrogate of arterial afterload in clinical practice, it is important to determine how well it correlates with LV remodeling and stiffness in patients with COA as compared to patients with idiopathic hypertension. METHODS: This is cross-sectional study of COA patients with hypertension (COA group) and adults with idiopathic hypertension (control group). Both groups were matched 1:1 based on age, sex, BMI and systolic BP. We hypothesized that the COA group will have higher LV systolic and diastolic stiffness, and more advanced left atrial remodeling and pulmonary hypertension. We assessed LV systolic stiffness using end-systolic elastance, and diastolic stiffness using LV stiffness constant and chamber capacitance (LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg) RESULTS: There were 112 patients in each group. Although both groups had similar systolic BP, the COA group had a higher end-systolic elastance (2.37 ± 0.74 vs 2.11 ± 0.54 mm Hg/mL, P= .008), higher LV stiffness constant (6.91 ± 0.81 vs 5.93 ± 0.79, P= .006) and lower LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg (58 ± 9 vs 67 ± 11 mL/m2, P< .001). Additionally, the COA group had more advanced left atrial remodeling and higher pulmonary artery pressures which is corroborating evidence of high LV filling pressure. CONCLUSIONS: COA patients have more LV stiffness and abnormal hemodynamics compared to non-COA patients with similar systolic BP, suggesting that systolic BP may underestimate LV systolic load in this population. Further studies are required to determine whether the observed LV stiffness and dysfunction translates to more cardiovascular events during follow-up, and whether adopting a stricter systolic BP target in clinical practice or changing threshold for COA intervention will lead to less LV stiffness and better clinical outcomes.

The effect of coarctation degrees on wall shear stress indices.

Coarctation of the aorta (CoA) is a congenital tightening of the proximal descending aorta. Flow quantification can be immensely valuable for an early and accurate diagnosis. However, there is a lack of appropriate diagnostic approaches for a variety of cardiovascular diseases, such as CoA. An accurate understanding of the disease depends on measurements of the global haemodynamics (criteria for heart function) and also the local haemodynamics (detailed data on the dynamics of blood flow). Playing a significant role in clinical processes, wall shear stress (WSS) cannot be measured clinically; thus, computation tools are needed to give an insight into this crucial haemodynamic parameter. In the present study, in order to enable the progress of non-invasive approaches that quantify global and local haemodynamics for different CoA severities, innovative computational blueprint simulations that include fluid-solid interaction models are developed. Since there is no clear approach for managing the CoA regarding its severity, this study proposes the use of WSS indices and pressure gradient to better establish a framework for treatment procedures in CoA patients with different severities. This provides a platform for improving CoA therapy on a patient-specific level, in which physicians can perform treatment methods based on WSS indices on top of using a mere experience. Results show how severe CoA affects the aorta in comparison to the milder cases, which can give the medical community valuable information before and after any intervention.

Analysis of 3-Dimensional Arch Anatomy, Vascular Flow, and Postnatal Outcome in Cases of Suspected Coarctation of the Aorta Using Fetal Cardiac Magnetic Resonance Imaging.

BACKGROUND: Identifying fetuses at risk of severe neonatal coarctation of the aorta (CoA) can be lifesaving but is notoriously challenging in clinical practice with a high rate of false positives. Novel fetal 3-dimensional and phase-contrast magnetic resonance imaging (MRI) offers an unprecedented means of assessing the human fetal cardiovascular system before birth. We performed detailed MRI assessment of fetal vascular morphology and flows in a cohort of fetuses with suspected CoA, correlated with the need for postnatal intervention. METHODS: Women carrying a fetus with suspected CoA on echocardiography were referred for MRI assessment between 26 and 36 weeks of gestation, including high-resolution motion-corrected 3-dimensional volumes of the fetal heart and phase-contrast flow sequences gated with metric optimized gating. The relationship between aortic geometry and vascular flows was then analyzed and compared with postnatal outcome. RESULTS: Seventy-two patients (51 with suspected fetal CoA and 21 healthy controls) underwent fetal MRI with motion-corrected 3-dimensional vascular reconstructions. Vascular flow measurements from phase-contrast sequences were available in 53 patients. In the CoA group, 25 of 51 (49%) required surgical repair of coarctation after birth; the remaining 26 of 51 (51%) were discharged without neonatal intervention. Reduced blood flow in the fetal ascending aorta and at the aortic isthmus was associated with increasing angulation (P=0.005) and proximal displacement (P=0.006) of the isthmus and was seen in both true positive and false positive cases. A multivariate logistic regression model including aortic flow and isthmal displacement explained 78% of the variation in outcome and correctly predicted the need for intervention in 93% of cases. CONCLUSIONS: Reduced blood flow though the left heart is associated with important configurational changes at the aortic isthmus in fetal life, predisposing to CoA when the arterial duct closes after birth. Novel fetal MRI techniques may have a role in both understanding and accurately predicting severe neonatal CoA.

Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.

[Figure: see text].

Image-Based Computational Model Predicts Dobutamine-Induced Hemodynamic Changes in Patients With Aortic Coarctation.

BACKGROUND: Pharmacological stress testing can help to uncover pathological hemodynamic conditions and is, therefore, used in the clinical routine to assess patients with structural heart diseases such as aortic coarctation with borderline indication for treatment. The aim of this study was to develop and test a reduced-order model predicting dobutamine stress induced pressure gradients across the coarctation. METHODS: The reduced-order model was developed based on n=21 imaging data sets of patients with aortic coarctation and a meta-analysis of subjects undergoing dobutamine stress testing. Within an independent test cohort of n=21 patients with aortic coarctation, the results of the model were compared with dobutamine stress testing during catheterization. RESULTS: In n=19 patients responding to dobutamine stress testing, pressure gradients across the coarctation during dobutamine stress increased from 15.7±5.1 to 33.6±10.3 mm Hg (paired t test, P<0.001). The model-predicted pressure gradients agreed with catheter measurements with a mean difference of -2.2 mm Hg and a limit of agreement of ±11.16 mm Hg according to Bland-Altman analysis. Significant equivalence between catheter-measured and simulated pressure gradients during stress was found within the study cohort (two 1-sided tests of equivalence with a noninferiority margin of 5.0 mm Hg, 33.6±10.33 versus 31.5±11.15 mm Hg, P=0.021). CONCLUSIONS: The developed reduced-order model can instantly predict dobutamine-induced hemodynamic changes with accuracy equivalent to heart catheterization in patients with aortic coarctation. The method is easy to use, available as a web-based calculator, and provides a promising alternative to conventional stress testing in the clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02591940.

Fully quantitative mapping of abnormal aortic velocity and wall shear stress direction in patients with bicuspid aortic valves and repaired coarctation using 4D flow cardiovascular magnetic resonance.

BACKGROUND: Helices and vortices in thoracic aortic blood flow measured with 4D flow cardiovascular magnetic resonance (CMR) have been associated with aortic dilation and aneurysms. Current approaches are semi-quantitative or when fully quantitative based on 2D plane placement. In this study, we present a fully quantitative and three-dimensional approach to map and quantify abnormal velocity and wall shear stress (WSS) at peak systole in patients with a bicuspid aortic valve (BAV) of which 52% had a repaired coarctation. METHODS: 4D flow CMR was performed in 48 patients with BAV and in 25 healthy subjects at a spatiotemporal resolution of 2.5 × 2.5 × 2.5mm3/ ~ 42 ms and TE/TR/FA of 2.1 ms/3.4 ms/8° with k-t Principal Component Analysis factor R = 8. A 3D average of velocity and WSS direction was created for the normal subjects. Comparing BAV patient data with the 3D average map and selecting voxels deviating between 60° and 120° and > 120° yielded 3D maps and volume (in cm3) and surface (in cm2) quantification of abnormally directed velocity and WSS, respectively. Linear regression with Bonferroni corrected significance of P < 0.0125 was used to compare abnormally directed velocity volume and WSS surface in the ascending aorta with qualitative helicity and vorticity scores, with local normalized helicity (LNH) and quantitative vorticity and with patient characteristics. RESULTS: The velocity volumes > 120° correlated moderately with the vorticity scores (R ~ 0.50, P < 0.001 for both observers). For WSS surface these results were similar. The velocity volumes between 60° and 120° correlated moderately with LNH (R = 0.66) but the velocity volumes > 120° did not correlate with quantitative vorticity. For abnormal velocity and WSS deviating between 60° and 120°, moderate correlations were found with aortic diameters (R = 0.50-0.70). For abnormal velocity and WSS deviating > 120°, additional moderate correlations were found with age and with peak velocity (stenosis severity) and a weak correlation with gender. Ensemble maps showed that more than 60% of the patients had abnormally directed velocity and WSS. Additionally, abnormally directed velocity and WSS was higher in the proximal descending aorta in the patients with repaired coarctation than in the patients where coarctation was never present. CONCLUSION: The possibility to reveal directional abnormalities of velocity and WSS in 3D provides a new tool for hemodynamic characterization in BAV disease.

Determinants of Physical Fitness in Children with Repaired Congenital Heart Disease.

The aim of this study was to determine factors associated with physical fitness (PF) in children who underwent surgery for congenital heart disease (CHD). Sixty-six children (7-14 years) who underwent surgery for ventricular septal defect (n = 19), transposition of great arteries (n = 22), coarctation of aorta (n = 10), and tetralogy of Fallot (n = 15) were included. All children performed PF tests: cardiorespiratory fitness, upper- and lower-limb muscle strength, speed, balance, and flexibility. Cardiac evaluation was done via echocardiography and cardiopulmonary exercise test. Factors related to child's characteristics, child's lifestyle, physical activity motivators/barriers, and parental factors were assessed. Linear regression analyses were conducted. The results showed no significant differences in physical activity (PA) level by CHD type. Boys had better cardiorespiratory fitness (difference = 1.86 ml/kg/min [0.51;3.22]) and were more physically active (difference = 19.40 min/day [8.14;30.66]), while girls had better flexibility (difference = - 3.60 cm [- 7.07;- 0.14]). Physical activity motivators showed an association with four out of six PF components: cardiorespiratory fitness, coefficient = 0.063 [0.01;0.11]; upper-limb muscle strength, coefficient = 0.076 [0.01;0.14]; lower-limb muscle strength, coefficient = 0.598 [0.07;1.13]; and speed, coefficient = 0.03 [0.01;0.05]. Age, sex, and motivators together reached a maximum adjusted R2 = 0.707 for upper-limb strength. Adding other possible determinants did not significantly increase the explained variance. Apart from age and sex as non-modifiable determinants, the main target which might improve fitness would be the introduction of an intervention which increases the motivation to be active.

Thoracic Endografting for Aortic Occlusion after Coarctation Surgery.

Acute occlusion of the descending thoracic aorta (DTA) is rare and associated with high morbidity and mortality. In the case described here, rescue thoracic endovascular aortic repair (TEVAR) was successful in a 59-year-old man with acute occlusion of the DTA accompanied by lower body hypoperfusion after two previous open repairs for aortic coarctation.

Implications of Left Ventricular Dysfunction at Presentation for Infants with Coarctation of the Aorta.

Infants with aortic coarctation may present with left ventricular (LV) dysfunction which may complicate the postoperative course and lead to increased healthcare costs. We aimed to define the prevalence of moderate to severe left ventricular (LV) systolic dysfunction, evaluate time to recovery, and compare health care costs. Single-center retrospective cohort study at a tertiary care hospital was conducted. Infants < 6 months old at diagnosis with aortic coarctation were identified using surgical codes for coarctation repair between January 2010 and May 2018. Moderate to severe dysfunction was defined as ejection fraction (EF) < 40%. Of 160 infants studied, 18 (11%) had moderate to severe LV dysfunction at presentation. Compared to those with better LV function, infants with moderate to severe LV dysfunction were older at presentation (12 vs. 6 days, p = 0.004), had more postoperative cardiac intensive care unit (ICU) days (5 vs. 3, p < 0.001), and more ventilator days (3.5 vs. 1, p < 0.001). The median time to normal LV EF (≥ 55%) was 6 days postoperatively (range 1-230 days). Infants presenting with moderate to severe LV dysfunction had higher index hospitalization costs ($90,560 vs. $59,968, p = 0.02), but no difference in cost of medical follow-up for the first year following discharge ($3,078 vs. $2,568, p = 0.46). In the current era, > 10% of infants with coarctation present with moderate to severe LV dysfunction that typically recovers. Those with moderate to severe dysfunction had longer duration of mechanical ventilation and postoperative cardiac ICU stays, likely driving higher costs of index hospitalization.

Aorta size mismatch predicts decreased exercise capacity in patients with successfully repaired coarctation of the aorta.

OBJECTIVE: Coarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair with no residual stenosis; however, the hemodynamic mechanism remains unknown. This study aims to correlate aortic arch geometry with exercise capacity in patients with successfully repaired CoA and explain hemodynamic changes using 3-dimensional-printed aorta models in a mock circulatory flow loop. METHODS: A retrospective chart review identified patients with CoA repair who had cardiac magnetic resonance imaging and an exercise stress test. Measurements included aorta diameters, arch height to diameter ratio, left ventricular function, and percent descending aorta (%DAo) flow. Each aorta was printed 3-dimensionally for the flow loop. Flow and pressure were measured at the ascending aorta (AAo) and DAo during simulated rest and exercise. Measurements were correlated with percent predicted peak oxygen consumption (VO2 max). RESULTS: Fifteen patients (mean age 26.8 ± 8.6 years) had a VO2 max between 47% and 126% predicted (mean 92 ± 20%) with normal left ventricular function. DAo diameter and %DAo flow positively correlated with VO2 (P = .007 and P = .04, respectively). AAo to DAo diameter ratio (DAAo/DDAo) negatively correlated with VO2 (P < .001). From flow loop simulations, the ratio of %DAo flow in exercise to rest negatively correlated with VO2 (P = .02) and positively correlated with DAAo/DDAo (P < .01). CONCLUSIONS: This study suggests aorta size mismatch (DAAo/DDAo) is a novel, clinically important measurement predicting exercise capacity in patients with successful CoA repair, likely due to increased resistance and altered flow distribution. Aorta size mismatch and %DAo flow are targets for further clinical evaluation in repaired CoA.

Assessment of hemodynamic responses to exercise in aortic coarctation using MRI-ergometry in combination with computational fluid dynamics.

In patients with aortic coarctation it would be desirable to assess pressure gradients as well as information about blood flow profiles at rest and during exercise. We aimed to assess the hemodynamic responses to physical exercise by combining MRI-ergometry with computational fluid dynamics (CFD). MRI was performed on 20 patients with aortic coarctation (13 men, 7 women, mean age 21.5 ± 13.7 years) at rest and during ergometry. Peak systolic pressure gradients, wall shear stress (WSS), secondary flow degree (SFD) and normalized flow displacement (NFD) were calculated using CFD. Stroke volume was determined based on MRI. On average, the pressure gradient was 18.0 ± 16.6 mmHg at rest and increased to 28.5 ± 22.6 mmHg (p < 0.001) during exercise. A significant increase in cardiac index was observed (p < 0.001), which was mainly driven by an increase in heart rate (p < 0.001). WSS significantly increased during exercise (p = 0.006), whereas SFD and NFD remained unchanged. The combination of MRI-ergometry with CFD allows assessing pressure gradients as well as flow profiles during physical exercise. This concept has the potential to serve as an alternative to cardiac catheterization with pharmacological stress testing and provides hemodynamic information valuable for studying the pathophysiology of aortic coarctation.