False Lumen Flow Assessment by Magnetic Resonance Imaging and Long-Term Outcomes in Uncomplicated Aortic Dissection.

BACKGROUND: Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist. OBJECTIVES: The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters. METHODS: One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD. RESULTS: After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter >45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events. CONCLUSIONS: High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter >45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.

Postsystolic thickening is a potential new clinical sign of injured myocardium in marfan syndrome.

The mechanisms leading to cardiac remodeling in Marfan syndrome (MFS) are a matter of debate since it could be either due to structural dysfunction of the myocardial extracellular matrix or to increased afterload caused by the dilated aorta. We aim to characterize the presence of abnormal myocardial function in MFS and to investigate its potential association with increased afterload. Aorta, left ventricle (LV) and the postsystolic thickening (PST) were analyzed in echocardiography in Fbn1C1039G/+ mice and in patients with MFS in comparison with wild type (WT) mice and healthy humans. PST was more frequent in MFS than in WT mice (p < 0.05). MFS mice with PST showed larger aorta than those without PST. Patients with MFS showed larger aorta, poorer LV function and a higher prevalence of PST (56%) than did the healthy controls (23%); p = 0.003. Blood pressure was similar. The higher prevalence of PST in an experimental murine model and in MFS patients, regardless of systemic arterial pressure, suggests an increased afterload on the LV myocardium. This finding supports the use of PST as an indicator of myocardial damage and encourage searching for novel early preventive therapy.

False Lumen Flow Patterns and their Relation with Morphological and Biomechanical Characteristics of Chronic Aortic Dissections. Computational Model Compared with Magnetic Resonance Imaging Measurements.

Aortic wall stiffness, tear size and location and the presence of abdominal side branches arising from the false lumen (FL) are key properties potentially involved in FL enlargement in chronic aortic dissections (ADs). We hypothesize that temporal variations on FL flow patterns, as measured in a cross-section by phase-contrast magnetic resonance imaging (PC-MRI), could be used to infer integrated information on these features. In 33 patients with chronic descending AD, instantaneous flow profiles were quantified in the FL at diaphragm level by PC-MRI. We used a lumped-parameter model to assess the changes in flow profiles induced by wall stiffness, tear size/location, and the presence of abdominal side branches arising from the FL. Four characteristic FL flow patterns were identified in 31/33 patients (94%) based on the direction of flow in systole and diastole: BA = systolic biphasic flow and primarily diastolic antegrade flow (n = 6); BR = systolic biphasic flow and primarily diastolic retrograde flow (n = 14); MA = systolic monophasic flow and primarily diastolic antegrade flow (n = 9); MR = systolic monophasic flow and primarily diastolic retrograde flow (n = 2). In the computational model, the temporal variation of flow directions within the FL was highly dependent on the position of assessment along the aorta. FL flow patterns (especially at the level of the diaphragm) showed their characteristic patterns due to variations in the cumulative size and the spatial distribution of the communicating tears, and the incidence of visceral side branches originating from the FL. Changes in wall stiffness did not change the temporal variation of the flows whereas it importantly determined intraluminal pressures. FL flow patterns implicitly codify morphological information on key determinants of aortic expansion in ADs. This data might be taken into consideration in the imaging protocol to define the predictive value of FL flows.

Understanding the Aortic Isthmus Doppler Profile and Its Changes with Gestational Age Using a Lumped Model of the Fetal Circulation.

OBJECTIVE: The aortic isthmus (AoI) blood flow has a characteristic shape with a small end-systolic notch observed during the third trimester of pregnancy. However, what causes the appearance of this notch is not fully understood. We used a lumped model of the fetal circulation to study the possible factors causing the end-systolic notch and the changes of AoI flow through gestation. METHODS: A validation of the model was performed by fitting patient-specific data from two normal fetuses. Then, different parametric analyses were performed to evaluate the major determinants of the appearance of the end-systolic notch. The changes in the AoI flow profile through gestation were assessed. RESULTS: Our model allows to simulate the AoI waveform. The delay in the onset of ejection together with the longer ejection duration of the right ventricle are the most relevant factors in the origin of the notch. It appears around 25 weeks of gestation and becomes more pronounced with advancing gestation. DISCUSSION: We demonstrated that the end-systolic notch on the AoI flow occurs mainly as a result of a delayed and longer ejection of the right ventricle. Our findings improve the understanding of hemodynamic changes in the fetal circulation and the interpretation of clinical imaging.

Patient-specific estimates of vascular and placental properties in growth-restricted fetuses based on a model of the fetal circulation.

INTRODUCTION: Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood-flow redistribution in order to maintain perfusion to the brain. However, some hemodynamic parameters that might be more directly related to staging of the disease cannot be measured non-invasively in clinical practice. For this, we developed a patient-specific model of the fetal circulation to estimate vascular properties of each individual. METHODS: A lumped model of the fetal circulation was developed and personalized using measured echographic data from 37 normal and IUGR fetuses to automatically estimate model-based parameters. A multivariate regression analysis was performed to evaluate the association between the Doppler pulsatility indices (PI) and the model-based parameters. The correlation between model-based parameters and the placental lesions was analyzed in a set of 13 IUGR placentas. A logistic regression analysis was done to assess the added value of the model-based parameters relative to Doppler indices, for the detection of fetuses with adverse perinatal outcome. RESULTS: The estimated model-based placental and brain resistances were respectively increased and reduced in IUGR fetuses while placental compliance was increased in IUGR fetus. Umbilical and middle cerebral arteries PIs were most associated with both placental resistance and compliance, while uterine artery PI was more associated with the placental compliance. The logistic regression analysis showed that the model added significant information to the traditional analysis of Doppler waveforms for predicting adverse outcome in IUGR. DISCUSSION: The proposed patient-specific computational model seems to be a good approach to assess hemodynamic parameters than cannot be measured clinically.

Assessment of wall elasticity variations on intraluminal haemodynamics in descending aortic dissections using a lumped-parameter model.

Descending aortic dissection (DAD) is associated with high morbidity and mortality rates. Aortic wall stiffness is a variable often altered in DAD patients and potentially involved in long-term outcome. However, its relevance is still mostly unknown. To gain more detailed knowledge of how wall elasticity (compliance) might influence intraluminal haemodynamics in DAD, a lumped-parameter model was developed based on experimental data from a pulsatile hydraulic circuit and validated for 8 clinical scenarios. Next, the variations of intraluminal pressures and flows were assessed as a function of wall elasticity. In comparison with the most rigid-wall case, an increase in elasticity to physiological values was associated with a decrease in systolic and increase in diastolic pressures of up to 33% and 63% respectively, with a subsequent decrease in the pressure wave amplitude of up to 86%. Moreover, it was related to an increase in multidirectional intraluminal flows and transition of behaviour as 2 parallel vessels towards a vessel with a side-chamber. The model supports the extremely important role of wall elasticity as determinant of intraluminal pressures and flow patterns for DAD, and thus, the relevance of considering it during clinical assessment and computational modelling of the disease.

Validation of numerical flow simulations against in vitro phantom measurements in different type B aortic dissection scenarios.

An aortic dissection (AD) is a serious condition defined by the splitting of the arterial wall, thus generating a secondary lumen [the false lumen (FL)]. Its management, treatment and follow-up are clinical challenges due to the progressive aortic dilatation and potentially severe complications during follow-up. It is well known that the direction and rate of dilatation of the artery wall depend on haemodynamic parameters such as the local velocity profiles, intra-luminal pressures and resultant wall stresses. These factors act on the FL and true lumen, triggering remodelling and clinical worsening. In this study, we aimed to validate a computational fluid dynamic (CFD) tool for the haemodynamic characterisation of chronic (type B) ADs. We validated the numerical results, for several dissection geometries, with experimental data obtained from a previous in vitro study performed on idealised dissected physical models. We found a good correlation between CFD simulations and experimental measurements as long as the tear size was large enough so that the effect of the wall compliance was negligible.

A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up.

An in vitro phantom study on the influence of tear size and configuration on the hemodynamics of the lumina in chronic type B aortic dissections.

OBJECTIVE: Management and follow-up of chronic aortic dissections continue to be a clinical challenge due to progressive dilatation and subsequent rupture. To predict complications, guidelines suggest follow-up of aortic diameter. However, dilatation is triggered by hemodynamic parameters (pressures/wall shear stresses) and geometry of false (FL) and true lumen (TL), information not captured by diameter alone. Therefore, we aimed at better understanding the influence of dissection anatomy on TL and FL hemodynamics. METHODS: In vitro studies were performed using pulsatile flow in realistic dissected latex/silicone geometries with varying tear number, size, and location. We assessed three different conformations: (1) proximal tear only; (2) distal tear only; (3) both proximal and distal tears. All possible combinations (n = 8) of small (10% of aortic diameter) and large (25% of aortic diameter) tears were considered. Pressure, velocity, and flow patterns were analyzed within the lumina (at proximal and distal sections) and at the tears. We also computed the FL mean pressure index (FPI(mean)%) as a percentage of the TL mean pressure, to compare pressures among models. RESULTS: The presence of large tears equalized FL/TL pressures compared with models with only small tears (proximal FPI(mean)% 99.85 ± 0.45 vs 92.73 ± 3.63; distal FPI(mean)% 99.51 ± 0.80 vs 96.35 ± 1.96; P < .001). Thus, large tears resulted in slower velocities through the tears (systolic velocity <180 cm/s) and complex flows within the FL, whereas small tears resulted in lower FL pressures, higher tear velocities (systolic velocity >290 cm/s), and a well-defined flow. Additionally, both proximal and distal tears act as entry and exit. During systole, flow enters the FL through all tears simultaneously, while during diastole, flow leaves through all communications. Flow through the FL, from proximal to distal tears or vice versa, is minimal. CONCLUSIONS: Our results suggest that FL hemodynamics heavily depends on cumulative tear size, and thus, it is an important parameter to take into account when clinically assessing chronic aortic dissections.

Influence of tear configuration on false and true lumen haemodynamics in type B aortic dissection.

The management and follow-up of chronic type B aortic dissections continues being a clinical challenge. Patients with chronic type B dissection have high mid/long term mortality mainly due to progressive aortic dilatation and subsequent rupture.