Fluid Dynamics of Coarctation of the Aorta and Effect of Bicuspid Aortic Valve

Up to 80% of patients with coarctation of the aorta (COA) have a bicuspid aortic valve (BAV). Patients with COA and BAV have elevated risks of aortic complications despite successful surgical repair. The development of such complications involves the interplay between the mechanical forces applied on the artery and the biological processes occurring at the cellular level. The focus of this study is on hemodynamic modifications induced in the aorta in the presence of a COA and a BAV. For this purpose, numerical investigations and magnetic resonance imaging measurements were conducted with different configurations: (1) normal: normal aorta and normal aortic valve; (2) isolated COA: aorta with COA (75% reduction by area) and normal aortic valve; (3) complex COA: aorta with the same severity of COA (75% reduction by area) and BAV. The results show that the coexistence of COA and BAV significantly alters blood flow in the aorta with a significant increase in the maximal velocity, secondary flow, pressure loss, time-averaged wall shear stress and oscillatory shear index downstream of the COA. These findings can contribute to a better understanding of why patients with complex COA have adverse outcome even following a successful surgery.     

A new approach for the evaluation of the severity of coarctation of the aorta using Doppler velocity index and effective orifice area: in vitro validation and clinical implications

Early detection and accurate estimation of COA severity are the most important predictors of successful long-term outcome. However, current clinical parameters used for the evaluation of the severity of COA have several limitations and are flow dependent. The objectives of this study are to evaluate the limitations of current existing parameters for the evaluation of the severity of coarctation of the aorta (COA) and suggest two new parameters: COA Doppler velocity index and COA effective orifice area. Three different severities of COAs were tested in a mock flow circulation model under various flow conditions and in the presence of normal and stenotic aortic valves. Catheter trans-COA pressure gradients and Doppler echocardiographic trans-COA pressure gradients were evaluated. COA Doppler velocity index was defined as the ratio of pre-COA to post-COA peak velocities measured by Doppler echocardiography. COA Doppler effective orifice area was determined using continuity equation. The results show that peak-to-peak trans-COA pressure gradient significantly increased with flow rate (from 83% to 85%). Peak Doppler pressure gradient also significantly increased with flow rate (80-85%). A stenotic or bicuspid aortic valve increased peak Doppler pressure gradient by 20-50% for a COA severity of 75%. Both COA Doppler velocity index and COA effective orifice area did not demonstrate significant flow dependence or dependence upon aortic valve condition. As a conclusion, COA Doppler velocity index and COA effective orifice area are flow independent and do not depend on aortic valve conditions. They can, then, more accurately predict the severity of COA.     

Hemodynamic Changes following Aortic Valve Bypass: A Mathematical Approach

Aortic valve bypass (AVB) has been shown to be a viable solution for patients with severe aortic stenosis (AS). Under this circumstance, the left ventricle (LV) has a double outlet. The objective was to develop a mathematical model capable of evaluating the hemodynamic performance following the AVB surgery. A mathematical model that captures the interaction between LV, AS, arterial system, and AVB was developed. This model uses a limited number of parameters that all can be non-invasively measured using patient data. The model was validated using in vivo data from the literature. The model was used to determine the effect of different AVB and AS configurations on flow proportion and pressure of the aortic valve and the AVB. Results showed that the AVB leads to a significant reduction in transvalvular pressure gradient. The percentage of flow through the AVB can range from 55.47% to 69.43% following AVB with a severe AS. LV stroke work was also significantly reduced following the AVB surgery and reached a value of around 1.2 J for several AS severities. Findings of this study suggest: 1) the AVB leads to a significant reduction in transvalvular pressure gradients; 2) flow distribution between the AS and the AVB is significantly affected by the conduit valve size; 3) the AVB leads to a significant reduction in LV stroke work; and 4) hemodynamic performance variations can be estimated using the model.     

Aortic wave dynamics and its influence on left ventricular workload

The pumping mechanism of the heart is pulsatile, so the heart generates pulsatile flow that enters into the compliant aorta in the form of pressure and flow waves. We hypothesized that there exists a specific heart rate at which the external left ventricular (LV) power is minimized. To test this hypothesis, we used a computational model to explore the effects of heart rate (HR) and aortic rigidity on left ventricular (LV) power requirement. While both mean and pulsatile parts of the pressure play an important role in LV power requirement elevation, at higher rigidities the effect of pulsatility becomes more dominant. For any given aortic rigidity, there exists an optimum HR that minimizes the LV power requirement at a given cardiac output. The optimum HR shifts to higher values as the aorta becomes more rigid. To conclude, there is an optimum condition for aortic waves that minimizes the LV pulsatile load and consequently the total LV workload.     

Non-Invasive Determination of Left Ventricular Workload in Patients with Aortic Stenosis Using Magnetic Resonance Imaging and Doppler Echocardiography

Early detection and accurate estimation of aortic stenosis (AS) severity are the most important predictors of successful long-term outcomes in patients. Current clinical parameters used for evaluation of the AS severity have several limitations including flow dependency. Estimation of AS severity is specifically challenging in patients with low-flow and low transvalvular pressure gradient conditions. A proper diagnosis in these patients needs a comprehensive evaluation of the left ventricle (LV) hemodynamic loads. This study has two objectives: (1) developing a lumped-parameter model to describe the ventricular-valvular-arterial interaction and to estimate the LV stroke work (SW); (2) introducing and validating a new index, the normalized stroke work (N-SW), to assess the global hemodynamic load imposed on the LV. N-SW represents the global hemodynamic load that the LV faces for each unit volume of blood ejected. The model uses a limited number of parameters which all can be measured non-invasively using current clinical imaging modalities. The model was first validated by comparing its calculated flow waveforms with the ones measured using Cardiovascular Magnetic Resonance (CMR) in 49 patients and 8 controls. A very good correlation and concordance were found throughout the cycle (median root mean square: 12.21 mL/s) and between the peak values (r = 0.98; SEE = 0.001, p<0.001). The model was then used to determine SW using the parameters measured with transthoracic Doppler-echocardiography (TTE) and CMR. N-SW showed very good correlations with a previously-validated index of global hemodynamic load, the valvular arterial impedance (), using data from both imaging modalities (TTE: r = 0.82, SEE = 0.01, p<0.001; CMR: r = 0.74, SEE = 0.01, p<0.001). Furthermore, unlike , N-SW was almost independent from variations in the flow rate. This study suggests that considering N-SW may provide incremental diagnostic and prognostic information, beyond what standard indices of stenosis severity and provide, particularly in patients with low LV outflow.     

Gender Difference in Ventricular Response to Aortic Stenosis: Insight from Cardiovascular Magnetic Resonance

Background

Although left ventricular hypertrophy (LVH) and remodeling is associated with cardiac mortality and morbidity, little is known about the impact of gender on the ventricular response in aortic stenosis (AS) patients. This study aimed to analyze the differential effect of gender on ventricular remodeling in moderate to severe AS patients.

Methods and Results

A total of 118 consecutive patients (67±9 years; 63 males) with moderate or severe AS (severe 81.4%) underwent transthoracic echocardiography and cardiovascular magnetic resonance (CMR) within a 1-month period in this two-center prospective registry. The pattern of LV remodeling was assessed using the LV mass index (LVMI) and LV remodeling index (LVRI; LV mass/LV end-diastolic volume) by CMR. Although there were no differences in AS severity parameters nor baseline characteristics between genders, males showed a significantly higher LVMI (102.6±29.1g/m² vs. 86.1±29.2g/m², p=0.003) and LVRI (1.1±0.2 vs. 1.0±0.3, p=0.018), regardless of AS severity. The LVMI was significantly associated with aortic valve area (AVA) index and valvuloarterial impedance in females, whereas it was not in males, resulting in significant interaction between genders (PInteraction=0.007/0.014 for AVA index/valvuloarterial impedance, respectively). Similarly, the LVRI also showed a significantly different association between male and female subjects with the change in AS severity parameters (PInteraction=0.033/<0.001/0.029 for AVA index/transaortic mean pressure gradient/valvuloarterial impedance, respectively).

Conclusion

Males are associated with greater degree of LVH and higher LVRI compared to females at moderate to severe AS. However, females showed a more exaggerated LV remodeling response, with increased severity of AS and hemodynamic loads, than males.     

Effects of sodium nitroprusside in aortic stenosis associated with severe heart failure: pressure-volume loop analysis using a numerical model

In the recently published clinical study [Use of Nitroprusside in Left Ventricular Dysfunction and Obstructive Aortic Valve Disease (UNLOAD)], sodium nitroprusside (SNP) improved cardiac function in patients with severe aortic stenosis (AS) and left ventricular (LV) systolic dysfunction. We explored the possible mechanisms of these findings using a series of numerical simulations. A closed-loop lumped parameters model that consists of 24 differential equations relating pressure and flow throughout the circulation was used to analyze the effects of varying hemodynamic conditions in AS. Hemodynamic data from UNLOAD study subjects were used to construct the initial simulation. Systemic vascular resistance (SVR), heart rate, and aortic valve area were directly entered into the model while end-systolic and end-diastolic pressure-volume (P-V) relationships were adjusted using previously published data to match modeled and observed end-systolic and end-diastolic pressures and volumes. Initial simulation of SNP treatment by a reduction of SVR was not adequate. To obtain realistic model hemodynamics that reliably reproduce SNP treatment effects, we performed a series of simulations while simultaneously changing end-systolic elastance (E(es)), end-systolic volume at zero pressure (V(0)), and diastolic P-V shift. Our data indicate that either an E(es) increase or V(0) decrease is necessary to obtain realistic model hemodynamics. In five patients, we corroborated our findings by using the model to duplicate individual P-V loops obtained before and during SNP treatment. In conclusion, using a numerical model, we identified ventricular function parameters that are responsible for improved hemodynamics during SNP infusion in AS with LV dysfunction.     

The influence of artery wall curvature on the anatomical assessment of stenosis severity derived from fractional flow reserve: a computational fluid dynamics study

This study aims to investigate the influence of artery wall curvature on the anatomical assessment of stenosis severity and to identify a region of misinterpretation in the assessment of per cent area stenosis (AS) for functionally significant stenosis using fractional flow reserve (FFR) as standard. Five artery models of different per cent AS severity (70, 75, 80, 85 and 90%) were considered. For each per cent AS severity, the angle of curvature of the arterial wall varied from straight to an increasingly curved model (0°, 30°, 60°, 90° and 120°). Computational fluid dynamics was performed under transient physiologic hyperemic flow conditions to investigate the influence of artery wall curvature on the pressure drop and the FFR. The findings in this study may be useful in in vitro anatomical assessment of functionally significant stenosis. The FFR decreased with increasing stenosis severity for a given curvature of the artery wall. Moreover, a significant decrease in FFR was found between straight and curved models discussed for a given severity condition. These findings indicate that the curvature effect was included in the FFR assessment in contrast to minimum lumen area (MLA) or per cent AS assessment. The MLA or per cent AS assessment may lead to underestimation of stenosis severity. From this numerical study, an uncertainty region could be evaluated using the clinical FFR cutoff value of 0.8. This value was observed at 81.98 and 79.10% AS for arteries with curvature angles of 0° and 120° respectively. In conclusion, the curvature of the artery should not be neglected in in vitro anatomical assessment.     

Reverse flow in the major infrarenal vessels--a capacitive phenomenon

The arterial blood flow waveform is shown to change abruptly when passing from the thoracic aorta into the abdominal aorta in humans. Although this change has been accurately predicted by numerical solution of complicated pulse propagation equations, this paper demonstrates the ability of a simple lumped parameter model to explain this change in the waveforms using easily understood physical terms. The model correctly predicts changes in flow waveform under conditions of exercise and peripheral vascular disease. This analysis is useful in understanding abdominal artery physiology and explains the basis for clinical ultrasound Doppler examination of the legs.     

A Bio-Inspired Approach for the Reduction of Left Ventricular Workload

Previous studies have demonstrated the existence of optimization criteria in the design and development of mammalians cardiovascular systems. Similarities in mammalian arterial wave reflection suggest there are certain design criteria for the optimization of arterial wave dynamics. Inspired by these natural optimization criteria, we investigated the feasibility of optimizing the aortic waves by modifying wave reflection sites. A hydraulic model that has physical and dynamical properties similar to a human aorta and left ventricle was used for a series of in-vitro experiments. The results indicate that placing an artificial reflection site (a ring) at a specific location along the aorta may create a constructive wave dynamic that could reduce LV pulsatile workload. This simple bio-inspired approach may have important implications for the future of treatment strategies for diseased aorta.     

Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation

Inhibition of myocardial fatty acid oxidation can improve left ventricular (LV) mechanical efficiency by increasing LV power for a given rate of myocardial energy expenditure. This phenomenon has not been assessed at high workloads in nonischemic myocardium; therefore, we subjected in vivo pig hearts to a high workload for 5 min and assessed whether blocking mitochondrial fatty acid oxidation with the carnitine palmitoyltransferase-I inhibitor oxfenicine would improve LV mechanical efficiency. In addition, the cardiac content of malonyl-CoA (an endogenous inhibitor of carnitine palmitoyltransferase-I) and activity of acetyl-CoA carboxylase (which synthesizes malonyl-CoA) were assessed. Increased workload was induced by aortic constriction and dobutamine infusion, and LV efficiency was calculated from the LV pressure-volume loop and LV energy expenditure. In untreated pigs, the increase in LV power resulted in a 2.5-fold increase in fatty acid oxidation and cardiac malonyl-CoA content but did not affect the activation state of acetyl-CoA carboxylase. The activation state of the acetyl-CoA carboxylase inhibitory kinase AMP-activated protein kinase decreased by 40% with increased cardiac workload. Pretreatment with oxfenicine inhibited fatty acid oxidation by 75% and had no effect on cardiac energy expenditure but significantly increased LV power and LV efficiency (37 +/- 5% vs. 26 +/- 5%, P < 0.05) at high workload. In conclusion, 1) myocardial fatty acid oxidation increases with a short-term increase in cardiac workload, despite an increase in malonyl-CoA concentration, and 2) inhibition of fatty acid oxidation improves LV mechanical efficiency by increasing LV power without affecting cardiac energy expenditure.     

Transvalvular left ventricular pressure measurement in the isolated working rat heart.

A method of continuously measuring left ventricular (LV) pressure in an isolated buffer-perfused working rat heart is described. Transvalvular placement of a micromanometer through the aorta is the unique feature of this procedure. Advantages include catheter stability and lack of myocardial trauma. Changes in cardiac function were quantified by exposing hearts to either isoproterenol (10(-9) M) or halothane (1.5% vol/vol). To examine if any obstruction to LV outflow was caused by the micromanometer, cardiac performance was assessed during pullback from the ventricle to the aorta. Complications such as aortic insufficiency and ventricular arrhythmias were also studied. The results indicate that the transvalvular placement of a micromanometer can provide continuous, high-fidelity reproduction of LV pressure in this small-organ preparation. The presence of the micromanometer did not significantly alter cardiac performance, and proper catheter placement was achieved easily in a high percentage (> 90%) of cases.     

Endovascular stenting for aortic (re)coarctation in adults

Objectives. Stenting for native and recurrent coarctation (COA) in adults has become an important therapeutic strategy. In this prospective observational study we evaluated the intermediate-term outcome of stent implantation for either native or recurrent (re)COA in adults. Methods. All adults who underwent stent implantation in our institution between January 2003 and December 2008 were included. Diagnosis of (re)COA was based upon a combination of clinical signs, noninvasive imaging or invasive gradient measurements. NuMED stents were implanted under general anaesthesia. Results. Twenty-four patients (50% male) underwent stent implantation for native (n=6) or reCOA (n=18) at a median age of 36 (18 to 60) years. There was significant improvement in pre- versus post-stent invasive systolic gradient (19 vs. 0 mmHg, p<0.001) and COA diameter (10 vs. 16 mm, p<0.001). Acute complications (12.5%) included death due to aortic rupture despite immediate successful coverage with a covered stent (n=1) and groin haematoma (n=2). During a median follow-up period of 33 (8 to 77) months (n=22), late complications occurred in three patients (13.6%): stent migration to the ascending aorta (n=1), pseudoaneurysm at the site of the initial stent (n=1), and occluded external iliac artery (n=1). Stent implantation did not reduce the need for antihypertensive medication or blood pressure at last follow-up. Conclusion. COA stenting results in a significant gradient decrease and increase in vessel diameter. However, serious complications do occur and hypertension remains in the majority of patients. (Neth Heart J 2010;18:430-6.)     

Mechanical work of the left ventricle of the human heart

By means of the echocardiographic techniques, morphometric and functional parameters of the heart left ventricle (HLV) were studied in male humans aged 20 to 23, in resting and under the effect of a physical load. The total ventricle work was found to be about 1 J, the relative one (per 100 g of the LV mass)--0.6 J. The total working power was found to be about 70 Watt, the relative one--about 40 Watt. The physical load resulted in increase of the LV mechanical work parameters due to the heart rate and systolic arterial pressure.     

Transthoracic echocardiographic imaging of coronary arteries: tips, traps, and pitfalls

Background

This study explores the feasibility of non-invasive evaluation of left ventricular (LV) flow-volume dynamics using 3-dimensional (3D) echocardiography, and the capacity of such an approach to identify altered LV hemodynamic states caused by valvular abnormalities.

Methods

Thirty-one patients with moderate-severe aortic (AS) and mitral (MS) stenoses (21 and 10 patients, respectively) and 10 healthy volunteers underwent 3D echocardiography with full volume acquisition using Philips Sonos 7500 equipment. The digital 3D data were post- processed using TomTec software. LV flow-volume loops were subsequently constructed for each subject by plotting instantaneous LV volume data sampled throughout the cardiac cycle vs. their first derivative representing LV flow. After correction for body surface area, an average flow-volume loop was calculated for each subject group.

Results

Flow-volume loops were obtainable in all subjects, except 3 patients with AS. The flow-volume diagrams displayed clear differences in the form and position of the loops between normal individuals and the respective patient groups. In patients with AS, an "obstructive" pattern was observed, with lower flow values during early systole and larger end-systolic volume. On the other hand, patients with MS displayed a "restrictive" flow-volume pattern, with reduced diastolic filling and smaller end-diastolic volume.

Conclusion

Non-invasive evaluation of LV flow-volume dynamics using 3D-echocardiographic data is technically possible and the approach has a capacity to identify certain specific types of alteration of LV flow-volume pattern caused by valvular abnormalities, thus reflecting underlying hemodynamic states specific for these abnormalities.     

Left Ventricular Systolic Dysfunction in Asymptomatic Marfan Syndrome Patients Is Related to the Severity of Gene Mutation: Insights from the Novel Three Dimensional Speckle Tracking Echocardiography

Background

In asymptomatic Marfan syndrome (MFS) patients we evaluated the relationship between the types of fibrillin-1 (FBN1) gene mutation and possible altered left ventricular (LV) function as assessed by three-dimensional speckle tracking echocardiography (3D-STE).

Methods and Results

Forty-five MFS patients (mean age 24±15 years) and 40 age-matched healthy controls were studied. Genetic evaluation for the FBN1 gene was carried on 32 MFS patients. Gene mutation (n = 15, 47%) was classified as mild when the mutation resulted in nearly normally functioning protein, while mutations resulting in abnormally function protein were considered to be severe (n = 17, 53%). All patients and controls underwent 3D-STE for evaluation of LV function by an echocardiographer blinded to the results of the genetic testing. Compared to controls, MFS patients had significantly lower 3D-STE derived LV ejection fraction (EF, 57.43±7.51 vs. 62.69±4.76%, p = 0.0001), global LV longitudinal strain (LS, 14.85±2.89 vs. 17.90±2.01%, p = 0.0001), global LV circumferential strain (CS, 13.93±2.81 vs. 16.82±2.17%, p = 0.0001) and global LV area strain (AS, 25.76±4.43 vs. 30.51±2.61%, p = 0.0001). Apart from the global LV LS all these parameters were significantly lower in patients with severe gene mutation than in those with mild mutation (p<0.05). In the multivariate linear regression analysis only the type of mutation had a significant influence on the 3D-STE derived LVEF (p = 0.017), global CS (p = 0.005) and global AS (p = 0.03).

Conclusions

In asymptomatic MFS patients latent LV dysfunction can be detected using 3D STE. The LV dysfunction is mainly related to the severity of gene mutation, suggesting possible primary cardiomyopathy in MFS patients.