The Cardiovascular Implications of Thoracic Endovascular Aortic Repair: how aortic stenting impacts LV function and coronary artery flow

Aortic stents are known to have harmful effects on the cardiovascular system. They augment left ventricular function by decreasing aortic compliance. How these cardiovascular parameters change during and immediately after deployment of aortic stents has not been rigorously quantified, despite the development of heart failure in as many as 40% of post-TEVAR survivors within one-year. Without a comprehensive understanding of how the cardiovascular system changes in response to aortic stenting, surgical or medical strategies to augment prevent these changes cannot be developed. The goal of this study is to evaluate alterations in cardiovascular physiology that develop during and after total aortic endografting in a swine model. We will employ left ventricular (LV) pressure-volume (PV) loop analysis, which provides comprehensive pump mechanical information about LV function including stroke work and cardiac output, coupled with direct coronary flow measurements to understand how these parameters change when an aortic stent is placed. Our hypotheses are that aortic stenting: 1) is associated with decreased aortic compliance and increased LV afterload, 2) augments the LV end systolic pressure relationship (i.e., stroke work and end systolic pressure increase) and 3) increases coronary blood flow but decreases the coronary flow/cardiac output ratio.

Disparate Information Provided by Pulse Wave Velocity versus Other Measures of Aortic Compliance in End-Stage Renal Disease

<b><i>Introduction:</i></b> Unfavorable changes in cardiac and arterial function are related to poor prognosis in chronic kidney disease (CKD). We compared hemodynamic profiles between subjects with end-stage renal disease and 2 control groups with corresponding pulse wave velocities (PWVs). <b><i>Methods:</i></b> Noninvasive hemodynamics were recorded during passive head-up tilt in CKD stage 5 patients (<i>n</i> = 35), patients with primary hypertension (<i>n</i> = 35, <i>n</i> = 30 with antihypertensive medications), and subjects without cardiovascular or renal diseases and cardiovascular medications (<i>n</i> = 70). The groups were selected to have corresponding age, sex, body mass index, and PWV. Hemodynamic data were captured using whole-body impedance cardiography and radial tonometric pulse wave analysis. <b><i>Results:</i></b> Supine blood pressure did not differ between the groups, but upright diastolic blood pressure was lower in CKD patients than in the 2 control groups (<i>p</i> ≤ 0.001 for both, RANOVA). Despite similar PWV, supine aortic pulse pressure was higher in CKD patients versus nonmedicated subjects (<i>p</i> = 0.029). Two additional measures indicated reduced aortic compliance in CKD patients versus both control groups: lower ratio of stroke index to aortic pulse pressure (<i>p</i> ≤ 0.023) and higher aortic characteristic impedance (<i>p</i> ≤ 0.003). The subendocardial viability ratio was lower in the CKD group than in both control groups (<i>p</i> ≤ 0.039). <b><i>Conclusion:</i></b> In the absence of differences in PWV, higher aortic pulse pressure and characteristic impedance, and lower ratio of stroke index to aortic pulse pressure, suggest reduced aortic compliance and impaired left ventricular function in CKD patients. A lower subendocardial viability ratio predisposes the CKD patients to impaired cardiac oxygen supply versus hypertensive patients and nonmedicated controls.

Acute and Long-Term Effects of Aortic Compliance Decrease on Central Hemodynamics: A Modeling Analysis

Aortic compliance is an important determinant of cardiac afterload and a contributor to cardiovascular morbidity. In the present study, we sought to provide in silico insights into the acute as well as long-term effects of aortic compliance decrease on central hemodynamics. To that aim, we used a mathematical model of the cardiovascular system to simulate the hemodynamics (a) of a healthy young adult (baseline), (b) acutely after banding of the proximal aorta, (c) after the heart remodeled itself to match the increased afterload. The simulated pressure and flow waves were used for subsequent wave separation analysis. Aortic banding induced hypertension (SBP 106 mmHg at baseline versus 152 mmHg after banding), which was sustained after left ventricular (LV) remodeling. The main mechanism that drove hypertension was the enhancement of the forward wave, which became even more significant after LV remodeling (forward amplitude 30 mmHg at baseline versus 60 mmHg acutely after banding versus 64 mmHg after remodeling). Accordingly, the forward wave’s contribution to the total pulse pressure increased throughout this process, while the reflection coefficient acutely decreased and then remained roughly constant. Finally, LV remodeling was accompanied by a decrease in augmentation index (AIx 13% acutely after banding versus −3% after remodeling) and a change of the central pressure wave phenotype from the characteristic Type A (“old”) to Type C (“young”) phenotype. These findings provide valuable insights into the mechanisms of hypertension and provoke us to reconsider our understanding of AIx as a solely arterial parameter.

Limited Effect of 60-Days Strict Head Down Tilt Bed Rest on Vascular Aging

BackgroundCardiovascular risk may be increased in astronauts after long term space flights based on biomarkers indicating premature vascular aging. We tested the hypothesis that 60 days of strict 6° head down tilt bed rest (HDTBR), an established space analog, promotes vascular stiffening and that artificial gravity training ameliorates the response.MethodsWe studied 24 healthy participants (8 women, 24–55 years, BMI = 24.3 ± 2.1 kg/m2) before and at the end of 60 days HDTBR. 16 subjects were assigned to daily artificial gravity. We applied echocardiography to measure stroke volume and isovolumetric contraction time (ICT), calculated aortic compliance (stroke volume/aortic pulse pressure), and assessed aortic distensibility by MRI. Furthermore, we measured brachial-femoral pulse wave velocity (bfPWV) and pulse wave arrival times (PAT) in different vascular beds by blood pressure cuffs and photoplethysmography. We corrected PAT for ICT (cPAT).ResultsIn the pooled sample, diastolic blood pressure (+8 ± 7 mmHg, p &lt; 0.001), heart rate (+7 ± 9 bpm, p = 0.002) and ICT (+8 ± 13 ms, p = 0.036) increased during HDTBR. Stroke volume decreased by 14 ± 15 ml (p = 0.001). bfPWV, aortic compliance, aortic distensibility and all cPAT remained unchanged. Aortic area tended to increase (p = 0.05). None of the parameters showed significant interaction between HDTBR and artificial gravity training.Conclusion60 days HDTBR, while producing cardiovascular deconditioning and cephalad fluid shifts akin to weightlessness, did not worsen vascular stiffness. Artificial gravity training did not modulate the response.

Abstract 14090: Multiparity is Associated With Aortic Pathology in Women From the Dallas Heart Study

Introduction: The proximal aorta has been shown to enlarge with aging in humans, but the long-term impact of hormonal and hemodynamic changes associated with pregnancy on aortic size and function are unknown. We examined if number of live births was independently associated with aortic dimensions and stiffness in a healthy multi-ethnic population-based cohort, the Dallas Heart Study (DHS). We hypothesized that multiparity (>/=4 live births) is independently associated with aortic dilation and aortic stiffness after adjustment for CV risk factors. Methods: Women with available thoracic aortic MRI measurements (n=1468, mean 44.5 years old) from DHS were stratified based on self-reported number of live births (0,1,2,3,>/=4). Sequential multivariable logistic regression models were used to assess independent associations of the number of live births with ascending aortic cross-sectional area/height, aortic pulse wave velocity (PWV) and aortic compliance. Models were adjusted for major CV risk factors. Results: Women with >/=4 live births were older, more likely to be Black, and had higher blood pressure, triglycerides and body mass index. Compared with nulliparous women, women with >/=4 had larger ascending aortic areas indexed to height [5.19 vs 4.74 cm2/m; p<0.0001; Table 1]. After adjustment for risk factors, multiparity remained a significant predictor of aortic size. Compared to nulliparous women, women with >/=4 live births also had higher aortic PWV (5.54 vs 4.54 m/s; p<0.0001) and lower aortic compliance (21.9 vs 27.2 mL/mmHg; p 0.0002), but these relationships were no longer significant after multivariable adjustment (Table 1). Analyzing live births as a continuous variable did not change these results. Conclusions: Multiparity was associated with thoracic aortic enlargement, independent of age and relevant risk factors. Parity is an emerging sex-specific risk factor in cardiovascular disease that may have an impact on aortic remodeling in women.

Two Methods to Assess Aortic Compliance Using Blood Pressure and Pulse-Wave Velocity

Aortic compliance has been well established as an independent predictor of cardiovascular morbidity and mortality. The current "gold standard" for assessing aortic compliance is to use the carotid-femoral pulse-wave velocity (PWV) as a surrogate; however, PWV alone has been discussed in the literature as being inadequate for assessing compliance, especially for elderly patients and others who have a stiff aorta. In this paper an equation for the aortic compliance is developed using two approaches: 1) lumped-parameter modeling based on blood-pressure data and 2) distributed modeling based on the PWV. In-vitro experiments are conducted using a silicone-rubber tube which simulates the aorta, and an actual aorta harvested from a 1-year old, Holstein heifer. For both the rubber aorta and the Holstein aorta, a comparison is made between the blood-pressure model and the PWV model. In conclusion it is shown that good agreement exists between the two models, suggesting that either model may be used depending upon the available data. Furthermore, due to differences in material properties, it is shown that the compliance of the rubber aorta increases with mean arterial-pressure, while the compliance of the Holstein aorta decreases with mean arterial-pressure. Clinical implications of this research are also discussed.

4242 Evaluating the effect of a compliant stent-graft prototype on effective stiffness in a cadaveric aorta

OBJECTIVES/GOALS: High aortic stiffness is associated with increased cardiovascular morbidity and mortality. The purpose of this work is to demonstrate the potential of our compliant stent-graft design to therapeutically increase aortic compliance over a standard aortic stent-graft. METHODS/STUDY POPULATION: The aorta from a human cadaver will be excised and placed into a pulse duplicator circuit. The stiffness of the system will be estimated using the pulse wave velocity (PWV), which will be calculated using the time delay between pressure measurements at proximal and distal locations in the system. Baseline measurements with the unstented aorta will be compared to two cases: (1) with a standard stent-graft placed, and (2) with our compliant stent-graft prototype in the descending thoracic aorta. PWV is calculated as the distance between the pressure sensors divided by the time delay. Faster PWV is associated with a stiffer vessel, or lower aortic compliance. RESULTS/ANTICIPATED RESULTS: Prior work in vitro showed that the compliant stent-graft reduced peak and pulse pressures compared a standard, rigid stent-graft. We also expect the compliant device to exhibit lower PWV compared to a rigid stent-graft. Depending on the aortic tissue stiffness, the compliant stent-graft could raise or lower PWV compared to no stent. Mean pressure in the compliant case is likely to be slightly higher than the other two cases because the compliant stent-graft’s narrower lumen increases flow resistance. Although mean pressure will be higher, peak pressure should be lower than in the standard stent-graft because the added compliance decreases overall pressure swing between systole and diastole. DISCUSSION/SIGNIFICANCE OF IMPACT: Lower PWV in the compliant stent-graft over the standard stent-graft will indicate its potential to therapeutically lower aortic stiffness in patients needing aortic stenting. Positive outcomes from this study will be a step toward the eventual translation of a compliant stent-graft to clinical use.