Patient-Specific Modeling of Altered Coronary Artery Hemodynamics to Predict Morbidity in Patients with Anomalous Origin of a Coronary Artery

Anomalous aortic origin of a coronary artery (AAOCA) is a condition where a coronary artery arises from the opposite aortic sinus, often with acute angle of origin (AO). AAOCA is associated with ischemia.1 This is especially concerning when the anomalous coronary artery takes an intramural course within the aortic wall, creating the potential for distortion or compression. Unroofing surgery replaces a restrictive ostium and intramural segment with a large ostium from the appropriate sinus and aims to create a less acute AO. Although these anatomical features may alter coronary artery blood flow patterns, hemodynamic indices such as time averaged wall shear stress (TAWSS), oscillatory shear index (OSI) and fractional flow reserve (FFR) that impact a patient’s future risk for ischemia and morbidity 2–6 remain largely unexplored. We hypothesized that morphology of the anomalous coronary artery has a significant impact on local hemodynamics of AAOCA and aimed to 1) characterize hemodynamic alterations in AAOCA by patient-specific simulation of patients pre-operative and post-unroofing using advanced coronary artery boundary conditions, 2) assess the impact of AO on the severity of hemodynamic alterations, and 3) characterize the hemodynamic effect of proximal narrowing of the anomalous artery and hyperemic resistance of the downstream vasculature (HMR) on FFR. Findings from Aim 1 suggested that different flow patterns exist natively between right and left coronary arteries, a reduction in TAWSS is observed post-unroofing, and that unroofing may normalize TAWSS but with variance related to the AO. Data from Aim 2 indicated that AO alters TAWSS and OSI in simulations run from a patient-specific model with virtually rotated AOs. The arterial wall experienced lower TAWSS for more acute AO near the ostium. Distal to the ostium, arterial wall experienced higher TAWSS for more acute AO. Findings from Aim 3 showed that for a given narrowing, higher HMR resulted in higher FFR thereby mimicking the interaction of the upstream and downstream micro-vasculature resistance to regulate FFR for the first time using computational models of AAOCA. Virtual manipulation of the anomalous artery provided a direct comparison for the effect of the anatomic high-risk features. Collectively, these results serve as the foundation for larger studies of AAOCA that could correlate hemodynamics with outcomes for risk stratification and surgical evaluation

Partial vs. full support of the heart with a continuous-flow left ventricular assist device : implications for myocardial recovery.

INTRODUCTION: Heart failure is a major and growing public health concern. Although heart failure has been considered an inexorable and progressive disorder, emerging evidence suggests that some patients may have reversible left ventricular dysfunction. Indeed, recent reports have documented the potential for myocardial recovery in humans in response to prolonged mechanical circulatory support with a left ventricular assist device (LVAD). However, myocardial recovery remains uncommon, and a strategy of unloading the failing left ventricle with a continuous-flow (non-pulsatile) LVAD has not been specifically developed to promote favorable myocardial remodeling. As a preliminary investigation, we developed a bovine model of chronic, ischemic heart failure and quantified the effects of different levels of support with a continuous-flow LVAD on myocardial mechanoenergetics. METHODS: Normal cows (n=8) and cows with chronic, ischemic heart failure (n=9) were studied. To induce heart failure, 90 µm micro spheres were percutaneously injected into the left main coronary artery. Heart failure developed over 60 days. In an acute surgery, a continuous-flow LVAD was implanted and operated at Low Partial Support (~1.5 L/min support, aortic valve opening every beat), High Partial Support (~3 L/min support, aortic valve opening every beat) and Full Support (~5 L/min, aortic valve maintained closed, left ventricle maximally unloaded). Cardiac and systemic arterial hemodynamics were measured with flow probes and pressure catheters. Myocardial blood flow was mapped with 15 µm fluorescent-labeled microspheres. After termination, molecular and histological markers of heart failure were quantified. RESUL TS: In normal animals, increasing levels of non-pulsatile support deranged the profile of cardiac and arterial hemodynamics. As cardiac workload decreased, myocardial vascular resistance increased, and myocardial blood flow decreased. The ratio between blood supply and demand did not change and indicated appropriate coronary autoregulation and the presence of an intact coronary reserve. Animals with chronic, ischemic heart failure exhibited hallmark signs of severe left ventricular systolic dysfunction that included a 50% reduction in ejection fraction, left ventricular dilatation, decreased cardiac output and arterial pressures, decreased end-organ blood flow, severe myocardial fibrosis, myocyte hypertrophy, and increased myocardial apoptosis. In animals with chronic heart failure, increasing levels of non-pulsatile support similarly deranged the profile of cardiac and arterial hemodynamics. As cardiac workload decreased, myocardial vascular resistance increased. However myocardial blood flow did not change and indicated a lack of a coronary reserve. Importantly, during full but not partial support, the ratio between blood supply and demand improved significantly to levels observed in normal control animals. CONCLUSIONS: After the implantation of an LVAD, full but not partial support of the failing left ventricle with an LVAD normalizes the myocardial blood supply/demand relationship. In the immediate postoperative period, the left ventricle should be completely unloaded. Chronic studies are necessary to determine whether a transition to partial support may prevent myocardial atrophy and fibrosis that is seen with prolonged full support. Our bovine model of chronic, ischemic heart failure is appropriate for such a study

Advances in saccular aneurysm biomechanics : enlargement via rate-sensitive inelastic growth, bio-mathematical stages of aneurysm disease, and initiation profiles.

I have created the first simulation of saccular aneurysm initiation and development from a healthy artery geometry. It is capable of growing saccular aneurysm geometries from patient-specific data. My model describes aneurysm behavior in a way that bridges fields. I assume arteries are made of a rate-sensitive inelastic material which produces irreversible deformation when it is overstressed. The material is assumed to consist of a 3D hyperelastic background material embedded with 1D transversely-isotropic fibers. I optionally use a Winkler foundation term to model support of external organs and distinguish healthy tissue from diseased tissue. Lesions are defined as a local degradation of artery wall structure. My work suggests passive mechanisms of growth are insufficient for predicting saccular aneurysms. Furthermore, I identify a new concept of stages of aneurysm disease. The stages connect mathematical descriptions of the simulation with clinically-relevant changes in the modeled aneurysm. They provide an evocative framework through which clinical descriptions of arteries can be neatly matched with mathematical features of the model. The framework gives a common language of concepts---e.g., collagen fiber, pseudoelastic limit, inelastic strain, and subclinical lesion---through which researchers in different fields, with different terminologies, can engage in an ongoing dialog: under the model, questions in medicine can be translated into equivalent questions in mathematics. A new stage of “subclinical lesion” has been identified, with a suggested direction for future biomechanics research into early detection and treatment of aneurysms. This stage defines a preclinical aneurysm-producing lesion which occurs before any artery dilatation. It is a stage of aneurysm development involving microstructural changes in artery wall makeup. Under the model, this stage can be identified by its reduced strength: its structural support is still within normal limits, but presumably would perform more poorly in ex vivo failure testing than healthy tissue from the same individual. I encourage clinicians and biomechanicians to measure elastin degradation, and to build detailed multiscale models of elastin degradation profiles as functions of aging and tortuosity; and similarly for basal tone. I hope such measurements will to lead to early detection and treatment of aneurysms. I give specific suggestions of biological tissue experiments to be performed for improving and reinforming constitutive modeling techniques.Mechanical Engineerin

An optical coherence tomography and endothelial shear stress study of a novel bioresorbable bypass graft

Endothelial shear stress (ESS) plays a key role in the clinical outcomes in native and stented segments; however, their implications in bypass grafts and especially in a synthetic biorestorative coronary artery bypass graft are yet unclear. This report aims to examine the interplay between ESS and the morphological alterations of a biorestorative coronary bypass graft in an animal model. Computational fluid dynamics (CFD) simulation derived from the fusion of angiography and optical coherence tomography (OCT) imaging was used to reconstruct data on the luminal anatomy of a bioresorbable coronary bypass graft with an endoluminal "flap" identified during OCT acquisition. The "flap" compromised the smooth lumen surface and considerably disturbed the local flow, leading to abnormally low ESS and high oscillatory shear stress (OSI) in the vicinity of the "flap". In the presence of the catheter, the flow is more stable (median OSI 0.02384 versus 0.02635, p < 0.0001; maximum OSI 0.4612 versus 0.4837). Conversely, OSI increased as the catheter was withdrawn which can potentially cause back-and-forth motions of the "flap", triggering tissue fatigue failure. CFD analysis in this report provided sophisticated physiological information that complements the anatomic assessment from imaging enabling a complete understanding of biorestorative graft pathophysiology

Clinical quantitative cardiac imaging for the assessment of myocardial ischaemia

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality

Application of Patient-Specific Computational Fluid Dynamics in Coronary and Intra-Cardiac Flow Simulations: Challenges and Opportunities

The emergence of new cardiac diagnostics and therapeutics of the heart has given rise to the challenging field of virtual design and testing of technologies in a patient-specific environment. Given the recent advances in medical imaging, computational power and mathematical algorithms, patient-specific cardiac models can be produced from cardiac images faster, and more efficiently than ever before. The emergence of patient-specific computational fluid dynamics (CFD) has paved the way for the new field of computer-aided diagnostics. This article provides a review of CFD methods, challenges and opportunities in coronary and intra-cardiac flow simulations. It includes a review of market products and clinical trials. Key components of patient-specific CFD are covered briefly which include image segmentation, geometry reconstruction, mesh generation, fluid-structure interaction, and solver techniques

Incorporating the Aortic Valve into Computational Fluid Dynamics Models using Phase-Contrast MRI and Valve Tracking

The American Heart Association states about 2% of the general population have a bicuspid aortic valve (BAV). BAVs exist in 80% of patients with aortic coarctation (CoA) and likely influences flow patterns that contribute to long-term morbidity post-surgically. BAV patients tend to have larger ascending aortic diameters, increased risk of aneurysm formation, and require surgical intervention earlier than patients with a normal aortic valve. Magnetic resonance imaging (MRI) has been used clinically to assess aortic arch morphology and blood flow in these patients. These MRI data have been used in computational fluid dynamics (CFD) studies to investigate potential adverse hemodynamics in these patients, yet few studies have attempted to characterize the impact of the aortic valve on ascending aortic hemodynamics. To address this issue, this research sought to identify the impact of aortic valve morphology on hemodynamics in the ascending aorta and determine the location where the influence is negligible. Novel tools were developed to implement aortic valve morphology into CFD models and compensate for heart motion in MRI flow measurements acquired through the aortic valve. Hemodynamic metrics such as blood flow velocity, time-averaged wall shear stress (TAWSS), and turbulent kinetic energy (TKE) induced by the valve were compared to values obtained using the current plug inflow approach. The influence of heart motion on these metrics was also investigated, resulting in the underestimation of TAWSS and TKE when heart motion was neglected. CFD simulations of CoA patients exhibiting bicuspid and tricuspid aortic valves were performed in models including the aortic sinuses and patient-specific valves. Results indicated the aortic valve impacted hemodynamics primarily in the ascending aorta, with the BAV having the greatest influence along the outer right wall of the vessel. A marked increase in TKE is present in aortic valve simulations, particularly in BAV patients. These findings suggest that future CFD studies investigating altered hemodynamics in the ascending aorta should accurately replicate aortic valve morphology. Further, aortic valve disease impacts hemodynamics in the ascending aorta that may be a predictor of the development or progression of ascending aortic dilation and possible aneurysm formation in this region