Flow Dynamics in Anomalous Aortic Origin of a Coronary Artery in Children: Importance of the Intramural Segment

Abstract

This study aims to assess the differences in pressure, fractional flow reserve (FFR) and coronary flow (with increasing pressure) of the proximal coronary artery in patients with anomalous aortic origin of a coronary artery with a confirmed ischemic event, without ischemic events, and before and after unroofing surgery, and compare to a patient with normal coronary arteries. Patient-specific flow models were 3D printed for 3 subjects with anomalous right coronary arteries with intramural course, 2 of them had documented ischemia, and compared with a patient with normal coronaries. The models were placed in the aortic position of a pulse duplicator and precise measurements to quantify FFR and coronary flow rate were performed from the aortic to the mediastinal segment of the anomalous right coronary artery. In an ischemic model, a gradual FFR drop (emulating that of pressure) was shown from the ostium location (~1.0) to the distal intramural course (0.48). In nonischemic and normal patient models, FFR for all locations did not drop below 0.9. In a second ischemic model prior to repair, a drop to 0.44 was encountered at the intramural and mediastinal intersection, improving to 0.86 postrepair. There is a difference in instantaneous coronary flow rate with increasing aortic pressure in the ischemic models (slope 0.2846), compared to the postrepair and normal models (slope >0.53). These observations on patient models support a biomechanical basis for ischemia and potentially sudden cardiac death in aortic origin of a coronary artery, with a drop in pressure and FFR in the intramural segment, and a decrease in coronary flow rate with increasing aortic pressure, with both improving after corrective surgery.

Graphical Abstract

The intramural course in AAOCA is the likely location where FFR drop happens.

INTRODUCTION

Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden cardiac death (SCD) in children and young adults, which typically occurs with exercise.^1–3 SCD may occur with anomalous left or right coronary arteries, however the incidence is higher in the left AAOCA.^4,5 The critical barrier to progress is a lack of understanding of the exact mechanism leading to ischemia and/or SCD in these patients and the subsequent inability to perform accurate risk stratification and decide management.^6,7 Likely mechanisms of SCD include proximal coronary hypoplasia, dynamic ostial narrowing, intussusception of the intimal wall of the intramural segment, and interarterial compression during exercise. Clinical evaluation, imaging and functional testing are of limited value in risk stratification. Different types of surgical operations are available⁸ to try to prevent the risk of ischemia or SCD. These procedures include unroofing of an intramural (IM) course, ostioplasty, coronary translocation/reimplantation into the correct aortic sinus, and, in rare instances, coronary artery bypass grafting. Coronary unroofing has produced good short-/medium-term outcomes although long-term outcomes are still unknown.⁹ The decision to operate and the type of surgery performed for the same condition can vary significantly between centers due to lack of clarity on surgical approaches that target the offending mechanism.

Biomechanical modeling using precision medicine approaches offers a valid and innovative approach to studying AAOCA by focusing on the patient-specific pathological mechanism for SCD. Using in-vitro patient-specific 3D-printed aortocoronary models derived from advanced imaging, this study aims to assess the differences in coronary blood flow and hemodynamics in patients with right (R)-AAOCA with a confirmed ischemic event, without ischemic events, and before and after unroofing surgery, and compare to a patient with normal coronary arteries. The targeted end-points are (1) the fractional flow reserve (FFR) variations along the intramural course, (2) the pressure variations along the intramural course, and (3) the variations of flow with increasing pressure in the anomalous coronary artery. Our hypothesis is that the patient with a confirmed ischemic event will demonstrate a decrease in pressure, FFR, and coronary flow rate under exercise conditions when compared to normal or nonischemic R-AAOCA patients, and that these findings will resolve after unroofing surgery. Moreover, our hypothesis is that the coronary flow will be characterized by a smaller slope in the case of ischemia compared with nonischemic and post-unroofing cases (Fig. 1).

Figure 1.

3D reconstructions and CT images of the tested R-AAOCA models. The models generated (CTs and 3D reconstructions shown in Figure 1) were 3D printed using Agilus, a compliant material. Five models from 4 subjects were utilized for the study. Model 1 represents the case of a 16-year-old male with normal coronary artery anatomy; Model 2 represents the case of an 11-year-old male with R-AAOCA with a 12-mm intramural course, slit-like ostium and confirmed ischemia on stress testing; Model 3 represents the case of a 9-year-old male patient without ischemia with a 13-mm intramural course; Model 4 represents a preoperative study on a 15-year-old male patient with a 9-mm intramural course and Model 5 a postoperative study on the same patient as Model 4, after coronary unroofing procedure.

METHODS

Patient Data

Patient-specific flow models were created after segmenting computed tomography angiography (CTA) raw data under an Institutional Review Board (IRB) approved retrospective study. The study is performed under Nationwide Children’s Hospital IRB 18–01146 approved on 11/7/2018, CR00000522 approved on 4/1/2019, and STUDY00000525 approved on 7/29/2020. The need for informed consent for 3D printing, modeling, and study data publication was waived by the IRB for this retrospective study. Five models from 4 subjects born between 2003 and 2010 who presented for coronary artery clinic at Nationwide Children’s Hospital (NCH) in 2018/2019 were utilized for the study, with the patient details as follows:

Model 1: Asymptomatic 16-year-old male who had a previous history of Kawasaki disease 4 years earlier during which there was questionable mild ectasia of the right coronary artery on echocardiography (echo), which had resolved on a 2-week follow-up echo. He was lost to follow-up for 4 years and presented to the coronary clinic for clearance to play competitive basketball. He received a CTA to screen the status of the coronaries, which demonstrated a normal appearance of the coronary arteries.

Model 2: Eleven-year-old male with history of exertional syncope while playing with his friends recreationally. Evaluation by echo revealed anomalous origin of the right coronary artery from the left sinus. CTA showed R-AAOCA with a 12-mm intramural course, slit-like ostium, and course through the right-left column. Exercise myocardial perfusion SPECT testing showed a reversible perfusion defect in the right coronary artery distribution. Patient was referred to surgery and underwent successful unroofing, followed by return to full activity.

Model 3: Nine-year-old healthy male with history of prematurity 28 weeks, surfactant deficiency syndrome, and retinopathy of prematurity who has followed in cardiology clinic for a patent ductus arteriosus discovered in the neonatal period which had spontaneously resolved. He was incidentally found to have an R-AAOCA arising from the left coronary sinus on echo. He has been followed serially and has remained asymptomatic from a cardiac standpoint. CT showed that the dominant right coronary arises above the left sinus of Valsalva (just above the sinotubular junction (STJ) and to the left of the right-left commissure) with a slit like ostium and a 6-mm proximal intramural course. Exercise stress testing was negative. He was placed on restricted activity. Parents opted for surgery to facilitate return to normal activity. Surgery showed slit like orifice to the right coronary artery and a 7-mm long intramural segment, which was unroofed. Patient and had an uneventful recovery and returned to full activity.

Model 4 and Model 5: Preoperative and postoperative studies: 15-year-old male with remote history of asthma presented to the emergency department with influenza. Review of symptoms elicited a history of intermittent and inconsistent chest pain with activity, which triggered an electrocardiogram (ECG) that demonstrated biventricular hypertrophy. Evaluation by echo showed an R-AAOCA from the left sinus of Valsalva on echo, no ischemia on exercise stress test, but a restrictive pattern on pulmonary function testing. A CTA confirmed the diagnosis and showed a dominant right coronary artery (RCA) with a slit-like orifice with a 9-mm intramural course. A nuclear perfusion (SPECT scan) study showed a reversible perfusion defect in the apex and distal anterior wall, but normal perfusion in the expected RCA territory. Patient was referred to surgery, which confirmed findings and revealed an 8-mm intramural course, with a slit like orifice which was unroofed. Patient experienced acute sharp chest pain and emesis 3 days after surgery. An ECG done immediately thereafter showed significant ST elevation in inferior leads, and elevated troponin, consistent with RCA ischemia. He went for emergent CTA which showed good flow in both coronaries and no evidence of obstruction in proximal RCA. Troponin levels continue to decline and ST segment changes on ECG resolved. Cath revealed widely patent RCA repair and normal left coronary artery, with no evidence of distal filling defects. The ischemic event was attributed to either short-lived vasospasm or tiny clot that had propagated from repair site into the distal right coronary, and no other intervention was warranted. Patient has done well on follow up with return to full activity.

3D PRINTING AND MATERIAL PROPERTIES

Patient-specific flow models of the aorta and coronaries were created from CTA DICOM images using MIMICS (Materialise, Belgium). The 3D mesh files were used to create the stereolithographic file of the aortocoronary segment, which was augmented with inflow and outflow tubes to allow for connection to the flow pump. The stereolithographic files were exported to a Stratasys CONNEX 350 3D printer. Agilus 30, a compliant material with a shore hardness of 30–35 scale A, tensile strength ASTM D-412 2.4–3.1 MPa, elongation at Break of 220%–270%, and tensile tear resistance 4–7 (22–39 lb/in) per the manufacturer was chosen as the printing material. The printing material and process were similar to those adopted in previous publications.^10–14

A comparative cyclic test was performed between samples of 2mm Agilus coated with a thin layer of PU and a native aortic root tissue (Fig. 2a) obtained postmortem under various frequencies of 1, 1.5, 2, and 8 Hz in a mechanical testing setup (Instron, Norwood, MA; Fig. 2b). The dynamic moduli obtained were close to those of the native tissue (Fig. 2c).

Figure 2.

Material Testing to check for the properties of the 3D-printed models compared with a native aortic root tissue. (a) The native aortic tissue from a postmortem specimen; (b) The Instron mechanical testing setup (E3000 V1.4; Norwood, MA); (c) The dynamic modulus obtained after coating the models with a thin layer of polyurethane (PU) and (d) Flow loop schematic showing the pulsatile flow setup and the right coronary branch. It consists of a fluid reservoir, a bladder pump connected to a compressor controlled by a LabVIEW program, a bioprosthetic valve between the reservoir and the bladder pump playing the role of a mitral valve, the aortic root model, and a compliance chamber. A surgical bioprosthetic valve was placed at the entrance of the aortic root model to incorporate aortic valve function. The right coronary artery (RCA) circuit was designed by connecting the flow from the ostium to the main fluid reservoir. RCA flow at baseline was set by adjusting a resistance element to account for 30% of a ratio of 4%–5% of the cardiac output.

Flow Model Setup

The 5 models were placed in the aortic position of a left heart pulse duplicator under baseline exercise conditions of 90 beats per minute, a cardiac output of 5 L/min, and mean aortic pressure of 100 mm Hg. The fluid used was a blood analog made of a mixture of water and glycerin (60%–40% by volume). The fluid is characterized by the same viscosity and density as those of blood. The flow setup (Fig. 2d) consists of a fluid reservoir, a bladder pump connected to a compressor controlled by a LabVIEW program, a bioprosthetic valve between the reservoir and the bladder pump playing the role of a mitral valve, the aortic root model and a compliance chamber.^10–12,14 The pump bladder contracts and expands based on instructions given from the LABVIEW program. The program specifies the cardiac cycle intervals during which contraction and expansion take place. A surgical bioprosthetic valve was placed at the entrance of the aortic root model to incorporate aortic valve function. The right coronary vasculature does not undergo compressive forces during ventricle contraction and hence, follows the aortic pressure. Therefore, a Starling resistance mechanism was not needed to model the RCA. The RCA circuit was designed by connecting the flow from the ostium to the main fluid reservoir as shown in Figure 2d. RCA flow at baseline was set by adjusting a resistance element to account for 30% of a ratio of 4%–5% of the cardiac output as specified by other publications.¹⁵ The models were coated with a thin coat of polyurethane to improve clarity and prevention of water absorption during the flow simulation. The models were then placed in the aortic position in a box and encompassed in Gellywax (RBC industries) to simulate the mediastinal environment (Fig. 3a).

Figure 3.

The various locations of pressure measurements in the 3D-printed aortic root models. (a) The catheter (Millar catheter) location with respect to the experimental model is shown. The measurements were taken along the measurement points indicated on (b) starting from the aortic position until the mediastinal segment. FFR was computed as the ratio of distal pressure to aortic pressure.

Pressure, FFR, and Flow Measurements

Pressure and flow waveforms were recorded at 100 Hz using a Millar catheter along points starting in the aorta, through the slit-like ostium, intramural segment, and into the mediastinal segment (the portion of the anomalous coronary artery distal to the intramural segment that is fully encased by mediastinum fat) of the RCA (Fig. 3). FFR was computed as the ratio of distal pressure to aortic pressure. An FFR value lower than 0.75–0.8 was considered as the threshold for experimental ischemia.^13,16 A simulated stress test was performed, increasing the aortic pressure from 100 to ~200 mm Hg to observe effects of pressure-driven anatomical deformation on coronary flow and a linear fit was performed in each case to compare the resulting slopes.

RESULTS

For the 5 models that were studied, Figure 4 compares the pressure variations as a function of the cardiac cycle, Figure 5 compares the instantaneous FFR changes as a function of the cardiac cycle, and Figure 6 compares instantaneous flow rate versus aortic pressure.

Figure 4.

Pressure variations versus time for the (a) normal patient, (b) ischemic patient, (c) nonischemic patient, (d) ischemic pre-unroofing patient and (e) post-unroofing patient cases at different locations along the coronary artery. For Model 1, the variation in the pressure waveform was similar between the 6 measured locations with the proximal RCA, with only a small drop in pressure noted at the mediastinal segment. For Model 2, the patient with ischemia, there is a gradual pressure drop from the aortic position to the distal IM course, where the pressure reaches its minimum value, until it recovers from the IM and mediastinal intersection onward. For Model 3, the nonischemic model, the pressure drops stayed within the 80–120 mm Hg range across the length of the proximal RCA including the intramural segment. For Model 4, the patient undergoing surgical unroofing, there is a large drop in pressure within the intramural segment. For Model 5, following coronary unroofing surgery, there is complete resolution of the previously noted drop in pressure.

Figure 5.

Instantaneous FFR variations versus time for the (a) normal patient, (b) ischemic patient, (c) nonischemic patient, (d) ischemic pre-unroofing patient and (e) post-unroofing patient cases at different locations along the coronary artery. For Model 1, the minimum FFR recorded corresponds to the mediastinal segment location with a value of 0.89. For Model 2, the patient with ischemia, there is a gradual drop from the aorta/ostium junction (FFR ratio of 1.0) to the distal IM course (minimum FFR of 0.48), with a subsequent increase thereafter to reach an average of 0.8 in the mediastinal segment. For Model 3, in the nonischemic model, the instantaneous variations of the FFR for all locations did not drop below 0.9. For Model 4, the patient undergoing surgical unroofing, there is a large drop in FFR to 0.44 at the intramural/mediastinal junction. For Model 5, following coronary unroofing surgery, the FFR drop averages 0.91 with a minimum value of 0.86 in the mediastinal segment.

Figure 6.

Coronary flow rate variations as a function of aortic pressure for the 5 different model cases. A linear fit was implemented for each case. The highest slope was 0.5438 obtained in the normal patient (Model 1), followed by the patient after unroofing surgery (Model 5) with a slope of 0.5302, the nonischemic patient (Model 3) with a slope of 0.4706, the ischemic patient preoperatively (Model 4) with a slope of 0.3211, and the lowest slope obtained in the ischemic patient (Model 2) with a value of 0.2846.

Model 1: Figure 4a shows the pressure curve from the aortic end through the proximal RCA in a normal coronary model (model 1). The variation in the pressure waveform was similar between the six measured locations with the proximal RCA. The instantaneous FFR for the normal model is shown in Figure 5a, with a minimum recorded value of 0.89.

Model 2: In the patient with ischemia (model 2), there were clear differences in the pressure waveforms as shown in Figure 4b compared with those of the normal patient. There is a gradual pressure drop from the aortic position to the distal IM course, where the pressure reaches its minimum value, until it recovers from the IM and mediastinal intersection onwards. Figure 5b depicts FFR values in this ischemic model with a gradual drop from the aorta/ostium junction (FFR ratio of 1.0) to the distal IM course to reach a minimum FFR of 0.48, with a subsequent increase thereafter to reach an average of 0.8 in the mediastinal segment.

Model 3: In the nonischemic model, as shown in Figure 4c, the pressure drops stayed within the 80–120 mm Hg range across the length of the proximal RCA including the intramural segment. As shown in Figure 5c, the instantaneous variations of the FFR for all locations did not drop below 0.9.

Model 4: In the patient with inducible ischemia prior to surgical unroofing, there is a drop in pressure within the distal intramural segment shown on Figure 4d, associated with a drop in FFR to 0.44 at the intramural/mediastinal junction as shown in Figure 5d.

Model 5: Following coronary unroofing surgery, there is complete resolution of the previously noted drop in pressure as shown on Figure 4e. Postoperatively, the FFR drop averages 0.91 with a minimum value of 0.86 as depicted in Figure 5e.

Coronary flow rate: Figure 6 shows the variation of coronary flow rate versus aortic pressure. A linear fit (best fit) was implemented for each case. The highest slope was 0.5438 obtained in the normal patient (model 1), followed by the patient after unroofing surgery (model 5) with a slope of 0.5302, the nonischemic patient (model 3) with a slope of 0.4706, the ischemic patient preoperatively (model 4) with a slope of 0.3211, and the lowest slope obtained in the ischemic patient (model 2) with a value of 0.2846.

DISCUSSION

Patient-Specific Biomechanical Basis of SCD in AAOCA

This observational study uses patient-specific and anatomically accurate 3D-printed models to evaluate the hemodynamics in the coronary arteries of a healthy patient and 3 other patients with R-AAOCA under exercise conditions. In 1 patient with ischemia, this information was obtained before and after surgery. The observations suggest compromise of coronary blood flow in patients who presented with documented ischemia, which is exacerbated under simulated stress, and resolves after surgery. There was no compromise in coronary blood flow in a patient without demonstrable ischemia. This preliminary work suggests that the risk of SCD in AAOCA may have a unique patient-specific morphological basis and is induced by biomechanically driven narrowing of the proximal coronary artery, especially at the ostium and intramural segment, during exercise.

Significance of the Study

The significance of this pilot observational study derives from the critical need to reduce the incidence of SCD in children using precision medicine approaches by (1) addressing the major research gap of risk stratification in AAOCA, (2) focusing on the patient-specific pathological mechanism for SCD, (3) improving surgical decision-making related to the need for surgery, and unroofing surgery. This pilot study is innovative in 3 ways: (1) Focuses on the anomalous right coronary artery, which is particularly plagued by poor understanding of patient-specific risk factors, difficult management decision making and risk related to treatment; (2) Addresses a critical technological challenge of creation and validation of patient specific 3D -printed models of AAOCA that incorporate pathological anatomy and vessel wall properties, and incorporating them into a scientifically robust biomechanical model; (3) Uses clinically valid metrics like FFR and coronary flow rate derived at rest and exercise, that are designed for incorporation into sophisticated and accurate future CFD models of AAOCA, greatly enhancing the potential for scalability.

None of the patients in this study underwent catheterization or FFR testing for direct validation of the in-vitro results. It is exceedingly rare for children and young adults with AAOCA to undergo invasive testing for FFR, and the development of predictive models for risk stratification will be facilitated by in-vitro experiments that can provide such data. However, it has been recently demonstrated the feasibility and safety of performing FFR in children with certain subtypes of AAOCA¹⁷ has been recently demonstrated. Doan at al¹⁸ recently published data in intraseptal AAOCA demonstrating correlation between inducible perfusion abnormalities on dobutamine stress (DS)-CMR and abnormal FFR on cardiac catheterization. Similarly, Agrawal et al¹⁹ reported good correlation between invasive FFR and DS-CMR findings in patients with AAOCA and myocardial bridges.

Even though it is common knowledge that interarterial AAOCA is associated with an increased risk of SCD, there is still lack of clarity on the role that intramurality and length of intramurality play. It is also likely that other factors such as ostial morphology, location of the ostium, etc. may contribute to ischemia in this population. This study represents a promising approach to elucidate the mechanistic aspects of SCD in this population. It is a pilot study with a limited sample size. As such, the results of this study do not allow us to provide specific guidelines for patients with AAOCA.

This pilot study is significant in that it demonstrates that (1) the creation of biomechanical 3D models can help risk stratify patients with AAOCA in a noninvasive way, (2) the use of these models can help elucidate the anatomic risk factors associated with ischemia in patients with AAOCA, and (3) defining the degree of risk conferred by specific anatomic characteristics can help create robust, noninvasive, and less cumbersome point-of-care predictive risk stratification models for particular patients with AAOCA.

Insights Into Mechanism of Ischemia in AAOCA

An ideal FFR is valued to be nearly 100% and any FFR value that drops below 0.7–0.8 is considered a finding associated with ischemia.¹⁶ Our data demonstrate that in the R-AAOCA patient with ischemia (model 2), FFR drops below 0.7 in the proximal IM course distal to the ostium, with a further drop to 0.44 in the distal IM segment, with recovery of FFR to normal levels beginning at the proximal mediastinal segment. We hypothesize that this observation may relate to the Bernoulli and Venturi effects in the long IM segment.²⁰ Flow acceleration occurred at the ostium as well as at the location of the right-left pillar which the anomalous coronary traversed along its mid-IM course, resulting in pressure drops in the proximal and distal IM segments respectively. When the diameter of the vessel increases as it emerges from the IM segment into the mediastinum, there is pressure recovery to physiological levels. However, in the non-ischemic R-AAOCA patient (model 3), FFR maintains a range exceeding 0.9 at all locations along the IM segment and beyond, throughout the cardiac cycle. These observations suggest that such experiments may play a role in elucidating the unique mechanism of ischemia in each patient, which can be correlated with findings noted on advanced imaging. There is lack of clarity regarding the specific role that presence and length of intramurality, and interarterial course play in the pathogenesis of ischemia and SCD in AAOCA. It is also likely that other factors such as ostial morphology, location of the ostium, ostial branching pattern and course through the pillar may contribute to ischemia in this population. This study represents a promising approach to elucidate the mechanistic aspects of SCD in this population. A modeling approach may help to define the degree of risk conferred by specific anatomic characteristics in AAOCA, and may help to create robust, noninvasive, and point-of-care predictive risk stratification options for patients in the future. Larger studies are needed in a nonselective cohort of AAOCA patients before such observations may be used for surgical decision-making, or to develop predictive models to guide risk stratification.

Comparison of Pre- and Post-unroofing Models to Demonstrate Surgical Outcome

Evaluating the findings in the R-AAOCA patient who underwent surgical unroofing, a large drop in instantaneous FFR is observed preoperatively (model 4) in this patient with clinical evidence of ischemia. Postoperatively, the FFR and the slope of the coronary flow rate returned to normal range (model 5), demonstrating the efficacy of unroofing in restoring coronary flow in AAOCA. Data from multiple centers suggested benefit of unroofing surgery in restoring normal coronary flow in patients with AAOCA and IM course. Surgical experience at Children’s Hospital of Wisconsin with IM AAOCA showed coronary flow restoration and normal exercise treadmill testing at 1.8 years of follow-up.²¹ A review of the Mayo Clinic cardiac surgical database reporting 75 patients after unroofing for AAOCA showed that surgical unroofing of AAOCA was accompanied by low morbidity and mortality.²² In a study performed at Texas Children’s Hospital, with unroofing utilized as the surgical treatment for AAOCA with IM course, the majority of the patients who underwent the operation was asymptomatic and cleared for exercise at medium-term follow-up.²³ However, there is still controversy over whether unroofing or reimplantation is more appropriate in patients with a short intramural course where unroofing may not resolve the entire length of the interarterial course, or when the coronary courses through a thickened commissure or pillar. There is also a small risk of recurrent ischemia in patients after surgery for AAOCA. Precision medicine approaches that help to delineate the mechanism of ischemia in a given patient may facilitate surgical decision making and determine residual risk after surgery. .

LIMITATIONS

The results of our study have several limitations, and only serve to illustrate a promising approach to studying pathophysiologic mechanisms in this entity but cannot be used to draw conclusions to guide management. In this pilot study, only 5 models were assessed. The current model did not incorporate a pulmonary artery to reproduce interarterial compression, one of the proposed mechanisms for ischemia during exercise. We are currently working on a model that includes the pulmonary artery with dual pulse duplicators to reproduce enlargement with exercise, only one nonischemic model (model 3) was studied, which did not demonstrate abnormal flow in the IM segment of the anomalous coronary. The intramural length in this case was shorter (7 mm) than the ischemic model 2 (12 mm), but not that different from the ischemic model 4 (8 mm). This patient had a slit-like ostium which was located above the sinotubular junction without a course through a thickened pillar. It is likely that a combination of static and dynamic mechanisms play a role in the development of compromised flow, and they require further elucidation.²⁴ This study represents an important step, but further refinement of the model and future studies are needed to further unravel the complex mechanisms leading to ischemia and SCD in AAOCA.

CONCLUSION

There is a decrease in pressure, FFR, and coronary flow rate with simulated stress in the intramural segment in AAOCA, which may be a potential explanation for ischemia and SCD with exercise in these patients as summarized in Video 1 and indicated in Figure 7.

Figure 7.

(Graphical Abstract): Fractional flow reserve gradual drop along the intramural course in R-AAOCA models.

Central Message

A drop in fractional flow reserve and decreasing coronary flow in the intramural segment with increasing aortic pressure may potentially explain sudden death with exercise in anomalous aortic origin of a coronary artery.

Perspective Statement

There is a drop in fractional flow reserve in the intramural segment and decreasing coronary flow with increasing aortic pressure in an ischemic model of anomalous aortic origin of a coronary artery, contrary to cases without ischemia. Larger studies may provide reliable data for incorporation into risk prediction models, and may aid decision regarding the need for and type of surgery in anomalous aortic origin of a coronary artery.

Abbreviations:

AAOCA

Anomalous Aortic Origin of a Coronary Artery

R-AAOCA

Right Anomalous Aortic Origin of a Coronary Artery

IM

Intramural Course

FFR

Fractional Flow Reserve