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Intravascular Ultrasound in the Assessment of Coronary Artery Anomalies in Young Patients: A Tertiary Center Experience
© 2024 HMP Global. All Rights Reserved.
Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of the Journal of Invasive Cardiology or HMP Global, their employees, and affiliates.
J INVASIVE CARDIOL 2024. doi:10.25270/jic/24.00238. Epub October 23, 2024.
Abstract
Objectives. Adult studies have shown that intravascular ultrasound (IVUS) is safe and efficacious to assess coronary artery anomalies (CAA) in select patients. Experience with IVUS in pediatrics has been reported, but pre- and postoperative data in young CAA patients is lacking. This study describes our population of young patients with anomalous aortic origin of a coronary artery (AAOCA) and myocardial bridge (MB) and reviews the safety of IVUS in this population.
Methods. This single institution retrospective review evaluated patients who underwent intracoronary flow measurement and IVUS, if indicated, from December 2012 to February 2023. Vessel compression was calculated as follows: (area in diastole – area in systole)/area in diastole. IVUS was repeated postoperatively to assess the repair.
Results. Fifty-eight IVUS studies were performed in 42 of the 68 (62%) patients undergoing cardiac catheterization aged 10 to 27 years (IQR 13.5-16.9), and not performed in 26 patients because of reassuring intracoronary flow, inability to engage the coronary ostium, or difficult coronary anatomy for vessel access. Nineteen AAOCA and 23 MB patients were evaluated with IVUS. The median pre- and post-surgery compression was 44% vs 16% for AAOCA (P = .050) and 53% vs 13% for MB (P = .015). Median compression in CAA patients not requiring surgery was 33% for AAOCA and 13% for MB. There were no major IVUS-related complications.
Conclusions. With a standardized approach and careful patient selection, IVUS is feasible and safe in young patients with CAA when clinically indicated preoperatively, and postoperatively to assess repair and vessel compression improvement. Its role in risk stratification in CAA remains to be determined.
Introduction
Anomalous aortic origin of a coronary artery (AAOCA) is a congenital abnormality of the origin or course of a coronary artery that arises from the aorta. The prevalence of AAOCA in the general population is estimated at 0.06% to 0.9% for right (R)-AAOCA and 0.02% to 0.1% for left (L)-AAOCA.1-3 AAOCA is a leading cause of sudden cardiac death in young athletes in the United States, with L-AAOCA carrying a higher risk than R-AAOCA.4 A myocardial bridge (MB) is defined as muscle overlying the coronary artery in the setting of a partial or total encasement of the coronary artery by myocardial fibers. Although the true prevalence of MB is unknown, autopsy studies report prevalence ranging from 15% to 85%, with lower prevalence reported in coronary angiography studies of 2% to 6%, and coronary computed tomography angiography (CTA) studies of 19% to 22%.5,6 Although MBs were previously considered a benign phenomenon, emerging data have shown that a combination of factors in the presence of this substrate may lead to ischemic symptoms in a small subset of adult and pediatric patients.5-9
Assessment of intraluminal anatomic details using intravascular ultrasound (IVUS) and physiologic testing such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) have been performed in adults with R-AAOCA to assess the severity of stenosis, ostial morphology, and more commonly coronary artery disease.10-12 IVUS has previously been shown to safely detect coronary artery vasculopathy and intimal disease earlier than traditional angiography in pediatric patients with a history of Kawasaki disease and those who have undergone heart transplantation.13-16 More recently, significant work has been done to further our knowledge in risk stratification of pediatric patients with intramyocardial coronary arteries (including AAOCA with an intraseptal course and MBs) utilizing stress perfusion non-invasive imaging and catheter-based anatomic and functional assessment (IVUS, FFR, iFR) of coronary arteries.7,14,17-19 While some pediatric patients with AAOCA and MB can be risk-stratified and managed based on non-invasive tests, a small sub-selection of patients who have symptoms concerning for ischemia and negative non-invasive testing require further invasive testing. In these patients, cardiac catheterization with coronary angiography, IVUS and FFR/iFR may provide important additional information for clinical decision making. In pediatric patients, no studies currently exist assessing AAOCA and MB pre- and postoperatively with cardiac catheterization and IVUS. The purpose of this study is to describe our population of patients with AAOCA and MB and to review the safety of IVUS in this select young population.
Methods
Patient population
All patients with AAOCA or MB evaluated at Texas Children’s Hospital/Baylor College of Medicine in the Coronary Artery Anomalies Program (CAAP) between December 2012 and February 2023 were enrolled in a longitudinal database. The protocol was approved by the Institutional Review Board, and written informed consent was obtained from all participants. Patients with AAOCA or MB who were younger than 28 years, completed evaluation with imaging and functional studies, were discussed at the multidisciplinary team meeting, and who had undergone cardiac catheterization were included. From the onset of our CAAP, a standardized algorithm was established with inclusion and exclusion criteria to allow us to prospectively evaluate, treat, and follow these patients.17,18,20,21 Since then, the program has evolved to include an algorithm for myocardial bridges7 and intraseptal coronary arteries.17
Clinical evaluation
All referred patients in early puberty (approximately older than 8-10 years) typically undergo testing with an electrocardiogram (ECG), echocardiogram, exercise stress test (EST), and a retrospective ECG-gated coronary CTA, which is used as the gold standard to delineate the details of the coronary artery anatomy, including anomalous sinus of origin, ostial morphology (ie, shape [slit-like/oval/round], acute angle of origin), course (ie, intramural/intraseptal), and coronary dominance. Utilizing the data from the CTA, an intraseptal course of the AAOCA was diagnosed when the anomalous CA coursed within the infundibular ventricular septum below the level of the pulmonary valve before returning to the epicardial surface. In some patients, the coronary artery tunneled beyond the infundibular septum with an extended intramyocardial course before exiting to the epicardium. In patients with MB, the CTA was used to determine the location and length of the MB and the presence of an additional AAOCA. Myocardial perfusion imaging in the form of dobutamine stress cardiac magnetic resonance imaging was performed in all patients older than 8 to 10 years and in younger patients with concerning symptoms for myocardial ischemia, as anesthesia is necessary to perform a good quality study in the younger age group. Previous reports have outlined the protocol followed for these studies.7,17,18,20,22-25 Given the perceived benign nature of MB and its prevalence in the population, patients diagnosed with MB on CTA with persistent symptoms concerning for ischemia or abnormal provocative stress tests (EST and/or dobutamine stress cardiac magnet resonance imaging [DSCMR]) were further evaluated with cardiac catheterization and invasive coronary artery functional assessment as outlined below. Although CTA-FFR has been utilized in adults, it is very challenging in the pediatric population because images are obtained without pharmacological manipulation of heart rate or coronary vasodilation; also, the small vessel size may hinder feasibility. Finally, all patients who undergo surgery repeat all testing at 3 months postoperative prior to returning to exercise.
Invasive coronary artery functional assessment
Generally, catheter-based invasive testing was recommended to gather additional information for risk stratification and consideration of surgical intervention in 2 main groups of individuals: (1) patients for whom there was significant concern for ischemic symptoms and negative non-invasive studies for inducible myocardial ischemia under provocative stress, or (2) asymptomatic patients with positive non-invasive studies suggestive of inducible myocardial ischemia under provocative stress. All procedures were performed under general anesthesia and with biplane fluoroscopy. Patients were heparinized for the duration of the procedure to achieve an activated clotting time of more than 250 seconds.19 Standard cardiac hemodynamic catheterizations were performed, followed by an aortic root angiogram and selective coronary angiography.
Prior to advancing a wire across the lesion of interest, intracoronary nitroglycerin was administered (1 mcg/kg, max dose 100-200 mcg) to prevent vessel spasm. Functional assessment (FFR, iFR, IVUS) was performed using 5- to 6-French (Fr) guide catheters. Per protocol, the 0.014-inch Volcano pressure guide wire (Philips) was normalized outside the patient and then zeroed in the aortic root. The wire was passed into the coronary vessel distal to the lesion. After ensuring the guide catheter tip was free of the coronary ostium as to not obstruct coronary flow, baseline and stress FFR/iFR measurements were acquired. Historically, at our institution, adenosine and dobutamine were used to create the stress condition, defined as 75% of the predicted maximal heart rate, to mimic the dynamic changes that occur during peak exercise. In the current protocol, only dobutamine was used to induce stress. Next, if anatomically feasible, imaging with IVUS was performed.26 Prior to introducing the IVUS catheter, either esmolol or labetalol was administered to reverse tachycardia from the stress condition.
Vessel area measurements were obtained during a pull back across the lesion. Vessel compression was assessed at the level of the lesion using the following equation: (vessel area in diastole – vessel area in systole)/vessel area in diastole (Figure 1). Some IVUS compression data from the earliest catheterizations were reported as qualitative metrics vs quantitative values. The qualitative data were excluded from the compression statistical analysis. Additionally, some of the earliest quantitative values were calculated using an older protocol method of comparing the minimum diameter of the vessel lesion to the proximal normal vessel caliber, and these values were also excluded. Prior to removing the coronary wire, angiograms were performed to assess for vessel spasm or injury. Additional nitroglycerin was administered if coronary artery spasm was detected, and angiography was repeated as indicated. Repeat postoperative cardiac catheterization was performed in patients who underwent surgical intervention using the technique described above.
Statistical analysis
Results are reported as medians (IQR) and percentages where indicated. Abnormal FFR and iFR values were considered less than or equal to 0.80 and 0.85, respectively.26 In patients with significant ischemic symptoms, stress iFR 0.85 to 0.89 was considered potentially abnormal. Statistical analysis was performed using Jamovi V2.3.28.0 and Microsoft Excel V16.16.10. A P-value of less than or equal to 0.050 was considered statistically significant. P-values for continuous variables were calculated using a Mann-Whitney U test, a paired t test was used for normally distributed paired data that passed the Shapiro-Wilk test, and a chi-square test was used for categorical variables.
Results
There were 482 patients evaluated in the CAAP at our institution, as delineated above, between December 2012 and February 2023. Of these, 68 of 482 (14%) patients were referred for additional invasive testing with a cardiac catheterization, and ultimately 42 of 68 (62%) patients underwent a total of 58 cardiac catheterizations with IVUS to further assess their CAA pre- and postoperatively. Nineteen patients with AAOCA underwent the procedure at a median age of 15.5 (13.5-17.7) years, and 23 patients with MB underwent the procedure at a median age of 15.7 (13.8-16.7) years (Table 1). Twelve of the 19 patients with AAOCA had CTA performed at our institution and 7 had CTA performed at local institutions with our independent review of the images. The CAA was seen by CTA in all patients with AAOCA; 11 (58%) had L-AAOCA (10 with an intraseptal course), 3 (16%) had R-AAOCA (all with an intramural course), and 5 (26%) had a single coronary origin (4 with an intraseptal course). In total, 14 of the 19 (74%) patients with AAOCA had a coronary artery lesion with an intraseptal course, 3 of 19 (16%) had an intramural course, and 2 of 19 (11%) had neither an intraseptal nor intramural course (1 L-AAOCA with juxtacommissural course, 1 SC with interarterial course). Eighteen of the 23 patients with MB had CTA performed at our institution and 5 had CTA performed at local institutions with our independent review of the images. Left anterior descending (LAD) MBs were not recognized in a patient who had undergone surgical unroofing of an intramural right AAOCA, nor in another patient with previous unroofing of an intramural left AAOCA. Both these patients had undergone initial CTA at outside institutions and prior to 2015.
Of 42 patients with AAOCA or MB who underwent cardiac catheterization, 31 (74%) had presenting symptoms concerning for ischemia but were found to have negative or equivocal non-invasive provocative stress testing for inducible myocardial ischemia (Table 2). The remaining 11 (26%) patients who underwent additional invasive functional assessment of their lesions were asymptomatic and diagnosed incidentally with abnormal non-invasive myocardial provocative stress testing. They were all referred for additional invasive functional assessment of their lesions (iFR/FFR and IVUS) to aid in risk stratification and management decision-making.
Of the 19 AAOCA patients who underwent IVUS, 6 patients were excluded from the analysis because of qualitative measurements or older protocol data. Thirteen baseline and 5 postoperative AAOCA measurements were included in the analysis using the current IVUS protocol. Similarly, of the 23 patients with MB who underwent IVUS, 4 patients were excluded, and 19 baseline and 5 postoperative MB measurements were included in the analysis. Patients with AAOCA and abnormal iFR/FFR (N = 11) had a median compression by IVUS of 42% compared with 18% in patients with reassuring iFR/FFR (P = .093; Table 3 and Central Illustration). Eight of the 11 (73%) patients were ultimately referred for surgery based on symptoms and iFR criteria, whereas medical management was recommended in the remaining three individuals who were clinically asymptomatic with incidental diagnoses of AAOCA with an intraseptal course given the complex nature of the surgical repair. Patients with MB and abnormal iFR/FFR (N=13) had a median compression by IVUS of 47% compared to 12% in patients with reassuring iFR/FFR (P = .007; Table 3). Twelve of the 13 (92%) patients were ultimately referred for surgery based on symptoms and iFR criteria. Medical management was recommended in the remaining 2 individuals, the first of whom had an incidental new diagnosis of a MB of the left anterior descending coronary artery while undergoing routine surveillance of his previously repaired R-AAOCA 5 years prior, and the second of whom was deemed unlikely to benefit from surgery given the small size and distal location of the MB.
Out of the 20 patients with AAOCA and MB referred for surgery, 18 (90%) have undergone surgery and 16 (80%) have undergone a repeat postoperative catheterization evaluation (others were awaiting repeat study). In the patients with AAOCA who underwent surgery and were included in the compression analysis using the current IVUS protocol, the median compression significantly reduced from 44% to 16% (P = .050; Figure 2). In the patients with MB who underwent surgery and were included in the compression analysis using the current IVUS protocol, the median compression significantly reduced from 53% to 13% (P = .015).
Of the patients initially referred for cardiac catheterization, IVUS was not performed in 26 patients due to reassuring iFR/FFR, inability to stably engage the ostium to pass a wire safely, or unsuitable coronary anatomy (small caliber/acute angulation). There were 2 minor (3.3%) and 1 major (1.7%) adverse events (AE), of which only 1 minor AE was IVUS-related. One of the minor AEs was a patient with vasospasm-related transient ST changes during iFR/FFR stress testing that was resolved with intracoronary nitroglycerin and did not recur during IVUS evaluation. The other minor AE was a patient with coronary vasospasm during IVUS evaluation of their single coronary during postoperative evaluation 4 months after undergoing transconal unroofing of the intraseptal portion of the coronary artery. The coronary vasospasm improved with intracoronary nitroglycerin. The major AE involved a patient with Noonan syndrome who experienced a catastrophic cerebral hemorrhage after extubation in the recovery unit, followed by cerebral herniation and neurologic injury resulting in withdrawal of life support by the family. There were no coronary dissections in our cohort.
Discussion
Previously, AAOCAs with an intraseptal course and MB were considered a benign entity. However, emerging prospective studies have begun to delineate the spectrum of risk associated with varying degrees of coronary artery compression in the segment traveling within the myocardium, resulting in cardiac ischemia.21,27,28 In 2017, our group first reported the use of FFR and IVUS in a small cohort of children with intramyocardial coronary arteries and concluded that it is feasible and safe.19 In 2020, Doan et al demonstrated that, when a systematic assessment with both non-invasive and invasive studies is performed, the clinical presentation of myocardial ischemia in children with AAOCA with an intraseptal course of the anomalous coronary artery may be subtle and more commonly seen than previously believed.21 Along with DSCMR, this standardized assessment of symptomatic patients with a CTA, which is the gold standard for diagnosing CAA and delineating detailed morphology of the anomalous vessel, is recommended during early puberty; however, younger patients may undergo evaluation if there are significant concerns for exertional symptoms (ie, exertional syncope) or in those with high-risk L-AAOCA. Subsequently, we have increasingly explored invasive assessment using FFR and iFR at rest and during pharmacologic stress, as well as IVUS, in patients either with symptoms concerning for ischemia with negative non-invasive provocative stress testing for inducible myocardial ischemia (ie, symptomatic patients with positive CTA and negative EST/DSCMR), or those with isolated positive non-invasive provocative stress testing in the setting of a high risk lesion (ie, patients with positive CTA and DSCMR but who remain asymptomatic), In this report, we describe the baseline and postoperative use of IVUS in young patients with AAOCA or MB to assess surgical results and improvement in coronary compression.
Data on the utility and safety of performing IVUS in the assessment of coronary arteries in young patients is limited. Its increased sensitivity over traditional coronary angiography in pediatric populations to detect intimal wall thickening in those with Kawasaki disease and transplant associated coronary artery disease (TCAD) has been demonstrated.15,16 IVUS-related AE in pediatric patients undergoing TCAD assessment has previously been reported as 1.2% (41% of which were vasospasm).13 There were 2 minor AEs (5%) in our cohort, 1 of which was related to IVUS (1.7%) as a result of a vasospasm after passing the IVUS catheter. There was 1 major non-IVUS-related AE (1.7%). The major AE involving a catastrophic cerebral hemorrhage in a patient with Noonan syndrome was thought to be related to a possible cerebral vasculopathy, as has been previously reported in this population.29 There were no coronary dissections seen or irreversible IVUS-related AEs. Our rate of IVUS-related complications in patients with CAA is comparable to those in other pediatric patients without CAA, which suggests that IVUS is feasible and may be safely performed in this population, when clinically indicated.
Although we do not recommend routine invasive testing with IVUS and iFR/FFR in all pediatric patients with AAOCA or MB, we believe that, with additional studies to delineate cut-off values, this information may be helpful in the risk stratification of patients with conflicting clinical symptoms and non-invasive diagnostic testing results. Additionally, IVUS may provide additional anatomical information that is useful for surgical management of these patients. The subset of patients with R-AAOCA and/or those with MB who may benefit from invasive diagnostic testing based on our institution’s algorithm was recently published.7,18 Of note, all 3 patients with MB who presented with sudden cardiac arrest underwent comprehensive evaluation to rule out potential causes other than the MB, including genetic testing for inherited disorders (cardiomyopathy and channelopathies); these results were negative.
While at this time we do not refer patients for surgery based solely on a specific degree of coronary vessel compression by IVUS, we do review this data in conjunction with abnormal iFR/FFR when making a recommendation following discussion with the CAAP multi-disciplinary team. Surgeries performed include transaortic coronary unroofing, transconal coronary unroofing, myotomy, and transection and reimplantation of the coronary artery.7,25,30,31 Postoperative invasive testing has given us the opportunity to assess the surgical repair in this subgroup of patients and to lift sports restrictions with functional and anatomic lesion improvement. All the patients with available postoperative IVUS assessment showed improvement in the degree of their vessel compression.
Limitations
This study was limited by the small number of patients, as AAOCA with an intraseptal course and MB only occurs in rare cases. Additionally, because of the retrospective study design, measurements that were performed as qualitative assessments or using the older IVUS protocol were excluded. Our management recommendations were largely based on a single-institution multidisciplinary team consensus using prospective data acquired thus far in the CAAP and the sparse literature available. We continue to collect data to further elucidate the relationship between invasive functional assessment, the vessel compression degree obtained by IVUS, and clinical signs of ischemia to better understand the role for IVUS in this patient population. Subsequent studies to determine the specific IVUS measurement cutoff and with larger patient data will help in the future risk stratification of children and young adults with CAA.
Conclusions
With a standardized approach and careful patient selection, IVUS is feasible and safe in young patients with CAA, when clinically indicated. IVUS is also a useful tool to assess pre and post-surgical compression. Further study is required to determine what degree of compression obtained by IVUS reliably correlates with invasive hemodynamics and to further delineate the role of IVUS in the risk stratification of CAA patients.
Affiliations and Disclosures
Mounica Y. Rao, MD1; Lindsay F. Eilers, MD1,2; Tam Doan, MD1,2; Srinath T. Gowda, MD1,2; Athar M. Qureshi, MD1,2; Shagun Sachdeva, MD1,2; Stephen J. Dolgner, MD1,2; Jeffrey Heinle, MD3; E. Dean McKenzie, MD2,3; Ziyad Binsalamah, MD4; Dana Reaves-O’Neal, APNC, CPNP/AC1,2; Silvana Molossi, MD, PhD1,2
From the 1Division of Cardiology, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; 2Coronary Artery Anomalies Program, Texas Children’s Hospital, Houston, Texas; 3Congenital Heart Surgery, Texas Children’s Hospital, Department of Surgery, Baylor College of Medicine, Houston, Texas; 4Pediatric Cardiac Surgery, MaineHealth, Portland, Maine.
Dr Rao and Dr Eilers served as co-first authors.
Disclosures: Dr Qureshi is a consultant for Medtronic Inc., W.L. Gore and Associates, and B. Braun, though none related to the current work presented. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.
Address for correspondence: Lindsay F. Eilers, MD, 6651 Main Street, MC E1920, Houston, TX 77030, USA. Email: Lindsay.Eilers@bcm.edu
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