Intravascular Ultrasound (IVUS) Provides the Filling for the Angiogram’s Crust: Benefits of IVUS in Pediatric Interventional Cardiology

Background. Intravascular ultrasound (IVUS) is a catheter-based imaging modality that generates cross-sectional views of vessel walls and lumens. This technique is used in adult interventional and vascular surgeries to guide the management of coronary artery and peripheral arterial disease. IVUS has been described as superior to angiography in providing data about lesions of interest, including degree of vessel stenosis and stent apposition following intervention. IVUS use to guide transcatheter management of congenital heart disease is limited. Objective. We reviewed our experience using IVUS as an adjunctive tool to diagnose lesions and assess intervention in pediatric patients during cardiac catheterization. Methods and Results. A retrospective chart review of all pediatric patients who underwent IVUS during cardiac catheterization to evaluate the cross-sectional lumen of non-coronary vessel(s) at Rady Children’s Hospital from January 2018 to December 2019 was performed. Median patient age was 637 days (range, 44-4328 days), with mean weight of 12.1 ± 9 kg. Twenty-six vessels were interrogated with IVUS (pulmonary venous stenosis [n = 8], coarctation [n = 5], branch pulmonary artery stenosis [n = 6], systemic shunts and conduits [n = 3], and other peripheral vasculature [n = 4]). IVUS added value in all cases (100%). We found that IVUS guided the intervention in 88% of procedures and defined the endpoint in 62% of transcatheter interventions. There were no IVUS-related complications. Conclusions. IVUS enhanced our diagnostic interpretation and identified occult lesions not visualized by angiography. IVUS was valuable in guiding and defining the endpoints of these interventions.

J INVASIVE CARDIOL 2021;33(12):E978-E985.

Key words: congenital heart disease, intravascular ultrasound

Intravascular ultrasound (IVUS) is a catheter-based imaging modality that generates cross-sectional views of vessel walls and lumens. This technique is widely used in adult interventional cardiology to assess coronary artery and peripheral arterial disease. Specifically, this modality provides excellent vessel wall anatomic characterization of intraluminal narrowing related to stenosis, calcification, or intraluminal proliferation, which may not be readily apparent on angiography. Most important, this imaging data guides therapeutic and interventional decisions.

Literature describing the use of IVUS in pediatric and congenital heart disease patients is limited. IVUS use in children to assess acquired coronary artery disease has been described.  Similar to adult experience, IVUS is more sensitive than angiography in children for early detection.^1,2 Sugimura et al investigated the use of IVUS compared with selective coronary angiography for coronary artery lesions in patients with Kawasaki disease.³ IVUS showed intimal thickening with calcification, similar to adult arteriosclerotic changes, at the site of prior coronary aneurysm years after acute illness.

Pedra et al explored IVUS to evaluate coronary wall morphology years after arterial switch operation for transposition of the great arteries in an attempt to understand intravascular changes that precede later coronary events.⁴ IVUS has been used to better understand intravascular dynamics in pulmonary vascular disease^5,6 and coarctation.⁷ Studies have evaluated the mechanical effect of angioplasty following aortic angioplasty.^7,8 Pepper et al explored IVUS for longitudinal surveillance of tissue-engineered vascular grafts in an ovine model. In addition to better anatomic characterization, there was a decrease in contrast administration and radiation duration.⁹

Adult experience has shown that IVUS overcomes the limitations of angiography, providing additional information, guiding interventions, and defining endpoints.^10-12 Similarly, in children and congenital heart disease patients, IVUS may aid in identifying lesions not identified or well characterized by angiography alone and guide transcatheter interventional therapy. We describe our IVUS experience in aiding diagnosis and guiding transcatheter interventions in pediatric and congenital heart disease.

Study patients. A retrospective chart review was performed on patients at Rady Children’s Hospital-San Diego in San Diego, California who underwent IVUS as part of their cardiac catheterization procedure from January 2018 to December 2019. This is a single-center, retrospective study approved by the institutional review board at the University of California San Diego. No informed consent was required.

IVUS imaging. Volcano Eagle Eye IVUS catheter (Philips) with a 20 MHz ultrasound probe was used for IVUS imaging. The catheter was introduced over an 0.014˝ guidewire. Real-time cross-sectional images of the vessels were obtained via pullbacks through the vessel. Images were continuously recorded and stored, from which measurements were obtained post processing. All images were analyzed using Volcano Core Mobile System intravascular imaging software (Philips), which traces vessel linear and area measurements by planimetry. Angiographic measurements of vessels of interest were obtained at the time of the procedure, with reference angiograms and bony landmarks confirming the same locations for comparisons between IVUS and angiographic measurements.

Data analysis measurements. IVUS measurements of minimum vessel size included linear diameter measurement (minimum luminal diameter [MLD]) and cross-sectional area. Cross-sectional area measurement included maximal and minimal diameters on multiple frames to determine the greatest area of narrowing. With angiography, only linear measurements (vessel diameter) could be obtained. Based on measurements of the MLD and the distal (or maximal) vessel diameter, we calculated absolute percent differences or percent stenosis of the vessel.

Statistical analyses. Demographic data are presented as mean ± standard deviation or median (range). IVUS and angiography measurement variance was compared for 2 specific lesions, pulmonary vein stenosis, and coarctation of the aorta. The paired Student’s t-test for parametric data was used with statistical significance at P<.05. All statistical analyses were performed using Excel (Microsoft 2010).

Assessment of whether IVUS added value to the procedure was determined based on whether the IVUS data provided information not obtained on standard angiography, guided intervention, or determined endpoint of the procedure. The authors had full access to the data and take responsibility for the data integrity. All authors have read and agree to the manuscript as written.

Patient demographics are summarized in Table 1. Nineteen patients (26 vessels) were assessed. Median patient age was 637 days (range, 44-4328 days). Mean patient weight was 12.1 ± 9 kg at the time of the procedure. Interrogated vasculature included pulmonary veins (n = 8), branch pulmonary arteries (n = 6), coarctation of the aorta (n = 5), surgical shunts (n = 3), and other peripheral vasculature (n = 4). Mean IVUS fluoroscopy time was 6 ± 4.1 minutes.

Assessments of IVUS utility were both qualitative and quantitative. IVUS added value in 100% of the cases in which it was utilized. IVUS-guided intervention was used in 88% of the procedures and defined the endpoint in 62% of the procedures.

In 2 select vessel groups— pulmonary vein stenosis and coarctation of the aorta — the luminal narrowing determined by angiography (linear measurement) was compared with luminal narrowing obtained from IVUS (linear measurement and cross-sectional luminal area). The measurements were considered paired if they were obtained from the MLD of interest along the vessel. A 2-tailed, paired student’s t-test was conducted to compare the angiographic absolute percent difference with IVUS area percent difference in the pulmonary vein cohort (Table 2). There was no significant difference (P=.94). In the coarctation cohort, this difference approached near statistical significance (P=.06) (Table 3).

Pulmonary vein stenosis. IVUS was performed to evaluate stenosis and intimal proliferation for 8 pulmonary veins (Table 4). Two subjects (M and O) had 2 separate pulmonary veins assessed and 1 subject (R) was assessed at 2 separate catheterizations. Pulmonary vein IVUS provided value in 100% of the investigations. IVUS was performed in most vessels for lesion assessment prior to intervention (vessels 20, 21, 23, 24, 25). IVUS-guided angioplasty balloon sizing was based upon the degree of stenosis and intimal proliferation. Post angioplasty, IVUS was useful in assessing stent patency and vessel wall apposition (vessels 14, 20). IVUS defined the endpoint of the interrogation of the pulmonary vein in 75% of the subjects. In other subjects, IVUS confirmed no vessel stenosis (vessel 17), suggesting that the pressure gradient measured in the vessel was likely flow related due to contralateral pulmonary venous obstruction.

Our understanding of intimal proliferation in this disease process proved to be the most efficacious use of IVUS (Figure 1 and Figure 2). In vessel 23, IVUS was performed within the left lower pulmonary vein, which was previously stented. Angiography was concerning for intimal proliferation with stenosis. With IVUS, we were better able to define the extent of suspected intimal proliferation and postulate that the reason for intimal proliferation location was due to direction of flow within the stented vessel. In another instance, IVUS provided more information about the disease process of the distal pulmonary venous vessels. Interestingly, subjects M and R had similar disease processes with discrete pulmonary venous stenosis. Both required multiple previous interventions including angioplasty and stent implantation in these vessels. Our evaluation with IVUS demonstrated that these 2 subjects had very different courses regarding behavior of the distal vessels. In vessel 18, while IVUS demonstrated 52% area stenosis, qualitatively IVUS within the stent and in the vessel distal to the stent demonstrated no intimal proliferation and no intervention was performed during said procedure upon this vessel. In vessel 24, IVUS demonstrated minimal (if any) intimal build-up within the stent as well as distal to the stent; angioplasty was performed to increase the size of the stent for anticipated somatic growth with angiographic increase in vessel size. The subject returned 2 months later for surveillance catheterization (recorded as vessel 25), at which time IVUS demonstrated significant concern for intimal proliferation and disease progression not just within the stent, but more concerning in the distal vessel.

Coarctation of the aorta. Five subjects with coarctation underwent IVUS to evaluate the degree of narrowing. Patient data are summarized in Table 5. IVUS added value in each case and was utilized to define the endpoint in 60% of cases. Each of these subjects had previous interventions upon the vessel investigated. Interestingly, in 80% of these subjects, angiographic measurements revealed <35% stenosis of the coarctation, which unto itself would not be a likely reason to intervene. IVUS area measurements, however, demonstrated >40% stenosis in all subjects, as illustrated in Figure 3. In 4 of these 5 subjects, IVUS guided the decision to perform a reintervention upon the vessel given the percent area difference in vessel caliber. In vessels 4, 16, and 19, IVUS was performed prior to intervention (angioplasty) revealing stenosis at the site of coarctation warranting intervention. IVUS was performed post intervention in vessels 4, 13, and 16, revealing improved caliber of the vessel at the site of intervention with adequate results, and no evidence of vessel dissection. In subject F, there was long-segment hypoplasia of the descending aorta noted on angiography as well as IVUS; however, after considering the patient’s other comorbidities (notably, Turner’s syndrome) and the mild hemodynamic gradient, no catheterization intervention was performed at the time of this procedure.

Branch pulmonary artery. There were 6 branch pulmonary arteries in which we utilized IVUS to evaluate the caliber of the vessel and stenosis. Each of the vessels had been previously intervened upon surgically. Patient data are summarized in Table 6. In vessels 3 and 22, IVUS provided adjunct information supporting angiographic findings of stenosis and subsequent improvement post angioplasty. In vessels 7 and 22, IVUS was valuable not only in defining the degree of stenosis, but also in elucidating that there was no dissection of the vessel post angioplasty, which aided the determination of the endpoint of the intervention. In vessel 5, preintervention IVUS demonstrated trivial intimal proliferation within the stent and a small caliber of the distal vessel. In this case, IVUS guided the treatment management because we opted to only perform angioplasty and not re-stent due to negligible intimal proliferation; in addition, IVUS defined the treatment endpoint since the balloon size was based upon the size of the distal vessel. In vessel 9, angiography failed to fully delineate the dimensions of the left pulmonary artery, although it qualitatively appeared narrow. IVUS provided a means of assessing the degree of stenosis, which was near 40% and warranted intervention.

In this cohort, we include subject I, who could not undergo angiography due to renal failure. IVUS was performed in the left pulmonary artery (vessel 11) and demonstrated 27% area stenosis, which in conjunction with no significant hemodynamic gradient aided with the decision to forego intervention.

Shunts/conduits. In this cohort of subjects, we grouped conduits and aortopulmonary shunts, and found 3 vessels that were evaluated by IVUS. Patient data are summarized in Table 7. In each case, IVUS played a pivotal role in understanding the vessel and determining whether or not an intervention was warranted. In vessel 6, IVUS was utilized to evaluate the right ventricular to pulmonary artery conduit, which appeared widely patent on angiography and fluoroscopy. IVUS demonstrated a lack of intimal proliferation, which suggested that we could successfully perform angioplasty only, without the need to re-stent the region. In subject H, IVUS was performed in the stented right ventricular outflow tract, which demonstrated no obvious obstruction of the stents and no area stenosis, thus confirming that we did not need to perform angioplasty of the stents. Lastly, and most importantly, IVUS was crucial in the evaluation of the Blalock-Taussig shunt for subject S. It was difficult to effectively evaluate the entire structure using angiography (Figure 4). With IVUS, we were able to clearly see that the shunt was widely patent, with no intimal proliferation or narrowing. No further intervention was warranted, and time and contrast were saved.

Other vessels. In this cohort potpourri, IVUS was utilized to evaluate peripheral vasculature as well as a left ventricular outflow tract. Patient data are summarized in Table 8. In subject A, IVUS was utilized to evaluate the left lower renal artery in a subject who had a history of a large aortic aneurysm at the level of the renal arteries and was status post aortic reconstruction with Gore-Tex (Gore Medical) and kidney autotransplantation, with concern for renal stenosis. IVUS was used in conjunction with angiography to better evaluate the renal artery. IVUS quantitatively demonstrated 54% focal area stenosis of the left lower renal artery. These data were used in conjunction with the clinical findings, which was largely reassuring in that the subject did not have hypertension or evidence of decreased perfusion to the kidney in addition to the close proximity of the upper and lower renal arteries to persuade us not to intervene at that time. IVUS was utilized in subject B to further evaluate multilevel left ventricular outflow obstruction, with significant subaortic region narrowing. With IVUS, we were able to perform virtual histology of this narrowed region (86% area stenosis), which showed it to be fibrofatty tissue. IVUS was pivotal in guiding our management and defining our endpoint, as no further aortic valvuloplasty was performed given that the narrowing and gradient was due to subvalvar tissue.

IVUS was employed in subject K (vessel 15) to evaluate significant iliac and femoral venous stenosis. The region had previously been ballooned and then subsequently stented. IVUS performed in the region due to angiographic concerns for narrowing revealed severe intimal build-up throughout the vessel, which improved post repeat angioplasty. However, distal to the previously placed stent, the vessel was shown to be diseased and to have severe intimal proliferation, prompting stent placement in that region.

We report our experience using IVUS as a complementary tool to aid with diagnostic catheterizations and in guiding the management and determining the endpoint of interventional studies. We found IVUS to be a safe tool for pediatric catheterization, with no complications during our study, which included subjects as small as 4 kg. While our findings did not reach statistical significance regarding quantitatively pairing our measured luminal diameter on angiography and IVUS cross-sectional area, IVUS was invaluable in a qualitative sense by enhancing our interpretation of identified pathology or by raising concern for occult lesions not seen on typical angiography. IVUS provides a three-dimensional understanding of vessel caliber with cross-sectional area, highlighting the limitations of angiography in certain situations.

In looking at our data, we could group our IVUS findings to include: (1) subjects in whom our IVUS findings guided our decision to intervene based on what we found; (2) subjects in whom the IVUS findings informed us not to intervene; and (3) subjects in whom IVUS influenced our endpoint. As with previous adult studies on the peripheral vasculature,¹¹ IVUS guided the appropriate angioplasty diameter, stent size, and stent apposition in our study when appropriate. As we saw most notably in the pulmonary vein cohort (vessels 20, 21, 23, 24, and 25), IVUS aided with the choice of balloon for angioplasty and was then useful in the evaluation performed post angioplasty to assess stent patency and apposition to the vessel (vessels 14 and 20).

Another important IVUS benefit that has been previously discussed in the adult literature as well as a pediatric case report from Japan is the advantage of no contrast when evaluating intravascular pathology in high-risk patients in whom contrast would be detrimental, such as those with renal impairment or severe allergy to contrast media.^13,14 In a 2017 case report by Muneuchi et al, IVUS was utilized to identify and intervene upon a significant veno-venous collateral with data solely provided by IVUS imaging.¹⁴ Similarly, we found that IVUS was profoundly helpful and pivotal in intervening on subject I in our study (vessels 11 and 12), who could not undergo angiography due to renal failure yet had concern for significant stenosis of the superior vena cava and left pulmonary artery post orthotopic heart transplant and was referred for catheterization. We were able to determine with hemodynamics and IVUS imaging that the vessels did not warrant acute intervention. This benefit of decreased contrast and radiation exposure in the pediatric population, particularly those requiring frequent trips to the catheterization suite, cannot be overstated.

Future directions. We anticipate that the findings from this review will be a pilot study for future endeavors, particularly in longitudinal surveillance (as proposed by Pepper et al), with the goal of branching off and investigating the utility of IVUS in treating some of the more recalcitrant lesions, such a recurrent pulmonary vein stenosis. IVUS influenced and enhanced the management of these lesions based on our small sample size and we believe these data will be helpful in guiding future multi-institutional studies. In particular, we hope to evaluate the integrity of the entire pulmonary vein vessel and categorize the vessel proximally and distally, and explore how these data longitudinally help in terms of interventions (particularly stenting). In our pulmonary vein cohort, we had several patients who happened to have multiple catheterizations during the investigation time frame with IVUS interrogation of the same pulmonary vein, but with different clinical courses regarding the progression of intimal proliferation. Investigating stent placement, sizing, and apposition within pulmonary veins and the progression of intimal proliferation will be the next areas of inquiry. Along these lines, use of virtual histology is an attractive future direction, particularly in pulmonary vein interrogation.

Study limitations. This was a retrospective study with small sample sizes in each cohort. Future, larger studies investigating the focused use of IVUS in particular vessels are needed to fully understand the benefits and further uses of this tool for the management of congenital heart disease. As with most things, there is a learning curve to using IVUS, which may initially add time to the procedures but will improve as familiarity is gained.

We found IVUS to be a safe tool for pediatric catheterization, with no complications during our study. IVUS was invaluable in enhancing our interpretation of identified pathology and in raising concern for occult lesions not seen on typical angiography. IVUS was particularly helpful with guiding interventional management and defining the procedural endpoint, and warrants further investigation in pediatric catheterization studies.

From the Division of Pediatric Cardiology, Rady Children’s Hospital and UC San Diego School of Medicine, San Diego, California.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript accepted February 25, 2021.

The authors report patient consent for the images used herein.

Address for correspondence: Howaida El-Said, MD, Department of Cardiology, Rady Children’s Hospital, 3020 Children’s Way, MC 5004, San Diego, CA 92123. Email: HEL-Said@rchsd.org

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