Abstract: Objectives. The evaluation of arterial plaque morphology and vessel diameter is a vital component of peripheral vascular interventions. Historically, digital subtraction angiography (DSA) has been considered the gold standard for vessel sizing and treatment. However, this modality has the limitation of providing a two-dimensional image of a three-dimensional luminal structure. Utilization of intravascular ultrasound (IVUS) has been incorporated into diagnostic and treatment algorithms to further characterize the arterial vessel. This study compared visual estimation of vessel diameter by angiographic imaging with IVUS measurements. Methods. A retrospective analysis was conducted on a cohort of 43 patients who underwent an endovascular intervention utilizing DSA and IVUS imaging. Angiographic measurements were determined by an interventionalist blinded to the IVUS findings. Results. Of the 43 patients, 58% were male, the majority (72%) were ages 60-89 years, 58% were Rutherford classification III, and 42% had critical limb ischemia (Rutherford classification IV or V). Arterial access sites were common femoral, posterior tibial, and anterior tibial in 37%, 37%, and 26%, respectively. Tibiopedal arterial minimally invasive (TAMI) retrograde revascularization was utilized in 63% of patients. Vessel sizing was consistently the same or smaller for female subjects with either imaging modality. Overall, measurements estimated from angiographic images were significantly smaller than those obtained from IVUS analysis. Conclusion. IVUS appears to offer a greater degree of accuracy in measuring arterial lumen diameter. As measurements obtained from angiographic imaging consistently under-estimated vessel size, utilization of IVUS may aid in the determination of treatment algorithms and lead to improved endovascular outcomes.
J INVASIVE CARDIOL 2020;32(3):99-103.
Key words: critical limb ischemia, femoropopliteal arteries, infrapopliteal, superficial femoral artery
The epidemic of peripheral arterial disease (PAD) and, foremost, critical limb ischemia (CLI), continues to escalate annually. Every week, vascular specialists are experiencing first-hand the acute influx of PAD patients and it is estimated that 1% of Americans over the age of 50 years manifest some form of PAD and CLI.1-3 According to the United States Census Bureau, the general population ≥65 years old is projected to number 83.7 million by 2020, and a recent analysis and projections by the Sage Group indicate that the number of CLI patients will reach 2.8-3.5 million by 2020.4
Digital subtraction angiography (DSA) has long been considered the gold standard to size and treat arterial vessels. Despite its critical role, the weakness of angiography falls in the two-dimensional nature of images attempting to extrapolate the three-dimensional space of the vessel lumen. From an anatomic perspective, an arterial vessel is not a straight in-line pipe that carries blood flow without interruption, and angiographic images can be confounded by vessel tortuosity and complex luminal irregularities.5,6 The utilization of intravascular ultrasound (IVUS) has been incorporated into diagnostic and treatment algorithms at all levels, allowing characterization of lumen size, plaque morphology, degree of stenosis, and measurement of residual lumen area.7,8 Ultrasound’s tomography allows for visualization of the full circumference of the vessel wall as opposed to a planar silhouette.9 The use of IVUS in addition to angiography in the femoropopliteal region has been shown to provide a more accurate assessment of postintervention residual stenosis than angiography alone.10 However, at many institutions, IVUS has not been readily adopted due to time and cost restraints. Recent studies have indicated that accuracy of vessel sizing may directly impact the outcomes of endovascular procedures. As the number and complexity of endovascular interventions increases at all infrainguinal levels — and especially infrapopliteal levels — accurate vessel sizing becomes of utmost importance.11
A retrospective analysis was conducted of patients undergoing revascularization via an antegrade as well as a retrograde approach (the tibiopedal arterial minimally invasive [TAMI]12 retrograde revascularization technique). The objective was to compare predicted diameters of treated vessels utilizing angiographic imaging and compare these measurements with diameters obtained via IVUS imaging.
Study design. Prior to study initiation, institutional review board approval was received and a waiver of informed consent was granted. A retrospective analysis was performed of imaging and procedural data from 43 patients who had angiography and IVUS utilized during an endovascular intervention. All procedures were completed from April 2016 to February 2017. Patients who underwent revascularization of any infrainguinal vessel with access and treatment from an antegrade or retrograde approach were eligible. IVUS was utilized per the center’s standard practice to evaluate the traversed arteries and assist with vessel sizing. Images obtained via angiography were reviewed retrospectively by an interventionalist blinded to the IVUS findings.
IVUS imaging. All IVUS data and images were acquired using the s5 Imaging System (Philips Volcano). Cross-sectional vessel diameters were obtained using Vision PV .014 or Vision PV .018 IVUS catheters (Philips Volcano); these IVUS catheters have a 20 mm and 24 mm field of view, respectively. Both catheters are equipped with ChromaFlow imaging technology. The measurement protocol employed for arterial sizing under IVUS was straight-line cross-sectional diameters from the internal border of the tunica media on each side of the vessel. An area with relatively low atherosclerotic burden was identified in each section of the vessel and the cursors were placed at the border of the intima and tunica media (Figures 1 and 2). This approach results in uniform measurements across all segments. The high temporal resolution of IVUS imaging allows for clear demarcation between the intima and the media. The operators avoided choosing segments with severe calcification where acoustic shadowing could limit visualization of the different layers of the vessel. All images were recorded and underwent assessment, tabulation, and sizing throughout the intervention.
Blinded angiographic assessment. DSA imaging was performed throughout the endovascular intervention utilizing the Vision RFD C-arm system (Ziehm Imaging). All vessel images were acquired with iopamidol contrast media (Figures 1 and 2). No carbon dioxide angiography was performed. All recorded images were reviewed retrospectively by a single experienced interventionalist who remained blinded to the IVUS images and corresponding measurements. All vessels were divided in three segments, namely proximal, middle, and distal. The maximum vessel diameter of the patent arteries was assessed based on visual estimation of at least two different planes of the DSA imaging. All vessels were selectively engaged when performing angiography.
Statistical analysis. The statistical analysis was performed with MedCalc statistical software, version 16.4.3 (MedCalc Software). Continuous data are presented as medians with ranges; categorical data are given as counts with percentages. Distributions of continuous data were tested using the D’Agostino-Pearson test. Continuous samples with normal distribution were compared by paired t-test, whereas samples with non-normal distribution were compared with the Wilcoxon test for paired samples. Differences reaching P-value <.05 were considered statistically significant.
Of the 43 patients enrolled, twenty-five were male and 18 were female, with 72% aged 60-89 years. The majority were overweight (mean body mass index, 27 kg/m2). Prior to their intervention, 58% of patients were Rutherford classification (RC) III and 42% had CLI (RC IV or V).
Arterial access was obtained in the common femoral (37%), posterior tibial (37%), and anterior tibial (26%) vessels. Twenty-seven of the 43 interventions utilized the TAMI technique, with pedal access obtained and treatment, including IVUS assessments and tabulations, performed from a retrograde approach (Figure 3).
Infrainguinal arterial IVUS measurements were compared with the estimated visual measurements from DSA imaging of the same arterial segments. Above- and below-the-knee vessels analyzed included the superficial femoral, popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, and peroneal. Overall, regardless of arterial segment, measurements estimated from angiographic images were significantly smaller than those obtained from IVUS analysis (Table 1).
A subgroup analysis was performed comparing IVUS and DSA measurements for males (n = 25) versus females (n = 18). Across all arterial segments, vessel sizing was consistently the same or smaller for female subjects regardless of the imaging modality utilized (Figure 4).
Since the original article by Kunlin published in 1949 in the Archives Mal Coeur,13 the prevalence of distal bypass to tibial vessels grew significantly, as it was the only method for limb salvage.14 However, through the advancement of medical technology, improvement of vascular imaging, and expansion of operator skills, an endovascular-first strategy has since evolved for even the most complex lesions.15,16 Patients with CLI commonly have diffuse, multilevel, and multivessel calcific involvement, and the ability to cross and intervene in this complicated patient subset requires a variety of techniques and a specific skillset tailored to the heterogeneous complexity of the disease.17 The treatment algorithm requires accurate characterization of the vessel size and plaque morphology to ensure successful and efficient access, crossing, and treatment.18
While DSA remains a crucial component of PAD and CLI diagnosis and intervention, its limitations can result in poor representation of the arterial lumen, and visual interpretation demonstrates significant operator variability.5,9 Anatomical and pathological arterial assessment in PAD patients revealed that calcium deposits range from intimal, medial, and adventitial locations.19 However, angiography underestimates the degree of calcification and cannot distinguish the location of calcium deposits. Furthermore, angiography has been found to underestimate the burden of atherosclerotic disease.6 Mustapha et al20 conducted an analysis comparing extravascular ultrasound vs angiography and found better correlation with selective angiography and ultrasound vs non-selective angiography. With non-selective contrast injection, the contrast dissipates, and clear visualization of the tibial vessels cannot be properly obtained.20 Due to altered renal function, the maximum allotted contrast volume is often limited in this patient population, which then constrains vessel imaging.
IVUS is a valuable tool in many respects, and its varied indications of use have been incorporated into diagnostic and treatment algorithms. IVUS’s high level of resolution provides detailed arterial wall characterization that is not interpreted with angiography, and the addition of flow characteristics allows for assessment of dissections and stent wall apposition. The versatile use of this modality was supported by this study, as IVUS was successfully utilized whether the operator delivered therapy from a groin approach or via TAMI technique.12 Despite the relatively small number of patients, IVUS was successfully utilized from a pedal approach in 63% of cases to gain a valuable assessment of appropriate sizing. From this approach, there were no reported adverse events and imaging quality was not impacted. In addition, while angiography alone may incorrectly describe the pathology, IVUS will afford the operator the ability to examine plaque composition and location (intimal vs medial). Utilization of this knowledge to determine treatment decisions could directly impact procedure success.
Poor long-term patency and the need for repeat intervention are challenges faced daily in the endovascular world. A prospective analysis by Arthurs et al5 found that when comparing the maximal diameter stenosis from angiography to the maximal area stenosis from IVUS, the IVUS findings were greater by 10%. Furthermore, the length of plaque stenosis determined by angiographic imaging was 3 mm shorter than the length generated by IVUS imaging.5 A study by Kashyap et al6 supported the conclusion that DSA underestimates the full atherosclerotic disease burden within peripheral vessels. This underestimation may result in inadequate treatment of the initial disease, and a subsequent need for future treatment of remnant rather than recurrent disease.5
Throughout this study’s analysis, visual estimation measurements obtained from angiographic images were consistently smaller across all arterial segments than those obtained from IVUS assessment. The implications of such a finding can directly alter the way we treat patients, and correspondingly alter treatment outcomes. In the IN.PACT DEEP (Drug-Eluting Balloon Versus Standard Balloon Angioplasty for Infrapopliteal Arterial Revascularization in Critical Limb Ischemia) randomized trial,21 a comparison was made between infrapopliteal tibial drug-eluting balloons and balloon angioplasty; the trial failed to show the superiority of drug-eluting balloons. One plausible reason may have been the misinterpretation of tibial vessel diameter, considering that the average balloon size utilized was 2.1 mm.21 This is a stark difference from the average IVUS diameter of tibial vessels obtained in our study. Accurate vessel sizing is necessary to optimize biologic delivery to the adventitia with drug-eluting devices. Additionally, optimal sizing may reduce complications such as stent thrombosis, arterial perforation, and dissection. When utilizing angiography alone, sizing for endovascular devices is determined by luminal rather than true vessel diameters. While further study is warranted, the incorporation of IVUS may aid in determining optimal vessel sizes, which may then translate into superior results.5,6
Study limitations. This was a retrospective analysis evaluating two different imaging modalities. Despite the physician being blinded to the findings of the opposing IVUS imaging modality, this was not a core-lab adjudicated study. In addition, we did not use qualitative coronary analysis of the angiographic images. However, it remains a valid hypothesis-generating approach to an issue that has long been debated among operators.
IVUS is a valuable tool to assist with treatment of the complex vascular anatomy spanning from the aortic arch to the infrainguinal space. Accuracy in vessel wall dimensions and plaque composition is a factor that requires consideration in the treatment plan determination for each vascular lesion. Tibial vessel diameters obtained via IVUS were significantly larger than diameters estimated by angiography across all segments. Currently, IVUS remains the pre-eminent tool in determining plaque morphology and vessel dimension in vivo, and these assessments can help the interventionalist to stratify the therapy based on the above parameters. This study supported that these assessments can be safely performed utilizing pedal access. As a significant number of PAD patients have chronic kidney disease, the amount of contrast that can be safely utilized for DSA imaging is often limited. In this common scenario, IVUS can assist with sizing, anatomic delineation, and evaluation of lesions prior to and after treatment. The incorporation of IVUS into daily practice may aid in the determination of treatment algorithms and, ultimately, improve clinical outcomes.
From the 1Premier Surgical Associates, Knoxville, Tennessee; 2Advanced Cardiac and Vascular Centers for Amputation Prevention, Grand Rapids, Michigan; 3Center of Vascular and Endovascular Surgery, University Clinic of Muenster, Germany; 4Clinic for Vascular Surgery, Athens Medical Centre, Athens, Greece; 5Metro Health – University of Michigan Health, Wyoming, Michigan; and the 6University of North Carolina REX Healthcare, Raleigh, North Carolina.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Adams, Dr Mustapha, and Dr Saab report consultant income from Boston Scientific and Philips. Dr Pliagas reports consultant income from Philips. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted November 1, 2019, provisional acceptance given November 6, 2019, final version accepted November 12, 2019.
Address for correspondence: George A. Pliagas, MD, FRCSC, FACS, Premier Surgical Associates, Vascular Division, 6408 Papermill Drive, Knoxville, TN 37919. Email: email@example.com
- Conte MS. Bypass versus angioplasty in severe ischaemia of the leg (BASIL) and the (hoped for) dawn of evidence-based treatment for advanced limb ischemia. J Vasc Surg. 2010;51:69S-75S.
- Saab F, Mustapha JA. The nuts and bolts of building a critical limb ischemia program. 2015. Available from American College of Cardiology: www.acc.org/latest-in-cardiology/articles/2015/09/02/13/22/the-nuts-and-bolts-of-building-a-critical-limb-ischemia-program.
- Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996;94:3026-3049.
- The SAGE group. Reports that in 2007 approximately 2.8 million people in Western Europe suffered from critical limb ischemia [press release]. October 20, 2008.
- Arthurs ZM, Bishop PD, Feiten LE, Eagleton MJ, Clair DG, Kashyap VS. Evaluation of peripheral atherosclerosis: a comparative analysis of angiography and intravascular ultrasound imaging. J Vasc Surg. 2010;51:933-938.
- Kashyap VS, Pavkov ML, Bishop PD, et al. Angiography underestimates peripheral atherosclerosis: lumenography revisited. J Endovasc Ther. 2008;15:117-125.
- Yock PG, Johnson EL, David DT. Intravascular ultrasound: development and clinical potential. Am J Cardiol Imaging. 1988;2:185-193.
- Weintraub AR, Erbel R, Gorge G, et al. Intravascular ultrasound imaging in acute aortic dissection. J Am Coll Cardiol. 1994;24:495-503.
- Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications. Circulation. 2001;103:604-616.
- Hitchner E, Zayed M, Varu V, Lee G, Aalami O, Zhou W. A prospective evaluation of using IVUS during percutaneous superficial femoral artery interventions. Ann Vasc Surg. 2015;29:28-33.
- Micari, A. The positive impact of proper vessel prep and balloon sizing in tibial interventions. Cath Lab Digest. 2017:19-23.
- Mustapha JA, Saab F, McGoff T, et al. Tibio-pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: the TAMI technique, original case series. Catheter Cardiovasc Interv. 2014;83:987-994.
- Kunlin J. La traitement de l’artérite oblitérante par la greffe veineuse. Arch Mal Coeur. 1949;42:371-374.
- Andros G. Bypass grafts to the ankle and foot. A personal perspective. Surg Clin North Am. 1995;75:715-729.
- TASC Steering Committee, Jaff MR, White CJ, et al. An update on methods for revascularization and expansion of the TASC lesion classification to include below-the-knee arteries: a supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Endovasc Ther. 2015;22:663-677.
- Goodney PP, Beck AW, Nagle J, Welch HG, Zwolak RM. National trends in lower extremity bypass surgery, endovascular interventions, and major amputations. J Vasc Surg. 2009;50:54-60.
- Mustapha JA, Finton SM, Diaz-Sandoval LJ, Saab FA, Miller LE. Percutaneous transluminal angioplasty in patients with infrapopliteal arterial disease: systematic review and meta-analysis. Circ Cardiovasc Interv. 2016;9:e003468.
- Saab F, Jaff MR, Diaz-Sandoval LJ, et al. Chronic total occlusion crossing approach based on plaque cap morphology: the CTOP classification. J Endovasc Ther. 2018;25:284-291.
- Mustapha JA, Diaz-Sandoval LJ, Saab F. Infrapopliteal calcification patterns in critical limb ischemia: diagnostic, pathologic and therapeutic implications in the search for the endovascular holy grail. J Cardiovasc Surg. 2017;58:383-401.
- Mustapha JA, Saab F, Diaz-Sandoval L, et al. Comparison between angiographic and arterial duplex ultrasound assessment of tibial arteries in patients with peripheral arterial disease: on behalf of the Joint Endovascular and Non-Invasive Assessment of LImb Perfusion (JENALI) Group. J Invasive Cardiol. 2013;25:606-611.
- Zeller T, Baumgartner I, Scheinert D, et al. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial. J Am Coll Cardiol. 2014;64:1568-1576.