Intravascular Ultrasound
Number: 0382
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses intravascular ultrasound.
-
Medical Necessity
Aetna considers intravascular ultrasound (IVUS) medically necessary for any of the following situations:
- As a clinical decision-making tool to evaluate the need for an intracoronary interventional procedure in a symptomatic member whose angiogram shows 50 to 70 % stenosis(es); or
- As a conclusive study to assess suspected left main stem coronary artery disease not revealed by coronary angiography; or
- As a guidance for placement of vena caval filter; or
- As a method for both guidance of placement of endoluminal devices and immediate assessment of the results of intracoronary interventional procedures (i.e., angioplasty, atherectomy, stenting), including those performed on coronary grafts; or
- As a method for evaluation of cardiac allograft vasculopathy in post-cardiac transplantation recipients; or
- Diagnosis and follow-up of treatment of iliac vein compression syndrome (May-Thurner syndrome) of the lower extremity; or
- For the treatment of type B aortic dissection with thoracic endovascular aneurysm repair when assessment via CT was compromised by poor image quality or was otherwise inconclusive; or
- For the management of infra-inguinal arterial vascular disease in a member with renal function or another documented health issue precluding the use of standard contrast angiography, so carbon dioxide (CO2) angiography is being used, and documentation supports that initial imaging with the CO2 angiography is suboptimal for clinical decision-making.
-
Experimental, Investigational, or Unproven
Aetna considers the clinical application of IVUS for the following indications experimental, investigational, or unproven because the effectiveness of this approach has not been established:
- Screening for coronary artery disease, diagnosing coronary vulnerable plaques, and its use in other coronary procedures;
- For any of the following (not an all-inclusive list) because its use for these indications has not been validated by clinical studies:
- Diagnosis of aortic dissection
- Diagnosis / evaluation of pulmonary hypertension
- Diagnosis and treatment of functional popliteal artery entrapment syndrome
- During endovascular interventions of failing hemodialysis access grafts
- Evaluation of carotid artery stenosis
- Evaluation of chronic venous obstruction/venous stenting
- Guidance during endovascular treatment of subclavian artery disease
- Guidance in percutaneous mechanical thrombectomy for the treatment of pulmonary embolism
- Prediction of clinical improvement following ilio-femoral vein stenting
- Prediction of outcome following carotid artery stenting
- Stenting of non-coronary arteries
- Thoracic endovascular aortic repair for blunt thoracic aortic injury
- Treatment of lower extremity arterial occlusive disease that does not meet criteria above
- Other non-coronary vascular (i.e., including veins) procedures (other than those listed above).
-
Related Policies
Background
Angiography is limited in determining the anatomic severity of coronary artery stenoses because it represents only a projectional image of the vessel lumen without providing any information concerning vascular wall architecture. Catheter-based intravascular ultrasound (IVUS) has been developed in the last few years to provide this unique perspective for viewing vascular disease and the effects of intervention. As a complement to the information provided by coronary angiography, it has the unique ability to study vessel wall morphology in vivo, accurately displaying the details of vessel structure and tissue characterization by providing such critical information as the presence and degree of calcified plaque, quantifying luminal dimensions, and characterizing the composition of stenotic lesions into soft plaque, hard plaque, calcification, and type of thrombus.
Although these devices have only been available for a relatively short time, an array of studies demonstrating numerous diagnostic and therapeutic applications in interventional cardiology have been reported. The maturity of the technology is such that IVUS currently has a place as a clinical decision-making tool in patients with symptoms and intermediate lesions, as a provisional study to assess left main stem disease suspected but not disclosed by coronary angiography, and as a method for both guidance of endoluminal devices and immediate assessment of the results of therapeutic techniques, including balloon angioplasty, atherectomy, and intravascular stent deployment.
More research is needed to answer some important questions regarding the whole array of potential applications of IVUS. Newer developments under scrutiny include combined devices, looking-forward ultrasound, high-frequency probes, imaging wires, tissue characterization and three dimensional (3-D) technology.
Its use in peripheral vascular disease remains as a research tool for investigation of blood vessel compliance, dynamic changes in the vessel wall caused by disease or pharmacologic intervention, and elucidation of the morphologic changes associated with the natural history of atherosclerosis. It has not been proven that changes in treatment made based on the results of intravascular ultrasound improve health outcomes in patients with non-coronary vascular diseases.
Intravascular ultrasound has been used as a guidance for for placement of inferior vena cava filters. Ashley et al (2001) reported that IVUS is a more accurate method of localizing the renal veins and measuring vena cava diameter for placement of vena cava filters than contrast venography. Mathews et al (2003) noted that imaging of the vena cava prior to the insertion of an inferior vena cava (IVC) filter is mandatory to assess IVC diameter and patency, delineate anatomy and venous anomalies, and to direct filter placement for appropriate deployment and avoidance of complications. The standard imaging technique is vena cavography, although alternative methods to evaluate the IVC include carbon dioxide venography, trans-abdominal duplex ultrasound, and IVUS.
Wellons et al (2004) stated that reports have demonstrated the benefit of prophylactic inferior vena cava filter (IVCF) placement to prevent pulmonary embolism. This study evaluated the potential for the bedside placement of a removable IVCF under "real-time" IVUS guidance. A total of 20 trauma patients underwent intensive care unit placement of a removable IVCF with IVUS guidance. All patients had ultrasonography of the femoral veins after placement to rule out post-procedure femoral vein thrombosis and radiographs to identify filter location. Nineteen of 20 IVCFs were placed at approximately the L2 level as verified by radiography. One patient had a large IVC (34 mm) and underwent bilateral common iliac IVCF placement under IVUS. Within 3 weeks of placement, 12 IVCFs were retrieved. Of the remaining 8 patients, 6 had indications for permanent implantation, 2 had contralateral deep venous thrombosis, and 1 had ipsilateral deep venous thrombosis. The authors concluded that bedside insertion of a removable IVCF with IVUS guidance and its removal are simple, safe, and accurate.
Passman et al (2005) stated that bedside placement of ICVF by using either trans-abdominal duplex ultrasonography or IVUS has been shown to be safe and effective. The authors reviewed techniques for bedside filter placement with trans-abdominal duplex ultrasonography, IVUS with dual venous access, and IVUS with single venous access. They noted that trans-abdominal duplex ultrasonography and IVUS remain their preferred techniques for filter placement when feasible, especially in critically ill and immobilized patients.
- to evaluate DES expansion by comparing IVUS-measured MSD and MSA against the values predicted by compliance charts and
- to compare each DES against its bare-metal stent (BMS) equivalent.
The randomized TAXUS II trial evaluates the polymer-based paclitaxel-eluting Taxus stent in slow- and moderate-release formulations. Tsuchida et al (2007) examined the consistency between angiographic and IVUS outcomes of late lumen loss (late loss) and neointimal growth to measure restenotic plaque load in Taxus and BMS. Serial angiographic and IVUS analyses were available in 155 event-free patients (BMS, n = 74; Taxus stent, n = 81) after the procedure, at 6 months, and at 2 years. For this sub-analysis, quantitative coronary angiographic (QCA) and IVUS measurements were used to derive late loss and neointimal volume. From after the procedure to 6 months, QCA and IVUS showed matching results for the 2 groups with significant decreases in late loss and neointimal volume in the Taxus versus the control group. From 6 months to 2 years, QCA and IVUS measurements also showed results similar to those in the control group, demonstrating neointimal compaction over time. However, in the Taxus group, QCA late loss showed a non-significant decrease from 6 months to 2 years, whereas IVUS neointimal volume increased. The authors concluded that although QCA and IVUS results were similar over the first 6 months, long-term assessment of changes in re-stenotic plaque load showed discrepant findings for the Taxus stent. These findings suggest the need for critical re-evaluation of current end points and the use of more precise techniques to detect lumen and stent boundaries.
Hoffmann and colleagues (2008) stated that the impact of incomplete stent apposition (ISA) after drug-eluting stent implantation determined by IVUS on late clinical events is not well-defined. These researchers assessed the clinical impact of ISA after sirolimus-eluting stent (SES) placement during a follow-up period of 4 years. Intravascular ultrasound at angiographic follow-up was available in 325 patients (SES, n = 180; BMS, n = 145); IVUS images were reviewed for the presence of ISA defined as one or more unapposed stent struts. Frequency, predictors and clinical sequel of ISA at follow-up after SES and BMS implantation were determined. Incomplete stent apposition at follow-up was more common after SES (n = 45 (25 %)) than after BMS (n = 12 (8.3 %), p < 0.001). Canadian Cardiology Society class III or IV angina at stent implantation (odds ratio (OR) = 4.69, 95 % confidence interval [CI]: 2.15 to 10.23, p < 0.001) and absence of diabetes (OR = 3.42, 95 % CI: 1.05 to 11.1, p = 0.041) were predictors of ISA at follow-up after SES placement. Rate of myocardial infarction tended to be slightly higher for ISA than for non-ISA patients. When only SES patients were considered, major adverse cardiac event free survival at 4 years was identical for those with and without ISA at follow-up (11.1 % versus 16.3 %, p = 0.48). The authors concluded that ISA at follow-up is more common after SES implantation than after BMS implantation. Considering the current very sensitive IVUS definition, ISA appears to be an IVUS finding without significant impact on the incidence of major adverse cardiac events even during long-term follow-up.
García-García et al (2008) stated that detection of coronary vulnerable plaques in vivo is essential for studying their natural history and assessing potential treatment modalities and, therefore, may have an important impact on the prevention of acute myocardial infarction and death. Currently, conventional grayscale IVUS, IVUS-virtual histology (IVUS-VH) and palpography data are being collected with the same catheter during the same pullback. A combination of this catheter with either thermography capability or additional imaging, such as optical coherence tomography or spectroscopy, would be an exciting development. Intravascular magnetic resonance imaging also holds much promise. To date, none of the techniques described above has been sufficiently validated and, most importantly, their predictive value for adverse cardiac events remains elusive. The authors noted that very rigorous and well-designed studies are needed for defining the role of each diagnostic modality. In this regard, Ibanez and colleagues (2009) consider IVUS as an investigational technique for the visualization as well as the compositional characterization of atheromatous plaques.
Clementi et al (2009) noted that plaque reduction with the use of pioglitazone and statin combination therapy has been observed in carotid plaque. These researchers examined the effect of combination therapy with statins and pioglitazone on coronary plaque regression and composition with the use of IVUS and IVUS-VH. These investigators analyzed 29 plaques in 25 diabetic patients with angiographic evidence of non-significant coronary lesions with IVUS-VH. Patients were treated with 80 mg of atorvastatin and 30 mg of pioglitazone daily for 6 months. After 6 months of therapy, IVUS-VH of each lesion was re-acquired. Mean elastic external membrane volume was significantly reduced between baseline and follow-up (343.0 mm versus 320.5 mm; p < 0.05) as was mean total atheroma volume (179.3 mm versus 166.6 mm; p < 0.05). Change in total atheroma volume showed a 6.3 % mean reduction. Areas of fibrous tissue, fibro-lipidic tissue and calcium decreased over the 6 months of follow-up, although not significantly. On the other hand, the necrotic core increased from 9 % to 14 % (p < 0.05). The authors concluded that these findings demonstrated that atorvastatin/pioglitazone association is able to induce significant regression of coronary atherosclerosis, acting on plaque composition. Moreover, they noted that their findings are preliminary results and will be confirmed in an ongoing randomized placebo-controlled multi-center trial.
An assessment prepared for the Agency for Healthcare Research and Quality (Lau et al, 2004) concluded that currently, neither IVUS nor other imaging technologies can reliably identify vulnerable plaque prospectively, i.e., before rupture.
Konig et al (2008a) noted that cardiac allograft vasculopathy (CAV) is the major limitation in survival of patients following heart transplantation. Cardiac allograft vasculopathy is angiographically silent in the early phase after operation. Intravascular ultrasound is a more sensitive method to detect the early stages of CAV and provides information about its development. Recent IVUS studies demonstrated a rapid progression of CAV within the 1st year after transplantation as a predictor of morbidity and mortality. These investigators evaluated the plaque composition of early atherosclerosis in transplant patients by radiofrequency (RF) analysis. Coronary angiography and IVUS with Virtual Histology (VH) software were used to assess 18 patients early after heart transplantation (1.71 +/- 0.47 months). The plaque composition was determined by IVUS radiofrequency data analysis. Tissue maps were reconstructed from RF data using VH-IVUS software. The VH-IVUS acquisition was performed with standardized IVUS and the VH-IVUS console. Coronary angiography did not show any wall irregularities; IVUS demonstrated donor-transmitted atherosclerosis in 6 of 18 patients (33.33 %). The incidence, amount of plaque burden, and plaque composition was significantly related to donor age. By VH-IVUS analysis, the plaque composition consisted mainly of fibrotic tissue. The authors concluded that donor-transmitted coronary atherosclerosis is present early after heart transplantation and can not be detected by coronary angiography; VH-IVUS gives detailed information about the plaque distribution and the plaque composition.
- Group I: 1 to 3 months (n =18);
- Group II: 1 to 5 years (n = 20); and
- Group III: 5 to 15 years (n = 18).
Hernandez et al (2009) characterized graft coronary artery disease by means of VH-IVUS at different time-points of follow-up and correlated plaque composition with clinical factors. These investigators included 67 patients (mean age of 7.6 +/- 5.7 years post-heart transplant (HTx); and IVUS gray-scale evaluation was performed on all patients. VH-IVUS analysis was done in those patients showing intimal thickening greater than 0.5 mm at the 3 more significant lesions (3 cross-sections for each) of the left anterior descending artery. VH-IVUS analysis was obtained on 58 patients (86.5 %). They found a significant correlation between time of HTx and IVUS gray-scale parameters (plaque area and plaque burden), with both increasing over time. They also found a significant correlation between time and VH-IVUS-derived plaque components, necrotic core and calcium, which increased with time, and fibrous and fibro-fatty components, both decreased at follow-up. VH-IVUS results were also related to donor age and cardiovascular risk factors. The authors observed a time-related change in VH-IVUS-derived plaque composition. Necrotic core and calcium, typical atheromatous components, become more prevalent with time after HTx, especially when influenced by cardiovascular risk factors. The presence of a necrotic core in the early stages was linked to older donor age.
Raichlin et al (2009a) investigated tissue characterization of the coronary allograft atherosclerotic plaque with VH-IVUS imaging to assess the presence and predictors of vessel wall inflammation and its significance in CAV progression. A total of 86 patients with CAV underwent VH-IVUS examination of the left anterior descending coronary artery 3.61 +/- 3.04 years following cardiac transplantation. Based on the VH-IVUS plaque characteristics, coronary allograft plaque was divided on VH-IVUS-derived "inflammatory" (VHD-IP) (necrotic core and dense calcium greater than or equal to 30 %) and "non-inflammatory" plaque (VHD-NIP) (necrotic core and dense calcium less than 30 %). Total rejection scores were calculated based on the 2004 International Society of Heart and Lung Transplantation rejection grading system. Overall, the mean percentage of fibrous, fibro-fatty, dense calcified, and necrotic core plaques in a mean length of 62.3 +/- 17.4 mm of the left anterior descending coronary artery were 50 +/- 17 %, 16 +/- 11 %, 15 +/- 11 %, and 18 +/- 9 %, respectively. Patients with a 6-month total rejection score greater than 0.3 had significantly higher incidence of VHD-IP than those with a 6-month total rejection score less than or equal to 0.3 (69 % versus 33 %, p = 0.011). The presence of VHD-IP at baseline was associated with a significant increase in plaque volume (2.42 +/- 1.78 mm(3)/mm versus -0.11 +/- 1.65 mm(3)/mm, p = 0.010), plaque index (7 +/- 9 % versus 0 +/- 8 %, p = 0.04), and re-modeling index (1.24 +/- 0.44 versus 1.09 +/- 0.36, p = 0.030) during 12 months of follow-up when compared with the presence of VHD-NIP at baseline and during follow-up. The authors concluded that the presence of VHD-IP as assessed by VH-IVUS is associated with early recurrent rejection and with higher subsequent progression of CAV. A VH-IVUS assessment may add important information in the evaluation of transplant recipients.
Raichlin et al (2009b) investigated the role of cellular rejection in CAV development. The study comprised 252 cardiac transplant recipients (mean age of 49.02 +/- 17.05 years; mean follow-up of 7.61 +/- 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R = 1, 2R = 2, 3R = 3) and any rejection score (ARS; calculated as 0R = 0, 1R = 1, 2R = 1; 3R = 1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. Cardiac allograft vasculopathy was defined as coronary stenosis of 40 % or more and/or distal pruning of secondary side branches. A total of 32 patients had undergone 3-dimensional IVUS at baseline and with VH-IVUS at 24 months. In uni-variate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95 % CI: 0.99 to 3.90, p = 0.05) and ARS (HR, 2.22; 95 % CI: 1.01 to 4.95; p = 0.047) were associated with increased risk of CAV. In multi-variate analysis, 6-month TRS (HR, 2.84; 95 % CI: 1.44 to 6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset (p = 0.018). There was direct correlation (r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core shown by VH-IVUS at 24 months. The authors concluded that recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.
Sarno and colleagues (2009) used VH-IVUS to characterize plaque burden and tissue composition over time in heart transplant recipients. These researchers recruited patients undergoing heart transplantation in 4 centers in Europe and the U.S. between 2004 and 2006. They used IVUS to obtain morphological plaque measurements and to perform virtual histology in the left anterior descending coronary artery. Data were characterized according to the duration between transplantation and IVUS assessment: less than or equal to 24, greater than 24 to 60, greater than 60 to 120 and greater than 120 to 192 months. They assessed vessels from 152 patients (mean age of 58 +/- 12 years) a mean of 70 +/- 53 months (range of 1 week to 16 years) after transplantation. Plaque burden of greater than 40 % was observed in 26 % of vessels analyzed, with increases from baseline being seen in all time categories. If assessed greater than 24 months after transplantation, necrotic core and dense calcified volumes were significantly greater than at baseline (p = 0.0005 and p = 0.01, respectively). Time since heart transplantation and donor age and recipient age were independent predictive factors of increased necrotic core content. Necrotic core volume greater than 2.01 mm(3), diabetes mellitus, donor age older than 40 years, follow-up from transplantation longer than 5 years and recipient age older than 58 years were associated with the need for re-vascularization. The authors concluded that in CAV, plaque burden and composition change over time and seem to affect clinical outcome. This relationship might facilitate identification of high-risk patients in whom the value of more aggressive medical therapy should be tested.
Diethrich and colleagues (2007) determined the diagnostic accuracy of virtual histology IVUS imaging (VH IVUS) of carotid plaque and assessed the feasibility of VH IVUS to identify plaque with embolic potential in patients undergoing carotid artery stenting (CAS). A total of 30 patients (17 men; mean age of 74 +/- 7 years) were entered non-randomly into a single-center, prospective, 2-arm study following FDA and Institutional Review Board approval. In the 1st arm, 15 patients underwent VH IVUS examination of carotid plaque with a cerebral protection device immediately followed by carotid endarterectomy (CEA). A comparison of "virtual" with true histology was then performed, classifying plaque type by VH IVUS and histopathology in a blinded study. In the 2nd arm, 15 patients undergoing CAS had a preliminary VH IVUS scan performed with cerebral protection. Debris collected from the filter following stenting was examined histologically and compared with the VH IVUS data. The diagnostic accuracy of VH IVUS to agree with true histology in different carotid plaque types was 99.4 % in thin-cap fibroatheroma, 96.1 % for calcified thin-cap fibroatheroma, 85.9 % in fibroatheroma, 85.5 % for fibrocalcific, 83.4 % in pathological intimal thickening, and 72.4 % for calcified fibroatheroma. Filter debris was captured in 2 patients prior to CEA and in 4 patients undergoing CAS for restenosis; VH IVUS classification of plaque composition was consistent with the histological evaluation of filter fragments. Calcified nodules projecting into the carotid artery lumen were associated with a higher incidence of previous neurological symptoms (66.7 % versus 33.3 %, p < 0.05), while patients on aspirin has significantly less necrotic lipid core plaque detected by VH IVUS than patients not taking aspirin (6.4 % +/- 4.7 % versus 9.7 % +/- 2.8 %, p < 0.05). The authors concluded that these findings showed a strong correlation between VH IVUS plaque characterization and the true histological examination of the plaque following endarterectomy, particularly in "vulnerable" plaque types. The feasibility study to examine VH IVUS data and the filter debris histology in CAS patients supports a larger prospective study.
Mokin et al (2013) noted that IVUS is an important diagnostic tool in many interventions, particularly coronary and carotid artery angioplasty and stenting. In contrast, its application in the management of diseases of the cerebral venous system remains an unexplored territory. These investigators reported the findings of 3 patients in whom IVUS was used during angiography for the evaluation of venous flow obstruction secondary to venous sinus thrombosis, venous sinus stenosis, and a transverse sinus mass lesion, respectively. In addition, these researchers reviewed current literature to summarize previous experience, focusing on the advantages and limitations of IVUS technology in interventional cardiology, carotid artery disease, and venous disease. In all 3 cases, IVUS was used without any complications and provided critical information that guided further management of these distinct diseases. Intravascular US helped diagnose the presence of intraluminal thrombus, severe stenosis, and a mass lesion in the transverse sinuses and also helped assess the response to angioplasty of the stenotic regions. The authors concluded that IVUS is a promising tool that has potential to improve diagnostic accuracy and to guide the management of several diseases of the cerebral venous system.
Hitchner et al (2014) stated that the clinical use of IVUS in carotid intervention is not well characterized. These investigators evaluated the role of IVUS in carotid plaque characterization and determine whether it could be predictive of procedure-related microemboli. From July 2010, patients with severe carotid stenosis who underwent elective carotid stenting procedures were prospectively enrolled. Intravascular US evaluation was performed before stent placement. Patient demographics, co-morbidities, and pre-operative images were recorded. Comparison of pre- and post-operative diffusion-weighted magnetic resonance images was used to identify the number of procedure-related microemboli. Intravascular US-derived minimal lumen diameter and vessel wall plaque characteristics were collected. Uni-variate and multi-variate logistic regressions were used to search for associations between IVUS-derived virtual histology (VH) data and incidence of microemboli. A total of 38 high-risk patients receiving carotid stenting were enrolled. Among them, 25 patients had type I aortic arches and 17 of the patients were symptomatic (pre-operative stroke or transient ischemic attack). Virtual histology IVUS data did not show strong associations with microemboli, however, a trend was found between the area of fibrous tissue and median or more incidence of microemboli (p = 0.099). Intravascular US-defined vessel diameter maximum was associated with median or more incidence of microemboli (p = 0.042). In addition, median or more incidence of microemboli showed trends with proximal common carotid artery calcification (p = 0.056) and with being over the age of 80 (p = 0.06). Contralateral carotid occlusion or high-grade stenosis was associated with post-operative contralateral microemboli (p = 0.036). The authors concluded that they demonstrated that peri-procedural carotid IVUS is clinically feasible. Moreover, they stated that VH IVUS may be helpful in better understanding plaque morphology and determining optimal stent placement. However, its use in predicting microembolization remains limited.
Witzenbichler et al (2014) examined if IVUS guidance is associated with improved clinical outcomes after DES implantation in an unrestricted patient population. Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multi-center, non-randomized "all-comers" study of 8,583 consecutive patients at 11 international centers designed to determine the frequency, timing, and correlates of stent thrombosis and adverse clinical events after DES. Propensity-adjusted multi-variable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes. IVUS was utilized in 3,349 patients (39 %), and larger-diameter devices, longer stents, and/or higher inflation pressures were used in 74 % of IVUS-guided cases. IIVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis (0.6 % [18 events] versus 1.0 % [53 events]; adjusted HR, 0.40; 95 % CI: 0.21 to 0.73; p = 0.003), myocardial infarction (MI) (2.5 % versus 3.7 %; adjusted HR, 0.66; 95 % CI: 0.49 to 0.88; p = 0.004), and composite adjudicated major adverse cardiac events (i.e., cardiac death, MI, or stent thrombosis) (3.1 % versus 4.7 %; adjusted HR, 0.70; 95 % CI: 0.55 to 0.88; p = 0.002). The benefits of IVUS were especially evident in patients with acute coronary syndromes (ACS) and complex lesions, although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease. The authors concluded that in ADAPT-DES, the largest study of IVUS use to-date, IVUS guidance was associated with a reduction in stent thrombosis, MI, and major adverse cardiac events within 1 year after DES implantation.
Ahn et al (2014) stated that there are conflicting data regarding the benefit of IVUS-guided percutaneous coronary intervention (PCI) over angiography-guided PCI. Since the last meta-analysis was published, several new studies have been reported. These researchers performed a comprehensive meta-analysis to evaluate the clinical impact of IVUS-guided PCI with DES compared with conventional angiography-guided PCI. This meta-analysis included 26,503 patients from 3 randomized and 14 observational studies; 12,499 patients underwent IVUS-guided PCI and 14,004 underwent angiography-guided PCI. Main outcome measures were total mortality, MI, stent thrombosis, and target lesion revascularization (TLR). IVUS-guided PCI was significantly associated with more stents, longer stents, and larger stents. Regarding clinical outcomes, IVUS-guided PCI was associated with a significantly lower risk of TLR (OR 0.81, 95 % CI: 0.66 to 1.00, p = 0.046). In addition, the risk of death (OR 0.61, 95 % CI: 0.48 to 0.79, p < 0.001), MI (OR 0.57, 95 % CI: 0.44 to 0.75, p < 0.001), and stent thrombosis (OR 0.59, 95 % CI: 0.47 to 0.75, p < 0.001) were also decreased. The authors concluded that the findings of this meta-analysis demonstrated that IVUS-guided PCI was associated with lower risk of death, MI, TLR, and stent thrombosis after DES implantation.
May-Thurner syndrome (MTS), also known as the iliac vein compression syndrome, is a rare condition in which compression of the common venous outflow tract of the left lower extremity may cause discomfort, swelling, pain or deep venous thrombosis (DVT) in the iliofemoral vein. May-Thurner syndrome should be considered in patients who have no other obvious reason for hypercoagulability and who present with left lower extremity thrombosis. Venography will demonstrate the classical syndrome when causing deep venous thrombosis. Intravascular ultrasound can detect nonthrombotic iliac vein lesions in symptomatic patients.
Hong et al (2015) examined if the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multi-center trial was conducted in 1,400 patients with long coronary lesions (implanted stent greater than or equal to 28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related MI, or ischemia-driven TLR at 1 year, analyzed by intention-to-treat. Overall, 1-year follow-up was complete in 1,323 patients (94.5 %). Major adverse cardiac events at 1 year occurred in 19 patients (2.9 %) undergoing IVUS-guided and in 39 patients (5.8 %) undergoing angiography-guided stent implantation (absolute difference, -2.97 % [95 % CI: -5.14 % to -0.79 %]) (HR, 0.48 [95 % CI: 0.28 to 0.83], p = 0.007). The difference was driven by a lower risk of ischemia-driven TLR in patients undergoing IVUS-guided (17 [2.5 %]) compared with angiography-guided (33 [5.0 %]) stent implantation (HR, 0.51 [95 % CI: 0.28 to 0.91], p = 0.02). Cardiac death and target lesion-related MI were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4 %) in the IVUS-guided group and 5 patients (0.7 %) in the angiography-guided group (HR, 0.60 [95 % CI: 0.14 to 2.52], p = 0.48). Target lesion-related MI occurred in 1 patient (0.1 %) in the angiography-guided stent implantation group (p = 0.32). The authors concluded that among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of TLR.
In reviewing the afore-mention study, Meyer (2015) noted that “Despite strikingly low adverse event rates with drug-eluting stent placement, intravascular ultrasound–guided stent implantation yielded modest benefits over angiography-guided implantation”. The editorial comment stated that “Although these findings show that everolimus-eluting stents are safe and effective in patients with long coronary lesions, IVUS-guided stent implantation yielded a relatively small absolute reduction in coronary events (2.9 %) over angiography-guided stent implantation – a difference primarily related to fewer TLRs. Considering this modest advantage (as well as the higher costs of IVUS-guided implantation), IVUS should be used only for selected lesions”.
With regard to intravascular ultrasound for treatment of lower extremity arterial occlusive disease, Secemsky, et al. (2022) reviewed the evidence on IVUS on peripheral vascular interventions. While there is some evidence to suggest that IVUS may be useful, there is no consensus on which scenario it would be more beneficial and if its use would impact care in the sense that it would affect the treatment plan.
Diagnosis of Aortic Dissection
The diagnosis of aortic dissection is generally made non-invasively using computed tomography (CT), magnetic resonance imaging (MRI), or trans-esophageal echocardiography (TEE).
On behalf of the American College of Emergency Physicians, Diercks et al (2015) stated that in adult patients with suspected non-traumatic thoracic aortic dissection, emergency physicians may use CT angiogram (CTA) to exclude thoracic aortic dissection because it has accuracy similar to that of magnetic resonance angiogram (MRA) and TEE. It did not mention IVUS.
Furthermore, an UpToDate review on “Clinical features and diagnosis of acute aortic dissection” (Manning and Black, 2016) does not mention IVUS as a diagnostic tool.
Diagnosing Functionally Significant Non-Left Main Coronary Artery Disease and Determining Whether or Not To Proceed With the PCI of Intermediate Non-Left Main Coronary Artery Stenosis
Jang and colleagues (2016) noted that IVUS-guided PCI frequently results in unnecessary stenting due to the low positive predictive value of IVUS-derived minimal lumen area (MLA) for identification of functionally significant coronary stenosis. In a meat-analysis, these investigators appraised the diagnostic accuracy of IVUS-derived MLA compared with the fractional flow reserve (FFR) to assess intermediate coronary stenosis. These investigators searched Medline and Cochrane databases for studies using IVUS and FFR methods to establish the best MLA cut-off values to predict significant non-left main coronary artery stenosis. Summary estimates were obtained using a random-effects model. The 17 studies used in this analysis enrolled 3,920 patients with 4,267 lesions. The weighted overall mean MLA cut-off value was 2.58 mm2. The pooled MLA sensitivity that predicted functionally significant coronary stenosis was 0.75 (CI: 0.72 to 0.77) and the specificity was 0.66 (CI: 0.64 to 0.68). The positive likelihood ratio (LR) was 2.33 (CI: 2.06 to 2.63) and LR (-) was 0.33 (CI: 0.26 to 0.42). The pooled diagnostic OR (DOR) was 7.53 (CI: 5.26 to 10.76) and the area under the summary receiver operating characteristic curve (ROC) for all the trials was 0.782 with a Q point of 0.720. Meta-regression analysis demonstrated that an FFR cut-off point of 0.75 was associated with a 4 times higher diagnostic accuracy compared to that of 0.80 (relative DOR: 3.92; 95 % CI: 1.25 to 12.34). The authors concluded that IVUS-derived MLA has limited diagnostic accuracy in predicting functionally significant coronary artery disease and cannot be used alone to make the decision whether or not to proceed with the PCI of intermediate non-left main coronary artery stenosis.
- the majority of studies included in this analysis were observational studies from different cohorts with no randomized controlled trials (RCTs). This caused the findings to have insufficient power,
- the proportion of the involved coronary arteries and extent of coronary diseases were different across the included studies. It was not possible to suggest the diagnostic performance of IVUS-MLA according to the lesion location,
- the researchers could not perform separate subgroup analyses of all coronary arteries and their location (proximal-, mid-, distal-) because very few studies presented such data,
- these investigators could not differentiate patients presenting with stable angina and acute coronary syndrome, despite differences in clinical significance of IVUS-derived MLA and FFR,
- the IVUS criteria to discriminate the functional significance of lesions in different locations were applied differently across studies, and
- the authors did not take into account the plaque composition that can affect clinical outcomes.
During Endovascular Interventions of Failing Hemodialysis Access Grafts
Ross and colleagues (2016) noted that arterio-venous (AV) access graft complications represent a serious complication in patients undergoing hemodialysis. Angiography is one method of visualizing them. However, angiography is not always an effective means of detecting lesions that occur in this context. Intravascular ultrasound is an adjunct modality used to identify stenoses responsible for failing access by identifying multiple stenoses, including those that are most severe. In a pilot, single-center randomized study, these researchers examined the value of IVUS in patients with failing AV access grafts by comparing digital subtraction angiography (DSA) alone with DSA followed by IVUS. They compared IVUS with DSA in patients with failing hemodialysis access grafts. It consisted of 100 randomized hemodialysis patients presenting with failing AV access who were being considered for endovascular intervention. Interventions in the control group were guided by DSA alone, whereas interventions in the test group were guided by DSA followed by IVUS. Patients were observed for 6 months after intervention. The primary end-point was the time in days to AV access graft failure after the index intervention, expressed as median and interquartile range (IQR). Secondary analyses included influence of DSA and IVUS on index procedure decision-making and percentage of patients with AV access graft re-interventions or discontinuation through 3 and 6 months. Median time to first AV graft re-intervention or discontinuation was 61 days in the test group and 30 days in the control group (p = 0.16), with analysis limited to patients who experienced re-intervention or discontinuation (n = 59). Intravascular US resulted in a change in treatment plan in 76 % (44/58) of patients, with no treatment change after IVUS in 24 % (14/58) of patients. At 6 months, approximately 35 % of patients in both the control and test groups remained free from re-interventions (p = 0.88). At 6 months, approximately 75 % of patients in the control group and 80 % of patients in the test group remained free from AV graft discontinuation or abandonment (p = 0.45). The authors concluded that the findings of this pilot study suggested that addition of IVUS to standard angiography during endovascular interventions of failing hemodialysis access grafts holds potential to extend the time to the first re-intervention. The data supported the design and execution of an adequately powered randomized trial with longer follow-up to reliably discern the clinical benefit of IVUS as an addition to standard angiography in the setting of failing AV access grafts.
Diagnosis and Treatment of Ilio-Femoral Vein Obstruction
Neglen and Raju (2002) compared IVUS with transfemoral venography in the assessment of chronic iliac vein obstruction. IVUS and standard, single-plane, transfemoral venography were performed in 304 consecutive limbs during balloon dilation and stenting of an obstructed iliac venous segment. The appearance of the obstruction was described, and the degree of stenosis (maximal diameter reduction) was estimated with venography and IVUS. The stenotic area was derived with diameter calculations (pir(2)) and also was measured with the built-in software of the IVUS apparatus before and after dilation and stenting in 173 limbs. Pre-operative hand/foot differential pressure and pre-operative dorsal foot venous and intra-operative transfemoral hyperemia-induced pressure elevations after intra-arterial injection of papaverine hydrochloride were measured. With IVUS, fine intraluminal and mural details were detected (e.g., trabeculation, frozen valves, mural thickness, and outside compression) that were not seen with venography. The median stenosis (with diameter reduction) on venographic results was 50 % (range of 0 to 100 %) and on IVUS results was 80 % (range of 25 % to 100 %). In a comparison with IVUS as the standard, venography had poor sensitivity (45 %) and negative predictive value (NPV; 49 %) in the detection of a venous area stenosis of greater than 70 %. The actual stenotic area was more severe when measured directly with IVUS (0.31 cm(2); range of 0 to 1.68 cm(2)) versus derived (0.36 cm(2); range of 0 to 3.08 cm(2); p < 0.001), probably as a result of the non-circular lumen geometry of the stenosis. No correlation was found between any of the pre-operative or intra-operative pressure measurements and degree of stenosis with or without collaterals. When collaterals were present, a more severe stenosis (median of 85 %; range of 25 % to 100 %) was observed (versus a 70 % stenosis in the absence of collaterals; range of 30 % to 99 %; p < 0.001), along with actual stenotic area (with collaterals: median, 0.24 cm(2); range of 0 to 1.18 cm(2); without collaterals: median of 0.45 cm(2); range of 0.02 to 1.68 cm(2); p < 0.01) and a higher rate of hyperemia-induced pressure gradient (greater than or equal to 2 mm Hg; with collaterals, 34 %; without collaterals, 11 %; p < 0.05). The authors concluded that venous IVUS appeared to be superior to single-plane venography for the morphologic diagnosis of iliac venous outflow obstruction and is an invaluable assistance in the accurate placement of venous stents after venoplasty. No pre-operative or intra-operative pressure test appeared to adequately measure the hemodynamic significance of the stenosis . In lieu of adequate hemodynamic tests, IVUS determination of morphologically significant stenosis appeared to be presently the best available method for the diagnosis of clinically important chronic iliac vein obstruction. Collateral formation should perhaps be looked on as an indicator of a more severe stenosis, although significant obstruction may exist with no collateral formation. Moreover, they stated that better tests for the evaluation of hemodynamic significance of venous obstruction must be developed.
Gagne and associates (2017) noted that the Venogram versus IVUS for Diagnosing Iliac vein Obstruction (VIDIO) trial was designed to compare the diagnostic efficacy of (IVUS with multi-planar venography for ilio-femoral vein obstruction. During a 14-month period beginning July 2014, a total of 100 patients with chronic Clinical, Etiologic, Anatomic, and Pathophysiologic clinical class C4 to C6 venous disease and suspected ilio-femoral vein obstruction were enrolled at 11 U.S. and 3 European sites. The inferior vena cava and common iliac, external iliac, and common femoral veins were imaged. Venograms were measured for vein diameter; IVUS provided diameter and area measurements. Multi-planar venograms included 3 views: antero-posterior and 30-degree right and left anterior oblique views. A core laboratory evaluated the de-identified images, determining stenosis severity as the ratio between minimum luminal diameter and reference vessel diameter, minimal luminal area, and reference vessel area. A 50 % diameter stenosis by venography and a 50 % cross-sectional area (CSA) reduction by IVUS were considered significant. Analyses assessed change in procedures performed on the basis of imaging method and concordance of measurements between each imaging method. Venography identified stenotic lesions in 51 of 100 subjects, whereas IVUS identified lesions in 81 of 100 subjects. Compared with IVUS, the diameter reduction was on average 11 % less for venography (p < 0.001). The intra-class correlation coefficient was 0.505 for vein diameter stenosis calculated with the 2 methods. IVUS identified significant lesions not detected with 3-view venography in 26.3 % of patients. Investigators revised the treatment plan in 57 of 100 cases after IVUS, most often because of failure of venography to detect a significant lesion (41/57 [72 %]). IVUS led to an increased number of stents in 13 of 57 subjects (23 %) and the avoidance of an endovascular procedure in 3 of 57 subjects (5 %). Overall, IVUS imaging changed the treatment plan in 57 patients; 54 patients had stents placed on the basis of IVUS detection of significant ilio-femoral vein obstructive lesions not appreciated with venography, whereas 3 patients with significant lesions on venography had no stent placed on the basis of IVUS. The authors concluded that IVUS is more sensitive for assessing treatable ilio-femoral vein stenosis compared with multi-planar venography and often led to revised treatment plans and the potential for improved clinical outcome.
Lower Limb Re-Vascularization in Patients with Peripheral Arterial Disease
Makris and colleagues (2017) examined the safety and effectiveness of IVUS during lower limb endovascular interventions in patients with peripheral arterial disease (PAD). These researchers carried out a systematic review of the PubMed and Scopus databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical studies evaluating IVUS as an adjunct to angiography during re-vascularization procedures in patients with PAD were included. A total of 13 studies were identified, with a total number of 2,258 patients having had IVUS for PAD intervention; 7 studies investigated the role of IVUS for angioplasty and stenting, with the majority being retrospective cohorts. Technical success and patency rates ranged from 90 to 100 % and 45 to 100 %, respectively, with a follow-up that ranged from 4.3 to 63 months; 3 of these studies compared IVUS and non-IVUS guided angioplasty and demonstrated a significant difference in the events of amputations or re-interventions in favor of the IVUS group. Furthermore, 5 studies evaluated IVUS use in true-lumen re-entry, with the technical success ranging between 97 to 100 %. In 1 study, where IVUS was used for atherectomy, the technical success was 100 % and the long-term patency was 90 % during a 12-month follow-up. Overall, no significant peri-/post-operative IVUS related complications were reported, whereas, 2 studies suggested an IVUS-associated increase in procedure costs that ranged from $1,080 to $1,333. The authors concluded that there is limited and heterogeneous evidence regarding the use of IVUS for the management of PAD. They stated that further research is needed to elucidate the optimal role of IVUS in PAD as well as the cost-effectiveness of this approach for routine use in the management of PAD.
Allan et al (2022) noted that IVUS is more accurate than angiography for assessment of vessel size and disease severity. Low-level studies suggested that the use of IVUS in femoro-popliteal (FP) EVTs improved outcomes, but currently, no Level-I evidence exists. In a prospective, single-center RCT, these researchers examined if the addition of IVUS guidance during FP artery interventions would reduce the rate of binary re-stenosis within 12 months compared with angiographic guidance alone. This trial entailed 150 patients undergoing FP EVT, randomized (1:1) to guidance by angiography or angiography and IVUS. The primary outcome measure was freedom from binary re-stenosis, on Duplex US, within 12 months. Secondary outcomes included clinically driven TLR, disagreements in imaging findings between modalities, and changes in treatment caused by IVUS. Freedom from binary re-stenosis at 12 months was significantly higher in the IVUS group (72.4 % versus 55.4 %; p = 0.008). There was no significant difference between groups for clinically directed TLR (84.2 % and 82.4 %; p = 0.776). Mean vessel diameter was significantly larger with IVUS (5.60 mm versus 5.10 mm; p < 0.001). A change in treatment occurred caused by IVUS in 79 % of cases. Binary re-stenosis was lower in the IVUS group for cases treated with drug-coated balloons (DCBs) (9.1 % versus 37.5 %; p = 0.001). The authors concluded that the use of IVUS resulted in a significant reduction in the rate of re-stenosis after endovascular intervention. This was the 1st RCT to show that IVUS improved outcomes in FP interventions. This benefit may primarily relate to cases treated with DCBs. Moreover, these researchers stated that while these findings were very encouraging, further studies are needed to determine the longer-term clinical benefits and cost-effectiveness of IVUS-assisted EVT.
The authors stated that this study had several drawbacks. First, while pre-treatment angiographic imaging data were collected before randomization; thus, should not be subject to randomization bias; however, the potential for bias in interpretation of post-treatment angiography was unavoidable. The results of IVUS imaging continued to be withheld from the clinical team after the procedure and decisions related to surveillance should therefore not be subject to bias related to IVUS results. Second, core laboratory adjudication was not available due to resource constraints, and this created potential limitations in the imaging data. The risk of observer variability in evaluating angiography data was reduced by the standardized acquisition of angiographic measurements with automated QVA software, rather than with visual assessment or manual caliper measurements. While there is the potential for variability in the surveillance Duplex US, these were carried out using standardized protocols by accredited sonographers blinded to the study randomization. Third, the study did not require angiography to be obtained in 2 planes. The planar nature of angiography is a limiting factor in accurately measuring lumen size and identifying vessel pathology. Reliance on primarily single-plane imaging may therefore have limited the accuracy of angiography. IVUS imaging was carried out primarily using the manual pull-back method. This was a practical necessity caused by the length of lesions included in the study; and has been previously shown to provide effective imaging. Fourth, functional outcomes such as quality of life (QOL) and walking impairment were not collected in this study. Procedural data such as procedure and fluoroscopic time were not collected for this study, therefore, a health economics analysis of cost-effectiveness was not able to be performed.
Natesan et al (2022) stated that although angiography has been the primary imaging modality used in peripheral vascular intervention (PVI), this technique has major limitations due to the evaluation of 3-D vessels in 2 dimensions; IVUS is an important adjunctive tool that can address some of these limitations. In a systematic review, these investigators examined the appropriateness of IVUS as an imaging modality for guiding PVI through evidence collection and clinical appraisal of studies. Following the PRISMA guidelines, a cohort of 48 studies (29 arterial; 19 venous) detailing IVUS use in PVI were extracted. Qualitative assessment of the studies examined pre- and post-procedure effectiveness of IVUS, and showed that IVUS-guided PVI in arterial and venous diagnosis and treatment was superior to other imaging techniques alone. Each study in the cohort was further assessed for reliability and validity using the Oxford Centre for Evidence Based Medicine (CEBM) level of evidence scale. The majority of both arterial (79.3 %) and venous (73.7 %) studies received a 2b rating, the 2nd highest level of evidence rating. The evidence to-date indicated that IVUS resulted in better clinical outcomes overall and should be more widely adopted as an adjunctive imaging modality during PVI. Moreover, these investigators stated that further investigations are needed to focus on improving adoption and utilization of this important adjunctive imaging device.
The author stated that this study has several drawbacks. While conducting the systematic search for potentially eligible studies to include in this review, the search criteria were designed to be as broad and to include as many applicable terms as possible. However, owing to differences in database sorting and algorithms between PubMed, Cochrane, and Embase, there was no feasible way to ensure that the search strategy was exactly the same across each platform. To mitigate this issue, the search strategy was vetted and examined by experts from the Harvard University library to ensure that there was continuity and accuracy between the various database searches. In addition, these researchers specifically chose PubMed, Cochrane, and Embase as the 3 databases to search. Other databases, including Medline and Web of Science, were omitted for redundancy or inability to maintain cohesiveness with search terms. Of note, all of the manuscripts captured in Medline were present in the PubMed search. To address missing studies that may have been outside of the time-frame of the authors’ search or excluded from the databases, these investigators searched the references of a number of related papers (namely other systematic reviews) to ensure that their list of eligible studies was as comprehensive as possible. Further drawbacks included the size and heterogeneity of eligible studies, including differences in the adjudication of target endpoints, and inconsistent reporting of individual patient-level data and outcomes. Furthermore, this systematic review included studies that span a broad time-frame (1996 to 2021), during which the quality of imaging, ease of operation, and technology of IVUS has improved. Although some earlier studies may have examined the clinical outcomes associated with using IVUS while it was still in a rudimentary form, the authors’ assertions regarding the use of IVUS today are strengthened by the improvement in IVUS technology over time. Although aggregating data into a meta-analysis would have been useful to further examine the role of IVUS during PVI, upon detailed review of the available studies, these researchers felt that the specific endpoint definitions, timing of outcome adjudication and consistency in endpoint reporting were too heterogeneous to accurately meta-analyze outcome data. As such, they elected to focus on summarizing available data and evaluating the quality of evidence.
Divakaran et al (2022) noted that IVUS has been demonstrated in limited prospective studies to improve procedural outcomes for patients undergoing lower extremity (LE) PVI. In an observational study, these researchers examined temporal trends, practice variation, and associated outcomes with the use of IVUS during PVI among Medicare beneficiaries. All PVIs performed from 2016 to 2019 among Medicare beneficiaries aged over 65 years were included. Temporal trends in IVUS use were stratified by procedural location (inpatient, outpatient, or ambulatory surgery center [ASC]/office-based laboratory [OBL]) as well as physician specialty. The primary outcome was major adverse limb events (MALE) . Inverse probability weighting was used to account for differences in baseline characteristics. Cox regression with competing risks was used to estimate weighted HRs. During the study period, a total of 543,488 PVIs were included, of which 63,372 (11.7 %) used IVUS. A substantial growth in IVUS use was observed, which was driven by procedures performed in ASCs/OBLs (23.6 % increase from quarter-1 of 2016 through quarter-4 of 2019). Among operators who used IVUS, there was also notable variation in use (median operator use 5.4 % of cases; IQR: 2.2 % to 15.0 %; range of less than 1 % to 100 %). In weighted analysis, IVUS use during PVI was associated with a lower risk of MALE through a median of 514 days (adjusted HR: 0.73; 95 % CI: 0.70 to 0.75; p < 0.0001). The authors concluded that in contemporary nationwide data, IVUS use during PVI has increased since 2016, driven by growth in the ASC/OBL setting.; however, there remains substantial variation in operator practice. When used during PVI, IVUS was associated with a lower risk of short- and long-term MALE. Moreover, these researchers stated that additional, prospective data are needed to confirm the association between IVUS use during PVI and improved long-term outcomes as well as aid in addressing specific clinical scenarios in which IVUS can be used to make treatment decisions.
The authors stated that this study had several drawbacks. First, IVUS use was identified using claims codes, and how it was incorporated into the procedure could not be discerned. Although the use of claims codes to define the primary exposure can result in mis-classification, appropriate and accurate billing is needed for reimbursement and likely reduces this risk. Second, CMS data do not include detailed procedural information, including lesion characteristics such as length and severity of disease, degree of calcification, and the presence of total occlusion. Third, the cohort only included patients who experienced re-vascularization; thus, did not include patients who underwent an unsuccessful endovascular re-vascularization attempt. Fourth, the instrumental variable analysis also has limitations, especially if physicians who used IVUS more or less often differ in other unmeasured ways. Fifth, other endpoints like TLR could not be evaluated because of the ambiguity of the claims codes. This was a principal drawback, and further investigation is needed to examine the impact of IVUS on re-stenosis and TLR rates. These investigators stated that a recent randomized study reported that IVUS use during femoro-popliteal re-vascularization resulted in an approximately 17 % reduction in binary re-stenosis at 1 year, supporting the findings of the current analysis. Sixth, despite the evaluation for residual and unmeasured confounding, there remains the possibility that these factored into the findings because of the observational study design.
Koo et al (2022) noted that in patients with CAD who are being evaluated for PCI, procedures can be guided by FFR or IVUS for decision-making regarding re-vascularization and stent implantation. However, the differences in clinical outcomes when only 1 method was used for both purposes are unclear. These investigators randomly assigned 1,682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 % to 70 % occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to examine PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mm2 or less or measuring 3 to 4 mm2 with a plaque burden of more than 70 %. The primary outcome was a composite of death, MI, or re-vascularization at 24 months after randomization. These researchers tested the non-inferiority of the FFR group as compared with the IVUS group (non-inferiority margin, 2.5 percentage points). The frequency of PCI was 44.4 % among patients in the FFR group and 65.3 % among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1 % of the patients in the FFR group and in 8.5 % of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the 1-sided 97.5 % CI, 2.2 percentage points; p = 0.01 for non-inferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the 2 groups. The authors concluded that in patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was non-inferior to IVUS guidance with respect to the composite primary outcome of death, MI, or re-vascularization at 24 months.
The authors stated that this study had several drawbacks. First, this study population included low-risk patients with a mean SYNTAX score of less than 10, indicating low anatomical complexity of the coronary lesions; thus, the results may not be applicable to higher-risk patients. Second, the operating physicians were necessarily aware of the trial-group assignments. This factor may have influenced the frequency of re-vascularization during follow-up because the operators knew the strengths and weaknesses of FFR and IVUS. Third, the frequency of re-vascularization can differ according to the criteria for PCI and baseline characteristics. Fourth, FFR and IVUS were representative tools for guidance regarding the evaluation of physiology and intra-coronary imaging in this trial. Several other techniques can be used in the cardiac catheterization laboratory, including the measurement of non-hyperemic pressure ratios, angiography-derived FFR, OCT, and near-infrared spectroscopy-IVUS. These researchers stated that additional studies are needed to determine the comparative roles of these methods in PCI guidance. Fifth, the criteria for PCI in this study did not incorporate lesion-level hemodynamic significance, and features of plaque vulnerability. Sixth, non-Asian patients were not included in this trial.
Jiang and Xu (2022) examined if IVUS-guided angioplasty in FP lesions would improve clinical outcomes and predict re-stenosis. Studies in which IVUS-guided angioplasty was employed for FP lesions were searched from the Medline, Embase, Web of Science, and Cochrane databases; studies with the full text were included. The primary endpoint of this study was primary patency at 12 months, while the secondary endpoints were primary patency at 24 months, freedom from TLR at 12 months, and correlation of re-stenosis with the distal external elastic membrane (EEM) area, post-intervention MLA, lesion length, dissection, and calcification. A total of 11 observational studies involving 1,521 patients (1,703 lesions) were analyzed. The quality of the evidence for 7 main outcomes was assessed as "very low" by The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) classification. The mean follow-up period was 1.5 years. The pooled rates were: 78 % for 12-month primary patency (95 % CI: 0.72 to 0.83), 74.3 % for 24-month primary patency (95 % CI: 0.71 to 0.78), and 80 % for 12-month freedom from TLR (95 % CI: 0.74 to 0.86). The 12-month primary patency of IVUS use (RR, 2.01; 95 % CI: 1.48 to 2.74) was higher compared to non-IVUS use. The stent MLA (standard mean difference [SMD] = -0.30; 95 % CI: -0.46 to -0.15) and dissection (OR 1.58; 95 % CI: 1.01 to 2.49, p = 0.047), were associated with mid-term patency in terms of re-stenosis. The authors concluded that in IVUS-guided angioplasty in patients with FP lesions, the stent MLA and dissection were associated with re-stenosis. Nevertheless, there is limited and heterogeneous evidence regarding the usefulness and predictability of IVUS in patients with PAD in the FP artery, especially in long-term patency, and as a predictor of declining patency. These researchers stated that the optimal role of IVUS in such patients should be elucidated in the future.
These investigators stated that the conclusions of this systematic review were limited by the heterogeneity of the included studies, and the possibility of publication bias. Only 2 of the included studies had control groups; making the quality of evidence in this review “very low”. Moreover, only 1 included study was not retrospective; therefore, there might be potential methodological flaws. Furthermore, the methodological quality of the included studies was moderate, according to the MINORS score. The loss to follow-up was either un-reported, or over 5 %. Moreover, there was sizeable clinical heterogeneity among studies, and the pooled data were insufficient due to the lack of raw data. Finally, the afore-mentioned studies only showed the clinical outcomes of patients with FP arterial lesions who underwent angioplasty with IVUS in Japan; thus, the findings could not be generalized for other populations.
Smith et al (2023) stated that IVUS use in LE interventions is growing in popularity owing to its imaging in the axial plane, superior detail in imaging lesion characteristics, as well as its enhanced ability to delineate lesion severity and extent compared with catheter angiograms. However, there are conflicting data regarding whether IVUS affects outcomes. In a retrospective cohort study, these researchers examined the effect associated with IVUS implementation in FP interventions. These investigators used Vascular Quality Initiative data. Patients undergoing an index endovascular FP re-vascularization from 2016 to 2021 were included. Patients were differentiated by whether or not IVUS was used to evaluate the FP segment during intervention (no IVUS, IVUS). Propensity score-matching, based on pre-operative demographics and measures of disease severity was used. Primary outcomes were major amputation-free survival (AFS), FP re-intervention-free survival (RFS), and primarily patent survival (PPS) at 12 months. IVUS use grew steadily throughout the study period, comprising 0.6 % of interventions in 2016, and increasing to 8.2 % of interventions by 2021; growth was most dramatic in ambulatory surgical center or office-based laboratory settings where IVUS use grew from 4.4 % to 43 % to 47 % of interventions. In unmatched cohorts, patients receiving interventions using IVUS tended to have lower prevalence of multiple cardiovascular co-morbidities (e.g., congestive heart failure [CHF], hypertension, diabetes mellitus [DM], and dialysis dependence) and presented more often with claudication and less often with chronic limb-threatening ischemia (CLTI). Intra-operatively, IVUS was used more often in complex FP lesions (TransAtlantic InterSociety Consensus [TASC] grade D versus A), and more often in conjunction with stenting and/or atherectomy. IVUS use was associated with improved AFS, but similar RFS and PPS at 12 months. However, in multi-variable analysis IVUS was not associated with any of the primary outcomes independently; rather, all outcomes were influenced primarily by CLTI, dialysis dependence, as well as prior major amputation status; technical outcomes (i.e., RFS and PPS loss) were further driven by complexity of lesion (worse in TASC grade D versus A lesions) and treatment setting (i.e., ambulatory surgical center or office-based laboratory setting associated with increased hazard for RFS and PPS loss). The authors concluded that IVUS implementation in FP interventions is growing, with rapid adoption among interventions in ambulatory surgical centers and office-based laboratories. However, these investigators stated that IVUS was not associated with an effect on technical outcomes at 12 months; improvement in major AFS was observed. These researchers noted that multi-variable analysis suggested that this finding may be an effect of confounding by multiple factors highly associated with IVUS use, namely, in patients with lower prevalence of CLTI, dialysis dependence, and prior major amputations; thus, conveying baseline lower risk for major amputation and death.
Tsukagoshi et al (2023) noted that IVUS is an important adjunctive tool for patients with LE PAD undergoing EVT. The evidence regarding the advantages of IVUS use is evolving, and recent studies have reported conflicting results. In a meta-analysis, these investigators examined the effectiveness of IVUS during angiography-guided EVT for patients with PAD. Medline and Embase were searched through April 2023 to identify studies that examined the outcomes of IVUS with angiography-guided EVT versus angiography-alone-guided EVT. The primary outcome was re-stenosis/occlusion rate; secondary outcomes were TLR, major amputation, and mortality. A total of 1 RCT and 14 observational studies, largely of moderate quality, were included, yielding a total of 708,808 patients with 709,189 lesions that were treated with IVUS-guided EVT (n = 101,405) versus angiography-alone (n = 607,784). Compared with angiography alone, IVUS-guided EVT was associated with a non-significant trend towards decreased re-stenosis/occlusion (RR, 0.74; 95 % CI: 0.54 to 1.00; I2 = 60 %). Although the risk of TLR and mortality were comparable (RR, 0.85; 95 % CI: 0.65 to 1.10; I2 = 70 %; RR, 1.01; 95 % CI: 0.79 to 1.28; I2 = 43 %, respectively), the use of IVUS was also associated with significantly lower risk of major amputation (RR, 0.74; 95 % CI: 0.67 to 0.82; I2 = 47 %). Subgroup analysis focusing on femoro-popliteal disease showed significantly higher patency (RR, 0.72; 95 % CI: 0.52 to 0.98; I2 = 73 %); however, superiority with major amputation was not observed. The authors concluded that IVUS-guided EVT for PAD may possibly be associated with a lower major amputation rate compared with angiography alone-guided EVT, although the difference in patency remained an insignificant trend in favor of IVUS-guided EVT. Moreover, these researchers stated that adjunctive use of IVUS during EVT may be beneficial, and further prospective studies are needed to examine this relationship and the applicability of this technology in routine practice.
In a scoping review, Meng et al (2023) examined if the use of additional IVUS can change the outcomes of EVT in FP atherosclerotic lesions compared with conventional angiography alone based on the existing study and evidence. Studies published until September 2022 were searched from PubMed, Embase, and Cochrane databases using the methods of combination of Medical Subject Headings and free text words. The outcomes included in these studies were primary patency rate or re-stenosis rate and freedom from clinically driven TLR (cdTLR) rate, and most studies were concerned about the 12-month results. Two independent authors conducted the process of study selection; and the pooled analysis was attempted. The inclusion criteria were met by 4 studies (1 RCT, and 3 retrospective studies) involving 1,160 patients. IVUS played its role in measuring lesions and/or guiding wiring passage. Most of the included studies showed that IVUS could achieve a higher 12-month primary patency rate (from 70 % to 90 %) and higher 12-month freedom from cdTLR rate (from 83.9 % to 94.7 %) than angiography. The tentative pooled analysis also showed that IVUS significantly improved the 12-month primary patency rate (OR: 2.21, 95 % CI: 1.38 to 3.55, p = 0.001), and the 12-month freedom from cdTLR rate (OR: 1.70, 95 % CI: 1.04 to 2.78, p = 0.03) compared with angiography alone. The authors concluded that IVUS-guided EVT of FP artery lesions may have its own advantages such as higher primary patency rate and freedom from cdTLR rate at 12 months. As a novel technology, IVUS is expected to become another beneficial option to guide clinicians performing EVT in addition to angiography and may achieve better clinical outcomes. Moreover, these researchers stated that further prospective and high-quality studies are needed to examine the role of IVUS in the process of FP artery lesions EVT.
Secemsky et al (2024) stated that percutaneous re-vascularization is the primary strategy for treating LE venous and arterial disease. Angiography is limited by its ability to accurately size vessels, precisely determine the degree of stenosis and length of lesions, characterize lesion morphology, or correctly diagnose post-intervention complications. These limitations are overcome with use of IVUS. These investigators stated that IVUS has shown the ability to improve outcomes following percutaneous coronary intervention, and there is increasing evidence to support its benefits in the setting of peripheral vascular intervention. At this stage in its evolution, there remains a need to standardize the use and approach to peripheral vascular IVUS imaging. This article represents considerations and consensus perspectives that emerged from a round-table discussion including 15 physicians with expertise in interventional cardiology, interventional radiology, and vascular surgery, representing 6 cardiovascular specialty societies, held on February 3, 2023. The round-table's aims were to assess the current state of lower extremity re-vascularization, identify knowledge gaps and need for evidence, and determine how IVUS can improve care and outcomes for patients with peripheral arterial and deep venous pathology.
The expert panel stated that the main evidence gap for arterial interventions was the need to determine whether greater incorporation of IVUS into clinical practice can result in improved overall procedural success. As an example, some have questioned whether greater use of IVUS in clinical trials, such as BEST-CLI, might have translated into better procedural outcomes. Additional evidence gaps include the need to define what lesion severity warrants treatment to support procedural decision making. Furthermore, consensus on IVUS-guided sizing of devices for treatment is needed. The expert panel noted that while the algorithm for using IVUS-derived media-to-media diameter for coronary stent sizing is well-established; this is not well-defined for peripheral arteries. The panel stated that future studies should be directed to reliably quantify how to size vessels to optimize luminal gain with balloons and for stent implantation. Lastly, post-intervention questions remain unanswered (e.g., IVUS is more sensitive than angiography for detecting procedure-related dissections, but there is no universal consensus on when to treat versus defer treatment of IVUS-detected dissection).
Diagnosis and Treatment of Functional Popliteal Artery Entrapment Syndrome
Boniakowski and associates (2017) stated that functional popliteal artery entrapment syndrome (PAES) can be difficult to diagnose, as the imaging modalities presently employed are designed to detect anatomic entrapment. These researchers described a novel imaging technique to aid in diagnosis in this cohort. A 22-year old cyclist presented with exercise-limiting claudication; MRA with provocative maneuvers was non-diagnostic. Digital subtraction angiography revealed long-segment occlusion of the popliteal artery with plantar flexion; however, the specific site of compression remained unclear; IVUS allowed specific localization of compression and further confirmed the diagnosis. The authors reported IVUs as an adjunctive imaging modality and proposed the use of this approach as a definitive diagnostic technique to aid in the diagnosis and treatment of PAES. These preliminary findings need to be validated by well-designed studies.
Furthermore, an UpToDate review on “Calf injuries not involving the Achilles tendon” (Rogers Rainbow and Fields, 2018) does not mention IVUS as a management tool.
Guidance During Endovascular Treatment of Subclavian Artery Disease
Chung and associates (2017) evaluated the short- and long-term efficacy of IVUS guidance during endovascular treatment (EVT) of subclavian artery disease. The multi-center SCALLOP registry (Subclavian artery disease treated with endovascular therapy; multi-center retrospective registry) was interrogated to identify 542 patients who underwent successful EVT for SCAD between January 2003 and December 2012. Lesions were classified according to the use of IVUS guidance: 177 patients (mean age of 68.9 ± 8.6 years; 149 men) with and 373 patients (mean age of 69.9 ± 8.7 years; 275 men) without. The main outcome was the difference in primary patency; secondary outcomes were differences in assisted primary patency, secondary patency, overall survival (OS), freedom from major adverse cardiovascular events [MACE; all-cause mortality, MI, and stroke], and freedom from major adverse events (MAE). Multi-variate analysis of the IVUS+ group was performed to identify predictors of failure; results were presented as the HR and 95 % CI. A total of 538 (97.8 %) lesions were treated with stents and 12 lesions by balloon angioplasty alone. Peri-procedural and in-hospital overall complication rates did not differ significantly between IVUS+ (10.2 %) and IVUS- (8.8 %, p = 0.617). Long-term follow-up demonstrated no significant difference between IVUS+ and IVUS- groups in 5-year all-cause mortality (p = 0.37), MI (p = 0.07), stroke (p = 0.31), or MACE (p = 0.07). However, 5-year primary patency was significantly higher in the IVUS+ group (88.5 % versus 77.7 %, p = 0.03). There were no group differences in 5-year assisted primary patency (90.4 % versus 89.9 %, p = 0.81) or secondary patency (99.4 % versus 97.1 %, p = 0.25). Multi-variate analysis of the IVUS+ group identified in-hospital stroke (HR 16.92, 95 % CI: 3.60 to 79.42, p < 0.01) and combined use of balloon-expandable and self-expanding stents (HR 5.59, 95 % CI: 1.22 to 25.65, p = 0.02) as independent negative predictors of primary patency. The authors concluded that these findings suggested that IVUS guidance can significantly improve long-term primary patency following endovascular treatment of subclavian artery disease. These findings need to be validated by well-designed studies.
Prediction of Clinical Improvement Following Ilio-Femoral Vein Stenting
Gagne and co-workers (2018) noted that selecting patients for ilio-femoral vein stenting has traditionally relied on the identification and quantification of stenotic lesions with imaging such as multi-planar venography. Recently, IVUS imaging has become more available. However, to-date, the usefulness of these imaging modalities using the customary greater than 50 % treatment threshold for diameter (multi-planar venography) and area (IVUS) stenosis of ilio-femoral veins has not been validated prospectively within the context of clinical improvement. The multi-center Venogram Versus Intravascular Ultrasound for Diagnosing and Treating Ilio-femoral Vein Obstruction (VIDIO) trial prospectively enrolled 100 symptomatic patients (Clinical Etiologic Anatomic Pathophysiologic [CEAP] classification of 4 to 6) with suspected ilio-femoral venous outflow disease. Venous stenting for presumed significant ilio-femoral vein stenosis, based on imaging and clinical findings, was performed on 68 patients. Based on imaging, stenosis was characterized as non-thrombotic in 48 patients and post-thrombotic in 20 patients. Each underwent baseline and post-stenting venography and IVUS to compare the diagnostic and clinical usefulness of the tests. The revised Venous Clinical Severity Score was used to assess clinical patient outcome. A greater than 4-point reduction in the revised Venous Clinical Severity Score (rVCSS) between baseline and 6 months was used as an indicator of clinically meaningful improvement. Receiver operating characteristic curve analysis was used to determine the optimal diameter and area thresholds for prediction of clinical improvement. Clinical improvement after stenting was best predicted by IVUS baseline measurement of area stenosis (area under the curve, 0.64; p = 0.04), with greater than 54 % estimated as the optimal threshold of stenosis indicating interventional treatment. With measurement of lumen gain from baseline to after the procedure, the optimal reduction in vein stenosis correlative of later clinical improvement was greater than 41 %; IVUS measurement of area stenosis was most predictive (area under the curve, 0.70; p = 0.004). Venographic measurements of baseline stenosis and stenotic change were not predictive of later improvement. In a 48-patient non-thrombotic subset analysis, IVUS diameter rather than area measurements of baseline stenosis were significantly predictive of clinical success, but indicated a higher optimal threshold of stenosis (greater than 61 %) may be necessary. The authors concluded that this analysis found that IVUS demonstrated predictive accuracy for imaging and guiding treatment of ilio-femoral venous lesions, whereas venography did not display significant predictive usefulness. Stenosis of greater than 54 % for the entire patient cohort, as measured by IVUS area stenosis, was estimated as the threshold for clinically significant stenosis to indicate stenting. A higher threshold for treatment of non-thrombotic stenosis may be necessary. Moreover, they stated that additional analyses – ideally larger studies with a control arm – of venous occlusive disease are needed to further validate these findings.
The authors stated that the major drawback of this study was its relatively small sample size (n = 68), which was insufficient for robust statistical comparisons. Another significant drawback was the study design, which did not include an observational control arm. Thus, the ROC threshold used to determine procedural success or failure was perhaps less precise, because a negative cohort had to be carved somewhat arbitrarily out of patients undergoing intervention, with many patients categorized as negative despite reporting substantial improvement (up to and including a 4-point improvement) on rVCSS at 6 months. Another drawback was a much greater proportion of patients categorized as non-thrombotic (71 %) than post-thrombotic (29 %), limiting the relevance and significance of these findings for post-thrombotic lesions.
Diagnosis / Evaluation of Pulmonary Hypertension
Tapson and colleagues (1994) stated that massive pulmonary embolism may result in rapid deterioration prior to diagnostic and therapeutic intervention. Intravascular ultrasound (IVUS) imaging has been utilized previously to evaluate vascular abnormalities as well as normal human pulmonary arteries. These researchers employed this technique to rapidly identify massive pulmonary emboli located in the main pulmonary arteries of 2 patients. The authors concluded that the presence of these emboli was confirmed with pulmonary arteriography; IVUS may be utilized to rapidly confirm the presence of large proximal pulmonary emboli.
Ishii and associates (1995) compared in-vitro IVUS images of human pulmonary arteries with corresponding histologic sections, and correlated the relation between IVUS findings and Heath-Edwards pathologic grade of pulmonary vascular changes. These researchers evaluated and compared IVUS images with histologic findings at identical sites in 40 pulmonary artery segments from 17 autopsy studies: group 1 = 7 patients with pulmonary hypertension (PH) (Heath-Edwards grade I to V, 20 segments); group 2 = 10 patients without cardio-pulmonary disease (20 segments). In group 2, the pulmonary artery wall echo consisted of a single layer. In group 1, all segments of pulmonary arteries from patients with PH showed a 3-layered appearance; in patients with mild PH (Heath-Edwards grades I and II), IVUS demonstrated increased thickness of the echo-lucent zone due to medial hypertrophy with no intimal reaction; patients with severe PH (Health-Edwards grade III or higher) had IVUS findings of increased medial thickness and a bright inner layer from intimal hyperplasia; percent wall thickness derived from IVUS showed a significant correlation with that determined by histologic examination (r = 0.89, p = 0.0001, n = 20). The authors concluded that changes observed with IVUS imaging correlated well with histopathologic grade. Thus, these investigators noted that IVUS may have significant utility in the evaluation of pulmonary vascular morphology in patients with PH. Moreover, these researchers stated that further developments in IVUS imaging could provide clinically important information for PH.
The authors stated that this study had several drawbacks. First, they could not compare IVUS findings with a hemodynamic study; 6 patients in group 1 were examined by cardiac catheterization; however, studies were not performed contemporaneously with IVUS imaging (taking place from 1 month to 6 years before autopsy). Thus, changes in the severity of PH may have occurred; 1 patient (transposition of great arteries) in group 1 and all subjects in group 2 did not have a hemodynamic study. Second, in the present study, the samples from 16 patients, not including the patient with transposition, were fixed with formalin. Initial studies had indicated that formalin has a major influence on echographic characteristics. Third, the pulmonary arteries were viewed in a saline bath. However, in-vivo pulmonary arteries were surrounded not only by tissue, but also by air-filled alveoli; thus, the adventitia was more difficult to discern.
Bressollette and co-workers (2001) stated that measurements of pulmonary pressure and resistance are still considered to be the "gold standard" in the evaluation PH, despite their limitations in predicting irreversible disease. Hemodynamic assessment also only provides a global evaluation of the pulmonary vascular bed, whereas PH is an inhomogeneous disease of the vessel wall. These researchers examined the value of IVUS in 30 patients with suspected PH and correlated the structural changes in distal pulmonary arteries found on IVUS with conventional hemodynamic data. Plasma endothelin (ET)-1 levels and pulmonary ET-1 extraction also were measured as markers of the severity of PH. The anatomic abnormalities revealed by IVUS were more severe in the lower lobes than in the upper lobes, as evidenced by the greater percentage of wall thickness (WT), the smaller lumen diameter/WT and lumen area/total vessel area (p < 0.05 for each). The authors noted that IVUS anatomic indexes correlated directly with hemodynamic data (e.g., with pulmonary arterial systolic pressure; r = 0.56; p < 0.001) and ET-1 levels but inversely with pulmonary ET-1 extraction. The authors concluded that patients with PH had greater pulmonary arterial WT that was more severe in the lower lobes than in the upper lobes. The severity of structural abnormalities found on IVUS was directly correlated with hemodynamic findings and ET-1 levels. These researchers stated that IVUS may provide useful additional information in the assessment of patients with PH.
Berger and colleagues (2002) examined if the dynamic properties of the pulmonary arterial wall are altered in patients with abnormal pulmonary hemodynamics due to congenital heart defects, and whether these changes are associated with the progression of pulmonary vascular disease (PVD). In 43 children with PVD due to congenital heart defects and 12 control subjects, pulmonary arterial pulsatility (the relative increase in vessel area during the cardiac cycle) and distensibility (the inverse of the stress/strain elastic modulus) were determined with IVUS. Results were correlated with clinical and hemodynamic parameters. Pulsatility correlated with pulmonary pulse pressure (p < 0.001), pulmonary-to-systemic vascular resistance ratio (PVR/SVR) [p = 0.001], and hemoglobin concentration (p = 0.01). However, when corrected for these variables, pulsatility did not differ between patients and control subjects. In contrast, arterial wall distensibility decreased with the severity of PVD and correlated independently with pulmonary-to-systemic arterial pressure ratio (p < 0.001) and PVR/SVR (p = 0.03), and with hemoglobin (Hb) concentration (p < 0.01). Adjusted for hemodynamic variables, distensibility was still decreased in patients with PVD compared to control subjects. The authors concluded that these results demonstrated that pulmonary arterial wall distensibility was progressively decreased in PVD. Moreover, this decreased distensibility was, in part, related to increased distending pressure as a result of PH but also, in part, to stiffening of the arterial wall during the disease process. They stated that arterial wall distensibility may be of additional value in the evaluation of pulmonary vasculature and ventricular work-load.
In a prospective, observational study, Rodes-Cabau and associates (2003) evaluated the structural and functional characteristics of pulmonary arteries by IVUS in the setting of primary PH, and correlated the US findings with hemodynamic variables and mortality at follow-up. A total of 20 consecutive patients with primary PH (16 women; mean (SD) age of 39 (14) years). Cardiac catheterization and simultaneous IVUS of pulmonary artery branches were carried out at baseline and after infusion of epoprostenol. A total of 33 pulmonary arteries with a mean diameter of 3.91 (0.80) mm were imaged, and wall thickening was observed in all cases, 64 % being eccentric. Mean wall thickness was 0.37 (0.13) mm, percentage wall area 31.0 (9.3) %, pulsatility 14.6 (4.8) %, and pulmonary/elastic strain index 449 (174) mm Hg. No correlation was observed between IVUS findings and hemodynamic variables. Epoprostenol infusion increased pulsatility by 53 % and decreased the pulmonary/elastic strain index by 41 % (p = 0.0001), irrespective of hemodynamic changes. At 18 (12) months follow-up, 9 patients had died. A reduced pulsatility and an increased pulmonary/elastic strain index were associated with increased mortality at follow-up (12.0 (4.4) % versus 16.4 (4.4) %, p = 0.03; 369 (67) versus 546 (216) mm Hg, p = 0.02). The authors concluded that IVUS demonstrated pulmonary artery wall abnormalities in all patients with primary PH, mostly eccentric. The severity of the changes did not correlate with hemodynamic variables, and epoprostenol improved pulmonary vessel stiffness. There was an association between impaired pulmonary artery functional state as determined by IVUS and mortality at follow-up. Moreover, they stated that larger series are needed to determine the exact prognostic value of this technique in the setting of primary PH.
The authors stated that this study had several drawbacks. First, as indicated in previous studies, the recognition of the elastic external membrane was the most important limiting factor for US pulmonary morphology evaluation. In this study, IVUS did not provide adequate images for morphological evaluation in up to 25 % of the pulmonary arteries evaluated, and 2 patients had to be excluded because of the poor quality of the images. However, in most cases US images were adequate for analysis, and IVUS measurements were reproducible. A relation between US and pathological findings could not be established because the mean delay between the US exploration and the histopathological studies was too long, and even if the pathologist had studied elastic pulmonary arteries from the same pulmonary lobe as had previously been imaged by IVUS, it would not have been possible to evaluate the same elastic pulmonary artery. Second, a control group would have provided more consistency in the study results, although previous studies with control subjects had already defined the US characteristics of pulmonary arteries with no pathological features. Also, the inclusion of a control group would have incurred ethical objections. Third, the small sample size (n = 20) inevitably lessened the potential of the results obtained and precluded the performance of multi-variate analysis to establish the prognostic value of the US findings more accurately.
Cai and co-workers (2015) examined the value of IVUS on assessing pulmonary vascular properties (PVPs) and its relationship with hemodynamics, and mortality rate in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (PAH-CTD). Patients (n = 51) with highly suspected PAH-CTD were prospectively enrolled in the authors’ department between July 2011 and March 2014. All patients underwent right heart catheterization (RHC) and IVUS, and were divided into 3 groups: PAH-CTD (n = 25), PAH due to other reasons (n = 15), and non-PAH control group (n = 11). Based on IVUS, PAH patients were divided into distal (n = 22) and proximal (n = 18) re-modeling subtypes. A total of 408 pulmonary segments were detected by IVUS, and all patients were followed-up to (19 ± 10) months. IVUS evidenced higher mean wall thickness (MWT) ((0.30 ± 0.02) mm and (0.33 ± 0.02) mm versus (0.21 ± 0.02) mm) and percentage of MWT (WTP) ((13.62 ± 0.59) % and (14.39 ± 0.77) % versus (9.57 ± 0.97) %) values in PAH patients compared to control patients (all p < 0.01). Pulmonary vascular mechanical properties (PVMPs) including compliance ((8.85 ± 0.82) × 10(-2)mm(2)/mmHg(1 mmHg = 0.133 kPa) and (6.28 ± 0.65) × 10(-2)mm(2)/mmHg versus (41.59 ± 5.02) × 10(-2) mm(2)/mmHg, all p < 0.01), distensibility ((0.83 ± 0.09) %/mmHg and (0.55 ± 0.06) %/mmHg versus (3.16 ± 0.38) %/mmHg, all p < 0.01), elastic modulus ((169.25 ± 15.10) mmHg and (253.00 ± 22.11) mmHg versus (43.78 ± 4.27) mmHg, all p < 0.01) and stiffness index β (4.19 ± 0.41 and 5.18 ± 0.34 versus 2.39 ± 0.27, p < 0.05 or 0.01) in PAH groups were all significantly worse than in control group (all p < 0.01). An inverse exponential association was found between PVMPs and hemodynamics with R(2) ranging from 0.544 to 0.777 (p < 0.001). PVMPs tended to be better in group PAH-CTD than in PAH group due to other reasons. Mortality rate was similar between the 2 PAH groups, while PAH with distal remodeling subtype was linked with significantly higher mortality rate than PAH with the proximal remodeling subtype (23 % versus 0, HR = 10.14, p < 0.05). The authors concluded that IVUS played an important role in the assessment of PAH-CTD patients in terms of evaluating PVPs and predicting mortality rate. PAH patients have deteriorated PVPs, but PVMPs tended to be better in PAH-CTD than in PAH patients due to other reasons. The mortality rate was similar between PAH groups, while PAH patients with the distal re-modeling subtype was linked with a higher mortality rate than PAH patients with the proximal re-modeling subtype.
Shen and colleagues (2016) examined the use of IVUS to evaluate PVPs and mortality in patients with PAH. Patients (n = 51) with systolic pulmonary artery pressures greater than or equal to 40 mm Hg on echocardiography were prospectively enrolled. All patients underwent RHC and IVUS and were divided into 3 groups: PAH associated with connective tissue diseases (group 1, n = 25), PAH due to other causes (group 2, n = 15), and patients with connective tissue diseases without PH (group 3, n = 11). PAH groups (groups 1 and 2) were divided into distal (n = 22) and proximal (n = 18) re-modeling sub-types on the basis of IVUS results. All patients were followed (19 ± 10 months) to compare the differences among clinical variables, PVPs, and survival rates. A total of 408 segments of pulmonary arteries were studied. The PAH groups demonstrated a greater mean wall thickness than group 3 (p < 0.01 for all). Pulmonary vascular mechanical properties, including compliance, distensibility, elastic modulus, and stiffness index β, were found to be worse in the PAH groups than in group 3 (p < 0.01 for all), but they tended to be better in group 1 than in group 2. An inverse exponential association was found between pulmonary vascular mechanical properties and hemodynamics, with R(2) values ranging from 0.54 to 0.78 (p < 0.001). In the PAH groups, the mortality in group 1 was similar to that in group 2 (12 % versus 13 %, p > 0.05), while the distal re-modeling sub-type had higher mortality than the proximal re-modeling sub-type (23 % versus 0 %, p < 0.05). The authors concluded that IVUS was useful in PAH assessment by evaluating PVPs and predicting mortality. The classification of the proximal and distal re-modeling type of PAH may be proposed to predict mortality and evaluate the prognosis of patients with PAH in clinical practice. This appeared to be the same study as that by Cai et al (2015).
Furthermore, UpToDate reviews on “Clinical features and diagnosis of pulmonary hypertension in adults” (Rubin and Hopkins, 2019) and “Clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension” (Fedullo, 2019) do not mention IVUS as a management tool.
Follow-Up of Treatment
Forauer et al (2002) noted that IVUS imaging and venography of the left common femoral and iliac veins were performed in 16 patients. The studies were evaluated for the anatomic cause of obstruction and how IVUS influenced endovascular management. IVUS demonstrated the cause of vessel compression in all 16 patients. Other findings, such as associated thrombus and guide wire localization within the residual vessel lumen, can modify the approach to intervention in as many as 50 % of patients. The authors concluded that IVUS is a useful adjunct in the diagnosis and endovascular management of iliac vein compression syndrome.
Furthermore, an UpToDate review on “May-Thurner syndrome” (Mousa, 2019) states that “Since its inception and use over the last decade, IVUS has become an integral component of the treatment of MTS. IVUS is useful for determining vessel diameter, aiding accurate stent placement, ensuring full stent expansion, estimating the gain in cross-sectional area, and, with follow-up, identifying the severity of in-stent restenosis”.
Treatment of Type B Aortic Dissection with Thoracic Endovascular Aneurysm Repair
Lortz and associates (2018) noted that the precise sizing of the stent graft in thoracic endovascular aortic repair (TEVAR) affects aortic re-modeling and hence, further outcome. Covering the proximal entry tear is essential for successful treatment of type B aortic dissection (TBAD). Intravascular ultrasound (IVUS) enables real-time aortic diameter assessment, and is especially useful when CT image quality is poor. IVUS, however, is not routinely utilized due to cost inefficiency. These investigators examined the impact of IVUS-assisted stent graft sizing on aortic re-modeling in TEVAR. In a retrospective, single-center study, these researchers evaluated patients with TBAD undergoing both CT and IVUS before TEVAR. They assessed the aortic diameter at the level of the left subclavian artery via both methods before stent implantation and analyzed due to which method the implanted stent graft was chosen, retrospectively. To determine the degrees of aortic re-modeling involved, these investigators evaluated true lumen and false lumen diameters, and total aortic re-modeling in CT. These researchers analyzed 45 patients with TBAD undergoing TEVAR. The mean ages were 66.9 ± 10.0 years for IVUS (n = 20) and 62.3 ± 14.2 years for CT-assisted TEVAR (n = 25; p = 0.226). The follow-up time for both groups did not differ between the 2 groups (IVUS: 22.9 ± 23.1 months, CT: 25.6 ± 23.0 months; p = 0.700). While both methods were associated with advantages regarding aortic re-modeling, IVUS-assisted sizing yielded a greater increase in true lumen (30.4 ± 6.2 versus 25.6 ± 5.3; p = 0.008) and reductions in false lumen (14.4 ± 8.5 versus 23.9 ± 9.3; p = 0.001) and total aortic diameter (35.5 ± 6.0 versus 39.9 ± 8.1; p = 0.045). The authors concluded that IVUS-assisted stent graft sizing in TBAD showed beneficial effects on aortic re-modeling, and emphasized the additional advantage of IVUS in aortic diseases. While IVUS will not replace CT as a state-of-the-art technique for stent graft sizing in TEVAR, it may be a valid additional approach, especially when assessment via CT was compromised by poor image quality or was otherwise inconclusive. It may reduce the need for repetition of previous external CT scans of low quality for accurate stent-graft sizing and after TEVAR it can further ensure the apposition of the stent-graft to the aortic wall both to improve aortic re-modeling.
Belkin and colleagues (2020) examined the potential survival benefit associated with IVUS in the treatment of TBAD. These researchers carried out a retrospective review of TEVARs performed for TBAD in the national Vascular Quality Initiative from January 2010 to August 2018. Data collected included demographics, intra-operative and post-operative variables, and long-term mortality. Multi-variable logistic regression evaluated variables associated with IVUS the use and mortality, and Cox regression was performed for adjusted survival analysis. In this study of 2,686 patients, the average age was 60.4 years, 69.3 % were men, and IVUS examination was used in 74.6 % of cases. IVUS patients were younger (60.0 years versus 61.7 years; p = 0.004), more often male (72.1 % versus 61.3 %; p < 0.001), exhibited less coronary disease, but had higher pre-operative creatinine (1.27 ± 0.89 mg/dL versus 1.14 ± 0.68 mg/dL; p < 0.001) and were more often treated in the acute setting (55.2 % versus 49.7 %; p = 0.03). Interestingly, there were no differences in contrast use (117.4 ± 77.6 ml versus 123.0 ± 81.90.1 ml; p = 0.11) or fluoroscopy time (20.3 ± 16.5 mins versus 19.0 ± 22.1 mins; p = 0.10). However, IVUS cases had a greater number of devices implanted (1.84 versus 1.65; p < 0.001), higher rates of Zone 0 to 2 proximal seal (43.9 % versus 30.7 %; p < 0.001), higher rates of distal seal zones beyond the diaphragm (53.9 % versus 37.4 %; p = 0.001), and larger proximal and distal graft diameters, with no differences in post-operative renal function. IVUS patients notably also had higher rates of follow-up imaging (61.3 % versus 54.8 %; p = 0.003), larger maximum aortic diameters at follow-up, and more re-interventions over time. The number of aortic devices (OR 1.56; 95 % CI: 1.24 to 1.97; p < 0.001), mal-perfusion indication (OR, 1.68; 95 % CI: 1.17 to 2.42; p = 0.005) and distal seal zone beyond the diaphragm (OR, 1.64; 95 % CI: 1.30 to 2.07; p < 0.001) were independently associated with IVUS use, whereas female gender showed a trend towards less IVUS use (OR, 0.79; 95 % CI: 0.62 to 1.01; p = 0.063). Even after controlling for age, pre-operative co-morbidities, and post-operative complications like spinal cord ischemia, IVUS was associated with a 61 % decrease in the odds of mortality (OR, 0.39; 95 % CI: 0.20 to 0.78; p = 0.008), with a clear survival advantage shown in adjusted survival curves. The authors concluded that IVUS examination was used in the majority of TBAD, although not universally; IVUS examination was used more often in acute TBAD and more complex aortic repairs, and was independently associated with improved long-term survival.
Furthermore, an UpToDate review on “Surgical and endovascular management of type B aortic dissection” (Black, 2020) states that “The initial technical approach for an endovascular intervention in acute type aortic dissection relies heavily upon intravascular ultrasound. Ultrasound can document the location of the proximal entry tear, the anatomy of visceral and renal branches in relation to the true and false lumens, and can identify the dissection septum that may be overlying branch orifices to produce malperfusion in a dynamic or static manner. For patients with iliofemoral thrombosis or leg malperfusion, ultrasound also identifies the compressed true lumen and can aid with needle and wire introduction”.
Intravascular Ultrasound (IVUS) for Prediction of Outcome Following Carotid Artery Stenting
In a prospective RCT, Chiocchi and associates (2019) examined the usefulness of IVUS in the identification of otherwise unnoticed complications during carotid stenting. The secondary objective was the evaluation of the impact of IVUS assistance in the procedural outcomes and long-term patency rates of CAS. A total of 60 patients who underwent CAS during a 14-month period were evaluated; 30 (50 %) underwent IVUS-assisted CAS, and 30 patients (50 %) underwent CAS using angiography as the unique diagnostic tool. All subjects were enrolled via a primary Duplex US evaluation; as a secondary evaluation, 54 patients (90 %) underwent a pre-procedural MR angiography (MRA), whereas 6 patients (10 %) underwent CT angiography (CTA). Patients with pre-occlusive stenoses (greater than 85 %) were excluded. Mean follow-up was 23 +/- 5.3 months. No peri-procedural or late complications were observed. No statistical significance was observed in long-term stent patency between the 2 groups. Mean procedural time length of IVUS-assisted procedures was 10.3 +/- 5 mins longer than non-IVUS-assisted procedures. Virtual histology (VH)-IVUS evaluation of plaque morphology led to a different stent choice in 3 patients. In 2 cases, the IVUS assessment revealed a sub-optimal stent deployment, solved by angioplasty; in 1 patient VH-IVUS detected plaque protrusion through stent cells, immediately treated by manual aspiration. The authors concluded that although not recommended as a routine intra-procedural evaluation, IVUS may be useful for a real-time CAS control when treating challenging plaques, such as “soft” or lipidic ones or those prone to rupture, or whenever an intra-procedural morphologic evaluation is needed for the appropriate stent choice, or when higher embolic risk is evaluated.
Mishra and colleagues (2022) noted that carotid plaque morphology plays an important role in determining outcome of CAS; IVUS and its extension VH-IVUS evaluate plaque characteristics in real time and guide decision-making during stenting. Currently, there is no consensus regarding indications of IVUS and its validated methods. In a systematic review and meta-analysis, these researchers examined the use of IVUS in CAS and developed a future consensus for research and practice parameters. They carried out a review of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings as well as its performance compared with other imaging modalities were included in review. Pooled prevalence with 95 % CI was calculated. The statistical analysis was conducted in R version 3.6.2. A total of 2,015 patients from 29 studies were included. Proportional meta-analysis was carried out on 1,566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4 % (95 % CI: 3 % to 5 %) while asymptomatic stroke had a pooled prevalence of 46 % (95 % CI: 31 % to 62 %) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n = 33/396 versus 11/396). IVUS led to stent type or size change in 8 of 48 cases that were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80 % to 85 % reported in 2 studies. The authors concluded that this systematic review and meta-analysis showed that although IVUS fared better than CTA/MRA for better stent selection during CAS, with low-to-moderate risk of bias in the included studies; however, large scale, preferably RCTs are needed to predict its role in determining clinical outcome.
Furthermore, an UpToDate review on “Overview of carotid artery stenting” (Jim, 2022) does not mention IVUS as a management option.
Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction
Groenland et al (2022) stated that IVUS can overcome the intrinsic limitations of coronary angiography for lesion assessment and stenting. IVUS improves outcomes of patients presenting with stable or complex coronary artery disease (CAD); however, dedicated data on the impact of IVUS-guided percutaneous coronary intervention (PCI) in patients with acute MI (AMI) remains scarce. In a systematic review and meta-analysis, these investigators compared clinical outcomes for IVUS- versus angio-guided PCI in patients with AMI. They searched Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar for relevant studies. The primary endpoint was all-cause mortality and the secondary endpoint major adverse cardiovascular events (MACE). Mantel-Haenszel random-effects model was used to calculate pooled risk ratios (RR) with 95 % CI. A total of 9 studies (8 observational, 1 RCT) with a total of 838,902 patients (796,953 angio-guided PCI, 41,949 IVUS-guided PCI) were included. In patients with AMI, IVUS-guided PCI was associated with a significantly lower risk of all-cause mortality (pooled RR: 0.70; 95 % CI: 0.59 to 0.82; p < 0.01), MACE (pooled RR: 0.86; 95 % CI: 0.74 to 0.99; p = 0.04) and target vessel re-vascularization (TVR) (pooled RR: 0.83; 95 % CI: 0.73 to 0.95; p < 0.01). In the subset of patients presenting with ST-segment elevation, IVUS-guided PCI remained associated with a reduced risk for both all-cause mortality (pooled RR: 0.79; 95 % CI: 0.66 to 0.95, p = 0.01) and MACE (pooled RR: 0.86; 95 % CI: 0.74 to 0.99, p = 0.04). The authors concluded that this was the 1st systematic review and meta-analysis comparing IVUS- versus angio-guided PCI in patients with AMI, showing a beneficial effect of IVUS-guided PCI on all-cause mortality, MACE and TVR. Moreover, these researchers stated that results of ongoing prospective studies are needed to confirm these findings.
The authors stated that this analysis had several drawbacks. First, mainly retrospective and prospective observational studies based on large AMI registries were included in this systematic review and meta-analysis. In general, data derived from registries is more prone to bias and might affect results. Quality assessment was carried out to provide a complete overview of each study's risk of bias per domain. Moreover, risk of publication bias was examined by visual inspection of funnel plots. The funnel plot for MACE showed a slightly asymmetric pattern, indicating that publication bias in favor of IVUS could not be completely excluded. However, visual inspection of funnel plots has been found a subjective tool for the assessment of publication bias. The afore-mentioned prospective studies are needed to confirm the potential positive impact of IVUS-guided PCI in patients with AMI. Second, follow-up time differed among studies (in-hospital and up to 5 years), although maximum follow-up in most included studies was 1 year. Third, inherent to using a composite endpoint in a meta-analysis is that definitions differ among included studies. In the present meta-analysis definitions for MACE were largely comparable. Fourth, differences in DES use, DES type (generation), and lesion complexity between studies and study groups, could potentially have impacted clinical outcomes. Meta-regression was not conducted, since less than 10 studies were included and data of the described variables was largely missing, significantly decreasing the potential reliability of adjusted results. Fifth, study heterogeneity was moderate-to-substantial for all clinical outcomes; however, Mantel-Haenszel random-effects model was used to account for this and subgroup analyses were performed to examine possible sources of study heterogeneity.
Thoracic Endovascular Aortic Repair for Blunt Thoracic Aortic Injury
Smith et al (2022) noted that thoracic endovascular aortic repair (TEVAR) for blunt traumatic aortic injuries (BTAIs) can be complicated by inaccurate aortic measurements at the initial CTA secondary to hypovolemic shock. The use of IVUS has been proposed for more accurate aortic sizing, with prior data showing larger aortic sizes measured by IVUS, potentially altering the vast majority of chosen endograft sizes. To-date, no studies have examined if IVUS would affect the clinical outcomes. In a retrospective cohort study, these researchers examined the effect of IVUS on the clinical outcomes following TEVAR for BTAIs. This trial included patients who had undergone TEVAR for BTAIs in the VQI registry. The cohorts were defined by the use of IVUS. The primary outcomes were mortality and re-intervention at 1 year. A total of 919 patients who had undergone TEVAR for BTAIs were included in the present analysis. The IVUS patients had presented with higher injury severity scores (36.2 versus 42; p = 0.0004) largely because of more extremity and external trauma. IVUS was more often used for patients with grade III injuries (49.1 % versus 56.9 %; p = 0.02) and less often for patients with rupture (21.1 % versus 12.4 %; p = 0.001). A trend toward a delay in TEVAR was observed for the patients for whom IVUS was used (1.8 versus 3.5 days; p = 0.38), with additional trends toward reduced intra-operative resuscitation and blood loss. The hemodynamic status of the patients and differences in aortic or endograft sizes could not be evaluated with the available data. IVUS use was not associated with any differences in survival or re-intervention rates in-hospital or at 1 year (Kaplan-Meier survival estimates: 0.91 no IVUS versus 0.92 IVUS; p = 0.46). A total of 15 aortic-related re-interventions occurred across the entire patient cohort for all-available follow-up with comparable rates of type I endoleaks (1 no IVUS versus 2 IVUS), with no recorded cases of sizing-related complications such as device rupture, migration, or dissection. The authors concluded that IVUS usage during TEVAR for BTAIs was associated with clinical scenarios in which patients were more stable and interventions to address BTAIs could be delayed. Despite this, the overall clinical outcomes were similar between cases in which IVUS was used and for which it was not.
Infra-Inguinal Re-Canalization
Torey et al (2016) noted that CENTRAL was a prospective, multi-center study (n = 100) designed to examine the ability of a re-canalization catheter system for the treatment of chronic total occlusions (CTOs) of the superficial femoral artery while staying within the central vessel lumen. The primary endpoint was the successful crossing of a CTO (90 % or greater of the length) with the re-canalization catheter in the central lumen of the superficial femoral artery in at least 50 % of the studied patient population, confirmed by IVUS. Secondary endpoints included standardized anatomic damage assessment (the TAPE method) and an assessment of the relationship between the percent of CTO crossing and TAPE scores to the rate of TLR at 30 days and 6 months. The mean age of the occlusions was 16.6 ± 22.28 months (range of 1 to 120 months), the average occlusion length reported by the sites was 132.1 ± 87.69 mm (range of 4 to 300 mm), and a majority of lesions were moderately (42.0 %) or severely (32.0 %) calcified. In 43/85 (50.6 %) of the evaluable IVUS images, the re-canalization catheter successfully navigated the central lumen of the CTO (i.e., 90 % or greater luminal crossing) with greater than 50% luminal crossing in 64/85 (75.3 %) of cases. The 6-month TLR rate was significantly lower in patients where the CTO was crossed 90 % or greater in the central vessel lumen (4.7 %) compared with crossings of less than 90 % (20.6 %; p = 0.04). The 6-month TLR rate was 3.5 % in patients with a favorable TAPE score of 0 to 4 and 36.8 % with an unfavorable TAPE score of 5 to 8 (p < 0.001). The authors concluded that the use of a re-canalization catheter in complex superficial femoral artery CTO crossings achieved intra-luminal crossings in greater than 50 % of cases and reduced anatomic damage, which appeared to offer a significant advantage in 6-month TLR rates.
Takahashi et al (2017) examined the 1-year outcomes of trans-venous IVUS-guided EVT for the management of CTO of the lower extremity (LE) arteries. Trans-venous IVUS-guided EVT was carried out in 44 patients (50 limbs) with CTO of the femoro-popliteal arteries or tibio-peroneal trunk. Treatment entailed crossing a guide-wire via the CTO under the guidance of both fluoroscopic and IVUS imaging, along with insertion of the IVUS catheter into a vein parallel to the target artery. Primary success rate, complications, and TLR at 12-month follow-up were assessed. Successful re-canalization, defined as grade-3 flow (Thrombolysis in Myocardial Infarction score) and no flow-limiting dissection, was observed in 48 (96 %) limbs; 2 limbs with failed re-canalization had a very long CTO lesion from the superficial femoral artery to below the knee. A bi-directional approach was selected in 11 (22 %) limbs. Complications at the access site occurred in only 2 patients. The rate of freedom from TLR at 12 months was 77.9 % (95 % CI: 61.4 to 87.9). The authors concluded that trans-venous IVUS-guided EVT was safe and could provide optimal short-term results for EVT of CTO in the infra-inguinal arteries. These investigators stated that IVUS-guided EVT may be one of the most effective treatment strategies for CTO of the femoro-popliteal arteries or tibio-peroneal trunk.
In a retrospective, single-center study, Soga et al (2018) examined the use of the TruePath crossing device as the primary re-canalization tool for the treatment of infra-inguinal CTO. This study was carried out on 50 patients (mean age of 75 years; 26 men) with 55 infra-inguinal CTOs treated with the TruePath between March 2017 and September 2017. The mean occlusion length was 138 ± 55 mm, and femoro-popliteal lesions accounted for 65 % of the 55 lesions. The primary outcome measure was CTO crossing using the TruePath alone; secondary outcomes were assisted success (greater than 50 % lumen gain using the TruePath), device-related complications, and intra-luminal crossing evaluated by IVUS. Complete success was achieved in 33 (60 %) of 55 lesions having a mean occlusion length of 145 ± 72 mm. Among these, the true lumen crossing rate was 97 % according to IVUS evaluation. Assisted success was achieved in 15 (68 %) of the 22 failures. Complete/assisted success, in which the TruePath was thought to have contributed to CTO crossing, was attained in 48 (87 %) of the 55 lesions; 3 (5.5 %) complications were observed: a perforation, an access-site hematoma, and acute occlusion; only the perforation was device-related (1.8 %). Multi-variate analysis showed PACCS grade-4 (OR 4.5, 95 % CI: 1.33 to 15.5, p = 0.02) was an independent predictor of TruePath failure. The authors concluded that primary use of the TruePath crossing device for infra-inguinal CTOs showed a satisfactory complete success rate and a high rate of IVUS-documented intra-luminal crossing with few device-related complications. Severe calcification was an independent predictor of TruePath failure.
In a prospective, multi-center study, Tomoi et al (2020) examined the crossing pathways of the TruePath re-entry device during primary antegrade re-canalization of infra-inguinal CTOs by means of IVUS. Between July 2017 and September 2018, this trial enrolled 143 consecutive patients (mean age of 75 ± 9 years; 101 men) with 146 CTOs treated in an antegrade approach using the TruePath re-entry device with IVUS assessment of the crossing pathway in successful cases. Outcome measures were complete success (re-entry device reached the distal true lumen), assisted success (re-entry device use followed by a conventional guide-wire to reach the distal true lumen), re-entry device crossing route by IVUS assessment, and procedure- and device-related complications. Regression analyses were used to identify any relevant associations between baseline patient variables and the outcome measures; results were presented as the ORs and 95 % CIs. Complete success was achieved in 82 (56.2 %) lesions; any success (complete plus assisted) was documented in 117 (80.1 %) lesions; 4 (3 %) peri-operative device-related complications were observed. The crossing route was intra-plaque for most of the total crossing distance in both complete success cases (95.3 % ± 13.2 %) and any success cases (94.8 % ± 14.4 %), with relatively short subintimal (3.6 % ± 10.2 % and 4.2 % ± 11.2 %, respectively) or intra-medial (1.2 % ± 5.8 % and 1.0 % ± 5.4 %, respectively) crossing. CTO length was a significant risk factor for not achieving complete success (OR 1.74, 95 % CI: 1.13 to 2.68, p = 0.012), and a history of failed re-vascularization was associated with not achieving any success (OR 6.40, 95 % CI: 1.28 to 28.9, p = 0.038). The authors concluded that the intra-plaque route was the primary pathway taken by the TruePath re-entry device as it crossed infra-inguinal CTOs. Crossing rates were acceptable, with few device-related complications; however, a longer CTO length and a failed re-vascularization history negatively affected the success rate.
Intravascular Ultrasound Guidance in Pulmonary Embolism Patients Undergoing Mechanical Thrombectomy
Kumar et al (2023) stated that iodinated contrast is often used during catheter-based mechanical thrombectomy for pulmonary embolism (PE). Recently, there have been disruptive contrast shortages. In addition, contrast can cause contrast-induced acute kidney injury (CI-AKI) especially in patients with pre-existing chronic kidney disease (CKD), necessitating an alternative imaging method. These investigators presented utilization and feasibility of an IVUS-guided strategy for mechanical thrombectomy in PE from the FLASH registry. In this FLASH patient subset, IVUS was used to image the pulmonary arteries (PAs) before and after mechanical thrombectomy with the FlowTriever System at 1 study site comprising 3 hospitals. The Philips Visions PV 0.035" IVUS catheter was used for all the IVUS-guided cases in a standardized manner. Between July 2019 and December 2021, a total of 26 FLASH patients enrolled at this site underwent IVUS-guided thrombectomy. Most patients (96.2 %) had intermediate-risk PE, and 3.8 % had high-risk PE. The mean baseline composite RV/LV ratio was 1.36 ± 0.27 and the mean simplified Pulmonary Embolism Severity Index (sPESI) score was 1.9 ± 1.2. A decreasing trend in contrast agent volume usage was observed over time and several later procedures were performed with IVUS guidance alone. Mean PA pressure significantly decreased immediately following thrombectomy from 34.8 ± 8.3 to 25.5 ± 7.3 mmHg (p < 0.0001). Systolic PA pressure also significantly decreased immediately from 55.4 ± 13.9 to 39.5 ± 12.5 mmHg (p < 0.0001). Significant improvements were observed in echocardiographic assessments of RV function at a mean 87-day follow-up compared with baseline. The authors concluded that the use of IVUS guidance with minimal or no angiographic contrast during mechanical thrombectomy for acute PE was technically feasible. These researchers stated that evidence is growing for mechanical thrombectomy as a front-line treatment for PE; however, minimal experience has been published on IVUS guidance for mechanical thrombectomy procedures. Published literature has been limited to case reports … however, the ultimate benefits of this approach over traditional pulmonary angiography are unknown and need to be studied in RCTs.
Desai et al (2023) noted that traditionally, mechanical thrombectomy conducted for PE necessitates the use of iodinated contrast; and IVUS has been employed as a diagnostic and therapeutic modality in the management of acute high and intermediate-risk PE. Recently, with the shortage of contrast supplies and the considerable incidence of CI-AKI, other safer and more feasible IVUS methods have become desirable. In a systematic review, these investigators examined the importance of IVUS in patients with PE undergoing thrombectomy. Medline/PubMed, Embase, Scopus, and Google Scholar were searched for review studies, as well as case-report and case-series studies. Clinical characteristics, outcomes, and the use of IVUS-guided mechanical thrombectomy during the treatment of acute high and intermediate-risk PE were examined in a descriptive analysis. In this systematic review, these investigators included 1 prospective study, 2 case-series studies, and 2 case-report studies from July 2019 to May 2023. A total of 39 patients were examined; most were female (53.8 %). The main presenting symptoms were dyspnea and chest pain (79.5 %); 3 patients (7.9 %) presented with syncope, 1 with shock, and 1 with cardiac arrest. Biomarkers (troponin and BNP) were elevated in 94.6 % of patients. Most patients (87.2 %) had intermediate-risk PE, and 12.8 % had high-risk PE. All patients presented with right-heart strain (RV/LV ratio of 0.9 or higher, n = 39). Most patients (56.4 %) had bilateral PE. Mechanical thrombectomy was carried out using IVUS without contrast utilization in 39.4 % of the patients. After the initial learning curve, contrast usage decreased gradually over time. There was a significant decrease in the composite mean arterial pressure (MAP) immediately following IVUS-guided thrombectomy from 35.1 ± 7.2 to 25.2 ± 8.3 mmHg (p < 0.001). Post-procedure, there was no reported (0 %) CI-AKI, no all-cause mortality, no major bleeding, or other adverse events (AEs). There was a significant improvement in symptoms and RV function at the mean follow-up. The authors concluded that the use of IVUS for mechanical thrombectomy in acute PE was technically feasible and exhibited a favorable safety profile. This could be particularly important for individuals with CKD or other risk factors for CI-AKI. These researchers stated that as new technology emerges and expertise advances, IVUS will likely become a prominent tool in the management of PE. However, these investigators stated that further RCTs and comparative data analyses are needed.
The authors stated that a main drawback of this review was the need for more literature in this area to provide conclusive evidence. The research is preliminary, and there is a need for further investigation in the field. In addition, data are available for only 1 IVUS catheter, and the catheter resolution and image quality may have had an impact on the outcomes of interest. Furthermore, the information obtained was mainly from case reports and 1 study, while other information needs to be extrapolated from the data available for different indications of IVUS. These researchers stated that given that they examined the potential of IVUS at times by drawing from related fields, the scientific gain may be viewed as small at this stage.
References
The above policy is based on the following references:
- Abizaid AS, Mintz GS, Abizaid A, et al. One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms. J Am Coll Cardiol. 1999;34(3):707-715.
- Abizaid AS, Mintz GS, Mehran R, et al. Long-term follow-up after percutaneous transluminal coronary angioplasty was not performed based on intravascular ultrasound findings: Importance of lumen dimensions. Circulation. 1999;100(3):256-261.
- Ahn JM, Kang SJ, Yoon SH, et al. Meta-analysis of outcomes after intravascular ultrasound-guided versus angiography-guided drug-eluting stent implantation in 26,503 patients enrolled in three randomized trials and 14 observational studies. Am J Cardiol. 2014;113(8):1338-1347.
- Alhalbouni S, Hingorani A, Shiferson A, et al. Iliac-femoral venous stenting for lower extremity venous stasis symptoms. Ann Vasc Surg. 2012;26(2):185-189.
- Allan RB, Puckridge PJ, Spark JI, Delaney CL. The impact of intravascular ultrasound on femoropopliteal artery endovascular interventions: A randomized controlled trial. JACC Cardiovasc Interv. 2022;15(5):536-546.
- Ascher E, Eisenberg J, Bauer N, et al. The bull's eye sign and other suprainguinal venographic findings to limit the use of intravascular ultrasound in patients with severe venous stasis. J Vasc Surg Venous Lymphat Disord. 2017;5(1):70-74
- Ashley DW, Gamblin TC, Burch ST, Solis MM. Accurate deployment of vena cava filters: Comparison of intravascular ultrasound and contrast venography. J Trauma. 2001;50(6):975-981.
- Aurshina A, Ganelin A, Hingorani A, et al. Clinical correlation of the area of inferior vena cava, iliac and femoral veins for stent use. Vascular. 2017:1708538117715343.
- Aurshina A, Kheyson B, Eisenberg J, et al. Clinical correlation of anatomical location of non-thrombotic iliac vein lesion. Vascular. 2017;25(4):359-363.
- Azizzadeh A, Valdes J, Miller CC 3rd, et al. The utility of intravascular ultrasound compared to angiography in the diagnosis of blunt traumatic aortic injury. J Vasc Surg. 2011;53(3):608-614.
- Belkin N, Jackson BM, Foley PJ, et al. The use of intravascular ultrasound in the treatment of type B aortic dissection with thoracic endovascular aneurysm repair is associated with improved long-term survival. J Vasc Surg. 2020;72(2):490-497.
- Berger RM, Cromme-Dijkhuis AH, Hop WC, et al. Pulmonary arterial wall distensibility assessed by intravascular ultrasound in children with congenital heart disease: An indicator for pulmonary vascular disease? Chest. 2002 g;122(2):549-557.
- Berry E, Kelly S, Hutton J, et al. Intravascular ultrasound-guided interventions in coronary artery disease: A systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness. Health Technol Assess. 2000;4(35): 1-117.
- Black JH, III. Surgical and endovascular management of type B aortic dissection. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2020.
- Boniakowski AE, Davis F, Campbell D, et al. Intravascular ultrasound as a novel tool for the diagnosis and targeted treatment of functional popliteal artery entrapment syndrome. J Vasc Surg Cases Innov Tech. 2017;3(2):74-78.
- Bourassa MG, Butnaru A, Lesperance J, Tardif JC. Symptomatic myocardial bridges: Overview of ischemic mechanisms and current diagnostic and treatment strategies. J Am Coll Cardiol. 2003;41(3):351-359.
- Bressollette E, Dupuis J, Bonan R, et al. Intravascular ultrasound assessment of pulmonary vascular disease in patients with pulmonary hypertension. Chest. 2001;120(3):809-815.
- Cai Z, Li J, Sun L, et al. Value of intravascular ultrasound in the assessment of pulmonary vascular properties and mortality in patients with pulmonary artery hypertension associated with connective tissue diseases. Zhonghua Xin Xue Guan Bing Za Zhi. 2015 43(12):1061-1067.
- Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Intravascular coronary ultrasound (IVUS). Pre-Assessment No. 23. Ottawa, ON: CCOHTA; October 2003.
- Cansella G, Klauss V, Otttani F, et al. Impact of intravascular ultrasound-guided stenting on long-term clinical outcome: A meta-analysis of available studies comparing intravascular ultrasound-guided and angiographyically guided stenting. Catheter Cardiovasc Interv. 2003;59(3):314-321.
- Cavaye DM, White RA, Kopchok GE, et al. Intravascular ultrasound imaging: The new standard for guidance and assessment of endovascular interventions? J Clin Laser Med Surg. 1992;10(5):349-353.
- Cavaye DM, White RA, Kopchok GE. Intravascular ultrasound imaging. Am J Card Imaging. 1993;7(2):109-119.
- Chen CJ, Yang Y, Zhou XL, et al. Latest cognition of treatment on deep vein thrombosis of lower extremity. Zhonghua Wai Ke Za Zhi. 2005;43(7):420-422.
- Chiocchi M, Morosetti D, Chiaravalloti A, et al. Intravascular ultrasound assisted carotid artery stenting: Randomized controlled trial. Preliminary results on 60 patients. J Cardiovasc Med (Hagerstown). 2019;20(4):248-252.
- Chung WJ, Soga Y, Tomoi Y, et al. Clinical impact of intravascular ultrasound guidance during endovascular treatment of subclavian artery disease. J Endovasc Ther. 2017;24(5):731-738.
- Crowner J, Marston W, Almeida J, et al. Classification of anatomic involvement of the iliocaval venous outflow tract and its relationship to outcomes after iliocaval venous stenting. J Vasc Surg Venous Lymphat Disord. 2014;2(3):241-245.
- Darmoch F, Alraies MC, Al-Khadra Y, et al. Intravascular ultrasound imaging-guided versus coronary angiography-guided percutaneous coronary intervention: A systematic review and meta-analysis. J Am Heart Assoc. 2020;9(5):e013678.
- Daugherty SF, Gillespie DL. Venous angioplasty and stenting improve pelvic congestion syndrome caused by venous outflow obstruction. J Vasc Surg Venous Lymphat Disord. 2015;3(3):283-289.
- de Figueiredo Neto JA, Nogueira IA, Figueiro MF, et al. Angioplasty guided by intravascular ultrasound: Meta-analysis of randomized clinical trials. Arq Bras Cardiol. 2013;101(2):106-116.
- de Ribamar Costa J Jr, Mintz GS, Carlier SG, et al. Intravascular ultrasound assessment of drug-eluting stent expansion. Am Heart J. 2007;153(2):297-303.
- Desai R, Raval M, Adompreh-Fia KS, et al. Role of intravascular ultrasound in pulmonary embolism patients undergoing mechanical thrombectomy: A systematic review. Tomography. 2023;9(4):1393-1407.
- Diercks DB, Promes SB, Schuur JD, et al; American College of Emergency Physicians. Clinical policy: Critical issues in the evaluation and management of adult patients with suspected acute nontraumatic thoracic aortic dissection. Ann Emerg Med. 2015;65(1):32-42.
- Diethrich EB, Pauliina Margolis M, Reid DB, et al. Virtual histology intravascular ultrasound assessment of carotid artery disease: The Carotid Artery Plaque Virtual Histology Evaluation (CAPITAL) study. J Endovasc Ther. 2007;14(5):676-686.
- Divakaran S, Parikh SA, Hawkins BM, et al. Temporal trends, practice variation, and associated outcomes with IVUS use during peripheral arterial intervention. JACC Cardiovasc Interv. 2022;15(20):2080-2090.
- Dzieciuchowicz Ł, Krzyżański R, Kruszyna Ł, et al. Prevalence of non-thrombotic iliac vein lesions in patients with unilateral primary varicose veins. Eur J Vasc Endovasc Surg. 2016;51(3):429-433.
- Escolar E, Weigold G, Fuisz A, Weissman NJ. New imaging techniques for diagnosing coronary artery disease. CMAJ. 2006;174(4):487-495.
- Fedullo PF. Clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension. UpToDate [online serial], Waltham, MA: UpToDate; reviewed January 2019.
- Forauer AR, Gemmete JJ, Dasika NL, et al. Intravascular ultrasound in the diagnosis and treatment of iliac vein compression (May-Thurner) syndrome. J Vasc Interv Radiol. 2002;13(5):523-527.
- Gagne PJ, Gasparis A, Black S, et al. Analysis of threshold stenosis by multiplanar venogram and intravascular ultrasound examination for predicting clinical improvement after iliofemoral vein stenting in the VIDIO trial. J Vasc Surg Venous Lymphat Disord. 2018;6(1):48-56.
- Gagne PJ, Tahara RW, Fastabend CP, et al. Venography versus intravascular ultrasound for diagnosing and treating iliofemoral vein obstruction. J Vasc Surg Venous Lymphat Disord. 2017;5(5):678-687.
- García-García HM, Gonzalo N, Granada JF, et al. Diagnosis and treatment of coronary vulnerable plaques. Expert Rev Cardiovasc Ther. 2008;6(2):209-222.
- German Agency for Health Technology Assessment at the German Institute for Medical Documentation and Information (DAHTA) (DIMDI). The value of intravascular ultrasound (IVUS) for diagnostic and therapeutic coronary angiography. A medical health technology assessment. Summary. Cologne, Germany: German Agency for Health Technology Assessment at the German Institute for Medical Documentation and Information (DAHTA) (DIMDI); 2003.
- Groenland FTW, Neleman T, Kakar H, et al. Intravascular ultrasound-guided versus coronary angiography-guided percutaneous coronary intervention in patients with acute myocardial infarction: A systematic review and meta-analysis. Int J Cardiol. 2022;353:35-42.
- Hager ES, Yuo T, Tahara R, et al. Outcomes of endovascular intervention for May-Thurner syndrome. J Vasc Surg Venous Lymphat Disord. 2013;1(3):270-275.
- Hardt SE, Bekeredjian R, Brachmann J, et al. Intravascular ultrasound for evaluation of initial vessel patency and early outcome following directional coronary atherectomy. Catheter Cardiovasc Interv. 1999;47(1):14-22.
- Hernandez JM, de Prada JA, Burgos V, et al. Virtual histology intravascular ultrasound assessment of cardiac allograft vasculopathy from 1 to 20 years after heart transplantation. J Heart Lung Transplant. 2009;28(2):156-162.
- Hibberd MG, Vuille C, Weyman AE. Intravascular ultrasound: Basic principles and role in assessing arterial morphology and function. Am J Card Imaging. 1992;6(4):308-324.
- Hitchner E, Zayed MA, Lee G, et al. Intravascular ultrasound as a clinical adjunct for carotid plaque characterization. J Vasc Surg. 2014;59(3):774-780.
- Hoffmann R, Morice MC, Moses JW, et al. Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: Intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials. Heart. 2008;94(3):322-328.
- Hong SJ, Kim BK, Shin DH, et al; IVUS-XPL Investigators. Effect of intravascular ultrasound-guided vs angiography-guided everolimus-eluting stent implantation: The IVUS-XPL randomized clinical trial. JAMA. 2015;314(20):2155-2163.
- Hurst DR, Forauer AR, Bloom JR, et al. Diagnosis and endovascular treatment of iliocaval compression syndrome. J Vasc Surg. 2001;34(1):106-113.
- Ibanez B, Badimon JJ, Garcia MJ. Diagnosis of atherosclerosis by imaging. Am J Med. 2009;122(1 Suppl):S15-S25.
- Ishii M, Kato H, Kawano T, et al. Evaluation of pulmonary artery histopathologic findings in congenital heart disease: An in vitro study using intravascular ultrasound imaging. J Am Coll Cardiol. 1995;26(1):272-276.
- Jang JS, Shin HC, Bae JS, et al. Diagnostic performance of intravascular ultrasound-derived minimal lumen area to predict functionally significant non-left main coronary artery disease: A meta-analysis. Korean Circ J. 2016;46(5):622-631.
- Jiang J, Xu W. Predictability and usefulness of intravascular ultrasound-guided angioplasty in patients with femoropopliteal lesions. Int Angiol. 2022;41(1):74-81.
- Jim J. Overview of carotid artery stenting. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2022.
- Johnston PW, Fort S, Cohen FA. Noncritical disease of the left main coronary artery: Limitations of angiography and the role of intravascular ultrasound. Can J Cardiol. 1999;15(3):297-302.
- Kayılıoglu SI, Köksoy C, Alaçayır İ. Diagnostic value of the femoral vein flow pattern for the detection of an iliocaval venous obstruction. J Vasc Surg Venous Lymphat Disord. 2016;4(1):2-8.
- Kibrik P, Eisenberg J, Alsheekh A, et al. Safety and efficacy of stenting nonthrombotic iliac vein lesions in octogenarians and nonagenarians in an office setting. Vascular. 2018;26(1):70-74.
- Klauss V, Mudra H, Uberfuhr P, et al. Intraindividual variability of cardiac allograft vasculopathy as assessed by intravascular ultrasound. Am J Cardiol. 1995;76:463-466.
- Klersy C, Ferlini M, Raisaro A, et al. Use of IVUS guided coronary stenting with drug eluting stent: A systematic review and meta-analysis of randomized controlled clinical trials and high quality observational studies. Int J Cardiol. 2013;170(1):54-63.
- Kolluri R, Fowler B, Ansel G, Silver M. A novel duplex finding of superficial epigastric vein flow reversal to diagnose iliocaval occlusion. J Vasc Surg Venous Lymphat Disord. 2017;5(3):358-362.
- Konig A, Kilian E, Rieber J, et al. Assessment of early atherosclerosis in de novo heart transplant recipients: Analysis with intravascular ultrasound-derived radiofrequency analysis. J Heart Lung Transplant. 2008a;27(1):26-30.
- Konig A, Kilian E, Sohn HY, et al. Assessment and characterization of time-related differences in plaque composition by intravascular ultrasound-derived radiofrequency analysis in heart transplant recipients. J Heart Lung Transplant. 2008b;27(3):302-309.
- Koo B-K, Hu X, Kang J, et al; FLAVOUR Investigators. Fractional flow reserve or intravascular ultrasonography to guide PCI. N Engl J Med. 2022;387(9):779-789.
- Kumar A, Shariff M, Adalja D, Doshi R. Intravascular ultrasound versus angiogram guided drug eluting stent implantation. A systematic review and updated meta-analysis with trial sequential analysis. Int J Cardiol Heart Vasc. 2019;25:100419.
- Kumar G, Jaber W, Sachdeva R. Intravascular ultrasound guidance in percutaneous mechanical thrombectomy: A single-center experience from the FLASH registry. Cardiovasc Revasc Med. 2023;50:19-25.
- Lau J, Kent D, Tatsioni A, et al. Vulnerable plaques. A brief review of the concept and proposed approaches to diagnosis and treatment. Prepared by theTufts-New England Medical Center AHRQ Evidence-based Practice Center. Contract No. 290-02-0022, Task Order #1. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); January 22, 2004.
- Lortz J, Tsagakis K, Rammos C, et al. Intravascular ultrasound assisted sizing in thoracic endovascular aortic repair improves aortic remodeling in Type B aortic dissection. PLoS One. 2018;13(4):e0196180.
- Makris GC, Chrysafi P, Little M, et al. The role of intravascular ultrasound in lower limb revascularization in patients with peripheral arterial disease. Int Angiol. 2017;36(6):505-516.
- Manning WJ, Black JH, III. Clinical features and diagnosis of acute aortic dissection. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2016.
- Massenburg BB, Himel HN, Blue RC, et al. Magnetic resonance imaging in proximal venous outflow obstruction. Ann Vasc Surg. 2015;29(8):1619-1624.
- Matthews BD, Joels CS, LeQuire MH. Inferior vena cava filter placement: Preinsertion inferior vena cava imaging. Am Surg. 2003;69(8):649-653.
- Medical Services Advisory Committee (MSAC). Intravascular ultrasound. Assessment Report. MSAC application 1032. Canberra, ACT: Department of Health and Ageing; 2001.
- Meng W, Guo J, Pan D, et al. Intravascular ultrasound-guided versus angiography-guided endovascular therapy for femoropopliteal artery disease: A scoping review. J Endovasc Ther. 2023 Sep 9 [Online ahead of print].
- Metzger PB, Rossi FH, Kambara AM, et al. Criteria for detecting significant chronic iliac venous obstructions with duplex ultrasound. J Vasc Surg Venous Lymphat Disord. 2016;4(1):18-27.
- Mintz GS, Nissen SE, Anderson WD, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37(5):1478-1492.
- Mishra B, Pandit AK, Miyachi S, et al. Clinical utility of intravascular ultrasound (IVUS) in carotid artery interventions: A systematic review and meta-analysis. J Endovasc Ther. 2022;29(5):678-691.
- Mokin M, Kan P, Abla AA, et al. Intravascular ultrasound in the evaluation and management of cerebral venous disease. World Neurosurg. 2013;80(5):655.e7-e13.
- Moriuchi M, Gordon IL, Bergman A, et al. Anatomic and functional assessment of stenosis severity with intravascular ultrasound imaging in vitro. Am J Card Imaging. 1992;6(2):109-116.
- Mousa AY, Broce M, Yacoub M, AbuRahma AF. Iliac vein interrogation augments venous ulcer healing in patients who have failed standard compression therapy along with pathological venous closure. Ann Vasc Surg. 2016;34:144-151.
- Mousa AY, Broce M, Yacoub M, et al. Validation of venous duplex ultrasound imaging in determining iliac vein stenosis after standard treatment of active chronic venous ulcers. J Vasc Surg Venous Lymphat Disord. 2016;4(3):307-312.
- Mousa AY. May-Thurner syndrome. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed July 2019.
- Murphy EH, Broker HS, Johnson EJ, et al. Device and imaging-specific volumetric analysis of clot lysis after percutaneous mechanical thrombectomy for iliofemoral DVT. J Endovasc Ther. 2010;17(3):423-433.
- Murphy EH, Johns B, Varney E, et al. Deep venous thrombosis associated with caval extension of iliac stents. J Vasc Surg Venous Lymphat Disord. 2017;5(1):8-17.
- Nakamura S, Conroy RM, Gordon IL, et al. A randomized trial of transcutaneous extraction atherectomy in femoral arteries: Intravascular ultrasound observations. J Clin Ultrasound. 1995;23:461-471.
- Natesan S, Mosarla RC, Parikh SA, et al. Intravascular ultrasound in peripheral venous and arterial interventions: A contemporary systematic review and grading of the quality of evidence. Vasc Med. 2022;27(4):392-400.
- Neglen P, Berry MA, Raju S. Endovascular surgery in the treatment of chronic primary and post-thrombotic iliac vein obstruction. Eur J Vasc Endovasc Surg. 2000;20(6):560-571.
- Neglen P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg. 2007;46(5):979-990.
- Neglen P, Raju S. Intravascular ultrasound scan evaluation of the obstructed vein. J Vasc Surg. 2002;35(4):694-700.
- Nerlekar N, Cheshire CJ, Verma KP, et al. Intravascular ultrasound guidance improves clinical outcomes during implantation of both first- and second-generation drug-eluting stents: A meta-analysis. EuroIntervention. 2017;12(13):1632-1642.
- Nishioka T, Amanullah AM, Luo H, et al. Clinical validation of intravascular ultrasound imaging for assessment of coronary stenosis severity: Comparison with stress myocardial perfusion imaging. J Am Coll Cardiol. 1999;33(7):1870-1878.
- Nissen SE. Application of intravascular ultrasound to characterize coronary artery disease and assess the progression or regression of atherosclerosis. Am J Cardiol. 2002;89(4A):24B-31B.
- Nomura M, Kurokawa H, Ishii J, et al. The role of angioscopy and intravascular ultrasound imaging in acute coronary syndrome. J Cardiol. 1999;33 Suppl 1:17-21.
- Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat (MAS). Intravascular ultrasound to guide percutaneous coronary interventions. Health Technology Literature Review. Toronto, ON: MAS; April 2006.
- Orford JL, Lerman A, Holmes DR. Routine intravascular ultrasound guidance of percutaneous coronary intervention: A critical reappraisal. J Am Coll Cardiol. 2004;43(8):1335-1342.
- Parise H, Maehara A, Stone GW, et al. Meta-analysis of randomized studies comparing intravascular ultrasound versus angiographic guidance of percutaneous coronary intervention in pre-drug-eluting stent era. Am J Cardiol. 2011;107(3):374-382.
- Passman MA, Dattilo JB, Guzman RJ, Naslund TC. Bedside placement of inferior vena cava filters by using transabdominal duplex ultrasonography and intravascular ultrasound imaging. J Vasc Surg. 2005;42(5):1027-1032.
- Pinto FJ. The value of intravascular ultrasound in interventional cardiology. Rev Port Cardiol. 1999;18 Suppl 1:I97-I104.
- Qian C, Feng H, Cao J, et al. Intravascular ultrasound guidance in drug-eluting stents implantation: A meta-analysis and trial sequential analysis of randomized controlled trials. Oncotarget. 2017;8(35):59387-59396.
- Raichlin E, Bae JH, Kushwaha SS, et al. Inflammatory burden of cardiac allograft coronary atherosclerotic plaque is associated with early recurrent cellular rejection and predicts a higher risk of vasculopathy progression. J Am Coll Cardiol. 2009a;53(15):1279-1286.
- Raichlin E, Edwards BS, Kremers WK, et al. Acute cellular rejection and the subsequent development of allograft vasculopathy after cardiac transplantation. J Heart Lung Transplant. 2009b;28(4):320-327.
- Raju S, Buck WJ, Crim W, Jayaraj A. Optimal sizing of iliac vein stents. Phlebology. 2017:268355517718763.
- Raju S, Darcey R, Neglen P. Iliac-caval stenting in the obese. J Vasc Surg. 2009;50(5):1114-1120.
- Raju S, Darcey R, Neglen P. Unexpected major role for venous stenting in deep reflux disease. J Vasc Surg. 2010;51(2):401-408.
- Raju S, Davis M, Martin A. Assessment of residual thrombus after venous thrombolytic regimens. J Vasc Surg Venous Lymphat Disord. 2014;2(2):148-154.
- Raju S, Davis M. Anomalous features of iliac vein stenosis that affect diagnosis and treatment. J Vasc Surg Venous Lymphat Disord. 2014;2(3):260-267.
- Raju S, Kirk OK, Jones TL. Endovenous management of venous leg ulcers. J Vasc Surg Venous Lymphat Disord. 2013;1(2):165-172.
- Raju S, McAllister S, Neglen P. Recanalization of totally occluded iliac and adjacent venous segments. J Vasc Surg. 2002;36(5):903-911.
- Raju S, Neglen P. High prevalence of nonthrombotic iliac vein lesions in chronic venous disease: a permissive role in pathogenicity. J Vasc Surg. 2006;44(1):136-143; discussion 144.
- Raju S, Oglesbee M, Neglen P. Iliac vein stenting in postmenopausal leg swelling. J Vasc Surg. 2011;53(1):123-130.
- Raju S, Owen S Jr, Neglen P. Reversal of abnormal lymphoscintigraphy after placement of venous stents for correction of associated venous obstruction. J Vasc Surg. 2001;34(5):779-784.
- Raju S, Owen S Jr, Neglen P. The clinical impact of iliac venous stents in the management of chronic venous insufficiency. J Vasc Surg. 2002;35(1):8-15.
- Raju S, Tackett P Jr, Neglen P. Spontaneous onset of bacterial cellulitis in lower limbs with chronic obstructive venous disease. Eur J Vasc Endovasc Surg. 2008;36(5):606-610.
- Raju S, Ward M. Utility of iliac vein stenting in elderly population older than 80 years. J Vasc Surg Venous Lymphat Disord. 2015;3(1):58-63.
- Razavi M, Marston W, Black S, et al. The initial report on 1-year outcomes of the feasibility study of the VENITI VICI VENOUS STENT in symptomatic iliofemoral venous obstruction. J Vasc Surg Venous Lymphat Disord. 2018;6(2):192-200.
- Regar E, Weissman NJ, Muhlestein JB. Intravascular ultrasound, optical coherence tomography, and angioscopy of coronary circulation. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2015.
- Rodes-Cabau J, Domingo E, Roman A, et al. Intravascular ultrasound of the elastic pulmonary arteries: A new approach for the evaluation of primary pulmonary hypertension. Heart. 2003;89(3):311-315.
- Rogers Rainbow C, Fields KB. Calf injuries not involving the Achilles tendon. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2018.
- Ross JR, Franga DL, Gallichio M, et al. Role of intravascular ultrasound imaging during endovascular interventions of failing hemodialysis access grafts. J Vasc Surg. 2017;65(5):1383-1389.
- Rossi FH, Kambara AM, Izukawa NM, et al. Randomized double-blinded study comparing medical treatment versus iliac vein stenting in chronic venous disease. J Vasc Surg Venous Lymphat Disord. 2018;6(2):183-191.
- Rubin LJ, Hopkins W. Clinical features and diagnosis of pulmonary hypertension in adults. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed January 2019.
- Santoshi RKN, Lakhanpal S, Satwah V, et al. Iliac vein stenosis is an underdiagnosed cause of pelvic venous insufficiency. J Vasc Surg Venous Lymphat Disord. 2018;6(2):202-211.
- Sarno G, Lerman A, Bae JH, et al. Multicenter assessment of coronary allograft vasculopathy by intravascular ultrasound-derived analysis of plaque composition. Nat Clin Pract Cardiovasc Med. 2009;6(1):61-69.
- Satokawa H, Hoshino S, Iwaya F, et al. Intravascular imaging methods for venous disorders. Int J Angiol. 2000;9(2):117-121.
- Schwartz L, Bui S. The role of intravascular ultrasound in the diagnosis and treatment of patients with coronary artery disease. Compr Ther. 2003;29(1):54-65.
- Secemsky EA, Aronow HD, Kwolek CJ, et al. Intravascular ultrasound use in peripheral arterial and deep venous interventions: Multidisciplinary expert opinion from SCAI/AVF/AVLS/SIR/SVM/SVS. J Vasc Interv Radiol. 2024;35(3):335-348.
- Secemsky EA, Mosarla RC, Rosenfield K, et al. Appropriate use of intravascular ultrasound during arterial and venous lower extremity interventions. JACC Cardiovasc Interv. 2022;15(15):1558-1568.
- Shaidakov EV, Porembskaia OI, Grigorian AG, et al. First experience with intravascular ultrasonographic examination in diagnosis of post-traumatic obstruction of deep veins. Angiol Sosud Khir. 2017;23(1):89-96.
- Sheikh AB, Anantha-Narayanan M, Smolderen KG, et al. Utility of intravascular ultrasound in peripheral vascular interventions: Systematic review and meta-analysis. Vasc Endovascular Surg. 2020;54(5):413-422.
- Shen JY, Cai ZY, Sun LY, et al. The application of intravascular ultrasound to evaluate pulmonary vascular properties and mortality in patients with pulmonary arterial hypertension. J Am Soc Echocardiogr. 2016;29(2):103-111.
- Simon C, Alvarez J Jr, Becker GJ, et al. May-Thurner syndrome in an adolescent: persistence despite operative management. J Vasc Surg. 1999;30(5):950-953.
- Smith JA, Bose S, Sarode A, et al. Effect of intravascular ultrasound on clinical outcomes after thoracic endovascular aortic repair for blunt thoracic aortic injury. J Vasc Surg. 2022;75(2):448-454.
- Smith JA, Yang L, Chen L, et al. Trends and outcomes associated with intravascular ultrasound use during femoropopliteal revascularization in the Vascular Quality Initiative. J Vasc Surg. 2023;78(1):209-216.
- Soga Y, Nakamura M, Hirose K, et al. Primary use of the TruePath crossing device for infrainguinal chronic total occlusions with intravascular ultrasound evaluation. J Endovasc Ther. 2018;25(5):592-598.
- Stanley GA, Murphy EH, Plummer MM, et al. Midterm results of percutaneous endovascular treatment for acute and chronic deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2013;1(1):52-58.
- Starksen NF, Yock PG. Clinical applications of intravascular ultrasound imaging. Am J Card Imaging. 1991;5(1):54-59.
- Stern JR, Patel VI, Cafasso DE, et al. Left-sided varicocele as a rare presentation of May-Thurner syndrome. Ann Vasc Surg. 2017;;42:305.e13-305.e16.
- Stone GW, Hodgson JM, St Goar FG, et al. Improved procedural results of coronary angioplasty with intravascular ultrasound-guided balloon sizing: The CLOUT Pilot Trial. Clinical Outcomes With Ultrasound Trial Investigators. Circulation. 1997;95:2044-2052.
- Takahashi Y, Sato T, Okazaki H, et al. Transvenous intravascular ultrasound-guided endovascular treatment for chronic total occlusion of the infrainguinal arteries. J Endovasc Ther. 2017;24(5):718-726.
- Tapson VF, Davidson CJ, Kisslo KB, Stack RS. Rapid visualization of massive pulmonary emboli utilizing intravascular ultrasound. Chest. 1994;105(3):888-890.
- The SH, Gussenhoven EJ, du Bois NA, et al. Femoro-popliteal vein bypass grafts studied by intravascular ultrasound. Eur J Vasc Surg. 1991;5(5):523-526.
- Tomoi Y, Takahara M, Fujihara M, et al. IVUS assessment of the crossing pathway of an intraluminal reentry device used in the primary treatment of infrainguinal chronic total occlusions. J Endovasc Ther. 2020;27(1):69-76.
- Torey J, Zaitoun A, Lalonde T, et al. Infrainguinal CTO recanalization assessed by intravascular ultrasound: Results of the CENTRAL Study. J Invasive Cardiol. 2016;28(11):430-439.
- Tsuchida K, Serruys PW, Bruining N, et al. Two-year serial coronary angiographic and intravascular ultrasound analysis of in-stent angiographic late lumen loss and ultrasonic neointimal volume from the TAXUS II trial. Am J Cardiol. 2007;99(5):607-615.
- Tsukagoshi J, Shimoda T, Yokoyama Y, et al. The mid-term effect of intravascular ultrasound on endovascular interventions for lower extremity peripheral arterial disease: A systematic review and meta-analysis. J Vasc Surg. 2023 Sep 9 [Online ahead of print].
- Tuzcu EM, Schoenhagen P. Atherosclerosis imaging: Intravascular ultrasound. Drugs. 2004;64 Suppl 2:1-7.
- Vaidya OU, Buersmeyer T, Rojas R, Dolmatch B. Successful salvage of a renal allograft after acute renal vein thrombosis due to May-Thurner syndrome. Case Rep Transplant. 2012;2012:390980.
- van der Lugt A, Gussenhoven EJ, Tai JA, et al. Femoropopliteal venous bypass studied with intravascular ultrasound: A case report. J Endovasc Surg. 1996;3(3):315-320.
- van der Lugt A, Gussenhoven EJ, The SH, van Essen J, et al. Femorodistal venous bypass evaluated with intravascular ultrasound. Eur J Vasc Endovasc Surg. 1995;9(4):394-402.
- Wang Y, Mintz GS, Gu Z, et al. Meta-analysis and systematic review of intravascular ultrasound versus angiography-guided drug eluting stent implantation in left main coronary disease in 4592 patients. BMC Cardiovasc Disord. 2018;18(1):115.
- Wellons ED, Rosenthal D, Shuler FW, et al. Real-time intravascular ultrasound-guided placement of a removable inferior vena cava filter. J Trauma. 2004;57(1):20-23; discussion 23-25.
- Witzenbichler B, Maehara A, Weisz G, et al. Relationship between intravascular ultrasound guidance and clinical outcomes after drug-eluting stents: The assessment of dual antiplatelet therapy with drug-eluting stents (ADAPT-DES) study. Circulation. 2014;129(4):463-470.
- Yang R-R, Lv Y-H, Guo C, et al. Intravascular ultrasound-guided percutaneous coronary intervention for patients with coronary bifurcation lesions: A systematic review and meta-analysis. Medicine (Baltimore). 2020;99(37):e20798.
- Zhang Y, Farooq V, Garcia-Garcia HM, et al. Comparison of intravascular ultrasound versus angiography-guided drug-eluting stent implantation: A meta-analysis of one randomised trial and ten observational studies involving 19,619 patients. EuroIntervention. 2012;8(7):855-865.
- Ziada KM, Kapadia SR, Tuzcu EM, et al. The current status of intravascular ultrasound imaging. Curr Probl Cardiol. 1999;24(9):541-566.