Validation of Segmental Post-PCI Physiological Gradients With IVUS-Detected Focal Lesions and Stent Underexpansion.

BACKGROUND: Segmental postpercutaneous coronary intervention (PCI) pressure gradients may detect residual disease and potential targets for optimization. However, universal definitions of relevant segmental gradients are lacking. OBJECTIVES: This study sought to evaluate the diagnostic performance of post-PCI fractional flow reserve (FFR), distal coronary pressure-to-aortic pressure ratio (Pd/Pa), and diastolic pressure ratio (dPR) gradients to detect residual focal lesions and stent underexpansion as observed by intravascular ultrasound (IVUS). METHODS: Patients from the IVUS-guided optimization arm of the FFR REACT (FFR-guided PCI Optimization Directed by High-Definition IVUS Versus Standard of Care) trial with complete IVUS and FFR pullback data were included. Patients with angiographically successful PCI and post-PCI FFR <0.90 underwent FFR, Pd/Pa, and IVUS pullbacks. dPR was calculated offline using dedicated software. Segmental pressure gradients (distal, in stent, and proximal) in segments ≥5 mm were evaluated against IVUS-detected residual disease (distal or proximal focal lesions and stent underexpansion). RESULTS: A total of 139 vessels were included (mean post-PCI FFR: 0.83 ± 0.05, range 0.56-0.89). Focal distal and proximal lesions were detected by IVUS in 23 (17.4%) of 132 and 14 (12.6%) of 111 vessels, respectively, whereas stent underexpansion was present in 86 (61.9%) vessels. Diagnostic ability of segmental FFR gradients to predict IVUS-detected distal and proximal lesions was moderate-to-good (area under the curve [AUC]: 0.69 and 0.84, respectively) and poor to moderate for segmental Pd/Pa and dPR gradients (AUC ranging from 0.58 to 0.69). In-stent gradients had no discriminative ability to detect stent underexpansion (FFR AUC: 0.52; Pd/Pa AUC: 0.54; dPR AUC: 0.55). CONCLUSIONS: In patients with post-PCI FFR <0.90, segmental post-PCI pressure gradients have moderate discriminative ability to identify IVUS-detected focal lesions but no discriminative ability to identify IVUS-detected stent underexpansion.

Culprit lesion plaque characterization and thrombus grading by high-definition intravascular ultrasound in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Dedicated prospective studies investigating high-definition intravascular ultrasound (HD-IVUS)-guided primary percutaneous coronary intervention (PCI) are lacking. The aim of this study was to qualify and quantify culprit lesion plaque characteristics and thrombus using HD-IVUS in patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: The SPECTRUM study is a prospective, single-center, observational cohort study investigating the impact of HD-IVUS-guided primary PCI in 200 STEMI patients (NCT05007535). The first 100 study patients with a de novo culprit lesion and a per-protocol mandated preintervention pullback directly after vessel wiring were subject to a predefined imaging analysis. Culprit lesion plaque characteristics and different thrombus types were assessed. An IVUS-derived thrombus score, including a 1-point adjudication for a long total thrombus length, long occlusive thrombus length, and large maximum thrombus angle, was developed to differentiate between low (0-1 points) and high (2-3 points) thrombus burden. Optimal cut-off values were obtained using receiver operating characteristic curves. RESULTS: The mean age was 63.5 (±12.1) years and 69 (69.0%) patients were male. The median culprit lesion length was 33.5 (22.8-38.9) mm. Plaque rupture and convex calcium were appreciated in 48 (48.0%) and 10 (10.0%) patients, respectively. Thrombus was observed in 91 (91.0%) patients (acute thrombus 3.3%; subacute thrombus 100.0%; organized thrombus 22.0%). High IVUS-derived thrombus burden was present in 37/91 (40.7%) patients and was associated with higher rates of impaired final thrombolysis in myocardial infarction flow (grade 0-2) (27.0% vs. 1.9%, p < 0.001). CONCLUSIONS: HD-IVUS in patients presenting with STEMI allows detailed culprit lesion plaque characterization and thrombus grading that may guide tailored PCI.

Optical coherence tomography-derived predictors of stent expansion in calcified lesions.

BACKGROUND: Severe coronary artery calcification is associated with stent underexpansion and subsequent stent failure. AIMS: We aimed to identify optical coherence tomography (OCT)-derived predictors of absolute (minimal stent area [MSA]) and relative stent expansion in calcified lesions. METHODS: This retrospective cohort study included patients who underwent percutaneous coronary intervention (PCI) with OCT assessment before and after stent implantation between May 2008 and April 2022. Pre-PCI OCT was used to assess calcium burden and post-PCI OCT was used to assess absolute and relative stent expansion. RESULTS: A total of 361 lesions in 336 patients were analyzed. Target lesion calcification (defined as OCT-detected maximum calcium angle ≥ 30°) was present in 242 (67.0%) lesions. Following PCI, median MSA was 5.37 mm2 in calcified lesions and 6.24 mm2 in noncalcified lesions (p < 0.001). Median stent expansion was 78% in calcified lesions and 83% in noncalcified lesions (p = 0.325). In the subset of calcified lesions, average stent diameter, preprocedural minimal lumen area, and total calcium length were independent predictors of MSA in multivariable analysis (mean difference 2.69 mm2 /mm2 , 0.52 mm2 /mm, and -0.28 mm2 /5 mm, respectively, all p < 0.001). Total stent length was the only independent predictor of relative stent expansion (mean difference -0.465% per mm, p < 0.001). Calcium angle, thickness, and the presence of nodular calcification were not significantly associated with MSA or stent expansion in multivariable analyses. CONCLUSION: Calcium length appeared to be the most important OCT-derived predictor of MSA, whereas stent expansion was mainly determined by total stent length.

FFR-Guided PCI Optimization Directed by High-Definition IVUS Versus Standard of Care: The FFR REACT Trial.

BACKGROUND: Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) <0.90 is common and has been related to impaired patient outcome. OBJECTIVES: The authors sought to evaluate if PCI optimization directed by intravascular ultrasound (IVUS) in patients with post-PCI FFR <0.90 could improve 1-year target vessel failure (TVF) rates. METHODS: In this single-center, randomized, double-blind trial, patients with a post-PCI FFR <0.90 at the time of angiographically successful PCI were randomized to IVUS-guided optimization or the standard of care (control arm). The primary endpoint was TVF (a composite of cardiac death, spontaneous target vessel myocardial infarction, and clinically driven target vessel revascularization) at 1 year. RESULTS: A total of 291 patients with post-PCI FFR <0.90 were randomized (IVUS-guided optimization arm: n = 145/152 vessels, control arm: n = 146/157 vessels). The mean post-PCI FFR was 0.84 ± 0.05. A total of 104 (68.4%) vessels in the IVUS-guided optimization arm underwent additional optimization including additional stenting (34.9%) or postdilatation only (33.6%), resulting in a mean increase in post-PCI FFR in these vessels from 0.82 ± 0.06 to 0.85 ± 0.05 (P < 0.001) and a post-PCI FFR ≥0.90 in 20% of the vessels. The 1-year TVF rate was comparable between the 2 study arms (IVUS-guided optimization arm: 4.2%, control arm: 4.8%; P = 0.79). There was a trend toward a lower incidence of clinically driven target vessel revascularization in the IVUS-guided optimization arm (0.7% vs. 4.2%, P = 0.06). CONCLUSIONS: IVUS-guided post-PCI FFR optimization significantly improved post-PCI FFR. Because of lower-than-expected event rates, post-PCI FFR optimization did not significantly lower TVF at the 1-year follow-up.

Tissue characterisation and primary percutaneous coronary intervention guidance using intravascular ultrasound: rationale and design of the SPECTRUM study.

INTRODUCTION: Intravascular ultrasound (IVUS) improves clinical outcome in patients undergoing percutaneous coronary intervention (PCI) but dedicated prospective studies assessing the safety and efficacy of IVUS guidance during primary PCI are lacking. METHODS AND ANALYSIS: The SPECTRUM study is a prospective investigator-initiated single-centre single-arm observational cohort study aiming to enrol 200 patients presenting with ST-segment elevation myocardial infarct undergoing IVUS-guided primary PCI. IVUS will be performed at baseline, postintervention and postoptimisation (if applicable), using a 40-60 MHz high-definition (HD) system. Baseline tissue characterisation includes the morphological description of culprit lesion plaque characteristics and thrombus as assessed with HD-IVUS. The primary endpoint is target vessel failure at 12 months (defined as a composite of cardiac death, target vessel myocardial infarction and clinically driven target vessel revascularisation). The secondary outcome of interest is IVUS-guided optimisation, defined as IVUS-guided additional balloon dilatation or stent placement. Other endpoints include clinical and procedural outcomes along with post-PCI IVUS findings. ETHICS AND DISSEMINATION: The protocol of this study was approved by the Ethics Committee of the Erasmus University Medical Center, Rotterdam, the Netherlands. Written informed consent is obtained from all patients. Study findings will be submitted to international peer-reviewed journals in the field of cardiovascular imaging and interventions and will be presented at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT05007535.

The prognostic value of angiography-based vessel fractional flow reserve after percutaneous coronary intervention: The FAST Outcome study.

BACKGROUND: Vessel Fractional Flow Reserve (vFFR) as assessed by three-dimensional quantitative coronary angiography has high correlation with pressure wire-based fractional flow reserve in both a pre- and post-PCI setting. The present study aims to assess the prognostic value of post-PCI vFFR on the incidence of target vessel failure (TVF), a composite endpoint of cardiac death, target vessel myocardial infarction and target vessel revascularization (TVR) at 5-year follow up. METHODS: Post-PCI vFFR was calculated after routine PCI in a total of 748 patients (832 vessels) with available orthogonal angiographic projections of the stented segment. RESULTS: Median age was 65 (IQR 55-74) years, 18.2% were diabetic, and 29.1% presented with stable angina. Median post-PCI vFFR was 0.91 (IQR 0.86-0.95). Vessels were categorized into tertiles based on post-PCI vFFR: low (vFFR <0.88), middle (vFFR 0.88-0.93), and upper (vFFR ≥0.94). Vessels in the lower and middle tertile were more often LADs and had smaller stent diameters (p<0.001). Vessels in the lower and middle tertile had a higher risk of TVF as compared to vessels in the upper tertile (24.6% and 21.5% vs. 17.1%; adjusted HR 1.84 (95%CI 1.15-2.95), p = 0.011, and 1.58 (95%CI 1.02-2.45), p = 0.040) at 5-years follow-up. Additionally, vessels in the lower tertile had higher rates of TVR as compared to vessels in the higher tertile (12.6% vs. 6.5%, adjusted HR 1.93 (95%CI 1.06-3.53), p = 0.033). CONCLUSION: Lower post-PCI vFFR values are associated with a significantly increased risk of TVF and TVR at 5-years follow-up.

The Prognostic Value of a Validated and Automated Intravascular Ultrasound-Derived Calcium Score.

BACKGROUND: Coronary calcification has been linked to cardiovascular events. We developed and validated an algorithm to automatically quantify coronary calcifications on intravascular ultrasound (IVUS). We aimed to assess the prognostic value of an IVUS-calcium score (ICS) on patient-oriented composite endpoint (POCE). METHODS: We included patients that underwent coronary angiography plus pre-procedural IVUS imaging. The ICS was calculated per patient. The primary endpoint was a composite of all-cause mortality, stroke, myocardial infarction, and revascularization (POCE). RESULTS: In a cohort of 408 patients, median ICS was 85. Both an ICS ≥ 85 and a 100 unit increase in ICS increased the risk of POCE at 6-year follow-up (adjusted hazard ratio (aHR) 1.51, 95%CI 1.05-2.17, p value = 0.026, and aHR 1.21, 95%CI 1.04-1.41, p value = 0.014, respectively). CONCLUSIONS: The ICS, calculated by a validated automated algorithm derived from routine IVUS pullbacks, was strongly associated with the long-term risk of POCE.

Automated Quantitative Assessment of Coronary Calcification Using Intravascular Ultrasound.

Coronary calcification represents a challenge in the treatment of coronary artery disease by stent placement. It negatively affects stent expansion and has been related to future adverse cardiac events. Intravascular ultrasound (IVUS) is known for its high sensitivity in detecting coronary calcification. At present, automated quantification of calcium as detected by IVUS is not available. For this reason, we developed and validated an optimized framework for accurate automated detection and quantification of calcified plaque in coronary atherosclerosis as seen by IVUS. Calcified lesions were detected by training a supported vector classifier per IVUS A-line on manually annotated IVUS images, followed by post-processing using regional information. We applied our framework to 35 IVUS pullbacks from each of the three commonly used IVUS systems. Cross-validation accuracy for each system was >0.9, and the testing accuracy was 0.87, 0.89 and 0.89 for the three systems. Using the detection result, we propose an IVUS calcium score, based on the fraction of calcium-positive A-lines in a pullback segment, to quantify the extent of calcified plaque. The high accuracy of the proposed classifier suggests that it may provide a robust and accurate tool to assess the presence and amount of coronary calcification and, thus, may play a role in image-guided coronary interventions.

In-vitro and in-vivo imaging of coronary artery stents with Heartbeat OCT.

To quantify the impact of cardiac motion on stent length measurements with Optical Coherence Tomography (OCT) and to demonstrate in vivo OCT imaging of implanted stents, without motion artefacts. The study consists of: clinical data evaluation, simulations and in vivo tests. A comparison between OCT-measured and nominal stent lengths in 101 clinically acquired pullbacks was carried out, followed by a simulation of the effect of cardiac motion on stent length measurements, experimentally and computationally. Both a commercial system and a custom OCT, capable of completing a pullback between two consecutive ventricular contractions, were employed. A 13 mm long stent was implanted in the left anterior descending branch of two atherosclerotic swine and imaged with both OCT systems. The analysis of the clinical OCT images yielded an average difference of 1.1 ± 1.6 mm, with a maximum difference of 7.8 mm and the simulations replicated the statistics observed in clinical data. Imaging with the custom OCT, yielded an RMS error of 0.14 mm at 60 BPM with the start of the acquisition synchronized to the cardiac cycle. In vivo imaging with conventional OCT yielded a deviation of 1.2 mm, relative to the length measured on ex-vivo micro-CT, while the length measured in the pullback acquired by the custom OCT differed by 0.20 mm. We demonstrated motion artefact-free OCT-imaging of implanted stents, using ECG triggering and a rapid pullback.

Changes in renal artery dimensions are associated with clinical response to radiofrequency renal denervation: a series of studies using quantitative angiography and intravascular ultrasound.

OBJECTIVE: Renal denervation (RDN) can cause focal (notches) and global (spasms) changes in renal artery dimensions. We quantified these changes and related them to renal norepinephrin tissue content in animals and to blood pressure (BP) changes in patients. METHODS: We measured renal artery dimensions pre-RDN and post-RDN, utilizing quantitative renal angiography (QRA) in a porcine model and in a retrospective patient cohort, and intravascular ultrasound (IVUS) in a prospective patient cohort. Focal and global measurements were minimum and mean diameter/area/volume with QRA, minimum lumen/vessel/wall area and volume with IVUS. BP was assessed with 24-h ambulatory monitoring, norepinephrin content with liquid chromatography. RESULTS: In 36 pigs treated unilaterally with RDN, norepinephrin content of the treated right kidney was 48.2% of the untreated left kidney. QRA measurements following RDN were associated with norepinephrin content only of the (treated) right kidney. In the human QRA study (n = 43 patients), mean 24-h BP fell by 8/4 and 12/6 mmHg at 1 and 12 months, respectively. More pronounced changes in QRA measurements were associated with a more pronounced BP drop. In multiple regression models, the change in minimum diameter was independently associated with BP changes at 12 months. In the prospective IVUS study (n = 17 patients), a larger decrease in minimum lumen/vessel area and larger increase of wall area/volume were associated with a larger BP drop. CONCLUSION: Focal and global changes in renal arteries following RDN can be quantified, using QRA or IVUS, and may serve as markers of a successful procedure.

Safety of optical coherence tomography in daily practice: a comparison with intravascular ultrasound.

AIMS: Previous studies have reported the safety and feasibility of both time-domain optical coherence tomography (TD-OCT) and Fourier-domain OCT (FD-OCT) in highly selected patients and clinical settings. However, the generalizability of these data is limited, and data in unselected patient populations reflecting a routine cathlab practice are lacking. We compared safety of intracoronary FD-OCT imaging to intravascular ultrasound (IVUS) imaging in a large real-world series of consecutive patients who underwent invasive imaging during coronary catheterization in our centre. METHODS AND RESULTS: This is a prospective, single-centre registry of patients scheduled for coronary angiography or intervention undergoing intracoronary imaging with FD-OCT or IVUS between April 2008 and December 2013. Intra-procedural and major in-hospital adverse events that could be possibly related to invasive imaging were registered routinely by the operator as part of our clinical report and prospectively recorded in our database. These events were retrospectively individually adjudicated by an independent safety committee. Between April 2008 and December 2013, 13 418 diagnostic or interventional coronary catheterization procedures were performed. Of these, 1142 procedures used OCT and 2476 procedures used IVUS. Invasive imaging-related complications were rare, did not differ between the two imaging methods (OCT: n = 7, 0.6%; IVUS: n = 12, 0.5%; P = 0.6), and were self-limiting after retrieval of the imaging catheter or easily treatable in the catheterization laboratory. No major adverse events, prolongation of hospital stay, or permanent patient harm was observed. CONCLUSION: FD-OCT is safe in an unselected and heterogeneous group of patients with varying clinical settings.

In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study.

AIMS: Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. METHODS AND RESULTS: Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09-3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60-5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15-5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). CONCLUSION: In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

Optical coherence tomography for evaluation of coronary stents in vivo.

Coronary optical coherence tomography (OCT) is a light-based imaging modality that emits light in the near-infrared range. Compared with intravascular ultrasound, OCT has an extraordinarily high resolution (nearly tenfold higher), with an axial resolution in the range of 12-15 µm and a lateral resolution of 20-40 µm. The main drawback of OCT is its relatively low penetration power, especially into lipid-rich atherosclerotic tissue. Second-generation OCT systems, known as frequency domain OCT, are now widely available in many catheter laboratories. The hallmark of OCT is its outstanding ability to depict superficial vessel wall structures with high accuracy. In this regard, OCT was used to evaluate stent expansion and stent strut apposition both early and late following stent deployment, as well as neointimal coverage over struts at long-term follow-up. It has discriminated the differences in strut malapposition and strut neointimal coverage among different stent designs and in various strut subsets. Similarly, OCT delineated many forms of vessel wall injury following percutaneous coronary intervention, such as dissections, thrombosis and tissue protrusion between struts. Recently, OCT was used to study the biodegradation of bioresorbable vascular scaffolds. This review focuses on the role of OCT in the in vivo evaluation of coronary stents.