Optical Coherence Tomography-Derived Changes in Plaque Structural Stress Over the Cardiac Cycle: A New Method for Plaque Biomechanical Assessment

Introduction: Cyclic plaque structural stress has been hypothesized as a mechanism for plaque fatigue and eventually plaque rupture. A novel approach to derive cyclic plaque stress in vivo from optical coherence tomography (OCT) is hereby developed.Materials and Methods: All intermediate lesions from a previous OCT study were enrolled. OCT cross-sections at representative positions within each lesion were selected for plaque stress analysis. Detailed plaque morphology, including plaque composition, lumen and internal elastic lamina contours, were automatically delineated. OCT-derived vessel and plaque morphology were included in a 2-dimensional finite element analysis, loaded with patient-specific intracoronary pressure tracing data, to calculate the changes in plaque structural stress (ΔPSS) on vessel wall over the cardiac cycle.Results: A total of 50 lesions from 41 vessels were analyzed. A significant ΔPSS gradient was observed across the plaque, being maximal at the proximal shoulder (45.7 [32.3, 78.6] kPa), intermediate at minimal lumen area (MLA) (39.0 [30.8, 69.1] kPa) and minimal at the distal shoulder (35.1 [28.2, 72.3] kPa; p = 0.046). The presence of lipidic plaques were observed in 82% of the diseased segments. Larger relative lumen deformation and ΔPSS were observed in diseased segments, compared with normal segments (percent diameter change: 8.2 ± 4.2% vs. 6.3 ± 2.3%, p = 0.04; ΔPSS: 59.3 ± 48.2 kPa vs. 27.5 ± 8.2 kPa, p < 0.001). ΔPSS was positively correlated with plaque burden (r = 0.37, p < 0.001) and negatively correlated with fibrous cap thickness (r = −0.25, p = 0.004).Conclusions: ΔPSS provides a feasible method for assessing plaque biomechanics in vivo from OCT images, consistent with previous biomechanical and clinical studies based on different methodologies. Larger ΔPSS at proximal shoulder and MLA indicates the critical sites for future biomechanical assessment.

The “Fracking” technique: a novel approach to crack deep calcified plaque in the common femoral artery with hydraulic pressure

Background The patency achieved by conventional peripheral interventions for atherosclerotic lesions in the common femoral artery (CFA), called the “no stenting zone”, is not superior to that achieved by surgical endarterectomy due to calcified plaque occupying the area. Plaque modification strategies to obtain acute gain in CFA patency provide the better clinical outcomes than standard balloon angioplasty. Atherectomy devices, which focus on the modification of superficial calcifications, contribute to the improvement of clinical outcomes. However, deep calcifications resist vessel expansion such that luminal gain is not easily achieved. Main text We propose a novel calcified plaque modification technique, named the “fracking technique” (FT). The term fracking refers to how a rock is fractured by the high hydraulic pressure. In this technique, deep calcifications are cracked with hydraulic pressure via a balloon indeflator through an 18-gauge needle, which punctures calcifications to achieve greater acute luminal gain. Case 1 involved an 81-year-old male with eccentric calcified plaque in the right CFA. Conventional balloon angioplasty for the lesion yielded a suboptimal minimal lumen area (MLA), which increased from 6.2 to 10.7-mm2 on intravascular ultrasound (IVUS). The FT was implemented to obtain a larger MLA. After the FT was repeated at three locations at up to 8-atm, a greater MLA of 27.1-mm2 was achieved without complications. Case 2 involved a 72-year-old male undergoing hemodialysis due to diabetes mellitus who presented with ischemic pain in his right limbs at rest due to severe stenosis with eccentric calcification in the distal CFA. The MLA on IVUS before and after balloon angioplasty was 10.0-mm2 and 13.1-mm2, respectively, and this result was still suboptimal. The FT was attempted and successfully yielded a greater MLA of 28.9-mm2 without complications. Restenosis has not been detected for 2 years follow-up period. Conclusions The FT is an effective option for treating calcified CFA lesions to achieve a larger lumen area. Long-term follow-up studies are necessary.

Focal Geometry and Characteristics of Erosion-Prone Coronary Plaques in vivo Angiography and Optical Coherence Tomography Study

Objective: This study compared focal geometry and characteristics of culprit plaque erosion (PE) vs. non-culprit plaques in ST-segment elevated myocardial infarction (STEMI) patients in whom optical coherence tomography (OCT) identified PE as the cause of the acute event.Background: Culprit PE is a distinct clinical entity with specific coronary risk factors and its own tailored management strategy. However, not all plaques develop erosion resulting in occlusive thrombus formation.Methods: Between January 2017 and July 2019, there were 484 STEMI patients in whom OCT at the time of primary percutaneous intervention identified culprit lesion PE to be the cause of the event; 484 culprit PE were compared to 1,132 non-culprit plaques within 1,196 imaged vessels.Results: Culprit PE were highly populated at “hot spots” within the proximal 40 mm in the left anterior descending artery (LAD) and tended to cluster proximal to a nearby bifurcation mainly in the LAD. Minimal lumen area (MLA) <2.51 mm2 and AS (area stenosis) >64.02% discriminated culprit PE from non-culprit plaques. In the multivariable analysis, focal geometry (LAD location, distance from coronary ostium <40 mm, and location proximal to a nearby bifurcation), luminal narrowing (MLA <2.51 mm2, AS > 64.02%), and TCFA phenotype were independent predictors of culprit PE overall. Cholesterol crystals were predictive of culprit PE with underlying LRP morphology while the absence of calcification and microchannels were risk factors for culprit PE with an underlying non-LRP. Similarities and differences in predictors of culprit PE were found between males and females; distance from coronary ostium <40 mm, MLA <2.51 mm2, TCFA, and less spotty calcium were risk factors of culprit PE in males, but not in females while smaller RVD was associated with culprit PE only in females.Conclusions: Irrespective of underlying lesion substrates and patient risk factors, there are lesion-specific and OCT-identifiable predictors of developing culprit PE in erosion-prone vulnerable patients.

Elevated Serum Levels of Soluble ST2 Are Associated With Plaque Vulnerability in Patients With Non-ST-Elevation Acute Coronary Syndrome

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS).Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques.Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = −0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups.Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04797819.

Fracking Technique: The Novel Approach To Crack Deep Calcified Plaque In Common Femoral Artery With Hydraulic Pressure.

Background:The patency of conventional peripheral intervention for atherosclerotic lesions in common femoral artery (CFA), called “no stenting zone”, are not superior to surgical endarterectomy due to calcified plaque occupying the area. Plaque modification strategies to obtain acute gain in CFA provide the better clinical outcome compared to standard balloon angioplasty. Atherectomy devices, which focus on modification of superficial calcification, contribute to the improvement of clinical outcomes. However, deep calcium resists vessel expansion so that luminal gain is not easily achieved. Main text:We propose a novel calcified plaque modification technique, named the” Fracking technique”. The term fracking refers to how a rock is fractured apart by the high hydraulic pressure. This technique is to crack deep calcification with hydraulic pressure with a balloon indeflator through 18-gauge needle, which punctures into calcification in order to obtain larger acute luminal gain. Case 1 involved an 81-year-old male with eccentric calcified plaque in right CFA. Conventional balloon angioplasty for the lesion provided the suboptimal minimal lumen area (MLA) from 6.2 to 10.7mm2 with intravascular ultrasound (IVUS) measurement. Fracking technique was implemented to obtain the larger MLA. After fracking was repeated three times until there were no more Fracking points, a much larger MLA of 27.1mm2 was achieved without complications. Case 2 involved a 72-year-old male undergoing hemodialysis presented with ischemic rest pain of his right limbs due to severe stenosis with eccentric calcification in distal CFA to proximal superficial femoral artery. MLAs with IVUS before and after ballooning were 10.0mm2, 13.1mm2, respectively. None of the results of MLA lived up to our expectation. Fracking technique was attempted, and MLA of 28.9mm2 was successfully obtained after this technique. No complications observed. Conclusions:Fracking technique was effective for severe calcified lesion in CFA to obtain significantly larger lumen area which will lead to long-term patency superior to conventional peripheral intervention.

The Association Between Quantitative Flow Ratio and Intravascular Imaging-defined Vulnerable Plaque Characteristics in Patients With Stable Angina and Non-ST-segment Elevation Acute Coronary Syndrome

Background: This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with intravascular imaging-defined vulnerable plaque features, such as thin cap fibroatheroma (TCFA) in patients with stable angina, and non-ST-segment elevation acute coronary syndrome.Methods: Patients undergoing optical coherence tomography (OCT) or intravascular ultrasound (IVUS) examinations were identified from two prospective studies and their interrogated vessels were assessed with QFR. Lesions in the OCT cohort were classified into tertiles: QFR-T1 (QFR ≤ 0.85), QFR-T2 (0.85 < QFR ≤ 0.93), and QFR-T3 (QFR > 0.93). Lesions in the IVUS cohort were classified dichotomously as low or high QFR groups.Results: This post-hoc analysis included 132 lesions (83 for OCT and 49 for IVUS) from 126 patients. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) (p = 0.003 and 0.018, respectively). Overall significant differences were also observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness, and minimal lumen area (p = 0.017, 0.040, and <0.001, respectively). Thrombus was more prevalent in QFR-T1 (39%) than in QFR-T2 (3%), and QFR-T3 (12%) (p = 0.001 and 0.020, respectively). In the multivariable analysis, QFR ≤ 0.80 remained as a significant determinant of OCT-TCFA regardless of the presence of NSTE-ACS and the level of low-density lipoprotein cholesterol (adjusted OR: 4.387, 95% CI 1.297–14.839, p = 0.017). The diagnostic accuracy of QFR was moderate in identifying lesions with OCT-TCFA (area under the curve: 0.72, 95% CI 0.58–0.86, p = 0.003). In the IVUS cohort, significant differences were found between two groups in minimal lumen area and plaque burden but not in the distribution of virtual histology (VH)-TCFA (p = 0.025, 0.036, and 1.000, respectively).Conclusions: Lower QFR was related to OCT-defined plaque vulnerability in angiographically mild-to-intermediate lesions. The QFR might be a useful tool for ruling out high-risk plaques without using any pressure wire or vasodilator.

Performance of Integrated Near-Infrared Spectroscopy and Intravascular Ultrasound (NIRS-IVUS) System against Quantitative Flow Ratio (QFR)

Quantitative flow ratio (QFR) is a new opportunity to analyze functional stenosis during invasive coronary angiography. Together with a well-known intravascular ultrasound (IVUS) and a new player in the field, near-infrared spectroscopy (NIRS), it is gaining a lot of interest. The aim of the study was to compare QFR results with integrated IVUS-NIRS results acquired simultaneously in the same coronary lesion. We retrospectively enrolled 66 patients in whom 66 coronary lesions were assessed by NIRS-IVUS and QFR. Lesions were divided into two groups based on QFR results as QFR-positive group (QFR ≤ 0.8) or QFR-negative group (QFR > 0.8). Based on ROC curve analysis, the best cut-off values of minimal lumen area (MLA), minimal lumen diameter (MLD) and percent diameter stenosis for predicting QFR ≤ 80 were 2.4 (AUC 0.733, 95%CI 0.61, 0.834), 1.6 (AUC 0.768, 95%CI 0.634, 0.872) and 59.5 (AUC 0.918, 95%CI 0.824, 0.971), respectively. In QFR-positive lesions, the maxLCBI4mm was significantly higher than in QFR-negative lesions (450.12 ± 251.0 vs. 329.47 ± 191.14, p = 0.046). The major finding of the present study is that values of IVUS-MLA, IVUS-MLD and percent diameter stenosis show a good efficiency in predicting QFR ≤ 0.80. Moreover, QFR-positive lesions are characterized by higher maxLCBI4mm as compared to the QFR-negative group.

Potential Relation between Plasma BDNF Levels and Human Coronary Plaque Morphology

Coronary artery disease (CAD) patients are at high ischemic risk, and new biomarkers reflecting atherosclerotic disease severity and coronary plaque vulnerability are required. The Brain-Derived Neurotrophic Factor (BDNF) affects endothelial and macrophage activation suggesting its involvement in atherosclerotic plaque behavior. To investigate whether plasma BDNF is associated with in vivo coronary plaque features, assessed by optical coherence tomography (OCT), in both acute myocardial infarction (AMI) and stable angina (SA) patients, we enrolled 55 CAD patients (31 SA and 24 AMI), and 21 healthy subjects (HS). BDNF was lower in CAD patients than in HS (p < 0.0001), and it decreased with the presence, clinical acuity and severity of CAD. The greater BDNF levels were associated with OCT features of plaque vulnerability in overall CAD as well as in SA and AMI patients (p < 0.03). Specifically, in SA patients, BDNF correlated positively with macrophages’ infiltration within atherosclerotic plaque (p = 0.01) and inversely with minimal lumen area (p = 0.02). In AMI patients a negative correlation between BDNF and cap thickness was found (p = 0.02). Despite a small study population, our data suggest a relationship between BDNF and coronary plaque vulnerability, showing that vulnerable plaque is positively associated with plasma BDNF levels, regardless of the clinical CAD manifestation.

OCT-Derived Plaque Morphology and FFR-Determined Hemodynamic Relevance in Intermediate Coronary Stenoses

Background: optical coherence tomography (OCT) might allow identifying lesion features reportedly associated with plaque vulnerability and increased risk of clinical events. Previous studies on correlation between OCT and functional lesion significance indices reported contradictory results, yet integration of complementary information from both modalities is gaining increased interest. The aim of the study was to compare plaque morphology using OCT in hemodynamically relevant vs. non-relevant lesions by fractional flow reserve (FFR). Methods: consecutive patients with intermediate grade coronary stenoses by angiography were evaluated by both FFR and OCT in this single-center study. Stenoses were labeled hemodynamically relevant in case of the FFR ≤ 0.80. Minimal lumen area (MLA), fibrous cap thickness (FCT), minimal cap thickness over the calcium, angle of the calcium, and necrotic core within the lesions were evaluated. Results: a total of 105 patients (124 vessels) were analyzed. Of them, 65 patients were identified with at least one lesion identified as hemodynamically relevant by FFR (72 vessels, 58.1%). Lesions with FFR ≤0.80 presented with lower mean and minimal lumen area (3.46 ± 1.29 vs. 4.65 ± 2.19, p =0.001 and 1.84 ± 0.97 vs. 2.66 ± 1.40, p = 0.001) compared to patients with FFR > 0.80. No differences were found between groups in the mean and minimal FCT, mean, and maximal necrotic core, calcium angle, as well as the overall rate of calcified and lipid plaques. Conclusion: hemodynamic relevance of intermediate grade lesions correlated moderately with the luminal assessment by OCT. No differences were identified in the plaque morphology between relevant and non-relevant coronary stenoses by FFR.

Quantitative Flow Ratio Is Related to Intraluminal Coronary Stenosis Parameters as Assessed with Optical Coherence Tomography

Background: Quantitative flow ratio (QFR) is a novel method for assessing hemodynamic relevance of a coronary lesion based on angiographic projections without the need of a pressure wire. Various studies demonstrated that QFR consistently related to fractional flow reserve (FFR); however, it is still unclear to what extent QFR reflects intraluminal stenosis parameters. Given that optical coherence tomography (OCT) is currently the gold standard to assess intraluminal stenosis parameters, we investigated the relationship between OCT-derived lesion geometry and QFR. Methods: We determined QFR in 97 lesions from 87 patients who underwent coronary angiography and OCT due to stable angina. QFR was measured with proprietary software and compared with OCT-based assessment of intraluminal stenosis parameters as well as lesion morphology. Results: Mean QFR was 0.79 ± 0.10. QFR demonstrated a consistent association with FFR (R = 0.834, p < 0.001). Interestingly, QFR was associated with OCT-derived parameters such as minimal lumen area (MLA, R = 0.390, p = 0.015), percent area stenosis (R = 0.412, p < 0.001), minimal lumen diameter (MLD, R = 0.395, p < 0.001), and percent diameter stenosis (R = 0.400, p < 0.001). Both minimal luminal area (ROC = 0.734, optimal cut-off 1.75 mm2) and minimal luminal diameter (ROC = 0.714, optimal cut-off 1.59 mm) presented a good diagnostic accuracy in diagnosing hemodynamic relevance (QFR ≤ 0.80). There was no significant association between QFR and anatomic features of plaque vulnerability. Conclusion: OCT-derived intraluminal stenosis parameters are related to QFR values and predict hemodynamic lesion relevance. The data supports the validity of QFR as 3D-vessel reconstruction method to assess coronary physiology without the need of a pressure wire.