Blockade of CD47 function attenuates restenosis by promoting smooth muscle cell efferocytosis and inhibiting their migration and proliferation.

Cluster of differentiation 47 (CD47) plays an important role in the pathophysiology of various diseases including atherosclerosis but its role in neointimal hyperplasia which contributes to restenosis has not been studied. Using molecular approaches in combination with a mouse vascular endothelial denudation model, we studied the role of CD47 in injury-induced neointimal hyperplasia. We determined that thrombin-induced CD47 expression both in human aortic smooth muscle cells (HASMCs) and mouse aortic smooth muscle cells. In exploring the mechanisms, we found that the protease-activated receptor 1-Gα protein q/11 (Gαq/11)-phospholipase Cß3-nuclear factor of activated T cells c1 signaling axis regulates thrombin-induced CD47 expression in HASMCs. Depletion of CD47 levels using its siRNA or interference of its function by its blocking antibody (bAb) blunted thrombin-induced migration and proliferation of HASMCs and mouse aortic smooth muscle cells. In addition, we found that thrombin-induced HASMC migration requires CD47 interaction with integrin ß3. On the other hand, thrombin-induced HASMC proliferation was dependent on CD47's role in nuclear export and degradation of cyclin-dependent kinase-interacting protein 1. In addition, suppression of CD47 function by its bAb rescued HASMC efferocytosis from inhibition by thrombin. We also found that vascular injury induces CD47 expression in intimal SMCs and that inhibition of CD47 function by its bAb, while alleviating injury-induced inhibition of SMC efferocytosis, attenuated SMC migration, and proliferation resulting in reduced neointima formation. Thus, these findings reveal a pathological role for CD47 in neointimal hyperplasia.

Revisiting the Evidence for Dipyridamole in Reducing Restenosis: A Systematic Review and Meta-analysis.

ABSTRACT: Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization.

Long-Term Outcomes of Percutaneous Coronary Intervention for Patients With In-Stent Chronic Total Occlusion Versus De Novo Chronic Total Occlusion.

Limited data are available on long-term outcomes and health status in the treatment of in-stent coronary chronic total occlusion (IS-CTO) and de novo coronary chronic total occlusion (de novo CTO). This study compared the long-term clinical outcomes and health status of percutaneous coronary intervention (PCI) for patients with IS-CTO versus patients with de novo CTO in the drug-eluting stent era. We screened 483 consecutive patients with 1 CTO lesion, including 81 patients with IS-CTO and 402 patients with de novo CTO. Propensity score matching was used to balance baseline characteristics between the 2 groups. The clinical end point was major adverse cardiac events (MACE). The success rates of CTO lesion revascularization were similar in both groups. In the propensity score-matched patients, after a median follow-up of 36 months, MACE was observed in 32.8% of patients with IS-CTO versus 13.5% of the patients with de novo CTO (P < .001), mainly driven by target-vessel revascularization (21.9% vs 6.7%; P < .01). Moreover, patients with IS-CTO had significantly worse Seattle Angina Questionnaire anginal stability scores than the patients with de novo CTO. In conclusion, patients with IS-CTO after PCI had a worse clinical outcome, mainly MACE, and a poorer anginal stability in the long term than patients with de novo CTO.

Predictive value of LncRNA on coronary restenosis after percutaneous coronary intervention in patients with coronary heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Evidence shows that long-stranded non-coding RNA (LncRNA) can predict coronary artery restenosis in patients suffering from coronary heart disease after percutaneous coronary intervention, suggesting that LncRNA may become a promising biomarker for the diagnosis of coronary artery restenosis after percutaneous coronary intervention. However, its accuracy has not been systematically evaluated. Therefore, it is necessary to perform meta-analysis to certify the diagnostic value of LncRNA on coronary artery restenosis after percutaneous coronary intervention. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant studies to explore the potential diagnostic values of LncRNA on coronary artery restenosis after percutaneous coronary intervention from inception to December 2020. Data were extracted by two experienced researchers independently. The risk of bias about the meta-analysis was confirmed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Data was synthesized and heterogeneity was investigated as well. All of the above statistical analysis was carried out with Stata 14.0. RESULTS: This study proved the pooled diagnostic performance of LncRNA on coronary artery restenosis after percutaneous coronary intervention. CONCLUSION: This study clarified confusions about the specificity and sensitivity of LncRNA on coronary artery restenosis after percutaneous coronary intervention, thus further guiding their promotion and application. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/4QT2P.

Local fluid dynamics in patients with bifurcated coronary lesions undergoing percutaneous coronary interventions.

Although the coronary arteries are uniformly exposed to systemic cardiovascular risk factors, atherosclerosis development has a non-random distribution, which follows the local mechanical stresses including flow-related hemodynamic forces. Among these, wall shear stress plays an essential role and it represents the major flow-related factor affecting the distribution of atherosclerosis in coronary bifurcations. Furthermore, an emerging body of evidence suggests that hemodynamic factors such as low and oscillating wall shear stress may facilitate the development of in-stent restenosis and stent thrombosis after successful drug-eluting stent implantation. Drug-eluting stent implantation represents the gold standard for bifurcation interventions. In this specific setting of interventions on bifurcated lesions, the impact of fluid dynamics is expected to play a major role and constitutes substantial opportunity for future technical improvement. In the present review, available data is summarized regarding the role of local fluid dynamics in the clinical outcome of patients with bifurcated lesions.

Prostaglandin E2 (PGE2) synthesis pathway is involved in coronary artery stenosis and restenosis.

The inflammatory events related to prostaglandins may play an important role in the progression of vessel stenosis. The aim of this study was to investigate the monocyte PTGES and 15-PGDH gene expression levels and the serum 13,14-dihyro-15-keto-PGF2α value involved in PGE2 metabolism in patients with coronary artery stenosis and restenosis. Moreover, the effects of miR-520, miR-1297 and miR-34 were studied on the gene expression levels. A total of sixty subjects referred for coronary angiography including healthy controls (stenosis <5%), subjects with stent no restenosis) SNR, stenosis <5%) and subjects in stent restenosis (ISR, restenosis >70%) were participated in the study. The gene expression levels and the serum 13,14-dihyro-15-keto- PGF2α value were measured by RT-qPCR and ELISA techniques, respectively. Moreover, the effects of miRNAs on the gene expression levels were investigated by the monocyte transfection of miR/PEI complexes. The PTGES and 15-PGDH gene expression levels and serum 13,14-dihyro-15-keto- PGF2α value increased significantly (P <0.05). Based on the miR-520 and miR-34 expression levels, the miR/PEI transfection studies were confirmed significantly the gene expression changes. The monocyte PGE2 synthesis pathway is actively considered in the SNR and ISR patients and might be related to miR-34 and miR-520 functions.

Physiological benefits evaluated by quantitative flow ratio in patients with reduced left ventricular ejection fraction who underwent percutaneous coronary intervention.

BACKGROUND: To explore the clinical benefits of revascularization in patients with different levels of left ventricular ejection fraction (LVEF) from the perspective of quantitative flow ratio (QFR). METHODS: Patients who underwent successful percutaneous coronary intervention (PCI) and one-year angiographic follow-up were retrospectively screened and computed by QFR analysis. Based on their LVEF, 301 eligible patients were classified into reduced LVEF (≤ 50%, n = 48) and normal LVEF (> 50%, n = 253) groups. Pre-PCI QFR, post-PCI QFR, follow-up QFR, late lumen loss (LLL), LVEF and major adverse cardiovascular and cerebrovascular events (MACCEs) at one year were compared between groups. RESULTS: The reduced LVEF group had a lower mean pre-PCI QFR than the normal LVEF group (0.67 ± 0.16 vs. 0.73 ± 0.15, p = 0.004), but no significant difference was found in the post-PCI or one-year follow-up QFR. No association was found between LVEF and QFR at pre-PCI or follow-up. The reduced LVEF group had greater increases in QFR (0.27 ± 0.18 vs. 0.22 ± 0.15, p = 0.043) and LVEF (6.05 ± 9.45% vs. - 0.37 ± 8.11%, p < 0.001) than the normal LVEF group. The LLL results showed no difference between the two groups, indicating a similar degree of restenosis. The reduced LVEF group had a higher incidence of MACCEs (14.6% vs. 4.3%, p = 0.016), which was mainly due to the higher risk of heart failure (6.3% vs. 0%, p = 0.004). CONCLUSION: Compared to the corresponding normal LVEF patients, patients with reduced LVEF who underwent successful PCI were reported to have greater increases in QFR and LVEF, a similar degree of restenosis, and a higher incidence of MACCEs due to a higher risk of heart failure. It seems that patients with reduced LVEF gain more coronary benefits from successful revascularization from the perspective of flow physiology evaluations.

Influence of the Adopted Balloon Modeling Strategies in the Stent Deployment Procedure: An In-Silico Analysis.

PURPOSE: As the promoter of the stent expansion, the balloon plays a very important role, offering a strong influence on the deployment process. Balloon-artery interaction is pointed as a probable cause of restenosis, stressing the relevance of balloon modeling when simulating the stenting procedure. In this work, an in-silico study of the balloon modeling strategies is performed. METHODS: Ultrasonic-microcasting is a novel technology that allows obtaining stents manufactured in magnesium alloys, being suggested as a promising solution. However, this technique demands superior stent strut thickness, which may have an impact on the stent deployment procedure. The influence of the balloon modeling is studied through the simulation of different balloon geometries (open- or taper-ended) and material constitutive model (linear elastic or hyperelastic) on the expanded configuration of a stent manufactured through ultrasonic-microcasting. RESULTS: The results obtained suggest that the choice of balloon type has small impact in terms of demanded pressure to inflate the balloon and in the stent final radius achieved at fully-expanded configuration. Additionally, it was proved that the balloon-type influences the stent expanded profile along its length and diameter as a result of the different deformation behavior exhibited by the balloon. CONCLUSION: The hyperelastic taper-ended balloon suggests being the model that better correlates with both experimental and clinical results regarding the expanded balloon profile during the procedure.

Computational Simulations of Provisional Stenting of a Diseased Coronary Artery Bifurcation Model.

Although stenting of non-branched arterial segments has acceptable clinical outcomes, in-stent restenosis (ISR) and stent thrombosis remain clinically significant issues for vascular bifurcations (15-28% restenosis). Local fluid and solid stresses appear to play an important role in restenosis and thrombosis. The combined role of wall shear stress (WSS) and circumferential wall stresses (CWS) is unclear in the case of stenting at vascular bifurcations. Using numerical simulations, we computed the fluid shear, solid stresses and the stress ratio at the the bifurcation region. Stenting of main vessel increased the maximum CWS in the the side branch (SB), resulting in a nearly two-fold increase of stress ratio in the SB compared to the MB (5.1 × 105 vs. 9.2 × 105). The existence of plaque decreased WSS and increased CWS near the carina, increasing the stress ratio at the SB. The changes of stress ratio were highly consistent with clinical data on bifurcation stenting. Fluid dynamics and solids mechanics should be considered in planning of stenting for a specific bifurcation, as their combined biomechanical effect may play an important role in stent restenosis and thrombosis.

Drug-Coated Balloons versus Everolimus-Eluting Stents in Patients with In-Stent Restenosis: A Pair-Wise Meta-Analysis of Randomized Trials.

OBJECTIVE: This study aimed to compare the effectiveness of drug-coated balloons (DCB) with everolimus-eluting stents (EES) in the treatment of in-stent restenosis (ISR) and the differential relative effect of DCB in patients with drug-eluting stents (DES)-ISR and bare metal stents (BMS)-ISR. BACKGROUND: The efficiency and safety of DCB and EES need to be assessed for the treatment of ISR. METHODS: A systematic literature search was conducted using PubMed and EMBASE to identify all relevant studies. Angiographic results and clinical events were separately assessed. Subgroup meta-analyses were performed according to the type of restenosed stent. RESULTS: Six randomized trials with 1134 patients were included. The overall pooled outcomes indicated that DCB was associated with lower minimum lumen diameter (mean difference (MD) = -0.17, 95% CI = -0.29 to -0.05, P = 0.006) and higher target lesion revascularization (risk ratio (RR) = 2.38, 95% CI = 1.36 to 4.18, P = 0.002) than EES. However, the subgroup meta-analyses showed that DCB was inferior to EES only in DES-ISR patients, with lower minimum lumen diameter (MD = -0.25, 95% CI = -0.37 to -0.14, P < 0.001), higher percent diameter stenosis (MD = 5.37, 95% CI = 1.33 to 9.42, P = 0.009), more binary restenosis (RR = 2.07, 95% CI = 1.20 to 3.58, P = 0.009), and higher incidence of target vessel revascularization (RR = 2.07, 95% CI = 1.22 to 3.50, P = 0.007) and target lesion revascularization (RR = 2.43, 95% CI = 1.28 to 4.22, P = 0.002). No differences in angiographic results and clinical events were found between DCB and EES in BMS-ISR patients. CONCLUSIONS: DCB was inferior to EES in DES-ISR and comparable in BMS-ISR in terms of angiographic results and clinical events.

The adipokine vaspin is associated with decreased coronary in-stent restenosis in vivo and inhibits migration of human coronary smooth muscle cells in vitro.

BACKGROUND: Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro. METHODS: We studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed. RESULTS: During the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment. CONCLUSION: We were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment.

Role of endothelial dysfunction in determining angina after percutaneous coronary intervention: Learning from pathophysiology to optimize treatment.

Endothelial dysfunction (EnD) is a hallmark feature of coronary artery disease (CAD), representing the key early step of atherosclerotic plaque development and progression. Percutaneous coronary intervention (PCI) is performed daily worldwide to treat symptomatic CAD, however a consistent proportion of patients remain symptomatic for angina despite otherwise successful revascularization. EnD plays a central role in the mechanisms of post-PCI angina, as it is strictly associated with both structural and functional abnormalities in the coronary arteries that may persist, or even accentuate, following PCI. The assessment of endothelial function in patients undergoing PCI might help to identify those patients at higher risk of future cardiovascular events and recurrent/persistent angina who might therefore benefit more from an intensive treatment. In this review, we address the role of EnD in determining angina after PCI, discussing its pathophysiological mechanisms, diagnostic approaches and therapeutic perspectives.

Mechanistic evaluation of long-term in-stent restenosis based on models of tissue damage and growth.

Development and application of advanced mechanical models of soft tissues and their growth represent one of the main directions in modern mechanics of solids. Such models are increasingly used to deal with complex biomedical problems. Prediction of in-stent restenosis for patients treated with coronary stents remains a highly challenging task. Using a finite element method, this paper presents a mechanistic approach to evaluate the development of in-stent restenosis in an artery following stent implantation. Hyperelastic models with damage, verified with experimental results, are used to describe the level of tissue damage in arterial layers and plaque caused by such intervention. A tissue-growth model, associated with vessel damage, is adopted to describe the growth behaviour of a media layer after stent implantation. Narrowing of lumen diameter with time is used to quantify the development of in-stent restenosis in the vessel after stenting. It is demonstrated that stent designs and materials strongly affect the stenting-induced damage in the media layer and the subsequent development of in-stent restenosis. The larger the artery expansion achieved during balloon inflation, the higher the damage introduced to the media layer, leading to an increased level of in-stent restenosis. In addition, the development of in-stent restenosis is directly correlated with the artery expansion during the stent deployment. The correlation is further used to predict the effect of a complex clinical procedure, such as stent overlapping, on the level of in-stent restenosis developed after percutaneous coronary intervention.

Preventing treatment failures in coronary artery disease: what can we learn from the biology of in-stent restenosis, vein graft failure, and internal thoracic arteries?

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent restenosis (ISR) is a major drawback for intracoronary stenting, while graft failure is the limiting factor for coronary artery bypass graft surgery (CABG), especially using veins. Conversely, internal thoracic artery (ITA) is known to maintain long-term patency in CABG. Understanding the biology and pathophysiology of ISR and vein graft failure (VGF) and mechanisms behind ITA resistance to failure is crucial to combat these complications in CAD treatment. This review intends to provide an overview of the biological mechanisms underlying stent and VGF and of the potential therapeutic strategy to prevent these complications. Interestingly, despite being different modalities of revascularization, mechanisms of failure of stent and saphenous vein grafts are very similar from the biological standpoint.

CT Perfusion Versus Coronary CT Angiography in Patients With Suspected In-Stent Restenosis or CAD Progression.

OBJECTIVES: The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard. BACKGROUND: Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation. METHODS: Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses. RESULTS: In the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv. CONCLUSIONS: In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard.

Longitudinal Stent Deformation: Precise Diagnosis With Optical Coherence Tomography.

Longitudinal stent deformation is a recognized complication of coronary angioplasty; however, it is difficult to detect angiographically. This case illustrates the value of OCT to identify and correctly diagnose longitudinal stent deformation.

Haemodynamics Study of Tapered Stents Intervention to Tapered Arteries.

PURPOSE: In-stent restenosis (ISR) is related to local haemodynamics in the arteries after stent intervention. However, the haemodynamics of stents implanted into tapered vessels is rarely studied and remains unclear. This study aimed to study the haemodynamic performance of a stent in a tapered artery to reveal the haemodynamic differences between tapered and cylindrical stents after stent implantation and guide the stent selection for the treatment of coronary artery stenosis. METHODS: Cylindrical and tapered stents were implanted into the tapered arteries. A model of a cylindrical stent implanted into a cylindrical artery was established as the contrast model. Using the finite element method, the flow velocity and wall shear stress distribution of the three models were compared. RESULTS: At t1, t2, t3 and t4, the flow rate of the tapered artery with tapered stents (TT) after the implantation increased by 8.59, 3.80, 12.81 and 3.66%, respectively. In addition, the wall shear stress in the tapered arteries of TT was 23.48, 36.67, 13.00 and 8.06% higher than that of the tapered arteries with cylindrical stents (TC). CONCLUSIONS: The implantation of a tapered stent in the tapered artery can effectively improve intravascular haemodynamics. The tapered stent allows the tapered artery to obtain better haemodynamics and reduces the probability of ISR.

Prediction of restenosis based on hemodynamical markers in revascularized femoro-popliteal arteries during leg flexion.

Endovascular therapy in patients suffering from peripheral arterial disease shows high rates of restenosis. The poor clinical outcomes are commonly explained by the demanding mechanical environment due to leg movements, but the mechanisms responsible for restenosis remain unknown. In this study, we hypothesized that restenosis following revascularization is associated with hemodynamical markers derived from blood flow during leg flexion. Therefore, we performed personalized computational fluid dynamics (CFD) analyses of 20 patients, who underwent routine endovascular femoro-popliteal interventions. The CFD analyses were conducted using 3D models of the arterial geometry in straight and flexed positions, which were reconstructed from 2D angiographic images. Based on restenosis rates reported at 6-month follow-up, logistic regression analyses were performed to predict restenosis from hemodynamical parameters. Results showed that severe arterial deformations, such as kinking, induced by leg flexion in stented arteries led to adverse hemodynamic conditions that may trigger restenosis. A logistic regression analysis based solely on hemodynamical markers had an accuracy of 75%, which showed that flow parameters are sufficient to predict restenosis (p = 0.031). However, better predictions were achieved by adding the treatment method in the model. This suggests that a more accurate image acquisition technique is required to capture the localized modifications of blood flow following intervention, especially around the stented artery. This approach, based on the immediate postoperative configuration of the artery, has the potential to identify patients at increased risk of restenosis. Based on this information, clinicians could take preventive measures and more closely follow these patients to avoid complications.

Real World Utilization of Computed Tomography Derived Fractional Flow Reserve: Single Center Experience in the United States.

BACKGROUND: Fractional flow reserve derived from computed tomography (FFRct) has shown higher accuracy for detection of significant coronary artery disease (CAD) compared to coronary computed tomography angiography (CCTA). The performance of a combined comprehensive qualitative interpretation of both CCTA and FFRct in patient management is unknown. We aimed to explore the clinical application of this combined approach. METHODS: We retrospectively reviewed cases referred to FFRct testing at our institution over a one-year period. Patients had documentation of whether invasive coronary angiography (ICA) was performed and revascularization were needed. Interpretations and recommendations of the adopted comprehensive approach (C-FFRct), that took into account focal versus diffuse disease, depth of ischemia and myocardium at risk, were compared to those of CCTA (binary > 50% stenosis) alone and FFRct binary approach (FFRct ≤ 0.8). C-FFRct performance was measured against the decision made upon revascularization. RESULTS: A total of 207 cases were referred to FFRct testing, 163 (79%) accepted and 44 (21%) rejected for quality. C-FFRct changed interpretations and recommendations of 39 (24%) and 14 (9%) CCTA and FFRct, respectively. ICA was deferred in 32 (59%) and 13 (32%) cases; whereas ICA referral rate was 7 (6%) and 1 (0.8%) cases, based on CCTA and FFRct, respectively. No major cardiac events were observed during follow up time (median = 6 months). C-FFRct sensitivity, specificity, and accuracy compared to decision upon revascularization were 89%, 79% and 82%. C-FFRct number needed to treat was 4, and 6, compared to CCTA and FFRct, respectively. CONCLUSION: FFRct is a feasible tool to improve the diagnostic performance of CCTA in CAD real-world workup. However, qualitative interpretation of the FFRct report combined with CCTA findings may yield more impactful results on patient management. Further prospective studies are warranted to validate the application of this approach and better define its components.