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Background: Recently, non-hyperemic pressure ratios (NHPRs) have been validated as a reliable alternative to fractional flow reserve (FFR). However, a discordance between FFR and NHPRs is observed in 20-25% of cases. The aim of this study is to evaluate predictors of discordance between FFR and diastolic Pressure ratio (dPR). Methods: PREDICT is a retrospective, single center, investigator-initiated study including 813 patients (1092vessels) who underwent FFR assessment of intermediate coronary lesions (angiographic 30%-80% stenosis). dPR was calculated using individual pressure waveforms and dedicated software. Clinical, angiographic and hemodynamic variables were compared between patients with concordant and discordant FFR and dPR values. Results: Median age was 65 (IQR:59-73) years and 70% were male. Hemodynamically significant lesions, as defined by FFR ≤ 0.80, and dPR ≤ 0.89, were identified in 29.6% and 30.3% of cases, respectively. Overall, FFR and dPR values were discordant in 22.1% patients (17.4% of the vessels). Discordance was related to FFR+/dPR- and FFR-/dPR + in 11.8% and 10.3% of patients, respectively.In case of FFR-dPR discordance, a higher prevalence of left anterior descending arteries lesions was observed (70.5% vs. 53.1%, p < 0.001) and mean values of both FFR and dPR were significantly lower (FFR 0.81 ± 0.05 vs 0.85 ± 0.08, p < 0.001, and dPR 0.89 ± 0.04 vs 0.92 ± 0.08,p < 0.001) as compared to vessels with FFR and dPR concordance. Following multivariable adjustment, dPR delta (defined as the absolute difference between measured dPR to the cut-off value of 0.89) turned out to be the only independent predictor of discordance (OR = 0.74, 95% CI 0.68-0.79, p < 0.001). Conclusion: Our study suggests that FFR-to-dPR discordance occurs in approximately one-fifth of patients. Absolute dPR delta appears to be the only independent predictor of discordance.

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Safety and efficacy of coronary drug-eluting stents (DES) are often preclinically tested using healthy or minimally diseased swine. These generally show significant fibrotic neointima at follow-up, while in patients, incomplete healing is often observed. The aim of this study was to investigate neointima responses to DES in swine with significant coronary atherosclerosis. Adult familial hypercholesterolemic swine (n = 6) received a high fat diet to develop atherosclerosis. Serial OCT was performed before, directly after, and 28 days after DES implantation (n = 14 stents). Lumen, stent and plaque area, uncovered struts, neointima thickness and neointima type were analyzed for each frame and averaged per stent. Histology was performed to show differences in coronary atherosclerosis. A range of plaque size and severity was found, from healthy segments to lipid-rich plaques. Accordingly, neointima responses ranged from uncovered struts, to minimal neointima, to fibrotic neointima. Lower plaque burden resulted in a fibrotic neointima at follow-up, reminiscent of minimally diseased swine coronary models. In contrast, higher plaque burden resulted in minimal neointima and more uncovered struts at follow-up, similarly to patients' responses. The presence of lipid-rich plaques resulted in more uncovered struts, which underscores the importance of advanced disease when performing safety and efficacy testing of DES.

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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.

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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.

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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.

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BACKGROUND: In January 2021, the Diamondback 360 orbital atherectomy (OA) system received CE mark approval and became available in Europe. The first procedure in Europe was performed at the Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands. AIMS: To report the procedural safety and efficacy of the initial experience with OA in a tertiary care institution in the Netherlands. METHODS: Patients with de novo severely calcified coronary artery disease who were treated with intended invasive imaging-guided OA were included in a prospective single-centre registry. Device success, defined as less than 50% stenosis after OA, and procedural success, defined as successful stent implantation with less than 50% residual stenosis, were evaluated. Calcium debulking effects were assessed by invasive imaging. Safety was assessed up to 30 days after the index procedure. RESULTS: Between February 2021 and June 2021, 29 patients with a total of 39 coronary arteries underwent OA. Target lesions were heavily calcified with a mean length of 32 mm and a calcium arc of 320 degrees. Invasive imaging was applied in all but one patient and 36 vessels. Superficial sanding was observed in almost all vessels (90%) and fracturing of deeper medial calcium in more than half of the vessels (63%), with a device success of 66% and procedural success of 94%. The mean stent symmetry index was 0.84, indicating good circular stent expansion. No primary safety events occurred during 30 days of follow-up. CONCLUSION: Our initial experience with OA for heavily calcified coronary lesions demonstrated favourable debulking effects and plaque modification, with high procedural success and clinical safety.

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OBJECTIVE: Thinner stent struts might lead to a higher risk of recoil and subsequently a smaller minimal stent area (MSA), which is known to be the strongest predictor of stent failure. We compared procedural performance between an ultrathin-strut biodegradable-polymer sirolimus-eluting stent (BP-SES) and a durable-polymer zotarolimus-eluting stent (DP-ZES) using intracoronary imaging. METHODS: A consecutive cohort of patients underwent percutaneous coronary intervention (PCI) with either BP-SES or DP-ZES in a pseudorandomized fashion between July 2018 and October 2019. In the present subanalysis, we included cases in which post-PCI imaging with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was performed. The primary endpoint of the study was MSA. Secondary endpoints included percentage stent expansion and presence of residual edge disease, malapposition, tissue protrusion, submedial edge dissections, or edge hematoma. RESULTS: A total of 141 treated lesions (78 BP-SES and 63 DP-ZES) in 127 patients were analyzed. Median age was 69.3 years (interquartile range [IQR], 57.3-75.6) and 74.0% of patients were male. All baseline and procedural characteristics were comparable between both groups. Median MSA was 5.80 mm² (IQR, 4.40-7.24) for BP-SES and 6.35 mm² (IQR, 4.76-8.31) for DP-ZES (P=.15). No significant differences in stent expansion, residual edge disease and presence of malapposition, tissue protrusion, submedial edge dissections, or edge hematomas were found. Stent diameter and stent length were found to be independent predictors of MSA. CONCLUSIONS: No significant differences in MSA were found between lesions treated with BP-SES vs DP-ZES. BP-SES and DP-ZES were comparable in terms of procedural performance.

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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.

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BACKGROUND: Vessel fractional flow reserve (vFFR) has a high diagnostic accuracy in assessing functional lesion significance compared with FFR. Nonhyperemic pressure ratios (NHPRs) were noninferior to FFR to guide revascularization of intermediate lesions. Therefore, the diagnostic performance of vFFR compared with NHPR warrants interest. AIM: To evaluate the diagnostic performance of vFFR with a generic diastolic pressure ratio (dPR) as a reference. METHODS: The study population was derived from the FAST EXTEND and FAST II studies. Between January 2016 and September 2020, a total of 475 patients were enrolled. RESULTS: Median dPR was 0.92 (interquartile range [IQR], 0.87-0.95), median vFFR was 0.86 (IQR, 0.80-0.90). The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of vFFR ≤0.80 for dPR ≤0.89 were 66%, 92%, 79%, 85%, and 84%, respectively. Vessel FFR showed a good agreement with dPR (r=0.68), consistent among specific clinical lesion subsets and a high diagnostic accuracy for dPR ≤0.89 (area under the curve=0.89). Discordance between vFFR and dPR was observed in 78/492 cases (15.6%) and logistic regression analysis did not reveal any clinical, angiographic, or hemodynamic variables associated with vFFR and dPR discordance. CONCLUSION: Vessel FFR shows a good agreement with dPR and a high diagnostic accuracy for dPR ≤0.89.

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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.

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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.

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BACKGROUND/PURPOSE: Identification of the culprit lesion in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) allows appropriate coronary revascularization but may be unclear in patients with multivessel coronary disease (MVD). Therefore, we investigated the rate of culprit lesion identification during coronary angiography in NSTE-ACS and multivessel disease. METHODS/MATERIALS: Consecutive patients presenting with NSTE-ACS and MVD, between January 2012 and December 2016 were evaluated. Coronary angiograms, intravascular imaging, and ECGs were analyzed for culprit lesion identification. Long-term clinical outcomes in terms of major adverse cardiac events (MACE) and mortality were reported in patients with or without culprit identification. RESULTS: A total of 1107 patients with NSTE-ACS and MVD were included in the analysis, 310 (28.0%) with unstable angina and 797 (72.0%) with non-ST elevation myocardial infarction. The culprit lesion was angiographically identified in 952 (86.0%) patients, while no clear culprit lesion was found in 155 (14.0%) patients. ECG analysis allowed to predict the location of the culprit vessel with low sensitivity (range 28.4%-36.7%) and high specificity (range 90.6%-96.5%). Higher lesion complexity was associated with inability to identify the culprit. Intravascular imaging was applied in 55 patients and helped to identify the culprit lesion in 53 patients (96.4%). There was no difference in all-cause mortality (21.4% vs. 25.8%, p = 0.24) and MACE (39.2% vs. 47.6%, p = 0.07) between the cohorts with or without culprit lesion identification by angiography. CONCLUSIONS: The culprit lesion appeared unclear by coronary angiography in >10% of patients with NSTE-ACS and MVD. Complementary invasive imaging substantially enhanced the diagnostic accuracy of culprit lesion detection.

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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.

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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.

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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.

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OBJECTIVES: The aim of this study was to evaluate the very long-term clinical outcome after radioactive stent (RS) implantation and intracoronary ß radiation brachytherapy (IRBT). BACKGROUND: Radioactive stents (RS) and intracoronary ß radiation brachytherapy (IRBT) were introduced to prevent restenosis after percutaneous coronary intervention (PCI). Both techniques were associated with a higher incidence of major adverse cardiac events (MACE) in the short and intermediate-term follow up as compared to conventional PCI. METHODS: One hundred and thirty-three patients received radioactive stents (32 P) and 301 patients were treated with IRBT adjunctive to PCI. These groups were propensity matched to respectively 266 and 602 control patients who were treated with routine PCI during the same inclusion period. Endpoints were all-cause mortality and MACE, defined as all-cause death, any myocardial infarction or any revascularization. RESULTS: Median follow-up duration was 17 years. All-cause mortality rates were similar in all groups. Adjusted hazard ratios for MACE and mortality in the RS cohort were 1.55 (95% CI 1.20-2.00) and 0.92 (95% CI 0.63-1.34), respectively. Adjusted hazard ratios for MACE and all-cause mortality in the IRBT cohort were 1.41 (95% CI 1.18-1.67) and 0.95 (95% CI 0.74-1.21), respectively. The difference in MACE rates was predominantly driven by coronary revascularizations in both groups, with a higher MI rate in the IRBT group as well. CONCLUSIONS: Coronary radiation therapy was associated with early increased MACE rates, but the difference in MACE rates decreased beyond 2 years, resulting in a comparable long-term clinical outcome. Importantly, no excess in mortality was observed.

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