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.

Two decades after coronary radiation therapy: A single center longitudinal clinical study.

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.

Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile: Findings From a Familial Hypercholesterolemia Pig Model.

OBJECTIVE: In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. To elucidate the underlying mechanisms of the observed inter-individual variation in disease severity, detailed lipoprotein profiles were determined. Approach and Results: FH pigs (3 years old, homozygous LDLR R84C mutation) received an atherogenic diet for 12 months. Coronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference was observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% [23%-34%]; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, 69% [57%-77%]) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly diseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion chromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine-1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory techniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular LDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 [1.3-1.9] versus 0.8 [0.6-0.9]; P=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and sphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios. CONCLUSIONS: In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to the distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet start. A similar LDL profile was detected in patients with homozygous FH.

The Effect of Stent Artefact on Quantification of Plaque Features Using Optical Coherence Tomography (OCT): A Feasibility and Clinical Utility Study.

BACKGROUND: Optical coherence tomography (OCT) can detect detailed plaque features in native coronary arteries. Stent struts cause shadows that partially obscure the vessel wall, but plaque features can still be seen. We investigated the impact of stent artefact on plaque quantification and whether the plaque behind struts is associated with microvascular dysfunction. METHODS: Patients retrospectively recruited from two centres, underwent OCT pre- and post-stenting on the same vessel segment. Lipid (LA) and calcium (CA) were measured as arcs. Macrophages, microchannels and cholesterol crystals were counted. Subsequently, we determined whether stented plaque features were associated with reduced Thrombolysis in Myocardial Infarction (TIMI) flow grade in consecutive patients who underwent OCT post-stenting. RESULTS: In 52 patients the lipid arc was similar pre- vs post-stent: median (55º [13º-93º] vs. 40º [18º-87°]; difference 1º [-7º to 16º], p = NS). Pre- and post-stent lipid were strongly correlated (r = 0.92, p < 0.001). In a further 128 patients those with reduced (TIMI ≤ II) vs normal flow post percutaneous coronary intervention (PCI) showed more plaque behind struts: lipid (89º [50º-139º] vs 62º [29º-88°]; p < 0.001); and calcium (24º [6º-45º] vs 7° [0º-34º]; p = 0.031). Multivariate logistic regression analysis showed that abnormal TIMI flow post-stenting was associated with diabetes (Odds ratio [OR] 2.87, CI 1.01-8.19, p = 0.048), LA (OR 1.29, 95% CI 1.14-1.38, p < 0.001) and CA (OR 1.26, CI 1.07-1.40, p = 0.005). CONCLUSIONS: Plaque behind the struts can be accurately quantified using OCT. Furthermore, OCT plaque features in stented segments are associated with microvascular dysfunction post PCI.

Reduced duration of dual antiplatelet therapy using an improved drug-eluting stent for percutaneous coronary intervention of the left main artery in a real-world, all-comer population: Rationale and study design of the prospective randomized multicenter IDEAL-LM trial.

BACKGROUND: Continuous improvements in stent technology make percutaneous coronary intervention (PCI) a potential alternative to surgery in selected patients with unprotected left main coronary artery (uLMCA) disease. The optimal duration of dual antiplatelet therapy (DAPT) in these patients remains undetermined, and in addition, new stent designs using a bioabsorbable polymer might allow shorter duration of DAPT. STUDY DESIGN: IDEAL-LM is a prospective, randomized, multicenter study that will enroll 818 patients undergoing uLMCA PCI. Patients will be randomized in a 1:1 fashion to intravascular ultrasound-guided PCI with the novel everolimus-eluting platinum-chromium Synergy stent with a biodegradable polymer (Boston Scientific, Natick, MA) followed by 4 months of DAPT or the everolimus-eluting cobalt-chromium Xience stent (Abbott Vascular, Santa Clara, CA) followed by 12 months of DAPT. The total follow-up period will be 5 years. A subset of 100 patients will undergo optical coherence tomography at 3 months. END POINTS: The primary end point will be major adverse cardiovascular events (composite of all-cause mortality, myocardial infarction, and ischemia-driven target vessel revascularization) at 2 years. Secondary end points will consist of the individual components of the primary end point, procedural success, a device-oriented composite end point, stent thrombosis as per Academic Research Consortium criteria, and bleeding as per Bleeding Academic Research Consortium criteria. SUMMARY: IDEAL-LM is designed to assess the safety and efficacy of the novel Synergy stent followed by 4 months of DAPT vs the Xience stent followed by 12 months of DAPT in patients undergoing uLMCA PCI. The study will provide novel insights regarding optimal treatment strategy for patients undergoing PCI of uLMCA disease (www.clinicaltrials.gov, NCT 02303717).

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.

Reproducibility of intravascular ultrasound iMAP for radiofrequency data analysis: implications for design of longitudinal studies.

BACKGROUND: iMAP is a new intravascular ultrasound (IVUS) derived technique for tissue characterization using spectral analysis. Since there is a need for reproducibility data to design longitudinal studies, we sought to assess the in vivo reproducibility of this imaging technique. METHODS: iMAP (40 MHz, Boston Scientific Corporation) was performed in patients referred for elective percutaneous intervention and in whom a nonintervened vessel was judged suitable for a safe IVUS analysis. Overall 20 patients with 20 non-angiographically significant lesions were assessed by two independent observers. Five of these 20 patients received an additional iMAP analysis using a new IVUS catheter and using the same catheter after its engagement and reengagement. RESULTS: The interobserver relative difference in plaque area was 2.5%. Limits of agreement for lumen, vessel, and plaque area measurements were 1.62, -2.47 mm(2) ; 2.09, -3.71 mm(2) ; 2.80, -3.72 mm(2) ; respectively. Limits of agreement for fibrotic, lipidic, necrotic, and calcified measurements were 1.32, -1.44 mm(2) ; 0.24, -0.36 mm(2) ; 1.50, -2.26 mm(2) ; 0.09, -0.11 mm(2) ; respectively. The intercatheter and intracatheter relative difference in plaque area were 0.9% and 4.1%, respectively. Although the variability for compositional measurements increased using two different catheters or using the same catheter twice, the variability for compositional measurements keeps always below 10%. CONCLUSIONS: Our analysis demonstrates that the geometrical and compositional iMAP analysis is acceptably reproducible.

Plaque burden is associated with minimal intimal coverage following drug-eluting stent implantation in an adult familial hypercholesterolemia swine model.

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.

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 Detection in Patients Presenting With Non-ST Elevation Acute Coronary Syndrome and Multivessel Disease.

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.

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.

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.

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.

Explanation of Postprocedural Fractional Flow Reserve Below 0.85.

BACKGROUND: Fractional flow reserve (FFR) after percutaneous coronary intervention is a predictor of adverse cardiovascular events during follow-up. However, the rationale for low post procedural FFR values remains often elusive based on angiographic findings alone. METHODS AND RESULTS: FFR SEARCH (Stent Evaluated at Rotterdam Cardiology Hospital) is a prospective single-center registry in which post-percutaneous coronary intervention FFR was assessed in 1000 consecutive all-comer patients. FFR measurements were performed with a microcatheter ±20 mm distal to the most distal stent edge. In 100 vessels with a post procedural FFR ≤0.85, and 20 vessels >0.85 high definition intravascular ultrasound analysis was performed. In 100 vessels with a post-percutaneous coronary intervention FFR ≤0.85, mean post procedural FFR was 0.79±0.05. Minimal lumen area was 2.19 (1.81-3.19) mm2, mean lumen area was 5.95 (5.01-7.03) mm2, and minimal stent area was 4.01 (3.09-5.21) mm2. Significant residual focal proximal lesions were found in 29% of the assessed vessels whereas, focal distal lesions were found in 30% of the vessels. Stent underexpansion and malapposition were found in 74% and 22% of vessels, respectively. Clear focal signs of luminal narrowing were found in 54% of the vessels analyzed. Although incidences of focal lesions, underexpansion, and malapposition were similar between both cohorts, minimal stent area was significantly smaller in vessels with a post-percutaneous coronary intervention FFR ≤0.85 as compared with those with an FFR >0.85. CONCLUSIONS: In patients with a post procedural FFR ≤0.85, intravascular ultrasound revealed focal signs of luminal narrowing in a significant number of cases.

Validation of Resting Diastolic Pressure Ratio Calculated by a Novel Algorithm and Its Correlation With Distal Coronary Artery Pressure to Aortic Pressure, Instantaneous Wave-Free Ratio, and Fractional Flow Reserve.

BACKGROUND: Instantaneous wave-free ratio (iFR) offers a reliable non-hyperemic assessment of coronary physiology but requires dedicated proprietary software with a fully automated algorithm. We hypothesized that dPR (diastolic pressure ratio), calculated with novel universal software, has a strong correlation with iFR, similar diagnostic accuracy relative to resting distal coronary artery pressure/aortic pressure and fractional flow reserve (FFR). METHODS AND RESULTS: The dPR study is an observational, retrospective, single-center cohort study including patients who underwent iFR or FFR. Dedicated software was used to calculate the dPR from Digital Imaging and Communications in Medicine (DICOM) pressure waveforms. The flat period on the pressure difference between sample (dP) to the time difference between the same sample points (dt) signal was used to detect automatically the period, where the resistance is low and constant, and to calculate the dPR, which is an average over 5 consecutive heartbeats. The software was validated by correlating iFR results with dPR. Software validation was done by comparing 78 iFR measurements in 44 patients who underwent iFR. Mean iFR and dPR were 0.91±0.10 and 0.92±0.10, respectively, with a significant linear correlation ( R=0.997; P<0.001). Diagnostic accuracy was tested in 100 patients who underwent FFR. Mean FFR, resting distal coronary artery pressure/aortic pressure, and dPR were 0.85±0.09, 0.94±0.05, and 0.93±0.07, respectively. There was a significant linear correlation between dPR and FFR ( R=0.77; P<0.001). Both distal coronary artery pressure/aortic pressure and dPR had good diagnostic accuracy in the identification of lesions with an FFR ≤0.80 (area under the curve, 0.84; 95% CI, 0.76-0.92 and 0.86; 95% CI, 0.78-0.93, respectively). CONCLUSIONS: dPR, calculated by a novel validated software tool, showed a strong linear correlation with iFR. dPR correlated well with FFR with a good diagnostic accuracy to identify positive FFR.