Core Laboratory Research Articles

Appropriate ischemic criteria for type 4a myocardial infarction: insights from the ALPHEUS trial

Abstract Background Different troponin thresholds have been proposed to define periprocedural myocardial injury based on post percutaneous coronary intervention (PCI) troponin increase only, whereas the definition of type 4a myocardial infarction (MI) needs the association of post procedural troponin and one ischemic criterion. These criteria which evolved from the 3rd to the 4th Universal Definition of Myocardial Infarction (UDMI) are frequently under-reported in studies on periprocedural MI. Purpose We aimed to describe rates of type 4a MI additional diagnostic criteria among the ranges of post PCI troponin elevation in the randomized ALPHEUS trial which compared ticagrelor to clopidogrel in high-risk elective PCI patients. Methods 1698 patients with normal pre-PCI troponin values and centralized core laboratory angiogram analyzes were divided into 4 groups according to maximal post PCI troponin elevations (≤ 1x upper reference limit (URL) for group 1; > 1xURL and ≤ 5xURL for group 2; > 5xURL and < 35xURL for group 3 and ≥ 35xURL for group 4). The type 4a MI additional criteria (ischaemic imaging changes, ischaemic ECG changes, chest pain and angiographic complications) as defined by the 3rd and 4th UDMI were reported and the different angiographic complications were detailed for each group. Results The most prevalent additional ischemic criterion was the presence of angiographic complications detected by the core laboratory. The rate of angiographic complications increased in a stepwise manner with higher post PCI troponin elevation (Figure). Interestingly, we found a similar rate of angiographic complications in patients without any increase in post PCI troponin and troponin elevations below the 5xURL threshold (8.4% and 9.9% respectively). Most angiographic complications were related to transient main branch dissection and/or thrombosis, and transient or permanent side branch occlusions (Table). ECG changes and chest pain ischemic criteria also increased in a stepwise manner and were rarely found below the 5-fold threshold increase, although they might be underreported. Conclusion When using a core laboratory, angiographic complications are found even in patients with no or minor troponin elevation. Above the 5 xURL threshold the rates of angiographic complications are 2 to 3-fold more frequent, and ECG changes and chest pain ischaemic criteria are likely to be present. Our findings support the use of angiographic core laboratory in clinical trial using periprocedural MI as an endpoint; similarly, chest pain -which disappeared from the 4th UDMI- should be reconsidered as a diagnostic ischemic criterion.

Inter-corelab agreement of angiography-derived wall shear stress distribution

Abstract Aims Wall shear stress (WSS) estimated in models reconstructed from intravascular imaging and 3D-quantitative coronary angiography (QCA) data provides important prognostic information and enables the identification of high-risk lesions. However, these analyses are time-consuming and require expertise limiting WSS applications and adoption in clinical practice. Recently, a novel software has been developed for real-time computation of WSS and multidirectional WSS distribution. The aim of this study is to examine its inter-corelab reproducibility. Methods and results Sixty lesions (20 in coronary bifurcations) with a borderline negative fractional flow reserve were selected and processed using the CAAS Workstation WSS prototype (version 6.0 PIE MEDICAL) to estimate WSS and multi-directional WSS. Analysis was performed by two Core laboratories; the estimations of the two corelabs for the WSS in 3 mm segments across each reconstructed vessel were extracted and compared. To examine the concordance between inter-observer analysis of clinically relevant values, the scatterplot was divided into 4 quadrants with AS 61.3% and maximum WSS 8.24 Pa based on the previous publications and Cohen’s Kappa value was presented using these cut-off values. In total 700 segments (256 located in bifurcated vessels) were included in the present analysis. Average analysis time on the software was 219±45s in straight model and 291±61s in bifurcation model. A high intraclass correlation was noted for all the WSS metrics for the estimations of the two core labs irrespective of the presence (range: 0.90 – 0.92) or absence (range: 0.89 - 0.90) of a coronary bifurcation, while the ICC was good-moderate for the multidirectional WSS (range: 0.72-0.86). In addition, the bias between the WSS estimations was low and the limits of agreement were narrow in Bland-Altman analyses (Figure 1). When using the cut-off value of maximum WSS and % AS, a substantial agreement was noted between the two estimations of the two core labs; κ=0.77 for identifying maximum WSS >8.24Pa and κ=0.71 for identifying AS >61.3% (Figure 2). Conclusion The CAAS workstation enables reproducible 3D-QCA reconstruction and computation of WSS metrics. Further research is needed to explore its efficacy in predicting cardiovascular events.Figure 1Figure 2

No difference on angiographic features between women and men in patients with acute coronary syndrome: insights from the ADDICT-ICCU study

Abstract Background Previous studies have observed poorer outcomes in women with acute coronary syndrome (ACS). Angiographic features and angioplasty techniques to explain this difference between women and men have rarely been analyzed in recent studies. Purpose To analyze by a core laboratory angiographic finding, coronary artery disease (CAD) complexity and percutaneous intervention outcomes in women and men in patients with ACS. Methods From April 7 to 22, 2021, the Addiction in Intensive Cardiac Care Unit (ADDICT-ICCU) study included prospectively 1575 patients admitted to ICCUs with a systematic urine multidrug test in 39 ICCUs across France. This prespecified study focuses on patients admitted for ACS (n=379) with an independent angiographic core laboratory evaluation. The prevalence, location, and severity of CAD (lesion≥50%), the Syntax score, the residual Syntax score and the characteristics of percutaneous coronary intervention (PCI) were compared between women and men. The primary endpoint was Major Adverse Cardiac Events (MACE) defined by death, resuscitated cardiac arrest, or cardiogenic shock. Results Among the 379 patients with ACS (mean age: 63±13 years), 23% were women (n= 86) and 77% were men (n=286). Cardiovascular risk factors and CAD history were well balanced between women and men except for active smoking with less smokers in women (59% vs 81%, p<0.001). Regarding location of CAD (stenosis ≥50%), there was no significant difference between women and men: left anterior descending artery (56% vs 57%; p=0.90), circumflex (28% vs 39%; p=0.12) and right coronary artery (50% vs 48%; p=0.81). No difference was found for baseline Syntax score (7.98 vs 9.64; p=0.13). Women and men have a similar rate of multivessels disease (44% vs 50%; p=0.46) and 3 vessels disease (16% vs 20%; p=0.57). Concerning PCI, Syntax score of the culprit lesion was significantly lower in women (4.5 vs 5.5, p=0.02). Women and men received a similar number of stents (2.3 vs 2.4; p=0.33). Stent length (28.9 vs. 30.3, p=0.43) or stent diameter (3.1 vs 3.2; p= 0.11) were not significantly different. Final TIMI 3 flow was found in 92.9% of women and 88.1% of men (p=0.23). The rate of procedural complications was low in both groups. At the end of the procedure, the residual Syntax score was similar in women and men (4.4 vs 5.4; p= 0.34). The rate of in-hospital MACE was not different between women and men (4.7% vs 4.4%; p=0.91). Conclusion In this study with an independent angiographic core laboratory analysis of ACS patients, no difference between women and men regarding CAD severity or PCI outcomes was observed. Other reasons should be considered if a difference in prognosis exists between women and men.Angiographic features in Women and menAngiographic analysis by Core Laboratory

GDF-15 adds to GRACE 2.0 for long-term risk prediction in ACS but echocardiographic parameters do not: A SWEDEHEART prognostication study

Abstract Background The risk stratification score GRACE 2.0 has lately been validated to predict all-cause death up to three years after acute coronary syndrome (ACS). GRACE 2.0 does not take important prognostic biomarkers and imaging measurements that may improve long-term risk prediction in to account. This study set out to evaluate the clinical value of such parameters analyzed on top of GRACE 2.0. Methods The study was performed in a subset of 773 patients from the TOTAL-AMI cohort with ACS subjects recruited from three Swedish hospitals between 2008 and 2014. Biomarkers were analyzed with a Proximity Extension Assay panel and the echocardiographic parameters, Left Ventricular Ejection Fraction (LVEF) and Global Longitudinal Strain (GLS), were assessed at a core lab. LVEF, GLS and two high yield biomarkers (NTproBNP and GDF-15) were analyzed with Cox proportional hazards regression by stepwise addition of each variable to a baseline model with GRACE 2.0. The C-index was assessed for each model. All models were adjusted for treatment with betablockers and/or RAAS-inhibitors. Outcome was all-cause death at three years. Results Forty-one patients had died at three years follow-up. The mean population age was 64 years and 77% were men. Median LVEF was 55 % (inter quartile range: 47-60). LVEF, GLS and GDF-15 all emerged as independent predictors of three-year death in the multivariable models with GRACE 2.0 and medical treatment. Only GDF-15 rendered substantial improvement in the C-index on top of GRACE 2.0 (0.755 to 0.810). The echocardiographic measurements did not improve prognostication on top of GRACE 2.0 and GDF-15. Conclusions GRACE 2.0 emerged as a strong long-term risk-predictor irrespective of the biomarkers and imaging measurements. Although LVEF, GLS and GDF-15 also emerged as independent predictors of three-year death only GDF-15 improved the C-index to an extent that may be considered clinically meaningful.

Core laboratory comparative assessment of angiography-derived index of microvascular resistance (IMR) in patients with wire-based IMR

Abstract Background Coronary microvascular disease (CMD) is responsible for nearly half of angina in the general population. The index of microvascular resistance (IMR) is the gold standard for the diagnosis of CMD. Abnormal IMR is independently associated with adverse outcomes and persistent angina after percutaneous coronary intervention (PCI) regardless of the achieved fractional flow reserve (FFR). However, the implementation of IMR in clinical practice is low due to cost and the need for hyperemia. Thus, multiple software and formulas have been developed to calculate wireless IMR via angiography analysis. However, these angiography-derived IMRs have never been compared head-to-head by an independent core laboratory. Aim In this study, we aim to investigate the diagnostic accuracies of five angiography-derived IMR software/formulas by an independent core lab in a retrospective cohort undergoing follow-up angiograms after successful PCI. Methods We analyzed 43 patients from the FUNCOMBO trial and 34 patients from the RETROFI II trial. All patients have received successful PCI for STEMI, and wire-based IMR was measured at six months (for FUNCOMBO) and three years follow-up (for RETROFI II). Angiography-derived IMR was calculated with the QFR®2.1 software, the Flashangio CaIMR® software, and the AngioPlus software. In addition, using QFR-derived data, we calculated the angio-IMR using the formula of Escaned et al. [angio-IMR = (Pa–[0.1*Pa])*QFR*e-Tmn (where e-Tmn is an estimation of hyperaemic mean transit time)] and Scarsini et al. [NH-IMRangio=Pa(resting)x QFR x N frame(resting)/frame per second]. The threshold of CMD diagnosis is 25 for all five angiography-derived IMR methods. The correlation and agreement of the five methods were evaluated against wire-based IMR measurement. Results The wire-based IMR was significantly correlated with Medis IMR (r= 0.396, p=0.001) and NH-IMRangio (r=0.378, p=0.001). The agreements between IMR and the angiography-derived IMRs are demonstrated in figure 1. The sensitivity, specificity, positive predicted value, negative predicted value, and accuracy were demonstrated in figure 2, which showed that using the published criteria, the accuracy of diagnosis was 52%, 68%, 67%, 68%, and 49% for Medis IMR, CaIMR, AngioPlus IMR, angio-IMR, and NH-IMRangio, respectively. Comparison of all angiography-derived IMR with wire-based IMR yielded the AUC’s of 0.648, 0.561, 0.606, 0.674, 0.688 for Medis IMR, CaIMR, AngioPlus IMR, angio-IMR, and NH-IMRangio respectively. (Figure 2.) Conclusion In this small validation cohort, we found that all five angiography-derived IMR calculation methods had either poor or very poor diagnostic accuracy. Among the five methods, the Medis IMR, Angio-IMR, and NH-IMRangio may be viable options for wireless CMD diagnosis.Figure 1Figure 2

CAD-RADS score, vascular inflammation, and plaque vulnerability

Abstract Background Coronary artery disease reporting and data system (CAD-RADS), which is widely used to report the severity of coronary artery disease on coronary computed tomography angiography (CTA), predicts the risk of future cardiovascular events. However, the relationship between the CAD-RADS score and vascular inflammation and plaque vulnerability has not been investigated. Objective The aim of this study was to correlate the CAD-RADS score with vascular inflammation and plaque vulnerability. Methods This is an observational, single-center cohort study with prospective clinical follow-up. Patients who underwent both coronary CTA and optical coherence tomography (OCT) before coronary intervention were enrolled. All OCT and CTA images were analyzed at the core laboratory. Patients were categorized into two groups according to the CAD-RADS score (≤4a or 4b/5). All coronary arteries were analyzed for high-risk plaque features (positive remodeling, low-attenuation plaque, napkin-ring sign, and spotty calcification) and peri-coronary adipose tissue (PCAT) attenuation. PCAT attenuation was measured around the culprit lesion and in the proximal segment of all 3 coronary arteries. OCT features of plaque vulnerability were evaluated in culprit vessels. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as composite endpoints of unplanned target vessel revascularization, unplanned non-target vessel revascularization, nonfatal acute coronary syndrome, stroke, and cardiac death. Results Among 369 patients with 902 lesions, 104 (28.2%) were categorized in CAD-RADS 4b/5 and 265 (61.8%) in CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had higher PCAT attenuation than those with CAD-RADS ≤4a at all three levels (mean of 3 coronary vessels: -67.9 ± 6.9 HU vs. -70.2 ± 6.5, P=0.004; culprit vessel: -67.4 ± 7.9 vs. -70.2 ± 7.6, P=0.004; culprit plaque: -67.0 ± 9.3 vs. -69.9 ± 10.5, P=0.009; respectively) (Figure 1 A). Lipid-rich plaque and macrophage, as detected by OCT, were more prevalent in the culprit vessel in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (89.0% vs. 78.5%, P=0.001; 76.6% vs. 64.9%, P=0.001; respectively) (Figure 1B). All HRP features, as detected by CTA, were more frequently observed in patients with CAD-RADS 4b/5 than those with CAD-RADS ≤4a (P for all <0.001) (Figure 2). The cumulative incidence of MACCE was higher in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (15.0% vs. 5.8%, P=0.045). Conclusions Higher CAD-RADS score was associated with a higher level of pan-coronary vascular inflammation and plaque vulnerability.Figure 1Figure 2

Ticagrelor or Clopidogrel to reduce ischemic events after Percutaneous Coronary Intervention in chronic coronary syndrome in clopidogrel naive patient: the ALPHEUS Naive sub-study

Abstract Background The ALPHEUS trial showed a similar rate of type 4 myocardial infarction (MI) or major myocardial injury in elective PCI treated by clopidogrel or ticagrelor. Whether clopidogrel therapy at baseline might have affected these results is unknown. Purpose We evaluated the impact of ticagrelor versus clopidogrel loading dose in clopidogrel naïve patients as compared to patients already treated by clopidogrel in this pre-specified analysis. Methods We divided 1882 randomized patients with complete data on baseline clopidogrel into 2 groups according to presence of clopidogrel therapy > 7 days (long term clopidogrel = Clopi+) or its absence (clopidogrel naïve = Clopi-). The primary endpoint was the rate of PCI-related MI and myocardial injury as defined by the 3rd and 4th universal definition of MI evaluated within 48 h of PCI (or hospital discharge if earlier) and major and minor bleeding. Angiographic complications evaluated by the core laboratory (coronary slow flow, no flow, dissection, and thrombus) were also compared. Event rates were compared and the interaction of the allocated treatment in the randomized groups was evaluated. Results 1077 patients (57.2%) were Clopi- and 805 patients were Clopi+. Patients in the Clopi- group were less frequently male (78.0% vs 81.9%, p= 0.04) with less often dyslipidemia (57.8% vs 65.6%, p< 0.001) and peripheral artery disease (11.1% vs 14.4%, p= 0.03) and had less acute coronary syndrome in the last 12 months (3.4% vs 8.7% p= 0.002). The primary endpoint was less frequent in Clopi- as compared to tClopi+ (32.8% vs 40%, OR =0.73, CI [0.60-0.88], p=0.001). This difference was mainly driven by a lower rate of major myocardial injury 24.% vs 31.6% while the rate of type 4a MI and stent thrombosis were similar (8.4% vs 8.2%) and (0.4% vs 0.2%) respectively. Angiographic complication rate was similar in the Clopi- and the Clopi+ groups (14.6% vs 12.9%) OR=1.15 CI [0.88-1.5], p=0.31. Major bleedings were infrequent in the trial. (0.1% vs 0%), and minor bleeding did not differ significantly between Clopi- and Clopi+ patients (7.0% vs 4.8% OR=1.47, CI [0.99-2.19], p=0.06). At 30 days, no difference in any outcomes were reported between the two groups. Alike for the main trial results, in the Clopi- group, ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis, p for interaction was 0.83. Conclusions Periprocedural MI and procedural angiographic complications were less frequent in clopidogrel naïve patients as compared to patients already on clopidogrel therapy, and not influenced by the potency of the P2Y12 inhibitor’s loading dose prior to PCI. These results globally suggest no benefit of a long term clopidogrel pretreatment in patients receiving a loading dose of P2Y12 in the 24 hours prior to PCI in chronic coronary syndrome undergoing elective PCI and support the use of clopidogrel as the standard of care.

Feasibility and accuracy of real-time 3D-holographic graft length measurement, a sub-study of the FAST-TRACK CABG trial

Abstract Background 3D Hologram is an emerging tool for intuitively manipulating and visualizing CT images. Mixed reality (MR) technology can display high-definition 3D holograms while preserving situational awareness. The new MR software offers the possibility to measure 3D objects using hand gestures and voice commands. However, these measurements made on 3D holograms have not been validated. Purpose We aimed to assess the feasibility and accuracy of using CT-derived 3D holograms for bypass graft length measurement. Methods Twenty-seven consecutive cases in the FAST TRACK CABG trial were included. The post-operative CT images performed at 30 days follow-up were analyzed in an independent core lab. Two analysts blinded to clinical information performed Holographic reconstruction and measurement using the CanaLife Holo software (Medapp, Krakow, Poland). (Figure 1) Inter-observer agreement was assessed in the first 20 cases. Another analyst with full access to clinical information performed the validation measurements on the CardIQ W8 system (GE Healthcare, Milwaukee, Wisconsin). (Figure 1) Results A total of 62 grafts (27 left internal mammary artery grafts, 27 saphenous vein grafts, and 8 right internal mammary artery grafts) were measured. There was an excellent inter-observer agreement between the analysts in the first 47 grafts analyzed (interclass correlation 0.9879 [0.9783-0.9933]). (Figure 2A, 2B) On average, holographic reconstruction and measurement of a case took 3 minutes and 36 seconds± 50.74 seconds compared to around 10 minutes per vessel on the traditional CT system. There was no significant difference between the graft length measured by hologram and CT (188.59±51.63 mm vs. 183.95±50.93 mm, p=0.616). The length measured by hologram and CT were similar across different graft types. The measurements of hologram and CT are highly correlated (r=0.973, p <0.001) with an excellent agreement (interclass correlation 0.9928 [0.9880-0.9957]). (Figure2C, 2D) Conclusion Holographic vessel length measurement is feasible, fast, and accurate even for tortuous coronary bypass grafts. This new methodology can empower surgeons to visualize and measure the results of their work by themselves and may provide insights for procedure evaluation. 3D Holograms can eventually empower surgeons to plan the precise length of the arterial and venous grafts to be harvested for every individual case.

Female gender is an independent predictor of clinical benefit from cardiac resynchronisation therapy - results from the BIOWOMEN study

Abstract Background Presently, only indirect evidence indicates that women may benefit more from CRT than men. Since some gender-specific baseline variables are related to CRT benefit, it is unclear whether gender by itself is predictive of CRT benefit after correction for all these differences. We aimed to examine the impact of gender-specific differences on CRT response. Methods The BIOWOMEN study is a prospective, multicenter, international study, that enrolled 206 women and 214 men with a standard indication for CRT. The change in left-ventricular ejection fraction (LVEF) at 12 months follow-up after CRT was used as a primary endpoint to measure CRT benefit. The LVEF was quantified by a core lab blinded to gender and other patient characteristics. We used a median split to dichotomize continuous variables, if required. Uni- and multivariate analyses were used to identify baseline variables that are connected to an increase in LVEF. The latter model allows to estimate the change in LVEF that can be attributed to gender and other baseline variables. Results At baseline, women and men had similar LVEF, age and QRS duration, but there was a significant difference in the presence of left bundle branch block (88.3% vs. 79.9%, P=0.023). Women had less often ischemic heart disease (18.4% vs. 51.4%, P<0.001) and previous history of myocardial infarction (MI, 6.8% vs. 32.2%, P<0.001), but more severe heart failure symptoms (NYHA I/II/III 7%/51%/42% vs. 10%/63%/27%, P=0.019) and a shorter 6 minute walk test (345±117 vs. 409±148 m, P<0.001). In univariate analysis, women presented a significantly larger gain of 3.1 points in LVEF (+14.6±12.4% vs. +11.5±11.6%, P=0.004) compared to men. Additionally, the rate of CRT responders (defined as an improvement in LVEF >5%) was higher in women (82.0% vs. 70.6%, p=0.008). Other variables predictive of larger improvement in LVEF were LBBB (13.9±11.9% vs. 8.4±12.2%, P<0.001), NYHA I compared to NYHA II or III (I: 18.4±11.8%; II: 12.2±12.0%; III: 13.1±12.0%), no history of MI (14.0±11.6% vs. 8.9±13.0%, P<0.001), and an LVEF <32% at baseline (16.9±11.8% vs. 9.7±11.3%, P< 0.001). In multivariate analysis, female gender remained a significant predictor of a better improvement in LVEF (+2.6% absolute, P=0.036). Other significant predictors were LBBB (+5.2%, P<0.001), NYHA I (+6.9%, P<0.001 vs. NYHA II and +6.3%, P=0.004 vs. NYHA III), no history of MI (+4.1%, P=0.007), baseline LVEF <32% (+7.5%, P<0.001). Conclusion Gender has an important impact on the relevant baseline clinical differences that determine CRT response. Whereas women more often have LBBB and no prior-MI, suggesting more benefit from CRT, the BIOWOMEN study shows for the first time that female gender itself is linked to a larger clinical benefit from CRT. These gender-based baseline parameters need to be considered in daily clinical practice when screening patients for CRT, with particular attention to females.

3-dimensional ct versus angiography guided pci for ostial rca lesions

Abstract Background Geographical stent-ostium mismatch is an important predictor of target lesion failure (TLF) after PCI of an aorto-ostial right coronary artery (RCA) lesion. Purpose We hypothesize that a pre-procedural 3-dimensional coronary CT angiography (3DCT) to determine the optimal C-arm angle of the X-ray system with the most accurate visualization of the aorto-ostial angle could allow optimal stent implantation at the level of the ostium and avoid excessive use of radiation and contrast. Methods This is a single centre trial randomizing 30 patients with an indication for non-emergent PCI of an ostial RCA lesion between 3DCT (intervention group) versus angiography guided strategy (control group). While in the control group the C-arm angle was at the operators’ discretion, in the intervention group the angle was determined based on a pre-PCI CT scan with 3D reconstruction using Materialise Mimics Innovation Suite software. A pre- and post-PCI IVUS is performed in all patients and analyzed by a blinded core lab. The primary endpoint is absence of geographical mismatch on IVUS defined as full stent coverage of the ostium and maximal aortic protrusion equal or less than 3mm. Secondary, we also aim to investigate whether a pre-procedural 3DCT may reduce procedural radiation, contrast use, may predict IVUS parameters (minimal luminal area (MLA), calcification), stent sizing and may promote stent expansion. Finally, MACE rate is evaluated at 1 month. Results The full patient dataset (n=30) including primary and all secondary endpoints will be available for presentation at the ESC congress. Currently, 27 patients were randomized. An interim analysis shows the following findings. There is significant patient heterogeneity considering the optimal angle for stent implantation, underscoring the potential benefit for individualized pre-procedural CT planning. In general, more extreme LAO angles were used in patients randomized to the intervention group (picture 1). While the stent was implanted in optimal position in 13/13 (100%) patients randomized to the intervention group, geographical stent mismatch was present in 5/14 (36%) patients randomized to the control group (interim p-value 0.07) (picture 2). The number of cine acquisitions performed before stent implantation (1±1.87 vs. 3.5±0.60; p=0.0007), the amount of contrast used (60±24.5 vs. 114±37.8 mL; p=0.0002), radiation dose (209 [186,315] vs. 497 [411,678] mGy; p=0.01) and procedure time (30 [20,38] vs. 50 [39,66] min; p=0.005) were significantly lower in patients randomized to the intervention group. There was a highly significant correlation between the calcium arc determined by CT and IVUS (R² = 0.84). No MACE occurred at 1 month. Conclusion We showed that pre-procedural CT planning for PCI of aorto-ostial RCA lesions allowed for optimal stent positioning while reducing procedure time, contrast and radiation use.Picture 1Picture 2

Hemodynamic assessment of pci using ultrasonic flow ratio in multivessel cad

Abstract Background Ultrasonic flow ratio (UFR) is a novel method for fast computation of fractional flow reserve (FFR) from intravascular ultrasound. Recently studies have shown the feasibility of morphofunctional computational methods to reliably estimate coronary physiology stemming from intravascular ultrasound images. Purpose The objective of the study was to evaluate the reasons for suboptimal physiological results after PCI using the UFR. Methods The study population comprised 150 consecutive patients (283 vessels) who underwent intravascular ultrasound for optimization of PCI in three-vessel-disease as mandated in the ongoing MULTIVESSEL TALENT trial (NCT04390672). The UFR analysis of final IVUS pullback was performed at the CORRIB Core Lab by an analyst who was blinded to the clinical data using a prototype software package (IvusPlus prototype, Shanghai Pulse Medical, Shanghai, China). Suboptimal physiological results were defined as post PCI UFR value of <0.91. UFR drop of ≥0.05 (gradient) was taken as a significant drop either intra or outside of the stent. Based on the definition of the HAWKEYE study, Focal lesions were defined as UFR drop of ≥0.05 in 10mm, diffuse lesions were defined as progressive decline of UFR of ≥0.05 without any clear evidence of focal drop, and mixed lesions were defined as the combination of focal and diffuse lesions. Results The median UFR with IQR among 283 vessels was 0.94 (0.91-0.97). Sixty-four (22.61%) of the 283 vessels had a UFR less than 0.91. We measured gradients using the UFR pull back curve intra-stent and outside of stent (Figure 1) in vessels with UFR <0.91. Significant "intra stent gradient", "out of stent gradient", combined "intra stent "and "out of stent" gradients were seen in 28 (44%), 18 (28%), and 10 (16%) vessels respectively. No clearly defined gradients were found in 8 (12%) vessels. Out of the 28 "out of stent" gradients, 20 were diffuse lesions, 5 were focal lesions and 3 was a mixed lesion. Conclusion IVUS has been widely used in optimization of PCI especially in scenarios with complex multi vessel disease. Combination of IVUS and FFR enable the operator to conform to the highest standards in PCI. This study has demonstrated that using UFR it is possible to identify the cause(s) of suboptimal PCI results and thereby to further optimize PCI results.

Minimum stent area, stent expansion and ultrasonic flow ratio post pci: insights from multivessel talent trial

Abstract Background Ultrasonic flow ratio (UFR) is a novel method for fast computation of fractional flow reserve (FFR) from intravascular ultrasound. Recently studies have shown the feasibility of morphofunctional computational methods to reliably estimate coronary physiology from intravascular ultrasound images. Purpose To assess minimum stent area and stent expansion and its relation to ultrasonic flow ratio post percutaneous coronary intervention. Methods The study population consisted of 150 consecutive patients (280 vessels) who underwent intravascular ultrasound for optimization of PCI for three vessel disease as mandated in the ongoing MULTIVESSEL TALENT trial (NCT04390672). The UFR analysis was performed at the CORRIB Core Lab by an analyst who was blinded to the clinical data using a prototype software package (IvusPlus prototype, Pulse Medical Imaging Technology, Shanghai, China). The stent expansion and minimum stent area was automatically detected by the software. Results The median and mean UFR of 280 vessels post-PCI was 0.94 (0.91-0.97).and 0.93±0.04, respectively. Twenty three percent (n=115) of the 280 vessels had a UFR less than 0.91.The average minimum stent area (MSA) among the population was 5.82 ± 1.95 mm2. The mean stent expansion among the population was 97% ± 22%. We compared the site reported MSA with the software derived MSA which showed strong correlation (r=0.859; P<0.001). There was no correlation between MSA and UFR (r= -0.13, P=0.81). The stent expansion among patients who had UFR <0.91 when compared to ≥0.91 was significantly lower (82% vs 98%, P<0.001). The delta UFR within the stent was significantly higher in patients who had a UFR<0.94 vs ≥0.94 (0.06 vs 0.02; P<0.01). Delta UFR within the stent was higher when the stent expansion was <80% and <90% when compared to >80% and >90% (0.07 vs 0.03; P<0.01) and (0.06 vs 0.02; P<0.01) respectively. Conclusion Combination of IVUS and FFR enables the operator to conform to highest standards in PCI. This study demonstrates that UFR is not related to the minimum stent area, and patients who have UFR <0.94 have sub-optimal stent expansion.MSA and UFRUFR and Stent expansion

Activation time at left ventricular pacing site (QLV) in relation to actual site of latest activation; effect on response to cardiac resynchronization therapy

Abstract Background Among techniques to improve CRT efficacy, longer QLV (activation time at the left ventricular (LV) pacing site (LVPS)) has been proposed to correlate to response to cardiac resynchronization therapy (CRT), supporting that pacing close to the latest LV electrically activated site (LEAS) improves CRT efficacy. A QLV cut-off of > 95 ms has been proposed, however, predictive value was modest. This may be because LEAS was not identified, and empirically delivered leads may have missed it (described by a longer interval QLEAS (activation time at LEAS) to QLV. Purpose We compared QLEAS to QLV, and assessed effect of the interval QLEAS-QLV, on response to CRT. Methods We studied patients who had received CRT for Class I or Class IIa indications, regardless of CRT response, at 5 European sites. LV lead placement, device programming and follow up (FU) followed physician preference and site protocol. All patients had clinical FU 6-12 months post-implant, including echocardiographic study. CRT non-response was defined as LV end-systolic volume (LVESV) reduction of <15%. Patients underwent noninvasive 3D electrical activation mapping and torso CT 6-24 months post-implant. QLV and QLEAS were assessed from the noninvasive activation map in a blinded core lab. Logistic regression modelling was conducted for QLV and the interval QLEAS-QLV against CRT response, and the optimal cut-off points were calculated. Results Of 111 patients (age 64±11 years (mean±SD), 74% male, 98% LBBB, QRS duration 172±21 ms, baseline LVEF 28±6%, LVESV 183±87 mL, implant duration 12±5 months, 31%/69% NYHA Class II/III, 38% ischemic heart disease), 67% responded at 10±3 months post-implant. QLV overall was 97±23 ms (range 42-148 ms), 103±21 ms for responders and 83±22 for non- responders (p<0.001), QLEAS was 109±19 ms (range 66-150 ms), 109±20 ms for responders and 110±19 ms for non- responders (p=0.74). QLEAS-QLV overall was 13±18 ms (range 0-120 ms), 6±10 ms for responders and 27±22 ms for non-responders (p<0.001) (Figure 1). Optimal cut-off point for QLV was 85 ms with sensitivity 0.89, specificity 0.57 and an AUC of 0.742 (95% CI: 0.637- 0.846). Optimal cut-off point for QLEAS-QLV was 6 ms (sensitivity 0.77, specificity 0.95, AUC 0.901 (95% CI: 0.844-0.957) (Figure 1). The AUC of QLV cut-off and QLEAS-QLV cut-off differed significantly (p<0.001). 18/111 patients (16%) were non-responders despite a QLV≥85 ms, whereas 2 patients (2%) were non-responders despite a QLEAS-QLV≤6 ms. Conclusion QLEAS has greater discriminatory power than a QLV cut-off of 85 ms to separate CRT responders from non-responders in patients with LBBB and long QRS duration. QLV guided LV lead placement without prior knowledge of the latest LV activation in individual patients will miss the ideal LV pacing site in 16% of cases. Using noninvasive 3D global mapping to identify LEAS pre-CRT implant and directing LV lead placement to within 6 ms of this may improve CRT efficacy.Figure 1

The integration of angio-IMR, QFR and FFR for the detection of ischemia

Abstract Background Fractional flow reserve (FFR) and quantitative flow ratio (QFR) are important tools to assess coronary-specific ischemia, but ischemia may be obscured in the presence of coronary microvascular dysfunction (CMD). Wire free angiography based index of microcirculatory resistance (angio-IMR) might aid in identifying ischemic territories with normal FFR or QFR. Purpose First we sought to validate angio-IMR against invasive resistance indices and [15O]H2O positron emission tomography (PET) derived resistance. Secondly, we investigated whether angio-IMR can help identifying ischemic vessels with normal FFR/QFR. Methods In this PACIFIC 1 and 2 sub study symptomatic patients underwent [15O]H2O PET and invasive coronary angiography with routine three vessel FFR. Invasive hyperemic microvascular resistance (HMR) and IMR were measured in a sub set of patients. A FFR/QFR ≤0.80 and hyperemic myocardial blood flow (hMBF) ≤2.3 ml/min/g were considered ischemic. Microvascular resistance on PET was defined as the ratio of mean distal coronary pressure to MBF. Angio-IMR, QFR and PET analyses were performed by core labs blinded to invasive angiography results. Results Among 259 patients (mean age 61 ± 9 years, 188 (73%) male) 494 vessels were included. Invasive IMR and or HMR were measured in 95 vessels. Angio-IMR did not correlate with invasive HMR/IMR for the right coronary artery (RCA) but correlated weakly with invasive HMR (r=0.39, p=0.03) and moderately (r=0.48, p<0.01) with invasive IMR for the left coronary artery (LCA). The RCA was excluded for further analysis. A very weak correlation between angio-IMR and PET resistance was observed (r=0.17, p<0.01). Territories with ischemia and a normal FFR showed a higher angio-IMR than ischemic territories with reduced FFR (31.3 ± 13.8 vs 22.2 ± 10.3, p<0.01). The same was observed after stratification by QFR/PET results (34.3 ± 15.5 vs 23.9 ± 9.9, p<0.01). Results remained consistent after stratification for diameter stenosis percentage. Conclusions A weak to moderate correlation was found between angio-IMR and invasive resistance indices for the LCA. In territories with an ischemic perfusion angio-IMR was higher in those with a normal FFR/QFR compared to patients with a reduced FFR/QFR. Integration of FFR/QFR and angio-IMR might lead to superior vessel-specific ischemia detection.

Echocardiographic characterization of patients with supranormal ejection fraction: pooled core laboratory analysis of the TOPCAT and PARAGON-HF trials

Abstract Background Patients with heart failure and supranormal ejection fraction (HFsnEF) may be phenotypically distinct from those with normal or below normal left ventricular ejection fraction (LVEF), and may demonstrate different prognostic trajectories or treatment responses. Purpose To characterize clinical features, cardiac structure and function among patients with HF with preserved EF (defined as 45% ≤ LVEF ≤ 65%) and supranormal EF (defined as LVEF>65%). Methods Baseline clinical characteristics and key echocardiographic parameters from patients enrolled in the echocardiographic substudies of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)-Americas and PARAGON-HF (Prospective Comparison of ARNI [angiotensin receptor–neprilysin inhibitor] with ARB [angiotensin-receptor blocker] Global Outcomes in Heart Failure with Preserved Ejection Fraction) were compared between patients with and without HFsnEF. Results Among 1,751 participants (mean age 73 years old, 51% women) in this pooled core laboratory analysis, 265 (15%) had HFsnEF. Participants in HFsnEF group were more likely to be women, and less likely to have prior myocardial infarction and atrial fibrillation (Table 1). Compared with those with LVEF ≤ 65%, those with LVEF > 65% had lower LV end-diastolic and end-systolic volume indices, lower LV mass index, higher LV relative wall thickness, and higher right ventricular fractional area change. LV geometry and measures of LV diastolic function were similar in both groups (Table 1). Global longitudinal strain (GLS) was abnormal (absolute GLS <16%) in 28% in those with HFsnEF compared with 53% in those with LVEF ≤ 65%. After adjusting for baseline LV ejection fraction and sex, and stratified by trial, abnormal GLS was associated with a higher risk of composite of first heart failure hospitalization or cardiovascular death (overall hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.23 – 1.98, P < 0.001), cardiovascular death (overall HR 2.06, 95% CI 1.35 – 3.13, P = 0.001), and heart failure hospitalization (overall HR 1.49, 95% CI 1.15 – 1.93, P = 0.003) in both HFsnEF and non-HFsnEF groups (P-interaction > 0.05 for all, Figure 1). Conclusions Among participants in the TOPCAT-Americas and PARAGON-HF trials, those with LVEF > 65% were predominantly women, had less LV remodeling, and had better RV function based on echocardiographic measures. Nevertheless, despite supranormal LVEF, GLS was abnormal in over a quarter of patients and remained an important predictor of adverse clinical outcomes in this cohort.Table 1Figure 1

The second phase-3 multi-center trial of flurpiridaz F-18 PET myocardial perfusion imaging for coronary artery disease evaluation

Abstract Background/Introduction Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. Purpose To further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as >50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET vs. Tc-99m SPECT in the detection of CAD in all patients and in the clinically important subgroups of women, obese [body mass index (BMI) ≥30 kg/m2], and diabetics. Also, PET and Tc-99m SPECT were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET was also evaluated. Methods 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert blinded to clinical and image data. Results 578 patients (age, 63.7±9.5 years) were evaluable. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. The secondary endpoints were also met in the overall population, in women, in obese patients, and in diabetics. Flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p<0.0001), in women (0.84 vs 0.70, p<0.01), and in obese patients (0.79 vs 0.67, p<0.001), but not in diabetics (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p<0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p<0.0001), pharmacological stress images (96% vs 78%, p<0.0001), and treadmill exercise images (97% vs 87%, p<0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT. Conclusion This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI≥30.

Anonymous comparative assessment by an academic core laboratory of four angiography-derived fractional flow ratio software in patients with pressure derived iFR and FFR

Abstract Background/Introduction Functional assessment of coronary artery stenoses plays an important role in guiding the clinical management of patients with ischemic heart disease. Software to compute angiography-derived fractional flow ratio (angio-FFR) have been validated against pressure-wire-derived FFR (PW-FFR) with an area under the receiver operator characteristic curve (AUC) of 0.93-0.97. However, it is unknown whether commercially available angio-FFR software are equally reliable, and to what extent each might over- or under-estimate the true functional severity of a coronary artery lesion. Purpose The aim of this study was to investigate the diagnostic accuracies of five angio-FFR software/methods by an independent core-lab in a prospective cohort of 390 vessels with carefully documented sites of PW instantaneous-wave-free ratio (PW-iFR) and PW-FFR. Methods One "matcher investigator (MI)" colocalized on angiography the sites of PW measurement with angio-FFR measurements and provided the same two optimal angiographic views and frame selection to independent analysts, who were blinded to invasive physiological results and results from other software. Results are anonymized and randomly presented. The AUC of each angio-FFR was compared with 2D-quantative coronary angiography percent diameter stenosis (2D-QCA%DS) using a 2-tailed paired comparison of ROC (DeLong’s method). Results All 5 software/methods yielded a high proportion of analysable vessels (A:100%, B:100%, C:92.1%, D:99.5%, E:92.1%). The AUC’s for predicting an FFR≤0.8 for software A, B, C, D, E, and 2D-QCA%DS were 0.75, 0.74, 0.74, 0.73, 0.73, and 0.65, respectively (Figure A). The AUC for each angio-FFR was significantly greater than that for 2D-QCA%DS. Furthermore, binary logistic regression analyses showed the predictors of false positives and false negative: severity of lesion stenosis, lesion location, microvascular resistance, and intermediate zone of angiography-derived FFR potentially reduce the diagnostic accuracy (Figure B). Conclusions This head-to-head comparison by an independent core-lab demonstrated that the diagnostic accuracy of various angio-FFR software for predicting a PW-FFR≤0.80 was useful, with a higher discrimination compared to 2D-QCA%DS, however it didn’t reach the diagnostic accuracy (AUC≥0.90) previously reported in validation studies of various vendors. The intrinsic clinical value of "angiography-derived FFR" therefore requires confirmation in large clinical trials.Figure AFigure B

Angiography-derived radial wall strain as a predictor of myocardial ischemia, high-risk plaque, and outcomes

Abstract Background Angiography-derived radial wall strain (RWS) is a novel method to assess the biomechanical characteristics of the underlying plaque. There is limited data regarding how the biomechanical attributes of atherosclerotic lesions relate to their physiologic and morphological attributes. Purpose This study aimed to investigate the association of RWS with myocardial ischemia and high-risk plaque, and their prognostic implication. Methods From the international CCTA-FFR registry, 484 deferred vessels underwent RWS analysis. Angiography-derived RWS was defined as relative changes of lumen diameter within the cardiac cycle, expressed as a percentage of the largest lumen diameter. Plaque characteristics were assessed in a coronary CT angiography core laboratory and high-risk plaque was defined as 3 or more high-risk plaque characteristics (HRPC) including minimum lumen area <4.0 mm2, plaque burden ≥70%, low-attenuation plaque, and positive remodeling. Functional significance of coronary lesion was assessed by invasively measured fractional flow reserve (FFR). The primary outcome was vessel-oriented composite outcome (VOCO), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization at 5 years. All clinical outcomes were adjudicated by an independent clinical event committee. Results The mean FFR was 0.89±0.07, and that for maximum RWS (RWSmax) was 11.2±2.5%. RWS proportionally increased along with the decrease in FFR values, and the increase in the number of HRPC (Both p-for-trend <0.001). The proportion of vessels with FFR ≤0.80 and that of vessels with high-risk plaque increased in the order of RWSmax quartile group (Both p-for-trend <0.001) and these associations maintained after the adjustment of clinical characteristics (adjusted odds ratio [OR] 1.31, p value <0.001 for FFR ≤0.80; adjusted OR 1.24, p value <0.001 for high-risk plaque) and angiographic parameters (adjusted OR 1.24, p value <0.001 for FFR ≤0.80; adjusted OR 1.14, p value 0.012 for high-risk plaque). High RWSmax (>14.2%, optimal cut-off value for VOCO) was an independent predictor for VOCO after adjusting for diabetes and % diameter stenosis, FFR ≤0.8, or high-risk plaque (Figure 1). In a mediation analysis, RWS showed an independent effect from lesion-specific ischemia or high-risk morphological attributes in defining prognosis (Figure 2). Conclusion(s) Angiography-derived RWS was closely related to coronary physiologic and plaque morphological attributes, but was an independent predictor of clinical events. This novel index can provide additional prognostic implications over physiological severity or plaque characteristics in patients with coronary artery disease.Prognostic implications of high RWSMediation analysis

Non-flow limiting non-culprit plaque characteristics in patients presenting with STEMI versus NSTEMI

Abstract Background Non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) are often considered distinct clinical entities. Although differences in culprit plaque characteristics have been described extensively, less is known about differences in non-culprit (NC) plaque characteristics. Purpose To compare plaque characteristics of fractional flow reserve (FFR)-negative NC lesions as assessed by optical coherence tomography (OCT) in STEMI and NSTEMI patients. Methods PECTUS-obs is a prospective, observational study in which 438 patients presenting with STEMI or NSTEMI underwent OCT of any intermediate FFR-negative NC lesion (defined as a FFR >0.80) after treatment of the infarct related artery. Quantitative and qualitative OCT analyses were performed by an independent core laboratory. A high risk plaque (HRP) was defined as the presence of ≥2 of the following prespecified criteria: 1) a lipid arc ≥90°, 2) a minimal fibrous cap thickness <65 µm, or 3) either cap rupture or thrombus presence. In the present sub-analysis, lesion-level plaque characteristics were compared between patients presenting with STEMI versus NSTEMI while accounting for within-patient clustering and correcting for prespecified clinical variables (age, history of myocardial infarction, diabetes, and estimated glomerular filtration rate (eGFR)). Results Among 420 patients with at least one analyzable OCT, 217 (51.7%) presented with STEMI and 203 (48.3%) with NSTEMI. Patients with STEMI were younger (mean age 62±10 vs 65±11 years, p=0.004) and less frequently had diabetes (11.1% vs 18.2%, p=0.037) and hypercholesterolemia (31.8% vs 41.6%, p=0.038). Baseline mean eGFR (84±19 vs 75±19 ml/min, p<0.001) and low density lipoprotein-cholesterol levels (3.2±1.2 vs 2.9±1.2, p=0.010) were higher in STEMI patients with fewer of these patients using lipid lowering therapy (18.9% vs 33.0%, p<0.001) before enrollment. A total of 494 NC lesions were analyzed, which were equally distributed in number and location between groups. The mean fractional flow reserve was 0.89±0.05 and was comparable between groups (p=0.26). Patients with STEMI had a smaller minimal lumen area (2.56±1.48 vs 2.84±1.58 mm2, p=0.031) and minimal lumen diameter (1.47±0.44 vs 1.55±0.45 mm, p=0.026) with a subsequent larger percentage area stenosis (64±15 vs 61±17%, p=0.022). Lipid plaques were more common in STEMI patients (81.7% vs 70.7%, p=0.006) and the maximal lipid arc more frequently was ≥90º (79.0% vs 69.0%, p=0.018). There was no difference in the presence of plaque ruptures (8.3% vs 11.2%, p=0.31) or HRP (32.9% vs 29.3%, p=0.40), whereas macrophage accumulation was more prevalent in STEMI patients (27.8% vs 18.2%, p=0.040). Conclusions FFR-negative NC lesions in patients with STEMI have smaller luminal dimensions, and more frequently harbor lipid plaques and macrophage accumulation. No difference was observed in the prevalence of HRP or plaque rupture.

Impacts of illicit drug use on coronary angiographic findings in a multicenter registry of patients with acute coronary syndrome

Abstract Background Although illicit drug use may induce acute coronary syndrome (ACS), its impacts on coronary angiographic characteristics and the coronary artery disease (CAD) burden are a matter of debate. Purpose To assess the association between illicit drugs use and coronary angiographic findings in a multicenter patients with ACS. Methods From April 7 to 22, 2021, the Addiction in Intensive Cardiac Care Unit (ADDICT-ICCU) study included prospectively 1,499 patients admitted to ICCUs with a systematic urine multidrug test in 39 ICCUs across France. This prespecified study focuses on patients admitted for ACS with an angiography analysed by an independent Angiographic Core Laboratory. Patients with history of coronary artery bypass graft surgery were excluded. We compared coronary angiographic findings between illicit drugs users and others for the following parameters: the prevalence, location, type, and severity of CAD obstruction (stenosis≥50%), SYNTAX score, residual SYNTAX score, and the characteristics of percutaneous coronary intervention (PCI). Results Among the 283 patients with ACS (62±13 years, 77% men), 38 (13.4%) had a positive test for illicit drugs (cannabis: 12%, cocaine: 1.1%, MDMA: 0.7%). Drug users were younger than other patients (51±12 vs 64±12 years, p<0.001), but there were no significant difference in sex ratio (89.5% vs 75.5%, p=0.088). There was no significant difference in the rate of STEMI (52.6% vs 45.7%, p=0.535) and NTSEMI (47.4% vs 54.3%, p=0.535) between drug users and others. Regarding the CAD burden, drug users had significantly less obstructive coronary lesions (1.6±1.1 vs 2.2±1.4, p=0.012), less multivessel obstructive CAD (31% vs 61%, p=0.001), and a trend for a lower initial SYNTAX score (8.3±7.8 vs 10.8±8.4; p=0.084) compared to others. Concerning culprit lesion, drug users had less bifurcation lesions (p=0.008), a trend for more left anterior descending (LAD) artery lesions (p=0.091), a higher thrombus burden score (p=0.057), and less lesions above 20 mm (p=0.183). Conclusion In patients with ACS, recent illicit drug use is associated with less number of significant lesions and less multivessel CAD. Concerning culprit lesions, illicit drugs use is associated with less bifurcation lesions, with a trend for more LAD lesions and a higher thrombus burden score.ACS analysed with Core LaboratoryAngiographic findings according to drug