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Aims: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in the real world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major cardiovascular (CV) events in the real world., Methods and Results: The lipid control outcome was the percentage of patients reaching the LDL-C target of <55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all-cause death, non-fatal MI, non-fatal stroke, and ischaemia-driven revascularization) during a follow-up in relation to quartiles of LDL-C at first lipid control. We included 771 patients with ACS from the AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischaemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C < 55 mg/dL., Conclusion: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early-strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

There is a paucity of data regarding the safety of a 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) presenting with acute coronary syndromes (ACS). We aimed to compare the clinical outcomes of patients at HBR with chronic coronary syndrome (CCS) or ACS treated with PCI using bioresorbable polymer everolimus-eluting stent (BP-EES) followed by 1-month DAPT. Patients at HBR who underwent PCI with BP-EES were prospectively enrolled in 10 Italian centers. All patients were treated with 1-month DAPT. In case of need for anticoagulation, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1 month, followed by oral anticoagulation only after that. The primary end point was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. Overall, 263 patients (59.4%) with CCS and 180 patients (40.6%) with ACS were enrolled. No significant difference was evident between patients with CCS and ACS for the primary end point (4.3% vs 5.6%, respectively, p = 0.497) and for each isolated component. The risk for Bleeding Academic Research Consortium (BARC) type 1 to 5 or type 3 to 5 bleedings was also similar between patients with CCS and ACS (4.3% vs 5.2%, p = 0.677, and 1.6% vs 2.9%, p = 0.351, respectively). In conclusion, among HBR patients with ACS who underwent PCI with BP-EES, a 1-month DAPT strategy is associated with a similar risk of ischemic and bleeding events compared with those with CCS., Competing Interests: Declaration of Competing Interest Dr. Testa has received consulting fees, personal and institutional honoraria, and has served on the advisory board participation from Abbott, Medtronic, Biotronik, Boston Scientific Corporation, Terumo Lifesciences, Meril, Cardionovum, Concept Medical. Dr. Piccolo has received speaker fees from Abbott Vascular and Biotronik and has served on the advisory board for Daiichi-Sankyo. Dr. De Luca has received speaker fees from AstraZeneca, Daiichi-Sankyo and Sanofi. Dr. Stefanini has received speaker fees from Abbott Vascular, Boston Scientific, and Pfizer (New York, NY, United States)/BMS. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Patients with acute coronary syndrome (ACS) often arrive in the catheterization (cath) lab directly from the field or an emergency department without an accurate triage for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Although in the pandemic period the treatment in the cath laboratory of high-risk ACS should not be delayed because the operators wear special protection systems, the subsequent risk of contagion in a non-Covid coronary care unit could be high in the case of patients positive for SARS-CoV-2., Methods: We tested the possibility of a fast-track protocol in 51 consecutive patients (mean age 65 ± 12 years) transferred from spokes centres or from the field to our HUB centre and admitted to our coronary care unit (CCU). Once the patient had arrived in the cath lab, the nasopharyngeal swab was performed. The real-time PCR to extract RNA for SARS-CoV-2 detection was performed with an automated rapid molecular Xpert Xpress test. Meanwhile, coronary angiography or percutaneous coronary intervention was performed if necessary., Results: In this fast-track protocol, the time to perform nasopharyngeal swab was 11 ± 11 min; time spent to transport nasopharyngeal swab to the laboratory was 29 ± 20 min; time to detect viral nucleic acid was 68 ± 16 min. The overall time from the execution of nasopharyngeal swab to the result was 109 ± 26 min. The results were immediately put into the hospital computer system and made readily available. Depending on the test result, patients were then transferred to the regular CCU or Covid area., Conclusion: This study demonstrates that 0-1.5 h fast-track triage for coronavirus disease 2019 (COVID 19) is feasible in patients with ACS. The execution of nasopharyngeal swab in the cath lab and its analysis with a rapid molecular test allows rapid stratification of SARS-CoV-2 infection.

Importance: Acute coronary syndromes are the leading cause of death worldwide and the leading cause of disease burden in high-income countries. Quick and accurate diagnosis of acute coronary syndromes is essential to avoid fatal events, for timely intervention, and to improve the prognosis., Objective: To prospectively investigate the feasibility and accuracy of a smartwatch in recording multiple electrocardiographic (ECG) leads and detecting ST-segment changes associated with acute coronary syndromes compared with a standard 12-lead ECG., Design, Setting, and Participants: A commercially available smartwatch was used in 100 participants to obtain multiple-channel ECGs. The study was conducted from April 19, 2019, to January 23, 2020. Fifty-four patients with ST elevation myocardial infarction, 27 patients with non-ST elevation myocardial infarction, and 19 healthy individuals were included in the study. The watch was placed in different body positions to obtain 9 bipolar ECG tracings (corresponding to Einthoven leads I, II, and III and precordial leads V1-V6) that were compared with a simultaneous standard 12-lead ECG., Main Outcomes and Measures: The concordance among the results of the smartwatch and standard ECG recordings was assessed using the Cohen κ coefficient and Bland-Altman analysis., Results: Of the 100 participants in the study, 67 were men (67%); mean (SD) age was 61 (16) years. Agreement was found between the smartwatch and standard ECG for the identification of a normal ECG (Cohen κ coefficient, 0.90; 95% CI, 0.78-1.00), ST-segment elevation changes (Cohen κ coefficient, 0.88; 95% CI, 0.78-0.97), and non-ST-segment elevation changes (Cohen κ coefficient, 0.85; 95% CI, 0.74-0.96). In addition, the Bland-Altman analysis demonstrated agreement between the smartwatch and standard ECG to detect the amplitude of ST-segment changes (bias, -0.003; SD, 0.18; lower limit, -0.36; and upper limit, 0.36). Use of the smartwatch ECG for the diagnosis of normal ECG showed a sensitivity of 84% (95% CI, 60%-97%) and specificity of 100% (95% CI, 95%-100%); for ST elevation, sensitivity was 93% (95% CI, 82%-99%) and specificity was 95% (95% CI, 85%-99%); and for NSTE ECG alterations, sensitivity was 94% (95% CI, 81%-99%) and specificity was 92% (95% CI, 83%-97%)., Conclusions and Relevance: The findings of this study suggest agreement between the multichannel smartwatch ECG and standard ECG for the identification of ST-segment changes in patients with acute coronary syndromes.

Background: There is recent new evidence regarding the combined use of direct oral antiocoagulants and antiplatelet agents in patients with Atrial Fibrillation undergoing PCI., Purpose: To compare the efficacy of dual antithrombotic treatment (DAT) including a direct oral anticoagulant (DOAC) and an antiplatelet agent versus triple antithrombotic treatment (TAT) with a vitamin K antagonist (VKA)., Data Sources: PubMed, SCOPUS and Google Scholar from through 09/09/2019; references of eligible studies; relevant scientific sessions abstracts and cardiology websites., Study Selection: Randomized controlled trials that compared DAT including a DOAC with TAT including a VKA and that reported at least the rates of stroke, Stent thrombosis and bleeding., Data Extraction: Two investigators independently extracted study data and assessed study quality., Data Synthesis: Four randomized trials that compared DAT including a DOAC with TAT including a VKA were available. Among these, one trial included two independent treatment arms with different DOAC dose, both compared against TAT. For this reason, the two arms were treated independently, resulting in 5 randomized comparisons available for meta-analysis, with a total of 8654 patients involved. The primary safety endpoint was significantly lower in the DAT arm (14.4%) compared to the TAT arm (23%) (RD = -0.08; p<0.001). In addition, we found no significant difference in the incidence of stroke between the treatment arms (p = 0.23). Similarly, no significant difference in the incidence of Stent Thrombosis between the treatment arms (p = 0.08)., Limitations: All trials included were open-label, even though data were blindly analyzed. Qualifying criteria are heterogeneous., Conclusions: Compared TAT including a VKA, a therapeutic DAT regimen including a DOAC was associated with a significant reduction of the primary safety endpoint in AF patients undergoing PCI with stent implantation for an ACS or chronic coronary syndrome, while no significant difference was found in the rate of ischemic adverse events, including stroke, acute myocardial infarction or stent thrombosis., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies., Background: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes., Methods: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization., Results: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 ± 0.51 vs. 0.43 ± 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 ± 0.09 vs. 0.91 ± 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 ± 0.09 vs. 0.85 ± 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919)., Conclusions: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Large prospective studies on the use of bioresorbable vascular scaffolds (BVS) for diffuse coronary artery disease are lacking. IT DISAPPEARS is a large multicentre prospective registry investigating the short and long-term outcomes of everolimus-eluting BVS in patients with long coronary lesions and/or multivessel coronary artery disease (ClinicalTrials.gov: NCT02004730). We hereby report the 2-year outcomes of the registry., Methods: We enrolled 1002 patients with complex lesions undergoing implantation of 2040 BVS with a prespecified technique including predilation, correct sizing, and postdilation with non-compliant balloons. The primary endpoint was the rate of device-oriented composite endpoint (DOCE), consisting of cardiac death, target vessel-related myocardial infarction (MI), and ischaemia-driven target lesion revascularization (TLR). Secondary endpoints included: 1) patient-oriented composite endpoint (POCE), consisting of all-cause mortality, all infarctions and all revascularisations; 2) definite/probable scaffold thrombosis., Results: Clinical presentation was an acute coronary syndrome in 59.8% of patients. Total BVS length implanted was 47 ± 22 mm. Postdilation of all scaffolds per patient was performed in 96.8%, while optimal implantation as per study guidelines was applied in 71.4%. Through 2-year follow-up, DOCE occurred in 9.5% of patients (cardiac death 0.6%, target vessel-related MI 5.3%, TLR 6.6%). The rate of POCE was 16.6% and of scaffold thrombosis 1.1%. Female gender, total length of coronary lesions, treatment of bifurcation lesions and use of 2.5 mm scaffolds were independent predictors of DOCE., Conclusions: The 2-year results of IT-DISAPPEARS show that BVS may yield acceptable clinical outcomes in patients with complex coronary lesions when the implantation technique is appropriate., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS)., Background: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization., Methods: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year., Results: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04)., Conclusions: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Aim of the present study was to perform a meta-analysis of all available studies comparing the instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR)., Methods and Results: Published trials comparing the iFR with FFR were searched for in PubMed, Google Scholar, and Scopus electronic databases. A total of 23 studies were available for the analysis, including 6381 stenoses. First, a meta-analysis of all studies was performed exploring the correlation between FFR and iFR. Interestingly, we found good correlation (0.798 [0.78-0.82]) between the 2 indices ( P <0.001). In addition, to evaluate the diagnostic performance of iFR to identify FFR-positive coronary stenoses, we performed an additional meta-analysis, summarizing the results of receiver operating characteristics analyses from individual studies reporting the area under the curve. Summing the results of these studies, we found that iFR has a good diagnostic performance for the identification of FFR-positive stenoses (area under the curve=0.88 [0.86-0.90]; P <0.001). Furthermore, our search results included 5 studies that compared iFR and FFR to a third independent reference standard. Interestingly, no significant differences between iFR and FFR were reported in those studies., Conclusions: The present meta-analysis shows that iFR significantly correlates with standard FFR and shows a good diagnostic performance in identifying FFR-positive coronary stenoses. Finally, iFR and FFR have similar diagnostic efficiency for detection of ischemia-inducing stenoses when tested against a third comparator., (© 2018 American Heart Association, Inc.)

Objectives: The aim of this study was to describe the incidence and clinical characteristics, including intracoronary imaging features, of clinical restenosis in bioresorbable coronary scaffolds (BRS). Further, the authors searched for clinical and procedural predictors of scaffold restenosis (ScR) and report on the clinical outcomes after treatment of ScR in a cohort of consecutive all-comer patients., Background: Data from randomized controlled trials demonstrate a higher rate of target lesion failure in patients treated with BRS as compared with those treated with metal drug-eluting stents. Although in-scaffold thrombosis has been thoroughly investigated, there are little data available on the incidence and characteristics of ScR., Methods: A total of 657 consecutive patients (age 63 ± 12 years, 79% men, 21% diabetics, 67% acute coronary syndrome) who received a total of 883 BRS for the treatment of coronary artery stenoses between May 2012 and January 2015 were enrolled in a retrospective registry., Results: During the median follow-up of 1,076 days (interquartile range: 762 to 1,206 days), a total of 49 cases of ScR were found in 41 patients (Kaplan-Meier incidence: 2.4%, 6.0%, and 9.0% at 12-, 24-, and 36-month follow-up, respectively). ScR presented as stable angina or as incidental finding in 73% of the cases. The angiographic pattern was complex (type II to IV) in 55% of the ScR lesions. The neointima was homogeneous with high signal intensity in all but 3 cases at optical coherence tomography. Prior revascularization (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.5 to 5.1; p = 0.002), diabetes (HR: 2.9; 95%CI: 1.5 to 5.4; p = 0.001), lesion types B2 or C (HR: 2.8; 95% CI: 1.5 to 5.4; p = 0.002), and implantation technique (HR: 0.3; 95% CI: 0.1 to 0.6; p = 0.001) emerged as independent predictors of ScR. Oversizing (HR: 6.29; 95% CI: 2.4 to 16.4), undersizing (HR: 5.15; 95% CI: 1.99 to 13.30), and a residual stenosis >27% (HR: 8.9; 95% CI: 3.6 to 21.8) were associated with an increased ScR risk., Conclusions: The 3-year incidence of ScR was similar to that observed in similar settings with newer-generation drug-eluting stents. It is often associated with a benign presentation and a complex angiographic pattern. Predictors of ScR match those of metallic stent restenosis, and the implantation technique used at index appears to play an important role., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR., Methods: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk., Results: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001)., Conclusions: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .).

Background. Circulating microRNAs are appealing biomarkers to monitor several processes underlying cardiovascular diseases. Platelets are a major source for circulating microRNAs. Interestingly, the levels of specific microRNAs were reported to correlate with the level of platelet activation. The aim of the present study was to test whether the treatment with the novel antiplatelet agent, ticagrelor, is associated with modulation in the levels of key platelet-derived microRNAs. Methods and Results. Patients were randomly selected from those participating in the SHIFT-OVER study, in which we had previously evaluated the effect of the therapeutic switch from clopidogrel to ticagrelor on platelet aggregation. Circulating levels of selected microRNAs were measured before and after the therapeutic switch from a dual antiplatelet therapy including acetylsalicylic acid (ASA) and clopidogrel to the more potent ticagrelor. Interestingly, the circulating levels of miR-126 (p = 0.030), miR-223 (p = 0.044), and miR-150 (p = 0.048) were significantly reduced, while the levels of miR-96 were increased (p = 0.038). No substantial differences were observed for the remaining microRNAs. Conclusions. Switching from a dual antiplatelet treatment with clopidogrel to ticagrelor is associated with significant modulation in the circulating levels of specific microRNAs. If confirmed in larger, independent cohorts, our results pave the way for the use of circulating microRNAs as biomarkers of platelets activity in response to specific pharmacological treatments.

Background: Adenosine administration is currently required for evaluation of stenosis severity with fractional flow reserve (FFR). The instantaneous wave-free ratio (iFR) was recently introduced as an adenosine-free alternative in patients with stable CAD. The aim of the present study was to replicate the findings of previous iFR studies using an independent calculation algorithm and to evaluate the iFR for the assessment of non-culprit vessels in patients with acute coronary syndrome (ACS)., Methods and Results: 53 patients with ACS (65%) and at least one non-culprit intermediate lesion and 29 (35%) with stable CAD were included. A total of 123 stenoses were evaluated with both FFR and iFR. Classification match of iFR in ACS was not inferior to stable CAD (79.5% in ACS and 84.4% in CAD; p=0.497). Accordingly, no difference was observed in iFR/FFR correlation between ACS and stable CAD (r=0.66 in ACS vs. r=0.69 in CAD). Overall, a significant correlation was found between iFR and FFR (r=0.68; p<0.001) with a good diagnostic efficiency at ROC analysis (area under the curve: 0.87). In addition, neither the localization of the stenosis within the coronary tree (p=0.147) nor the time interval from the acute event (p=0.550) significantly influenced the concordance of iFR with FFR., Conclusions: The iFR is a promising method for the assessment of non-culprit lesion severity in patients with acute coronary syndrome., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: To our knowledge, no randomised study has compared rates of uncovered stent struts in everolimus (EES) vs. new-generation zotarolimus-eluting (ZES-R) stents in acute coronary syndrome (ACS). The aim of our study was to evaluate the completeness of neointimal coverage with optical coherence tomography (OCT) in ACS patients treated with drug-eluting stents (DES) comparing EES versus new-generation ZES-R., Methods and Results: All eligible ACS patients admitted to four Italian centres with a clinical indication for culprit lesion intervention were randomised 1:1 to EES or ZES-R. The primary study endpoint was the percentage of uncovered stent struts evaluated by optical coherence tomography (OCT) at six months. Secondary endpoints were the percentage of malapposed stent struts, percent neointimal hyperplasia cross-sectional area (CSA) and major adverse cardiac events (MACE) at six months. A total of 60 patients were randomised to EES (n=29) or ZES-R (n=31). No differences were observed in baseline characteristics between the two groups. Overall, 31.7% presented with STEMI, of which 68.4% were anterior. The other patients comprised 41.7% NSTEMI and 26.7% troponin-negative ACS. A mean of 1.3±0.6 lesions were treated per patient, with a mean of 1.3±0.5 stents per lesion. At 30 days there was one sudden death. Six-month OCT analysis was performed in 25 lesions in the EES group and in 24 lesions in the ZES-R group. There was no difference in the primary endpoint of uncovered stent struts between groups (EES 6.42% [3.27, 9.57] vs. ZES-R 7.07% [3.22, 10.92]; p=0.80). Furthermore, there were no differences between groups in the percentage of malapposed stent struts, either with (EES 1.19% [0.34, 2.04] vs. ZES-R 0.85% [0.40, 1.30]; p=0.49) or without coverage (EES 1.06% [0.12, 2.01] vs. ZES-R 0.24% [0.05, 0.44]; p=0.09). Percent neointima CSA was similar in both groups (EES 37.0% [18.6, 55.3] vs. ZES-R 26.6% [18.4, 34.8]; p=0.31). At six-month clinical follow-up, no additional patients died or suffered MI. There were four MACE in the EES group and one in the ZES-R group., Conclusions: In our study, in patients presenting with ACS, both EES and ZES-R had low percentages of malapposed and uncovered stent struts at six-month OCT analysis.

Background: Ticagrelor outperforms clopidogrel in preventing cardiovascular events in acute coronary syndrome. Despite the inclusion of a loading dose in the Platelet Inhibition and Patient Outcomes (PLATO) trial for all patients randomized to ticagrelor, it may not be necessary in patients receiving ongoing clopidogrel therapy. The aim of the present study was to assess whether a ticagrelor loading dose is associated with a further platelet inhibition during the switch from clopidogrel to ticagrelor in patients with acute coronary syndrome receiving ongoing antiplatelet treatment., Methods and Results: Fifty patients with acute coronary syndrome receiving aspirin and clopidogrel treatment were randomly assigned to a starting dose of ticagrelor (group 1, 90 mg; group 2, 180 mg). Platelet aggregation was measured using multiple electrode aggregometry and standard light transmission aggregometry just before the switch and at 2, 6, 24, and 72 hours. No relevant difference in platelet aggregation was observed between the 2 study arms at baseline (P=0.256). Residual platelet aggregation was significantly reduced in both arms 2 hours after the first administration of ticagrelor (P<0.001 for both), with no difference in aggregation between groups (multiple electrode aggregometry, 17.6±7.2 versus 18.1±6 U; P=0.281). Similar results were observed with LTA., Conclusions: Switching from clopidogrel to ticagrelor without a reloading dose is feasible, and it does not hinder platelet aggregation inhibition in patients with acute coronary syndrome. Further prospective studies are needed to assess the clinical relevance of our findings., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01795820.

Background: Successful reperfusion of epicardial coronary arteries does not necessarily result in actual myocardial perfusion. Local intracoronary (IC) delivery of GP IIb/IIIa inhibitors (GPI) has been proposed to achieve further clinical efficacy when compared to standard intravenous (IV) administration. However clinical trials have shown conflicting results. The aim of the present study was to compare IC with IV abciximab administration on mortality and MACEs in patients with ACS undergoing PCI., Methods: We performed a meta-analysis of all available clinical trials comparing intracoronary versus intravenous abciximab administration., Results: At short-term analysis, incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.56; 95% CI 0.35-0.89; p=0.015). Interestingly, subgroup analysis showed that most benefit was coming from those studies with a main baseline LVEF<50% (OR=0.33 95% CI 0.18-0.59). Similarly, long-term incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.47; 95% CI 0.31-0.71; p<0.001), with most benefit coming from those studies enrolling patients with a main baseline EF<50% (OR=0.38 95% CI 0.23-0.63 p<0.001). In addition, long-term incidence of death was also lower in the IC group than in the IV group (OR=0.42; 95% CI 0.20-0.86; p=0.009)., Conclusions: Our meta-analysis provides evidence of a net clinical benefit for intracoronary versus intravenous abciximab administration, with the highest benefit observed in high-risk ACS patients, such as those with reduced baseline LVEF., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Affective symptoms have adverse effects in hospital and long-term cardiac outcomes of post Acute Coronary Syndrome (ACS) patients. This study aims to identify personality traits and maladaptive coping strategies that could predict affective symptoms in early post-ACS patients., Methods: Seventy patients undergoing revascularization procedures were examined within a week after their admission by means of the Hospital Anxiety-Depression Scale. Personality was analyzed through the Type D Personality Scale and the Coping Inventory for Stressful Situation. Multiple logistic regression analysis was used to determine independent predictors of anxiety and depressed mood., Results: A high rate of depressive and anxious symptoms was found and 76% of patients resulted Type D personality. Depression was associated with b-blocker therapy, Type D personality, and specific coping strategies. Unmarried status, low education, unstable angina, Type D personality, emotion, and avoidance oriented coping independently predicted anxiety., Conclusion: These findings underlie the importance of assessment for Type D personality and coping strategies that could be useful to identify post-ACS patients at higher risk for affective symptoms. Using these brief instruments, as sensitive screening measures, we investigated the prevalence of depressive and anxiety symptoms in patients with ACS, we identified personality traits and coping strategies used to manage stress and estimated independent predictors of affectivity disorders after ACS.

Current available biomarkers cannot identify myocardial ischemia without necrosis. To overcome this issue and to increase diagnostic power, we evaluated the activation of the three MAPK pathways, ERK1/2, JNK and p38, in T lymphocytes of patients with acute coronary syndromes (ACS). We included sixty consecutive patients affected by either unstable angina (UA, N = 22), Non- ST-segment elevation MI (NSTEMI, N = 19) or ST-segment elevation MI (STEMI, N = 19). Two separate groups of patients were matched as controls: healthy subjects (CTRL, N = 20) and patients with stable coronary artery disease (CAD, N = 21). MAPK activation in T lymphocytes, measured by phospho-ERK1/2, phospho-JNK and phospho-p38 levels, was assessed by flow cytometry analysis which revealed significantly increased phosphorylated levels of ERK1/2 in patients with UA, compared to controls. In UA patients no significant changes were detected for phospho-JNK compared to both control groups. NSTEMI and STEMI groups showed a statistically significant increase in both phospho-ERK1/2 and phospho-JNK, compared to control groups. All ACS groups demonstrated significantly increased phosphorylation of p38 compared to CTRL, but not CAD. ROC curves showed that a cut-off value of 22.5 intensity of fluorescence for phospho-ERK1/2 was able to significantly discriminate UA patients from patients with stable angina with 78% sensitivity and 90% specificity. Therefore, a differential MAPK activation in T lymphocytes denotes patients with ACS. Indeed, patients with unstable angina are identified with high specificity by activated ERK1/2 and normal JNK levels. These data could represent a valuable new molecular signature to be used as specific biomarkers for the diagnosis of unstable angina within ACS.

Artificial intelligence (AI) applied to cardiovascular disease (CVD) is enjoying great success in the field of scientific research. Electrocardiograms (ECGs) are the cornerstone form of examination in cardiology and are the most widely used diagnostic tool because they are widely available, inexpensive, and fast. Applications of AI to ECGs, especially deep learning (DL) methods using convolutional neural networks (CNNs), have been developed in many fields of cardiology in recent years. Deep learning methods provide valuable support for rapid ECG interpretation, demonstrating a diagnostic capability overlapping with specialists in the diagnosis of CVD by a classical analysis of macroscopic changes in the ECG trace. Through photoplethysmography, wearable devices can obtain single-derivative ECGs for the recognition of AI-diagnosed arrhythmias. In addition, CNNs have been developed that recognize no macroscopic electrocardiographic changes and can predict, from a 12-lead ECG, atrial fibrillation, even from sinus rhythm; left and right ventricular function; hypertrophic cardiomyopathy; acute coronary syndromes; or aortic stenosis. The fields of application are many, but numerous are the limitations, mainly associated with the reliability of the acquired data, an inability to verify black box processes, and medico-legal and ethical problems. The challenge of modern medicine is to recognize the limitations of AI and overcome them. [ABSTRACT FROM AUTHOR]

This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22–23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides. [ABSTRACT FROM AUTHOR]

• Advances in single-cell biology have revolutionized the understanding of atherosclerosis, highlighting the interaction between different cell populations and molecular pathways in plaque progression and regression. • The formation and progression of atherosclerotic plaques are driven by LDL cholesterol and chronic exposure to pro-inflammatory stimuli, resulting in endothelial dysfunction and the formation of foam cells. • The concept of "vulnerable plaque" describes plaques prone to rupture, erosion, or calcified nodules, leading to acute coronary syndrome (ACS). Modern imaging techniques like IVUS, NIRS, and OCT are crucial for identifying and assessing these high-risk plaques. • Intensive lipid-lowering therapies, particularly statins and PCSK9 inhibitors, have shown efficacy in reducing plaque volume and stabilizing plaque features, with ongoing research needed to confirm their long-term benefits in reducing cardiovascular events. Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death globally despite advances in preventive therapies. Understanding of the initiation and progression of atherosclerosis, the interplay between lipoproteins, endothelial dysfunction, inflammation, and immune responses is critical to treating this disease. The development of vulnerable coronary plaques prone to thrombosis, can lead to acute coronary syndromes, for these reasons, the potential plaque stabilization and regression through pharmacological interventions, particularly lipid-lowering agents like statins and PCSK9 inhibitors is crucial. The imaging techniques such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) play a key role in assessing plaque composition and guiding interventional therapeutic strategies. Clinical evidence supports the efficacy of intensive lipid-lowering therapy in inducing plaque regression, with studies demonstrating reductions in plaque volume and improvements in plaque morphology assessed by IVUS, OCT and NIRS. While pharmacological interventions show promise in promoting plaque regression and stabilization, their impact on long-term cardiovascular events requires further investigation. Multimodality imaging and comprehensive outcome trials are proposed as essential tools for elucidating the relationship between plaque modification and clinical benefit in coronary atherosclerosis. The stabilization or regression of atherosclerotic plaque might serve as the phenomenon linking the reduction in LDL-C levels to the decrease in cardiovascular events. Overall, this review emphasizes the ongoing efforts to advance our understanding of ASCVD pathophysiology and optimize therapeutic approaches for improving patient outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

The respective ischemic and bleeding risks of early aspirin discontinuation following an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remain uncertain. We performed a prospero-registered review of randomized controlled trials (RCTs) comparing a P2Y12 inhibitor-based single antiplatelet strategy following early aspirin discontinuation to a strategy of sustained dual antiplatelet therapy (DAPT) in ACS or PCI patients requiring, or not, anticoagulation for another indication (CRD42019139576). We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included nine RCTs comprising 40,621 patients. Compared to prolonged DAPT, major bleeding (2.2% vs. 2.8%; RR 0.68; 95% CI: 0.54 to 0.87; p = 0.002; I2: 63%), non-major bleeding (5.0 % vs. 6.1 %; RR: 0.66; 95% CI: 0.47 to 0.94; p = 0.02; I2: 87%) and all bleeding (7.4% vs. 9.9%; RR: 0.65; 95% CI: 0.53 to 0.79; p < 0.0001; I2: 88%) were significantly reduced with early aspirin discontinuation without significant difference for all-cause death (p = 0.60), major adverse cardiac and cerebrovascular events (MACE) (p = 0.60), myocardial infarction (MI) (p = 0.77), definite stent thrombosis (ST) (p = 0.63), and any stroke (p = 0.59). In patients on DAPT after an ACS or a PCI, early aspirin discontinuation prevents bleeding events with no significant adverse effect on the ischemic risk or mortality. [ABSTRACT FROM AUTHOR]

Percutaneous coronary interventions with stent-based restorations of vessel patency have become the gold standard in the treatment of acute coronary states. Bioresorbable vascular scaffolds (BVS) have been designed to combine the efficiency of drug-eluting stents (DES) at the time of implantation and the advantages of a lack of foreign body afterwards. Complete resolution of the scaffold was intended to enable the restoration of vasomotor function and reduce the risk of device thrombosis. While early reports demonstrated superiority of BVS over DES, larger-scale application and longer observation exposed major concerns about their use, including lower radial strength and higher risk of thrombosis resulting in higher rate of major adverse cardiac events. Further focus on procedural details and research on the second generation of BVS with novel properties did not allow to unequivocally challenge position of DES. Nevertheless, BVS still have a chance to present superiority in distinctive indications. This review presents an outlook on the available first and second generation BVS and a summary of results of clinical trials on their use. It discusses explanations for unfavorable outcomes, proposed enhancement techniques and a potential niche for the use of BVS. [ABSTRACT FROM AUTHOR]

• Functional evaluation plays a key role to identify the mechanisms underlying myocardial ischemia also in patients with non-obstructive CAD. • Treatment of myocardial ischemia should be targeted to the underlying pathogenic mechanism, and for these reasons the use of an invasive functional approach may have important therapeutic implications. • Invasive functional assessment has important therapeutic and prognostic implications in patients with both acute and chronic coronary syndromes. [ABSTRACT FROM AUTHOR]

Background Little data are available on the long-term outcomes of bioresorbable scaffold (BRS) in the setting of ST-segment elevation myocardial infarction (STEMI). The aim of this study is to investigate three-years outcomes and predictors of BRS failure in patients presenting with STEMI. Methods and results Two prospective, single-arm registries were pooled. Incidence and predictors of clinical outcome were assessed with Kaplan-Meier and Cox regression analyses. From May-2012 to January-2015, 183 STEMI patients (58 ± 13 years, 77% males, 29% diabetics) who received a total of 256 BRS (1.4 ± 0.8 per patient) were included. 248 patients (65 ± 11 years, 74% males, 27% diabetics) treated for stable coronary artery disease (SCAD) served as control. 3-years follow-up was available in 386 (90%) patients. Device-oriented composite endpoint and scaffold thrombosis (ScT) rates were similar in the two groups (STEMI: 11.5% vs SCAD: 12.9%, P  = 0.84; STEMI: 3.6% vs SCAD: 3.3%, P  = 0.90). While early ScT was more frequent in SCAD patients, late/very late ScT was a feature of STEMI. While in STEMI patients the incidence of ScT was higher in vessels with RVD > 3.5 mm, a RVD < 2.5 mm was a predictor of events in stable patients. Similarly, BRS undersizing predicted events in STEMI patients, while oversizing was a predictor in stable ones. Finally, the incidence of ScT was reduced in both STEMI and stable patients (from 6.3% to 0% and from 5.80% to 0.9%) when an optimized implantation technique was used. Conclusions The incidence of events for three years follow-up was similar in STEMI and SCAD patients, although different timing and features underlie ScT in the two groups. [ABSTRACT FROM AUTHOR]

Bioresorbable scaffolds have the potential to introduce a paradigm shift in interventional cardiology, a true anatomical and functional “vascular restoration” instead of an artificial stiff tube encased by persistent metallic foreign body. Early clinical studies using the first commercially available drug-eluting bioresorbable vascular scaffold (BVS) reported very promising safety and efficacy outcomes, comparable to best-in-class second-generation drug-eluting metal stent. To date, more than 60,000 Absorb BVSs have been implanted with only the interim analysis of one randomized trial (ABSORB II RCT) available. Recent registries have challenged the initial claim that BVS is immune from Scaffold Thrombosis (ST). However, suboptimal device expansion and insufficient intracoronary imaging guidance can explain higher than expected ST, especially in complex lesions. The aim of this review article is to critically evaluate the results of the available Absorb BVS studies and discuss the lessons learned to optimize lesion selection and implantation technique of such devices. [ABSTRACT FROM AUTHOR]