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Mariana Muñoz-Esquerre,1 José Luis Ferreiro,2 Daniel Huertas,1,3 Ana Lucrecia Marcano,2 Marta López-Sánchez,1 Gerard Roura,2 Joan Antoni Gómez-Hospital,2 Jordi Dorca,1 Angel Cequier,2 Salud Santos1,3 1Department of Pulmonary Medicine, Bellvitge University Hospital, IDIBELL, University of Barcelona, L’Hospitalet de Llobregat, 2Heart Diseases Institute, Bellvitge University Hospital, IDIBELL, University of Barcelona, L’Hospitalet de Llobregat, 3Biomedical Research Networking Centre Consortium Respiratory Diseases, CIBERES, Barcelona, Spain Background: A higher risk of atherothrombotic cardiovascular events, which are platelet-driven processes, has been described during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the relevance of platelet reactivity during AECOPD and whether this is affected by antiplatelet agents are not fully elucidated to date. This study aimed to evaluate whether platelet reactivity is augmented during an exacerbation in COPD patients with and without antiplatelet therapy and its association with systemic inflammatory parameters.Materials and methods: Prospective, observational, ex vivo investigation was conducted in consecutive patients suffering an exacerbation of COPD. Platelet reactivity was assessed during AECOPD and at stable state. Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay expressed as P2Y12 reactivity index (PRI), 2) multiple electrode aggregometry and 3) optical aggregometry. Systemic inflammatory parameters such as leukocyte count, interleukin-6 and fibrinogen were also assessed.Results: Higher platelet reactivity was observed during AECOPD compared to stability measured by vasodilator-stimulated phosphoprotein (PRI: 75.2%±1.9% vs 68.8%±2.4%, p=0.001). This augmented platelet aggregability was also observed in the subset of patients on antiplatelet therapy (PRI: 72.8%±3.1% vs 61.7%±7.5%, p=0.071). Consistent findings were observed with all other platelet function tests. Patients with greater enhancement of inflammatory markers during AECOPD were more likely to present a higher increase in platelet reactivity.Conclusion: Platelet reactivity is increased during AECOPD, which may contribute to the augmented cardiovascular risk of these patients. Additionally, the increase in platelet reactivity might be associated with an increment in inflammatory markers during exacerbations. Keywords: airflow limitation, inflammation, platelet aggregation, antiplatelets agents, thrombosis

Introduction and Objectives: This article presents the 2023 activity report of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC)., Methods: All interventional cardiology laboratories in Spain were invited to participate in an online survey. Data analysis was carried out by an external company and subsequently reviewed and presented by the members of the ACI-SEC board., Results: A total of 119 hospitals participated. The number of diagnostic studies decreased by 1.8%, while the number of percutaneous coronary interventions (PCI) showed a slight increase. There was a reduction in the number of stents used and an increase in the use of drug-coated balloons. The use of intracoronary diagnostic techniques remained stable. For the first time, data on PCI guided by intracoronary imaging was reported, showing a 10% usage rate in Spain. Techniques for plaque modification continued to grow. Primary PCI increased, becoming the predominant treatment for myocardial infarction (97%). Noncoronary structural procedures continued their upward trend. Notably, the number of left atrial appendage closures, patent foramen ovale closures, and tricuspid valve interventions grew in 2023. There was also a significant increase in interventions for acute pulmonary embolism., Conclusions: The 2023 Spanish cardiac catheterization and coronary intervention registry indicates a stabilization in coronary interventions, together with an increase in complexity. There was consistent growth in procedures for both valvular and nonvalvular structural heart diseases., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown., Aims: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain., Methods: Multicenter, ambispective, observational nationwide registry., Results: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device., Conclusions: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) non-invasive scar evaluation is not included among the diagnostic criteria or the predictors of ventricular arrhythmias (VA) and sudden death (SD). Computed tomography (CT) has excellent spatial resolution and allows a clear distinction between myocardium and fat; thus, it has great potential for the evaluation of myocardial scar in ARVC. Objective: The objective of this study is to evaluate the feasibility, and the diagnostic and prognostic value of semi-automated quantification of right ventricular (RV) fat replacement from CT images. Methods: An observational case-control study was carried out including 23 patients with a definite (19) or borderline (4) ARVC diagnosis and 23 age- and sex-matched controls without structural heart disease. All patients underwent contrast-enhanced cardiac CT. RV images were semi-automatically reconstructed with the ADAS-3D software (ADAS3D Medical, Barcelona, Spain). A fibrofatty scar was defined as values of Hounsfield Units (HU) <-10. Within the scar, a border zone (between -10 HU and -50 HU) and dense scar (<-50 HU) were distinguished. Results: All ARVC patients had an RV scar and all scar-related measurements were significantly higher in ARVC cases than in controls ( p < 0.001). The total scar area and dense scar area showed no overlapping values between cases and controls, achieving perfect diagnostic performance (sensitivity and specificity of 100%). Among ARVC patients, 16 (70%) had experienced sustained VA or aborted SD. Among all clinical, ECG and imaging parameters, the dense scar area was the only one with a statistically significant association with VA and SD ( p = 0.003). Conclusions: In ARVC, RV myocardial fat quantification from CT is feasible and may have considerable diagnostic and prognostic value.

Background: Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two common causes of nonatherosclerotic acute cardiac syndrome particularly frequent in women. Currently, there is no information comparing long-term clinical outcomes in unselected patients with these conditions., Methods: We compared the baseline characteristics, in-hospital outcomes, and the 12-month and long-term clinical outcomes of two large prospective registries on SCAD and TTS., Results: A total of 289 SCAD and 150 TTS patients were included; 89% were women. TTS patients were older with a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS patients, while emotional triggers and depressive disorders were more common in the SCAD group. Left ventricular ejection fraction was lower in TTS patients, but SCAD patients showed higher cardiac biomarkers. In-hospital events (43.3% vs. 5.2%, P <0.01) occurred more frequently in TTS patients. TTS patients also presented more frequent major adverse events at 12-month (14.7% vs. 7.1%, HR 5.3, 95% CI: 2.4-11.7, P <0.01) and long-term (median 36 vs. 31 months, P =0.41) follow-up (25.8% vs. 9.6%, HR 4.5, 95% CI: 2.5-8.2, P <0.01). Atrial fibrillation was also more frequent in TTS patients. Moreover, TTS patients presented a higher 12-month and long-term mortality (5.6% vs. 0.7%, P =0.01; and 12.6% vs. 0.7%, P <0.01) mainly driven by noncardiovascular deaths., Conclusion: Compared to SCAD, TTS patients are older and present more cardiovascular risk factors but less frequent depressive disorder or emotional triggers. TTS patients have a worse in-hospital, mid-term, and long-term prognosis with higher noncardiac mortality than SCAD patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Objectives: This article presents the annual activity report of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC) for the year 2022., Methods: All Spanish centers with catheterization laboratories were invited to participate. Data were collected online and were analyzed by an external company in collaboration with the members of the board of the ACI-SEC., Results: A total of 111 centers participated. The number of diagnostic studies increased by 4.8% compared with 2021, while that of percutaneous coronary interventions (PCI) remained stable. PCIs on the left main coronary artery increased by 22%. The radial approach continued to be preferred for PCI (94.9%). There was an upsurge in the use of drug-eluting balloons, as well as in intracoronary imaging techniques, which were used in 14.7% of PCIs. The use of pressure wires also increased (6.3% vs 2021) as did plaque modification techniques. Primary PCI continued to grow and was the most frequent treatment (97%) in ST-segment elevation myocardial infarction. Most noncoronary procedures maintained their upward trend, particularly percutaneous aortic valve implantation, atrial appendage closure, mitral/tricuspid edge-to-edge therapy, renal denervation, and percutaneous treatment of pulmonary arterial disease., Conclusions: The Spanish cardiac catheterization and coronary intervention registry for 2022 reveals a rise in the complexity of coronary disease, along with a notable growth in procedures for valvular and nonvalvular structural heart disease., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P =0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P =0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% ( P =0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

Aims: Spontaneous coronary artery dissection (SCAD) is a relatively infrequent cause of acute coronary syndrome. Clinical features, angiographic findings, management, and outcomes of SCAD patients who present reduced left ventricular ejection fraction (LVEF) remain unknown., Methods and Results: The Spanish multicentre prospective SCAD registry (NCT03607981), included 389 consecutive patients with SCAD. In 348 of these patients, LVEF could be assessed by echocardiography during the index admission. Characteristics and outcomes of patients with preserved LVEF (LVEF ≥50%, n = 295, 85%) were compared with those with reduced LVEF (LVEF <50%, n = 53, 15%). Mean age was 54 years and 90% of patients in both groups were women. The most frequent clinical presentation in patients with reduced LVEF was ST-segment elevation myocardial infarction (STEMI) (62% vs. 36%, P < 0.001), especially anterior STEMI. Proximal coronary segment and multi-segment involvement were also significantly more frequent in these patients. No differences were found on initial revascularization between groups. Patients with reduced LVEF significantly received more often neurohormonal antagonist therapy, and less frequently aspirin. In-hospital events were more frequent in these patients (13% vs. 5%, P = 0.01), with higher rates of death, cardiogenic shock, ventricular arrhythmia, and stroke. During a median follow-up of 28 months, the occurrence of a combined adverse event did not statistically differ between the two groups (19% vs. 12%, P = 0.13). However, patients with reduced LVEF had higher mortality (9% vs. 0.7%, P < 0.001) and readmission rates for heart failure (HF) (4% vs. 0.3%, P = 0.01)., Conclusion: Patients with SCAD and reduced LVEF show differences in clinical characteristics and angiographic findings compared with SCAD patients with preserved LVEF. Although these patients receive specific medications at discharge, they had higher mortality and readmission rates for HF during follow-up., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Growing interest in i-motif DNA as a transcriptional regulatory element motivates development of synthetic molecules capable of targeting these structures. In this study, we designed unmodified peptide nucleic acid (PNA) and gamma-modified PNA (γPNA) oligomers complementary to an i-motif forming sequence derived from the promoter of the KRAS oncogene. Biophysical techniques such as circular dichroism (CD) spectroscopy, CD melting, and fluorescence spectroscopy demonstrated the successful invasion of the i-motif by PNA and γPNA. Both PNA and γPNA showed very strong binding to the target sequence with high thermal stability of the resulting heteroduplexes. Interestingly fluorescence and CD experiments indicated formation of an intermolecular i-motif structure via the overhangs of target-probe heteroduplexes formed by PNA/γPNA invasion of the intramolecular i-motif. Targeting promoter i-motif forming sequences with high-affinity oligonucleotide mimics like γPNAs may represent a new approach for inhibiting KRAS transcription, thereby representing a potentially useful anti-cancer strategy., (© 2022 The Authors. Biopolymers published by Wiley Periodicals LLC.)

Background: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. Multivessel (MV) SCAD is a challenging clinical presentation that might be associated to a worse prognosis compared with patients with single-vessel (SV) involvement., Methods: The Spanish multicentre nationwide prospective SCAD registry included 389 consecutive patients. Patients were classified, according to the number of affected vessels, in SV or MV SCAD. Major adverse events (MAE) were analyzed during hospital stay and major cardiac or cerebrovascular adverse events (MACCE) at long-term clinical follow-up., Results: A total of 41 patients (10.5%) presented MV SCAD. These patients had more frequently a previous history of hypothyroidism (22% vs 11%, p = 0.04) and anxiety disorder (32% vs 16%, p = 0.01). MV SCAD patients presented more often as non-ST segment elevation myocardial infarction (73% vs 52%, p = 0.01) and showed less frequently type 1 angiographic lesions (12% vs 21%, p = 0.04). An impaired initial Thrombolysis In Myocardial Infarction (TIMI) flow 0-1 was less frequent (14% vs 29%, p < 0.01) in MV SCAD. In both groups, most patients were treated conservatively (71% vs 79%, p = NS). No differences were found regarding in-hospital MAE or MACCE at late follow-up (median 29 ± 11 months). However, the rate of stroke was higher in MV SCAD patients, both in-hospital (2.4% vs 0%, p < 0.01) and at follow-up (5.1% vs 0.6%, p = 0.01)., Conclusions: Patients with MV SCAD have some distinctive clinical and angiographic features. Although composite clinical outcomes, in-hospital and at long-term follow-up, were similar to those seen in patients with SV SCAD, stroke rate was significantly higher in patients with MV SCAD., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute myocardial infarction. Coronary angiography remains the best diagnostic tool; however, clinical suspicion and experience is required to interpret angiographic findings. This study sought to assess the clinical implications of the "broken line" (BKL) angiographic pattern in a large, nationwide, cohort of patients with SCAD. The Spanish SCAD registry (NCT03607981) prospectively enrolled consecutive patients with SCAD. All angiograms were centrally analyzed and the BKL pattern was systematically assessed. The BKL angiographic pattern was found in 64 of 389 patients (16%). Patients with the BKL appearance were more frequently female (97 vs 87%, p <0.05), presented more often as intramural hematoma (83 vs 58%, p <0.001), had longer lesions (47 ± 29 vs 36 ± 22 mm, p <0.01), and had severe tortuosity (25 vs 10%, p <0.01) but showed better initial coronary flow (thrombolysis in myocardial infarction flow 2.6 ± 0.8 vs 2.1 ± 1.2, p <0.01). Patients with BKL received more frequently conservative medical management (91 vs 76%, p <0.01). At late clinical follow-up (median 29 months, interquartile range 17 to 38) predefined adverse events (death, myocardial infarction, revascularization, recurrent SCAD, or stroke) occurred less frequently (3.5 vs 15%, p <0.05) in patients with the BKL appearance. The better clinical outcomes of patients in the BKL group persisted after adjusting for potential confounders (adjusted hazard ratio 0.2, 95% confidence interval 0.1 to 0.9, p <0.05). In conclusion, patients with SCAD presenting the BKL angiographic pattern are more frequently female and present more often as intramural hematoma with longer lesions and severe vessel tortuosity but have better coronary flow. Patients with the BKL morphology have a favorable prognosis (NCT03607981)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y 12 inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS., Materials and Methods: In this prospective, randomized, crossover study, patients ( n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y 12 ., Results: The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 μM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed., Conclusion: In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy., Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02457130]., Competing Interests: JF reports: Speaker fees from Eli Lilly Co., Daiichi Sankyo, Inc., AstraZeneca, Roche Diagnostics, Pfizer, Abbott, Ferrer, Rovi, Boehringer Ingelheim, and Bristol-Myers Squibb; consulting fees from AstraZeneca, Eli Lilly Co., Ferrer, Boston Scientific, Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Bristol-Myers Squibb; and research grant from AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marcano, Gracida, Roura, Gomez-Lara, Romaguera, Teruel, Fuentes, Muntané-Carol, Meroño, Sosa, Gómez-Hospital, Comin-Colet and Ferreiro.)

Objective: Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute coronary syndrome. Our aim was to assess adverse events at follow-up from a nationwide prospective cohort., Methods: The Spanish Registry on SCAD (SR-SCAD) included patients from 34 hospitals. All coronary angiograms were analysed by two experts. Those cases with doubts regarding the diagnosis of SCAD were excluded. The angiographic SCAD classification by Saw et al was followed. Major adverse cardiovascular and cerebrovascular event (MACCE) was predefined as composite of death, myocardial infarction, unplanned revascularisation, SCAD recurrence or stroke. All events were assigned by a Clinical Events Committee., Results: After corelab evaluation, 389 patients were included. Most patients were women (88%); median age 53 years (IQR 47-60). Most patients presented as non-ST-segment-elevation myocardial infarction (54%). A type 2 intramural haematoma (IMH) was the most frequent angiographic pattern (61%). A conservative initial management was selected in 78% of patients. At a median time of follow-up of 29 months (IQR 17-38), 46 patients (13%) presented MACCE, mainly driven by reinfarctions (7.6%) and unplanned revascularisations (6.2%). Previous history of hypothyroidism (HR 3.79; p<0.001), proximal vessel involvement (HR 2.69; p=0.009), type 2 IMH (HR 2.12; p=0.037) and dual antiplatelet therapy (DAPT) at discharge (HR 2.18; p=0.042) were independent predictors of MACCE., Conclusions: In this large prospective cohort of patients with SCAD, prognosis was overall favourable, with events mainly driven by reinfarctions or unplanned revascularisations. History of hypothyroidism, proximal vessel involvement, type 2 IMH and DAPT at discharge were associated with MACCE., Trial Registration Number: NCT03607981., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Objectives: To assess, in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous intervention, the pace of introduction in clinical practice (2010-2017) of drug-eluting stents (DES), ticagrelor, prasugrel, and prolonged dual antiplatelet therapy (DAPT) duration, and their potential impact on the risk of 2-year outcomes., Methods: Prospective and exhaustive community-wide cohort of 14 841 STEMI patients undergoing primary percutaneous intervention between 2010 and 2017. Index episodes were obtained from the Catalan Codi IAM Registry, events during follow-up from the Minimum Data Set and DAPT were defined by pharmacy dispensation. Follow-up was 24 months. The temporal trend for exposures and outcomes was assessed using regression models., Results: Age> 65 years, diabetes, renal failure, previous heart failure, and need for anticoagulation at discharge were more frequent in later periods (P <.001). From 2010 to 2017, the use of DES increased from 31.1% to 69.8%, ticagrelor from 0.1% to 28.6%, prasugrel from 1.5% to 23.8%, and the median consecutive months on DAPT from 2 to 10 (P <.001 for all). Adjusted analysis showed a temporal trend to a lower risk of the main outcome over time: the composite of death, acute myocardial infarction, stroke and repeat revascularization (absolute odds reduction 0.005% each quarter; OR, 0.995; 95%CI, 0.99-0.999; P=.028). The odds of all individual components except stroke were reduced, although significance was only reached for revascularization., Conclusions: Despite a strong increase between 2010 and 2017 in the use and duration of DAPT and the use of ticagrelor, prasugrel and DES, there was no substantial reduction in major cardiovascular outcomes., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes., Methods and Results: We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44-0.96; Pnon-inferiority < 0.001; Psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46-0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups., Conclusion: In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome., Clinical Trial Registration: ClinicalTrials.gov: NCT03321032., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute coronary syndrome. Many patients with SCAD have associated coronary risk factors. However, the implications of arterial hypertension in SCAD patients remain unknown., Objective: This study sought to assess the clinical implications of arterial hypertension in a nationwide cohort of patients with SCAD., Methods: The Spanish SCAD registry (NCT03607981) prospectively enrolled 318 consecutive patients. All coronary angiograms were centrally analyzed to confirm the diagnosis of SCAD. Patients were classified according to the presence of arterial hypertension., Results: One-hundred eighteen patients (37%) had a diagnosis of arterial hypertension. Hypertensive SCAD patients were older (60 ± 12 vs. 51 ± 9 years old) and had more frequently dyslipidemia (56 vs. 23%) and diabetes (9 vs. 3%) but were less frequently smokers (15 vs. 35%) than normotensive SCAD patients (all P < 0.05). Most patients in both groups were female (90 vs. 87%, NS) and female patients with hypertension were more frequently postmenopausal (70 vs. 47%, P < 0.05). Hypertensive SCAD patients had more severe lesions and more frequently multivessel involvement (15 vs. 7%, P < 0.05) and coronary ectasia (19 vs. 7%, P < 0.05) but showed a similar prevalence of coronary tortuosity (34 vs. 26%, NS). Revascularization requirement was similar in both groups (17 vs. 26%, NS) but procedural success was significantly lower (65 vs. 88%, P < 0.05) and procedural-related complications more frequent (65 vs. 41%, P < 0.05) in SCAD patients with hypertension., Conclusion: Patients with SCAD and hypertension are older, more frequently postmenopausal and have more coronary risk factors than normotensive SCAD patients. During revascularization SCAD patients with hypertension obtain poorer results and have a higher risk of procedural-related complications (NCT03607981)., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Objectives: The vasomotor function of new-generation drug-eluting stents designed to enhance stent healing and reendothelialization is unknown. This study aimed to compare the endothelial function of the infarct-related artery (IRA) treated with bioactive circulating endothelial progenitor cell-capturing sirolimus-eluting stents (COMBO) vs polymer-free biolimus-eluting stents (BioFreedom) in ST-segment elevation myocardial infarction patients at 6 months. Secondary objectives were to compare the microcirculatory function of the IRA and stent healing at 6 months., Methods: Sixty patients were randomized to bioactive sirolimus-eluting stent vs polymer-free biolimus-eluting stents implantation. At 6 months, patients underwent coronary angiography with vasomotor, microcirculatory and optical coherence tomography examinations. Endothelial dysfunction of the distal coronary segment was defined as ≥ 4% vasoconstriction to intracoronary acetylcholine infusion., Results: Endothelial dysfunction was similarly observed between groups (64.0% vs 62.5%, respectively; P=.913). Mean lumen diameter decreased by 16.0 ±20.2% vs 16.1 ±21.6% during acetylcholine infusion (P=.983). Microcirculatory function was similar in the 2 groups: coronary flow reserve was 3.23 ±1.77 vs 3.23±1.62 (P=.992) and the index of microcirculatory resistance was 24.8±16.8 vs 21.3±12.0 (P=.440). Optical coherence tomography findings were similar: uncovered struts (2.3% vs 3.2%; P=.466), malapposed struts (0.1% vs 0.3%; P=.519) and major evaginations (7.1% vs 5.6%; P=.708) were observed in few cases., Conclusions: Endothelial dysfunction of the IRA was frequent and was similarly observed with new-generation drug-eluting stents designed to enhance stent reendothelialization at 6 months. Endothelial dysfunction was observed despite almost preserved microcirculatory function and complete stent coverage. Larger and clinically powered studies are needed to assess the role of residual endothelial dysfunction in ST-segment elevation myocardial infarction patients. Registered in ClinicalTrials.gov: NCT04202172., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background Early generation drug-eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium-dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device-related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable-polymer everolimus-eluting Xience (n=44), bioresorbable-polymer sirolimus-eluting Orsiro (n=35), polymer-free biolimus-eluting Biofreedom (n=24), bioactive endothelial-progenitor cell-capturing sirolimus-eluting Combo DES (n=25), polymer-based everolimus-eluting Absorb (n=44), and Mg-based sirolimus-eluting Magmaris BRS (n=34) underwent endothelium-dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow-up. Crude vasomotor responses of distal segments to low-dose acetylcholine (10 -6  mol/L) were different between groups: bioresorbablepolymer DEShad the worst (-8.4%±12.6%) and durable-polymer DES had the most physiologic (-0.4%±11.8%; P =0.014). High-dose acetylcholine (10 -4  mol/L) showed similar responses between groups (ranging from -10.8%±11.6% to -18.1%±15.4%; P =0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable-polymer DES) to 2.5%±4.5% (bioactive DES; P =0.056). In multivariate models, endothelium-dependent vasomotor response was associated with age, bioresorbable-polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low-dose and 68.9% with high-dose acetylcholine, without differences between groups. Conclusions At follow-up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.

Aims: Spontaneous coronary artery dissection (SCAD) is a relatively rare but well-known cause of acute coronary syndrome. Clinical features, angiographic findings, management and outcomes of SCAD in old patients (>65 years of age) remain unknown., Methods and Results: The Spanish multicentre prospective SCAD registry (NCT03607981), included 318 consecutive patients with SCAD. Data were collected between June 2015 and April 2019. All angiograms were analysed in a centralized corelab. For the purposes of this study, patients were classified according to age in two groups <65 and ≥65 years old and in-hospital outcomes were analysed. Fifty-five patients (17%) were ≥65 years old (95% women). Older patients had more often hypertension (76% vs. 29%, P < 0.01) and dyslipidaemia (56% vs. 30%, P < 0.01), and less previous (4% vs. 18%, P < 0.001) or current smoking habit (4% vs. 33%, P < 0.001). An identifiable trigger was less often present in old patients (27% vs. 43%, P = 0.028). They also had more often severe coronary tortuosity (36% vs. 11%, P = 0.036) and showed more frequently coronary ectasia (24% vs. 9%, P < 0.01). Older patients were more often managed conservatively (89% vs. 75%, P = 0.025), with no significant differences in major adverse cardiac events during index admission (7% vs. 8%, P = 0.858). There were no differences between groups in terms of in-hospital stay, new acute myocardial infarction, unplanned coronary angiography or heart failure., Conclusion: Older patients with SCAD show different clinical and angiographic characteristics compared with younger patients. Initial treatment strategy was different between groups, though in-hospital outcomes do not significantly differ (NCT03607981)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction and Objectives: Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute coronary syndrome. The characteristics and in-hospital clinical course of patients with SCAD in Spain remain unknown., Methods: We present data from consecutive patients included in the national prospective SCAD registry. Angiographic analysis was performed in a centralized core laboratory., Results: Between June 2015 and April 2019, we included 318 patients with SCAD (358 lesions) from 31 centers. Median age was 53 years, and 88% were women. The most frequent presentation was non-ST-segment elevation acute myocardial infarction (53%). The most frequently involved artery was the left anterior descending coronary artery (44%), predominantly affecting the distal segments (39%) and secondary branches (54%). Most lesions (62%) appeared on angiography as intramural hematoma, without double lumen. Conservative management was selected as the initial approach in most patients (78%). During the index admission, 6% of patients had a major adverse event and 4 patients (1.3%) died. Independent predictors of adverse events were initial management with percutaneous coronary intervention (OR, 5.97; P=.004) and angiographic presentation as intramural hematoma (OR, 4.96; P=.028)., Conclusions: In Spain, SCAD affects mainly middle-aged women. In most patients, the initial management strategy was conservative with excellent in-hospital survival. Initial management with percutaneous coronary intervention and angiographic presentation as intramural hematoma were related to the presence of in-hospital adverse events. Registered at ClnicalTrials.gov (Identifier: NCT03607981)., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Patients with heart failure (HF) display elevated levels of soluble fractalkine, a chemokine involved in inflammation processes, atherosclerosis and platelet activation. Further, fractalkine has been associated with reduced pharmacodynamic (PD) responsiveness to clopidogrel. The aim of this study was to investigate the association of fractalkine with the severity of HF and its impact on platelet activation and clopidogrel response in patients with coronary artery disease (CAD) with and without HF., Materials and Methods: This prospective PD study included 116 stable CAD patients on DAPT with aspirin and clopidogrel. Subjects were classified in two groups: patients with HF and reduced (<40%) left ventricular ejection fraction (HFrEF group, n = 56) and patients without HF (no HF group, n = 60). Clinical severity of HF was graded according to NYHA classification. Platelet function assays included vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry and light transmittance aggregometry. Fractalkine and P-selectin concentrations were determined by ELISA., Results: Fractalkine levels progressively increased with the severity of the disease in the HFrEF group (NYHA I: 471.2 ± 52.4 pg/ml, NYHA II: 500.5 ± 38.4 pg/ml, NYHA III: 638.9 ± 54.3 pg/ml, p for linear trend 0.023). Numerically higher concentrations of fractalkine were observed in the HFrEF group compared to the no HF group with borderline significance (p = 0.052). No significant differences in clopidogrel-induced platelet inhibition according to fractalkine values were observed in any of the groups., Conclusions: Fractalkine levels were increased in patients with HFrEF and positively associated with the functional severity of the disease. No evident impact of fractalkine on clopidogrel PD efficacy was found., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We present a case of atypical LMNA cardiomyopathy associated with the pathogenic variant p.Arg541Ser. The patient had early-onset severe ventricular arrhythmias but atrioventricular conduction was normal. Segmental motion abnormalities and a large transmural scar, mainly apical and lateral, were found at cardiac magnetic resonance, corresponding to areas of severe wall thinning at computed tomography and of low voltages at electroanatomic mapping. Ventricular tachycardia ablation was successful in controlling ventricular arrhythmias. Few other cases described patients with pathogenic variants in the Arg541 residue, and they displayed similar atypical features, suggesting a genotype-phenotype correlation which may have specific prognostic and therapeutic implications., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Aims: The aim of this study was to compare the hyperaemic flow and vasomotor response to endothelium-dependent stimuli between bioresorbable vascular scaffolds (BVS) and metallic everolimus-eluting stents (EES) at 13 months., Methods and Results: Seventy non-diabetic patients aiming to achieve complete revascularisation were randomised 1:1 to BVS or EES implantation. At 13 months, invasive coronary angiography was performed using intracoronary pressure and Doppler ultrasound measurements at rest and maximal hyperaemia. A vasomotor test to endothelium-dependent (acetylcholine) and independent (nitroglycerine) stimuli and optical coherence tomography (OCT) were also performed. Fifty-nine patients (30 BVS and 29 EES) underwent 13-month examination. Doppler ultrasound average peak velocity (49.0±17.5 vs 49.3±18.3 cm/sec; p=0.95), coronary blood flow (97.4±53.5 vs 88.3±46.7 ml/min; p=0.51), coronary flow reserve (2.6±0.9 vs 2.7±0.8; p=0.84) and fractional flow reserve (0.92±0.06 vs 0.94±0.04; p=0.17) were similar between the groups. The vasomotor test showed vasoconstriction response to acetylcholine in 75.6% proximal and 72.2% distal peri-scaffold segments without differences between study devices. BVS had larger in-scaffold vasoconstriction than EES (60.0% vs 27.6%; p=0.01) despite similar neointima response as assessed by OCT., Conclusions: BVS and EES had similar microcirculatory response to hyperaemia and predominant vasoconstrictive response in the peri-scaffold segments to endothelium-dependent stimuli. However, BVS exhibited larger vasoconstriction to endothelium-dependent stimuli in the scaffold segment.

Background: Diabetes mellitus predicts poorer outcomes in patients with acute coronary syndrome (ACS), but the magnitude of this association in patients at older ages remains controversial., Methods: Data were extracted from the Codi Infart database. All consecutive patients with diagnosis of ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) between 2010 and 2015 were included. We assessed the impact of diabetes mellitus on 30-day and one-year mortality in patients aged less than and at least 75 years., Results: A total of 12 792 cases were registered, of whom 3023 (23.6%) were aged at least 75 years. About 20% patients had previous diabetes mellitus diagnosis. Patients aged at least 75 years had higher prevalence of comorbidities, higher proportion of heart failure at admission, a more extensive coronary artery disease and significant delay to reperfusion (P < 0.001). Diabetes mellitus was associated with higher 30-day mortality both in young [odds ratio (OR) 1.97, 95% confidence interval (CI): 1.43-2.70] and in elderly patients (OR 1.43, 95% CI: 1.07-1.91). After adjusting for potential confounders, this association remained significant in young patients (OR 1.47, 95% CI: 1.00-2.16, P = 0.047), but not in the elderly (OR 1.14, P = 0.43). Likewise, a crude association between diabetes mellitus and one-year mortality was observed in both groups (young patients: HR = 1.93; 95% CI: 1.51-2.46; older patients: HR = 1.33; 95% CI: 1.08-1.64). However, after adjusting for potential confounders, this association remained significant in younger patients (HR = 1.46; 95% CI: 1.13-1.89; P < 0.001), but not in the elderly (HR = 1.16; P = 0.17)., Conclusion: A significant proportion of these nonselected patients with STEMI had previous diabetes mellitus. The association between diabetes mellitus and outcomes is different according to age.

Background: Thrombocytopenia after transcatheter aortic valve implantation (TAVI) is common and has been related to higher mortality and major complications. No comparison between balloon-expandable (BEV) and self-expanding valves (SEV) regarding drop platelet count (DPC) has been reported to date. The objectives of this study were to analyze the differences in DPC between BEVs or SEVs and their prognostic implications in clinical outcomes., Methods: We retrospectively analyzed patients undergoing TAVI. Platelet counts after TAVI were collected. Two groups were created: DPC ≤ 30% and DPC > 30%. VARC-2 criteria were used to define outcomes., Results: Study population was composed of 195 patients (age 77.5 ± 6.7, 57.4% males). All of them but one experienced DPC (mean DPC 31.9 ± 15.3%). DPC was significantly higher among the patients treated with BEV compared to those treated with SEV (36.3 ± 15.1% vs 27.7 ± 14.4, P < 0.001). After multivariate analysis, the use of BEV was independently associated with a higher rate of DPC > 30% (67.4% vs 36.0%; OR 3.4; 95% CI, 1.42-8.16). At 30 days, the DPC > 30% was associated with a higher rate of life-threatening/major bleeding, major vascular complications, in-hospital sepsis and mortality. At one year, there were no statistically significant differences in the mortality rate between groups (6.35% vs 10.0%, HR 1.54; 95% CI, 0.56-4.25)., Conclusions: In this study, the use of BEV was associated with a higher risk of DPC after TAVI. A DPC rate > 30% was associated with an increased risk of major complications at 30 days., (© 2018 Wiley Periodicals, Inc.)