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Dual antiplatelet therapy combining aspirin with a P2Y 12 -receptor inhibitor reduces atherothrombotic events following an acute coronary syndromes (ACS), but the relative merits of different P2Y 12 inhibitors remain unclear, despite several recent large-scale trials. We performed a network meta-analysis, representing the largest evidence to date to inform P2Y 12 inhibitor choice in patients with ACS. Fourteen studies were included, for a total population of 145,019 patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review. A network meta-analysis using a frequentist approach with surface under the cumulative ranking probability calculation was performed. Major adverse cardiovascular events (MACE), all-cause death, myocardial infarction (MI), definite stent thrombosis (ST) and major bleeding at 30-day and 1-year all-cause death and MI were the study endpoints. At 30-day, prasugrel was superior to both clopidogrel and ticagrelor in MACE, all-cause death and definite ST endpoints. Both prasugrel and ticagrelor were superior to clopidogrel in MI endpoint. Ticagrelor also reduced all-cause death compared with clopidogrel. Ticagrelor, prasugrel, and clopidogrel resulted equivalent in terms of the safety outcome of 30-day major bleeding. No significant difference was found among clopidogrel, prasugrel, and ticagrelor with respect to 1-year MACE outcome. Both prasugrel and ticagrelor reduced the occurrence of 1-year all-cause death compared with clopidogrel. Prasugrel reduced 1-year MI rate as compared with clopidogrel, while ticagrelor did not. At probability analyses, prasugrel ranked best in all 30-day and 1-year efficacy and safety endpoints. In conclusion, in this network meta-analysis, prasugrel showed the highest efficacy in reducing adverse outcomes in ACS patients and had the highest probability of being the best P2Y 12 inhibitor to reduce hard adverse events both at 30-day and 1-year follow-up., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Since an association between myocardial infarction (MI) and respiratory infections has been described for influenza viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. The initial data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss the pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; and learnings that have emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.

Background: The optimal approach to guide percutaneous coronary intervention (PCI) has yet to be defined. The aim of this study was to compare functional driven (fractional flow reserve) versus intravascular imaging (intravascular ultrasound, IVUS, and/or optical coherence tomography, OCT) versus standard (coronary angiography only, CA)-guided PCI., Methods: Randomized controlled trials (RCTs) and propensity score weight-matched studies (PSWMs) comparing FFR versus IVUS versus OCT versus CA-guided PCI were included. Major adverse cardiovascular event (MACE; a composite end point of death or myocardial infarction [MI] or revascularization) was the primary endpoint, whereas definite stent thrombosis (ST) and single components of MACE were the secondary ones. Primary analyses were performed including only RCTs, secondary also with PSWMs., Results: Thirty-three studies were included in the analysis, 16 RCTs and 17 PSWMs. After 2 (1-3) years, IVUS performed better for MACE than CA (odds ratio [OR] 0.75 0.52-0.88), whereas there was just a trend for FFR (OR 0.81, 0.64-1.02). These results were mainly driven by reduced risk of all cause death, MI (FFR OR 0.74:0.57-0.99 and IVUS OR 0.82:0.54-0.94) and revascularization. IVUS reduced ST while FFR did not, and at meta-regression analysis, there was a trend for superiority of IVUS versus FFR to reduce subsequent MI in acute coronary syndrome (ACS) patients. The present results were consistent also after adding studies with PSWMs., Conclusions: Functional and intravascular imaging approaches seem to perform similarly in term of clinical outcomes, while both performed better compared with the standard approach. Imaging showed a potential benefit for ACS patients. The present results stress the need for a wider use of functional or imaging driven PCI., (© 2019 Wiley Periodicals, Inc.)

Background: Provisional T-stenting (PS) is generally recommended to treat patients with coronary bifurcation disease (CBD) percutaneously, but PS may not fit all complex bifurcation anatomies. Therefore, several types of up-front 2-stent techniques have been described. We aimed to identify the best percutaneous coronary intervention (PCI) technique to manage patients with CBD., Methods: We systematically reviewed randomized controlled trials (RCTs) including patients undergoing CBD PCI which included several types of PCI techniques-PS, double-kissing (DK) crush, T-stenting and protrusion, culotte, dedicated bifurcation stents, crushing, and T-stenting-and we compared device-oriented clinical events (DOCEs), a composite of cardiac death, target-vessel myocardial infarction, stent thrombosis, and target-lesion or target-vessel revascularization, in a network meta-analysis. We included 26 RCTs, leading to a pooled population of 10,339 patient-years and a total of 1229 DOCEs., Results: The DK-crush technique was associated with the lowest DOCE rate, with a relative risk of 0.62 (95% CI 0.42-0.92) compared with the PS technique. DK-crush had the highest probability (model likelihood 90.2%, area under the cumulative ranking curve 98.0%) of being the best technique among those explored to reduce DOCEs in patients receiving CBD PCI., Conclusions: When a 2-stent strategy is considered in a patient with CBD, the DK-crush technique reduces DOCEs compared with other bifurcation techniques based on all available RCTs., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks., Methods: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents., Results: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events., Conclusion: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Background: There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations., Methods: In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 μm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed., Results: From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12-22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES., Conclusion: In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events., Trial Registration: ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.

Introduction: The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel., Methods: All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3-5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2-5 bleeding, cardiovascular death and stent thrombosis., Results: A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs . D2 6.7% vs . D3 7.2%, p  = 0.003) and MACE (10% vs . 6.2% vs . 2.4%, p  < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs . 1.3% vs . 1.6%, p  < 0.001), cardiovascular death (5.1% vs . 1.0% vs . 1.2%, p  < 0.0001) and recurrent myocardial infarction (8.3% vs . 5.2% vs . 3.5%, p  = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2-5 bleedings (4.6% vs . 5.7% vs . 6.2%, p  = 0.04) and a trend towards a higher risk of BARC 3-5 bleedings (2.4% vs . 3.3% vs . 3.9%, p  = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction., Conclusion: In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk-benefit ratio for longer DAPT due to excess of bleedings.

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

Background: Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients., Objectives: This study aimed to investigate age-related differences in TTS., Methods: Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups., Results: Of 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups., Conclusions: A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance., Methods: In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients' care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h., Results: 80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function., Conclusion: Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion., Drain Trial: ClinicalTrials.gov number NCT03592836.

Background: The incidence of cardiovascular disorders in people living with HIV (PLWH) is higher than that in non-infected individuals. Traditional and specific risk factors have been described but the role of the gut microbiota-dependent choline metabolite, trimethylamine-N-oxide (TMAO) is still unclear., Methods: A cross-sectional analysis and a longitudinal analysis (with high-dose probiotic supplementation) were performed to measure serum TMAO concentrations through UHPLC-MS/MS. Stable outpatients living with HIV on highly active antiretroviral treatment with no major cardiovascular disease were enrolled. Non-parametric tests (bivariate and paired tests) and a multivariate linear regression analysis were used., Results: A total of 175 participants were enrolled in the study. Median serum TMAO concentrations were 165 (103-273) ng/mL. An association with age, serum creatinine, number of antiretrovirals, multimorbidity and polypharmacy was observed; at linear logistic regression analysis, multimorbidity was the only independent predictor of TMAO concentrations. Carotid intima media thickness (IMT) was 0.85 (0.71-1.21) mm, with a trend towards higher TMAO concentrations observed in patients with IMT >0.9 mm (P=0.087). In the 25 participants who received probiotic supplementation, TMAO levels did not significantly change after 24 weeks (Wilcoxon paired P=0.220)., Conclusion: Serum TMAO levels in PLWH were associated with multimorbidity, higher cardiovascular risk and subclinical atherosclerosis and were not affected by 6 months of high-dose probiotic supplementation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The association between prior stroke/transient ischemic attack (TIA) and clinical outcomes in patients with acute coronary syndrome (ACS) has not been well explored. We evaluated the impact of prior stroke/TIA on this specific patient population. We conducted an international multicenter study including 15 401 patients with ACS from the Bleeding Complications in a Multicenter Registry of Patients Discharged With Diagnosis of Acute Coronary Syndrome registry. They were divided into 2 groups: patients with and without prior stroke/TIA. The primary end point was death at 1-year follow-up. Prior stroke/TIA was associated with higher rate of 1-year death (8.7% vs 3.4%; P < .001). It was an independent predictor of 1-year death even after adjustment for confounding variables (odds ratio, 1.705; 95% confidence interval, 1.046-2.778; P = .032). Besides, patients with prior stroke/TIA had significantly increased 1-year reinfarction (5.6% vs 3.8%, P = .015), in-hospital bleeding (8.7% vs 5.8%, P < .001), and 1-year bleeding (5.2% vs 3.0%, P < .001). No difference of antithrombotic therapies or dual antiplatelet therapy (DAPT) types on outcomes was observed in patients with prior stroke/TIA. Prior stroke/TIA was associated with higher 1-year death for patients with ACS who underwent percutaneous coronary intervention. No benefits or harms were observed with different antithrombotic therapies or DAPT types in these patients.

Background: Although the majority of venous thromboembolic events occurs in primary care, most of the studies concerning its prophylaxis investigate hospitalized patients. Therefore, in primary care, many clinical decisions have to be taken in the absence of great clinical evidence derived from studies performed directly on outpatients. The objective of our study is to evaluate the clinical approach of Italian General Practitioners to the prophylaxis of venous thromboembolism in medical outpatients., Methods: A web-based questionnaire was emailed to 766 Italian General Practitioners. In the questionnaire there were four exemplary clinical cases concerning hypothetical patients at venous thromboembolic risk., Results: Overall 232 questionnaires were returned. Approximately 40% of the participants reported to assess thrombotic and hemorrhagic risk with a risk assessment model but nevertheless only a narrow minority had recourse to a suitable and validated score for this purpose. In the chronically bedridden patient about half of the participants administered a heparin or an antiplatelet drug for long time. In acute outpatients at high venous thromboembolic risk there was a considerable underuse of heparin prophylaxis and graduated compression stockings were often considered as a first prophylactic option. Prolonged heparin prophylaxis in the post-acute setting was also the practice for half of the participants., Conclusions: Italian General Practitioners approach these "grey" areas of uncertainty in a significantly heterogeneous way and sometimes in sharp contrast to the recent evidence.  The present findings stress the need for further targeted educational programs and new high quality studies to further deep this clinical context.

Background: Stent thrombosis (ST) is a rare, but potentially fatal complication. Procedural problems, such as stent under-dimension/under-expansion or dual antiplatelet drug resistance may result into ST. These conditions are more frequent during primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI)., Case Summary: A 60-year-old male patient presented to our hospital with an inferior STEMI. In the emergency department, a dual antiplatelet therapy was administered with ticagrelor 180 mg and aspirin 250 mg IV. During the observation, the patient experienced a ventricular fibrillation. Urgent coronary angiography showed an occlusion of the proximal right coronary artery. Thrombus aspiration was performed followed by implantation of one drug-eluting stent. After 45 min early ST occurred and was treated by immediate thrombus aspiration and post-dilatation. Intravascular ultrasound sonography (IVUS) showed severe strut malapposition due to a partial crush after post-dilatation. Since it was not possible to directly insert the first guidewire in the stent lumen, the IVUS probe was placed between the vessel wall and the crushed stent to guide the manoeuvre., Discussion: Crushed stent is a rare complication, being caused by an incorrect passage of the guidewire between the stent's struts and the vessel wall in case of severe underexpansion. In this case, an IVUS-guided re-entry could be an option to gain the stent true lumen and avoid a second stent implantation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Among survivors of pediatric acute lymphoblastic leukemia (ALL), those who received hematopoietic stem cell transplantation (HSCT) conditioned with total-body irradiation (TBI) show the highest risk of late complications, including cardiovascular (CV) disease. Advanced glycation end products (AGEs) have been associated with CV disease in diabetes mellitus and other clinical conditions. This study explores AGEs plasma levels, inflammatory status, and lipid profile in survivors of pediatric ALL who received HSCT conditioned with TBI., Procedure: Inclusion criteria were (a) previous diagnosis of ALL at age < 18 years, treated with HSCT conditioned with TBI; (b) age > 18 at the time of the study enrollment; (c) off-therapy for at least five years. Radiotherapy other than TBI, preexisting heart disease, glucose metabolism impairment, body mass index > 25, active graft versus host disease (GvHD), smoking, or treatment with cholesterol lowering medications were exclusion criteria. Eighteen survivors and 30 age-matched healthy controls were enrolled., Results: AGEs plasma levels were markedly higher in ALL survivors than in healthy subjects (2.15 ± 2.21 vs 0.29 ± 0.15 pg/mL, P < 0.01). Survivors also showed higher levels of high-sensitivity C-reactive protein (2.32 ± 1.70 vs 0.88 ± 1.09 mg/dL, P < 0.05), IL-1β (7.04 ± 1.52 vs 4.64 ± 2.02 pg/mL, P < 0.001), IL17 (37.44 ± 3.51 vs 25.19 ± 6.34 pg/mL, P < 0.001), an increased glutathione/reduced glutathione ratio (0.085 ± 0.07 vs 0.041 ± 0.036, P < 0.05) and slight alterations in their lipid profile., Conclusions: Our data show AGEs accumulation and chronic inflammation in ALL survivors who received HSCT conditioned with TBI. These alterations may contribute to the increased risk of CV disease reported in these subjects., (© 2019 Wiley Periodicals, Inc.)

Aim: To evaluate sex difference in culprit plaque features at optical coherence tomography (OCT) and major adverse cardiovascular events at follow-up. Patients and methods: We analyse data from the OCT-FORMIDABLE (OCT-Features Of moRphology, coMposItion anD instABility of culprit and pLaquE in acute coronary syndrome [ACS] patients) registry. A total of 285 patients (20%, 58 females) were included. Results:  Females with ST segment elevation myocardial infarction showed a longer ruptured area of the plaque (8.6 ± 7.6 vs 4.6 ± 5.4; p = 0.003) and a major necrotic core macrophage infiltration (43 vs 17%; p = 0.017). Females with non-ST segment elevation-ACS had less lipidic plaques (62 vs 80%; p = 0.04). No between-group sex differences in major adverse cardiovascular events emerged at follow-up (5 vs 9%; p = 0.88 in ST segment elevation myocardial infarction group and 19 vs 15%; p = 0.6 in non-ST segment elevation-ACS group). At multivariate analysis, female sex was not a major risk of plaque rupture (hazard ratio [HR]: 1.59, CI: 0.44-5.67; p = 0.48). Conclusion: Female sex seems to have no significant impact. ClincalTrial. gov registration number: NCT02486861.

Background: There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations., Methods: All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [<3 mm] versus long overlap), strategy (provisional versus 2-stent), routine versus bail-out FKI, and the use of imaging and proximal optimization technique., Results: Two thousand seven hundred forty-two patients were included. At 16 months (8-20) follow-up, inverse probability of treatment weighting adjusted rates of major adverse cardiac event were similar between FKI and no-FKI group (15.1% versus 15.5%; P =0.967), this result did not change with use of imaging, proximal optimization technique, or routine versus bail-out FKI. In the 2-stent subgroup, FKI was associated with lower rates of target vessel revascularization (7.8% versus 15.9%; P =0.030) and target lesion revascularization (7.3% versus 15.2%; P =0.032). Short overlap FKI was associated with a lower rate of target lesion revascularization compared with no FKI (2.6% versus 5.4%; P =0.034), while long overlap was not (6.8% versus 5.4%; P =0.567)., Conclusions: In patients with bifurcations or unprotected left main treated with ultrathin stents, short overlap FKI is associated with less restenosis. In a 2-stent strategy, FKI was associated with less target vessel revascularization and restenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03544294.

Objectives: Evaluate safety and efficacy of polymer-free biolimus-eluting stents (PF-BESs) versus ultrathin stents in unprotected left main (ULM) or bifurcation., Background: PF-BESs due to reduced length of dual antiplatelet therapy (DAPT) are increasingly used. However, there are limited data about safety and efficacy for ULM or bifurcation., Methods: We selected all-patients treated for ULM or bifurcation from two multicenter real life registries (RAIN [NCT03544294] evaluating ultrathin stents, CHANCE [NCT03622203] appraising PF-BES). After propensity score with matching, the primary endpoint was major adverse cardiac events (MACE; a composite of all-cause death, myocardial infarction, target lesion revascularization [TLR], and stent thrombosis [ST]), while its components along with target vessel revascularization (TVR) secondary endpoints., Results: Three thousand and three patients treated with ultrathin stents and 446 with PF-BESs, resulting respectively in 562 and 281 after propensity score with matching (33 and 22%, respectively, with ULM disease). After 12 (8-20) months, rates of MACE were similar (9 vs. 8%, p = 0.56) without difference in TLR and ST (3.0 vs. 1.7%, p = .19 and 1.8 vs. 1.1%, p = .42). These results were consistent for ULM group (3 vs. 1.7% and 1.8 vs. 1.1%, p = .49 and .76), for non-ULM group (2.1 vs. 3.4%, p = .56 and 1.2 vs. 1.7%, p = .78) and for two-stent strategy (8.7 vs. 4.5% and 4.3 vs. 3.2%, p = .75 and .91). Among patients treated with 1 month of DAPT in both groups, those with ultrathin stents experienced higher rates of MACE related to all-cause death (22 vs. 12%, p = .04) with higher although not significant rates of ST (3 vs. 0%, p = .45)., Conclusions: PF-BES implanted on ULM or BiF offered freedom from TLR and ST comparable to ultrathin stents. PF-BESs patients assuming DAPT for 1 month experienced a lower despite not significant incidence of ST., (© 2019 Wiley Periodicals, Inc.)

Background: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario., Methods: 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared., Results: After a median follow-up of 14 (interquartile range 12-20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p = .01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p = .05 for comparison)., Conclusion: Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (<100 microns) in unprotected left main (ULM) or coronary bifurcation remain undefined. All consecutive patients presenting with a critical lesion of an ULM or involving a main coronary bifurcation who were treated with very thin strut stents were included. MACE (a composite end point of cardiovascular death, myocardial infarction [MI], target lesion revascularization [TLR], and stent thrombosis [ST]) was the primary endpoint, whereas target vessel revascularization (TVR) was the secondary endpoint, with particular attention to type and occurrence of ST and occurrence of ST, CV death, and MI during DAPT or after DAPT discontinuation. All analyses were performed according to length of DAPT dividing the patients in 3 groups: Short DAPT (3-months), intermediate DAPT (3 to 12 months), and long DAPT (12-months). A total of 117 patients were discharged with an indication for DAPT ≤3 months (median 1: 1 to 2.5), 200 for DAPT between 3 and 12 months (median 8: 7 to 10), and 1,958 with 12 months DAPT. After 12.8 months (8 to 20), MACE was significantly higher in the 3-month group compared with 3 to 12 and 12-month groups (9.4% vs 4.0% vs 7.2%, p ≤0.001), mainly driven by MI (4.4% vs 1.5% vs 3%, p ≤0.001) and overall ST (4.3% vs 1.5% vs 1.8%, p ≤0.001). Independent predictors of MACE were low GFR and a 2 stent strategy. Independent predictors of ST were DAPT duration <3 months and the use of a 2-stent strategy. In conclusion, even stents with very thin strut when implanted in real-life ULM or coronary bifurcation patients discharged with short DAPT have a relevant risk of ST, which remains high although not significant after DAPT cessation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: A large trial established the favourable clinical profile of a new polymer-free biolimus A9-eluting stent (PF-BES) with a one-month dual antiplatelet therapy (DAPT) regimen in patients at high bleeding risk (HBR). We aimed to evaluate the real-world patterns of indications, DAPT strategies and outcomes for the PF-BES following this evidence., Methods and Results: CHANCE is a multicentre registry including all patients who underwent percutaneous coronary intervention (PCI) with at least one PF-BES. The reasons for the PF-BES PCI and planned antithrombotic regimens were collected. Primary outcomes were the 390-day Kaplan-Meier estimates of patient-oriented and device-oriented composite endpoints (POCE: death, myocardial infarction [MI] or target vessel revascularisation [TVR]; DOCE: cardiac death, target vessel MI or ischaemia-driven target lesion revascularisation [ID-TLR]). Between January 2016 and July 2018, 858 patients (age 74±10 years, 64.6% male, 58.7% acute coronary syndrome presentation) underwent PF-BES PCI. The main reasons for the physicians' choice of PF-BES reflected a perceived HBR in 77.7% of patients. One-month DAPT was planned in 40.3% of patients. At 390-day follow-up (median 340 days, interquartile range: 187-390 days), the estimated incidence of POCE was 13.1% (any MI 3.7%, any TVR 3.4%) and of DOCE was 7.1% (TV-MI 3.6%, ID-TLR 1.4%), while the 390-day estimate of any bleeding event was 11.1% (BARC 3-5 bleeding 3.0%)., Conclusions: In a large all-comers registry, PF-BES was used mostly in HBR patients, frequently followed by a very short DAPT regimen. The reported outcomes suggest a favourable safety and efficacy profile for the PF-BES in a real-world clinical setting. ClinicalTrials.gov identifier: NCT03622203.

A significant proportion of patients undergoing percutaneous coronary intervention (PCI) is deemed at high bleeding risk. Definition and identification of high bleeding risk patients at the time of PCI is extremely important to inform decision-making regarding antithrombotic treatment selection and optimize the balance between ischemic and bleeding risk. The recent introduction of standardized definitions and tools to identify and treat patients at high bleeding risk is promising to improve evidence-based care in this subgroup of patients.

Aims: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS)., Methods and Results: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting., Conclusion: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Introduction and Objectives: For patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), it is unclear whether angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are associated with reduced mortality, particularly with preserved left ventricular ejection fraction (LVEF). The goal of this study was to determine the association between ACEI/ARB and mortality in ACS patients undergoing PCI, with and without reduced LVEF., Methods: Data from the BleeMACS registry were used. The endpoint was 1-year all-cause mortality. The prognostic value of ACEI/ARB was tested after weighting by survival-time inverse probability and after adjustment by Cox regression, propensity score, and instrumental variable analysis., Results: Among 15 401 ACS patients who underwent PCI, ACEI/ARB were prescribed in 75.2%. There were 569 deaths (3.7%) during the first year after hospital discharge. After multivariable adjustment, ACEI/ARB were associated with lower 1-year mortality, ≤ 40% (HR, 0.62; 95%CI, 0.43-0.90; P=.012). The relative risk reduction of ACEI/ARB in mortality was 46.1% in patients with LVEF ≤ 40%, and 15.7% in patients with LVEF> 40% (P value for treatment-by-LVEF interaction=.008). For patients with LVEF> 40%, ACEI/ARB was associated with lower mortality only in ST-segment elevation myocardial infarction (HR, 0.44; 95%CI, 0.21-0.93; P=.031)., Conclusion: The benefit of ACEI/ARB in decreasing mortality after an ACS in patients undergoing PCI is concentrated in patients with LVEF ≤ 40%, and in those with LVEF> 40% and ST-segment elevation myocardial infarction. In non-ST-segment elevation-ACS patients with LVEF> 40%, further studies are needed to assess the prognostic impact of ACEI/ARB., (Copyright © 2019. Published by Elsevier España, S.L.U.)

Background: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies., Methods: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup., Results: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively)., Conclusions: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: In experimental animal models, exogenous aldosterone excess has been linked to the progression of renal disease. However, the evidence of an increased risk of renal damage in patients affected by primary aldosteronism remains controversial. We aimed at evaluating the association between primary aldosteronism and renal damage through a meta-analysis., Methods: We performed a quantitative review of studies evaluating parameters of renal function in patients affected by primary aldosteronism compared with hypertensive patients without primary aldosteronism and in patients affected by primary aldosteronism before and after treatment. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1960 up to April 2019., Results: Forty-six studies including 6056 patients with primary aldosteronism and 9733 patients affected by arterial hypertension without primary aldosteronism were included. After 8.5 years from hypertension diagnosis, patients with primary aldosteronism had an increased estimated glomerular filtration rate (eGFR) compared with hypertensive patients without primary aldosteronism [by 3.37 ml/min IQR (0.82-5.93)] and a more severe albuminuria [standard mean difference 0.55 (0.19-0.91)], resulting into an association with microalbuminuria [odds ratio (OR) 2.09 (1.40; 3.12)] and proteinuria [OR 2.68 (1.89;3.79)]. Following primary aldosteronism treatment, after a median follow-up of 12 months, a reduction in eGFR was observed [by -10.69 ml/min (-13.23; -8.16)], consistent in both medically and surgically treated patients. Similarly, a reduction in albumin excretion and an increase in serum creatinine were observed after treatment., Conclusion: Patients affected by primary aldosteronism, compared with patients affected by arterial hypertension without primary aldosteronism, display a more pronounced target organ damage, which can be mitigated by the specific treatment.

Aims: To assess the long-term outcomes of patients treated with sirolimus-eluting Stentys stent in a real-life setting., Background: Few data regarding the safety and effectiveness of self-apposing sirolimus-eluting Stentys stent are available., Methods: 278 patients (30% stable coronary artery disease, 70% acute coronary syndromes, and 54% on unprotected left main) treated with sirolimus eluting Stentys stent were retrospectively included in the self-aPposing, bAlloon-delivered, siRolimus-eluting stent for the Treatment of the coronary Artery disease multicenter registry. Major adverse cardiovascular events (MACE, a composite of cardiac death, myocardial infarction, target lesion revascularization, stent thrombosis) were the primary end-point, single components of MACE were the secondary ones., Results: After 13 months (interquartile range 5-32), MACE was 14%. Stent thrombosis occurred in 3.9% of the patients (2.5% definite stent thrombosis and 1.4% probable stent thrombosis), 66% of them presenting with ST-segment elevation myocardial infarction (STEMI) at admission. Cardiovascular death, target lesion revascularization and myocardial infarction was 4.7%, 8.3%, and 7.2%, respectively. At multivariate analysis, risk of MACE was increased by diabetes (hazard ratios 4.76; P = 0.002) but was not affected by the indication leading to sirolimus-eluting Stentys stent implantation (marked vessel tapering vs. coronary ecstasies, hazard ratios 0.74, P = 0.71)., Conclusion: Sirolimus-eluting Stentys stent may represent a potential solution for specific coronary anatomies such as bifurcation, ectasic, or tapered vessels. Risk of stent thrombosis appears related to clinical presentation with STEMI and to anatomic features, stressing the importance of the use of intracoronary imaging for self-expandable stents implantation.

Aims: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction., Methods and Results: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985)., Conclusion: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 3 cells/μL emerged as independent predictors for thrombus formation or embolism., Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Background: Early hypo-attenuated leaflet thickening after transcatheter aortic valve implantation (TAVI) has been recently described presumably reflecting thrombus apposition. Although its clinical relevance is still unknown, oral anticoagulant therapy (OAT) led to almost complete resolution., Methods: The retrospecitve Italian Transcatheter balloon-Expandable valve registry that included all patients undergoing balloon-expandable TAVI in 33 Italian centers. Patients discharged after TAVI with aspirin alone were compared with those assuming aspirin and OAT before and after propensity score with matching. Prosthetic heart valve dysfunction at follow-up was the primary end point. All-cause death, cardiovascular death, bleeding, vascular complications and cerebrovascular accidents at 30 days and at follow-up were the secondary ones., Results: Among the 1904 patients enrolled in the Italian Transcatheter balloon-Expandable valve registry, 716 patients on OAT and aspirin or aspirin alone were identified and analyzed: 555 were on aspirin alone and 161 on OAT and aspirin. The median follow-up was 44.0 ± 12 months. After matching, risk of prosthetic valve dysfunction at follow-up did not differ between the two groups: 3.1% in patients treated with aspirin alone vs. 1.9% in those treated with OAT and aspirin, (P = 0.72). Nevertheless patients treated with aspirin alone at follow-up had a significantly lower risk of death (21 vs. 33%, P = 0.03) and major bleeding (4 vs. 14%, P = 0.04) with a similar rate of stroke/transient ischemic attack (TIA) (1.2 vs. 3.1%, P = 0.45). At 30 days rates of Valve Academic Research Consortium death were similar in both groups (0.6 vs. 3.7%, P = 0.12) with higher risk of life threatening bleeding and minor vascular complications in patients on OAT and aspirin., Conclusion: After TAVI with Edwards Sapien valve OAT did not reduce the incidence of valve dysfunction and stroke but was responsible for mortality and bleeding increases.

Prognosis in pulmonary hypertension is strictly linked to right ventricle failure, which results from uncoupling between right ventricle function and its afterload. This study sought to describe how to estimate with echocardiography right ventricular wall tension, its correlation with right ventricle haemodynamics and its prognostic role. A total of 190 patients without overt right ventricle failure but with suspected pulmonary hypertension on a previous echocardiogram underwent right heart catheterization and nearly-simultaneous echocardiography. Right ventricular wall tension was estimated according to Laplace's law as right ventricle length × tricuspid regurgitation peak gradient and it was correlated with right ventricle haemodynamic profile; its potential prognostic impact was tested along with canonical right ventricle function parameters. Right ventricular wall tension correlated significantly with invasive estimation of right ventricle end-diastolic pressure (R: 0.343, p  < 0.001) and with several other haemodynamic variables, such as mean pulmonary artery pressure, pulmonary artery compliance, transpulmonary gradient, pulmonary vascular resistance, right atrial pressure and right ventricle stroke work index (all p  < 0.001). At a mean follow-up of five years and three months, only right ventricular wall tension was associated to all-cause mortality ( p  = 0.036), while tricuspid annular plane systolic excursion ( p  = 0.536), right ventricle fractional area change ( p  = 0.383), right ventricle fractional area change ( p  = 0.076), tricuspid regurgitation peak gradient ( p  = 0.107) and tricuspid annular plane systolic excursion/tricuspid regurgitation peak gradient ( p  = 0.181) could not. We identified a novel bedside echocardiographic predictor of altered right ventricle haemodynamics, which is precociously altered in patients without overt right ventricle failure and is associated to all-cause mortality at a long-term follow-up. Further studies are needed to confirm its role in pulmonary hypertension patients., (© The Author(s) 2019.)

Percutaneous cardiovascular interventions have changed dramatically in recent years, and the impetus given by the rapid implementation of novel techniques and devices have been mirrored by a refinement of antithrombotic strategies for secondary prevention, which have been supported by a significant burden of evidence from clinical studies. In the current manuscript, we aim to provide a comprehensive, yet pragmatic, revision of the current available evidence regarding antithrombotic strategies in the domain of percutaneous cardiovascular interventions. We revise the evidence regarding antithrombotic therapy for secondary prevention in coronary artery disease and stent implantation, the complex interrelation between antiplatelet and anticoagulant therapy in patients undergoing percutaneous coronary intervention with concomitant atrial fibrillation, and finally focus on the novel developments in the secondary prevention after structural heart disease intervention. A special focus on treatment individualization is included to emphasize risk and benefits of each therapeutic strategy.

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide-ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut-off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In-hospital outcomes and 1-year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P =0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P =0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1-year outcome compared with patients with early recovery ( P =0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1-year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Ischemic diseases in an aging population pose a heavy social encumbrance. Moreover, current therapeutic approaches, which aimed to prevent or minimize ischemia-induced damage, are associated with relevant costs for healthcare systems. Early reperfusion by primary percutaneous coronary intervention (PPCI) has undoubtedly improved patient's outcomes; however, the prevention of long-term complications is still an unmet need. To face these hurdles and improve patient's outcomes, novel pharmacological and interventional approaches, alone or in combination, reducing myocardium oxygen consumption or supplying blood flow via collateral vessels have been proposed. A number of clinical trials are ongoing to validate their efficacy on patient's outcomes. Alternative options, including stem cell-based therapies, have been evaluated to improve cardiac regeneration and prevent scar formation. However, due to the lack of long-term engraftment, more recently, great attention has been devoted to their paracrine mediators, including exosomes (Exo) and microvesicles (MV). Indeed, Exo and MV are both currently considered to be one of the most promising therapeutic strategies in regenerative medicine. As a matter of fact, MV and Exo that are released from stem cells of different origin have been evaluated for their healing properties in ischemia reperfusion (I/R) settings. Therefore, this review will first summarize mechanisms of cardiac damage and protection after I/R damage to track the paths through which more appropriate interventional and/or molecular-based targeted therapies should be addressed. Moreover, it will provide insights on novel non-invasive/invasive interventional strategies and on Exo-based therapies as a challenge for improving patient's long-term complications. Finally, approaches for improving Exo healing properties, and topics still unsolved to move towards Exo clinical application will be discussed.

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence., (The article has been co-published with permission in the European Heart Journal and EuroIntervention. All rights reserved. © The Author(s) 2018. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Objectives: We examined the incidence, the impact of subsequent cerebrovascular events and the clinical or procedural predictors of leaflet thrombosis (LT) in patients undergoing transcatheter aortic valve implantation (TAVI)., Methods: MEDLINE/PubMed was systematically screened for studies reporting on LT in TAVI patients. Incidence [both clinical and subclinical, i.e. detected with computed tomography (CT)] of LT was the primary end point of the study. Predictors of LT evaluated at multivariable analysis and impact of LT on stroke were the secondary ones., Results: Eighteen studies encompassing 11 124 patients evaluating incidence of LT were included. Pooled incidence of LT was 0.43% per month [5.16% per year, 95% confidence interval (CI) 0.21-0.72, I2 = 98%]. Pooled incidence of subclinical LT was 1.36% per month (16.32% per year, 95% CI 0.71-2.19, I2 = 94%). Clinical LT was less frequent (0.04% per month, 0.48% per year, 95% CI 0.00-0.19, I2 = 93%). LT increased the risk of stroke [odds ratio (OR) 4.21, 95% CI 1.27-13.98], and was more frequent in patients with a valve diameter of 28-mm (OR 2.89: 1.55-5.8), for balloon-expandable (OR 8: 2.1-9.7) or after valve-in-valve procedures (OR 17.1: 3.1-84.9). Oral anticoagulation therapy reduced the risk of LT (OR 0.43, 95% CI: 0.22-0.84, I2 = 64%), as well as the mean transvalvular gradient., Conclusions: LT represents an infrequent event after TAVI, despite increasing risk of stroke. Given its full reversal with warfarin, in high-risk patients (those with valve-in-valve procedures, balloon expandable or large-sized devices), a protocol which includes a control CT appears reasonable., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The real prognostic impact of MitraClip in patients with significant functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction remains to be elucidated. Two randomized controlled trials (RCTs) with conflicting results have been recently published. We conducted a comprehensive meta-analysis of all RCTs and adjusted observational studies to evaluate the clinical impact of percutaneous mitral valve repair when compared with optimal medical therapy (OMT) alone, in patients with symptomatic FMR and LV dysfunction. Death from any cause and heart failure rehospitalizations at the longest available follow-up were the primary endpoints. Cardiac death, one year and short-term death were the secondary ones. 2255 patients (1207 for MitraClip and 1048 for OMT-only) from 8 studies (2 RCTs and 6 observational studies) were included. At a median (mid-term) follow-up of 438 days (IQR 360-625) MitraClip was associated with a significant reduction of all-cause death (odds Ratio [OR] 0.55, 95%CI 0.41-0.73, p < 0.001; [ORadj] 0.66, 95%CI 0.49-0.90, p = 0.009) and rehospitalization (OR 0.49, 95%CI 0.24-1.00, p = 0.05 and ORadj 0.63, 95%CI 0.43-0.94, p = 0.02). At one year, adjusted analysis demonstrated a trend favoring the experimental cohort (ORadj 0.73, 95%CI 0.53-1.02, p = 0.07). Meta-regression suggested that benefit of MitraClip on mid-term survival persists even after accounting for the prevalence of implanted CRT, burden of comorbidities, NYHA class, cardiomyopathy etiology and LV function and dimensions. In conclusion, MitraClip for FMR in patients with LV dysfunction is associated with a considerable reduction of death and HF hospitalization at mid-term follow-up. Further ongoing RCTs are needed to strengthen present results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Percutaneous coronary intervention (PCI) for complex lesions, including unprotected left main (ULM) and bifurcations, is gaining a relevant role in treating coronary artery disease with good outcomes, also thanks to new generation stents. The daily risk of adverse cardiovascular events and their temporal distribution after these procedures is not known., Methods: All consecutive patients presenting with a critical lesion of ULM or bifurcation treated with very thin struts stents, enrolled in the RAIN-Cardiogroup VII study, were analyzed. The daily risk of major acute cardiovascular events (MACE), target lesion revascularization (TLR) and stent thrombosis (ST) and their temporal distribution in the first year of follow-up was the primary endpoint. Differences among subgroups (ULM, patient presentation, kind of stent polymer) were the secondary endpoint., Results: 2745 patients were included, mean age 68 ± 11 years, 33.3% diabetics, 54.5% had an acute coronary syndrome (ACS); 88.5% of treated lesions were bifurcations, 27.2% ULM. Average daily risk was 0.022% for MACE, 0.005% for TLR and 0.004% for ST, in the first year. Bimodal distribution of adverse events, especially TLR, with an early peak in the first 50 days and a late one after 150 days, was observed. Patients with ULM presented a significantly higher daily risk of events, and ACS patients presented higher MACE risk. No difference emerged according to the type of stent polymer., Conclusions: The daily risk of adverse events in the first year after complex PCI in our study is acceptably low. PCI on ULM carries a higher risk of complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: The safety and efficacy of prasugrel and ticagrelor in patients with diabetes mellitus presenting with acute coronary syndrome and treated with percutaneous coronary intervention remain to be assessed., Methods: All diabetes patients admitted for acute coronary syndrome and enrolled in the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) were compared before and after propensity score matching. Net adverse cardiovascular events (composite of death, stroke, myocardial infarction and BARC 3-5 bleedings) and major adverse cardiovascular events (composite of death, stroke and myocardial infarction) were the co-primary endpoints. Single components of primary endpoints were secondary endpoints., Results: Among 4424 patients enrolled in RENAMI, 462 and 862 diabetes patients treated with prasugrel and ticagrelor, respectively, were considered. After propensity score matching, 386 patients from each group were selected. At 19±5 months, major adverse cardiovascular events and net adverse cardiovascular events were similar in the prasugrel and ticagrelor groups (5.4% vs. 3.4%, P =0.16 and 6.7% vs. 4.1%, P =0.11, respectively). Ticagrelor was associated with a lower risk of death and BARC 2-5 bleeding when compared to prasugrel (2.8% vs. 0.8%, P =0.031 and 6.0% vs. 2.6%, P =0.02, respectively) and a clear but not significant trend for a reduction of BARC 3-5 bleeding (2.3% vs. 0.8%, P =0.08). There were no significant differences in myocardial infarction recurrence and stent thrombosis., Conclusion: Diabetes patients admitted for acute coronary syndrome seem to benefit equally in terms of major adverse cardiovascular events from ticagrelor or prasugrel use. Ticagrelor was associated with a significant reduction in all-cause death and bleedings, without differences in recurrent ischaemic events, which should be confirmed in dedicated randomised controlled trials.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.