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Although there is substantial evidence on the harmful effects of air pollution on human health, these are scarcely considered in the general clinical practice and also in the context of cardiovascular disease prevention. In light of the numerous epidemiological and basic research studies that have demonstrated the unfavorable impact of air pollution on the cardiovascular system, this review aims to bring this aspect to the attention of clinicians. This work describes the main air polluting components that can contribute to the onset and progression of cardiovascular diseases. The pathophysiological mechanisms underlying the impact of pollutants on the cardiovascular system and the available evidence regarding their effect on cardiovascular risk factors are reported. This article also examines the evidence relating to the correlation between environmental pollutants and some specific cardiovascular diseases, including acute coronary syndromes, cerebrovascular diseases, heart failure, and arrhythmias. Finally, the possible strategies to be implemented to limit pollution-induced cardiovascular damage are analyzed.

Aims: Ischemic strokes in patients on oral anticoagulant therapy (OAT) despite optimal adherence pose a therapeutic challenge. We assessed the utility of transesophageal echocardiography (TEE) in identifying potential competing cardiac causes for stroke that occurred despite adequate OAT., Methods: This retrospective observational study included patients admitted for acute ischemic stroke between January 2022 and June 2023 who were on OAT for an established long-term indication. Transthoracic and transesophageal echocardiography, along with assessment of OAT adherence, were conducted. Demographic data, OAT details, and stroke characteristics were analysed to determine the influence of TEE findings on therapeutic decisions., Results: We included 26 patients. TEE identified potential cardiac competing stroke mechanisms in 88% of cases, with valvular thrombi and left atrial or appendage thrombus being predominant. Infective endocarditis, often asymptomatic, was unexpectedly prevalent. TEE significantly influenced therapeutic decisions, especially in cases where transthoracic echocardiography was inconclusive., Conclusions: TEE may be crucial for unravelling the mechanisms of ischemic stroke in patients on adequate OAT, guiding precise therapeutic strategies and potentially reducing the risk of recurrent embolic events. Our findings underscore the limitations of standard echocardiography in detecting cardiac embolic sources and emphasize the importance of tailored decision-making in secondary stroke prevention., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Transcatheter aortic valve implantation may be complicated by the development of conduction disturbances, including left bundle branch block and high-grade atrioventricular blocks, especially in patients with predisposing risk factors, such as pre-existing right bundle branch block. Permanent pacemaker implantation is a procedure with potential short- and long-term complications, and it should be reserved to patients with appropriate indications. Electrophysiological testing and/or prolonged ambulatory ECG monitoring are valuable tools for stratifying the risk of pacemaker implantation. However, the management of new-onset conduction disorders is not always straightforward, and there are different approaches depending on the center's attitude. Therefore, the purpose of this review is to define clinical management based on current evidence, while awaiting data from randomized trials.

Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high-risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001)., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

In recent decades, increases in temperature and tropical rainfall have facilitated the spread of mosquito species into temperate zones. Mosquitoes are vectors for many viruses, including West Nile virus (WNV) and dengue virus (DENV), and pose a serious threat to public health. This review covers most of the current knowledge on the mosquito species associated with the transmission of WNV and DENV and their geographical distribution and discusses the main vertebrate hosts involved in the cycles of WNV or DENV. It also describes virological and pathogenic aspects of WNV or DENV infection, including emerging concepts linking WNV and DENV to the reproductive system. Furthermore, it provides an epidemiological analysis of the human cases of WNV and DENV reported in Europe, from 1 January 2018 to 31 December 2023, with a particular focus on Italy. The first autochthonous cases of DENV infection, with the most likely vector being Aedes albopictus , have been observed in several European countries in recent years, with a high incidence in Italy in 2023. The lack of treatments and effective vaccines is a serious challenge. Currently, the primary strategy to prevent the spread of WNV and DENV infections in humans remains to limit the spread of mosquitoes.

Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant proteins A (SP-A) and D (SP-D) are collectins that play a crucial role in ensuring proper alveolar function and an alteration of their serum levels was reported in several pulmonary diseases characterized by Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis. Considering that such clinical manifestations can also occur during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. In this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n = 51) at admission (T0) and after seven days (T1) and compared with healthy donors (n = 11). SP-D increased in COVID-19 patients compared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. In light of these results, SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia, and the early detection of SP-D serum levels could be crucial for preventive clinical management.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

Introduction: Considering the reported efficacy of monoclonal antibodies (mAbs) directed against the Spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reducing disease severity, the aim of this study was to investigate the innate immune response before and after mAbs treatment in 72 vaccinated and 31 unvaccinated SARS-CoV-2 patients., Methods: The mRNA levels of IFN-I, IFN-related genes and cytokines were evaluated using RT/real-time quantitative PCR., Results: Vaccinated patients showed increased rate of negative SARS-CoV-2 PCR tests on nasopharyngeal swab compared with unvaccinated ones after mAbs treatment (p = .002). Unvaccinated patients had lower IFN-α/ω and higher IFN-related genes (IFNAR1, IFNAR2, IRF9, ISG15, ISG56 and IFI27) and cytokines (IL-6, IL-10 and TGF-β) mRNA levels compared to vaccinated individuals before mAbs (p < .05 for all genes). Increased IFN-α/ω, IFNAR1, IFNAR2 and IRF9 levels were observed in unvaccinated patients after mAbs treatment, while the mRNA expression ISGs and IL-10 were reduced in all patients., Conclusion: These data suggest that anti-S vaccinated patients have increased levels of innate immune genes compared to unvaccinated ones. Also, gene expression changes in IFN genes after mAbs administration are different according to the vaccination status of patients., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years., Methods: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built., Results: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4 + T cell count and in CD4 + /CD8 + ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up., Conclusion: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55.

Background: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19., Methods: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56 bright and CD56 dim ), as well as CD4 + and CD8 + T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry., Results: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors ( p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients ( p > 0.05). The only exception was for peripheral naïve CD4 + T cells levels that were reduced in non-survivors ( p = 0.04). An increase in the levels of CD56 bright ( p = 0.012) and a decrease in CD56 dim ( p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4 + and CD8 + T cell levels in the lung compartment were lower compared to blood ( p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4 + and CD8 + T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 ( p < 0.05)., Conclusions: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome.

Contradictory results have been reported regarding interferon (IFN) lambda (λ1-3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1-3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) ( n = 32) and in cells of paired bronchoalveolar lavages (BALs) ( n = 12). Lower IFNλ1-3 values ( p < 0.001 for IFNλ1 and 3 and p = 0.013 for IFNλ2) in the PBMCs of severely ill patients were found compared to healthy donors ( n = 15). Reduced levels of IFNγ were also detected in patients' PBMCs ( p < 0.01) and BALs ( p = 0.041) compared to healthy donors. The presence of secondary bacterial infections was associated with decreased IFNλ amounts in PBMCs ( p = 0.001, p = 0.015 and p = 0.003, respectively) but increased concentrations of IFNλ3 ( p = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFNλ1 and 3 ( p = 0.003 and p < 0.001) and increased IFNγ ( p = 0.08) in PBMCs. Analyzing Toll-like receptors (TLRs) involved in IFN production, we found that TLR3 was highly expressed ( p = 0.033) in patients with bacterial superinfections, while TLR7 and 8 ( p = 0.029 and p = 0.049) were reduced in BALs of deceased patients. Overall, severe COVID-19 might be characterized by dysregulation in IFNγ, IFNλ and TLR3, 7 and 8 production.

The incidence of left ventricular thrombosis (LVT) after acute myocardial infarction has declined significantly in recent decades, thanks to advances in the field of revascularization and antithrombotic therapy. Despite oral anticoagulation, embolic events are the most feared complication of LVT. From a pathophysiological point of view, the development of LVT depends on Virchow's triad, that is, endothelial damage caused by myocardial infarction, blood stasis due to left ventricular dysfunction, and hyper-coagulability determined by inflammation. The diagnostic modalities of LVT include transthoracic echocardiography preferably implemented by contrast administration, and cardiac magnetic resonance. Most thrombi develop in the first 2 weeks after acute myocardial infarction, so the role of systematic screening with short to medium term repeated imaging appears limited. Vitamin K antagonists remain the cornerstone of therapy, since the effectiveness of direct oral anticoagulants remains to be established. Only weak evidence supports the routine use of prophylactic anticoagulant therapy, even in high-risk patients.

The etiological diagnosis of ischemic stroke is crucial for secondary prevention, but often complex for the patients' cardiovascular comorbidities, each of which may cause a stroke. We report the case of an 84-year-old patient with severe left ventricular systolic dysfunction due to dilated cardiomyopathy and implantable cardioverter-defibrillator in primary prevention, hospitalized for atherothrombotic ischemic stroke treated conservatively and later by carotid thromboendarterectomy for ulcerated plaque of the right internal carotid artery. A week after discharge, an embolic ischemic stroke occurred due to thrombosis of the left atrial appendage in absence of atrial fibrillation. A careful analysis of the patient's cardiovascular risk factors, clinical signs and neuroimages allowed for the etiological diagnosis of both cerebral ischemic events. The case is also peculiar because of left atrial appendage thrombus formation in the context of severe left ventricular systolic dysfunction in absence of atrial fibrillation. In the same patient, the recurrent stroke was not due to the same cause and, owing to the complexity of the differential diagnosis, a multidisciplinary neurological and cardiological approach is pivotal for the management of these patients.

Gut microbiota impacts host health by mediating beneficial physiological processes. However, growing evidence supports the potential role of microbiota in disease development and progression. In this review, we report current knowledge on pathophysiologic processes mediated by gut microbiota that may be implicated in atherosclerosis development and progression. We also summarize findings provided by clinical studies that indicate an association between gut microbiota composition and/or function and atherosclerotic cardiovascular diseases. Finally, we discuss potential strategies to impact gut microbiota composition and/or function in order to reduce the atherosclerotic cardiovascular risk.

Whether contrast-associated acute kidney injury (CA-AKI) is only a bystander or a risk factor for mortality in older patients undergoing percutaneous coronary intervention (PCI) is not well understood. Data from FRASER (NCT02386124) and HULK (NCT03021044) studies have been analysed. All patients enrolled underwent coronary angiography. The occurrence of CA-AKI was defined based on KDIGO criteria. The primary outcome of the study was to test the relation between CA-AKI and 3-month mortality. Overall, 870 older ACS adults were included in the analysis (mean age 78 ± 5 years; 28% females). CA-AKI occurred in 136 (16%) patients. At 3 months, 13 (9.6%) patients with CA-AKI died as compared with 13 (1.8%) without it ( p < 0.001). At multivariable analysis, CA-AKI emerged as independent predictor of 3-month mortality (HR 3.51, 95%CI 1.05-7.01). After 3 months, renal function returned to the baseline value in 78 (63%) with CA-AKI. Those without recovered renal function ( n = 45, 37%) showed an increased risk of mortality as compared to recovered renal function and no CA-AKI subgroups (HR 2.01, 95%CI 1.55-2.59, p = 0.009 and HR 2.71, 95%CI 1.45-5.89, p < 0.001, respectively). In conclusion, CA-AKI occurs in a not negligible portion of older MI patients undergoing invasive strategy and it is associated with short-term mortality.

Objectives: To define the incidence of high residual gradient (HRG) after transcatheter aortic valve replacement (TAVR) in BAVs and their impact on short term outcome and 1-year mortality., Background: Transcatheter heart valves (THVs) offer good performance in tricuspid aortic valves with low rate of HRG. However, data regarding their performance in bicuspid aortic valves (BAV) are still lacking., Methods: The BEAT (Balloon vs Self-Expandable valve for the treatment of bicuspid Aortic valve sTenosis) registry included 353 consecutive patients who underwent TAVR (Evolut R/PRO or Sapien 3 valves) in BAV between June 2013 and October 2018. The primary endpoint was device unsuccess with post-procedural HRG (mean gradient ≥ 20 mmHg). The secondary endpoint was to identify the predictors of HRG following the procedure., Results: Twenty patients (5.6%) showed HRG after TAVR. Patients with HRG presented higher body mass index (BMI) (30.7 ± 9.3 vs. 25.9 ± 4.8; p < 0.0001) and higher baseline aortic mean gradients (57.6 ± 13.4 mmHg vs. 47.7 ± 16.6, p = 0.013) and more often presented with BAV of Sievers type 0 than patients without HRG. At multivariate analysis, BMI [odds ratio (OR) 1.12; 95% confidence interval (CI) 1.05-1.20, p = 0.001] and BAV type 0 (OR 11.31, 95% CI 3.45-37.06, p < 0.0001) were confirmed as independent predictors of high gradient., Conclusion: HRG following TAVR in BAVs is not negligible and is higher among patients with high BMI and with BAV 0 anatomy.

Contrast-induced acute kidney injury (CI-AKI) represents a common but serious complication of percutaneous coronary interventions (PCI)-and in general of all those examinations requiring iodinated contrast injection-which affects not only renal function but also long-term prognosis. While several prophylactic approaches were designed in order to prevent CI-AKI, most failed to demonstrate clear benefits in randomized trials, and their implementation is therefore discouraged in clinical practice. The most notorious examples include pre-procedural bicarbonate or N-acetylcysteine, and preprocedural withdrawal of ACE inhibitors/Angiotensin receptor blockers. Those strategies that were instead demonstrated effective include the appropriate use of preprocedural hydration, reduction in contrast volume utilization, adoption of techniques for zero- or ultra-low-contrast procedures, and pharmacological treatments with statins. In this brief review, we summarize the main preventive strategies into brief and pragmatic recommendations designed to improve everyday clinical practice., (© 2020 Wiley Periodicals, Inc.)

Objective: To establish the benefits of an early, tailored and low-cost exercise intervention in older patients hospitalised for acute coronary syndrome (ACS)., Methods: The study was a multicentre, randomised assessment of an exercise intervention in patients with ACS ≥70 years with reduced physical performance (as defined by the short physical performance battery (SPPB), value 4-9). The exercise intervention included four supervised sessions (1, 2, 3, 4 months after discharge) and home-based exercises. The control group attended a health education programme only. The outcomes were the 6-month and 1-year effects on physical performance, daily activities, anxiety/depression and quality of life. Finally, 1-year occurrence of adverse events was recorded., Results: Overall, 235 patients with ACS (median age 76 (73-81) years) were randomised 1 month after ACS. Exercise and control groups were well balanced. Exercise intervention improved 6-month and 1-year grip strength and gait speed. Exercise intervention was associated with a better quality of life (as measured by EuroQol-visual analogue scale at 6 months 80 (70-90) vs 70 (50-80) points, p<0.001 and at 1 year 75 (70-87) vs 65 (50-80) points, p<0.001) and with a reduced perception of anxiety and/or depression (6 months: 21% vs 42%, p=0.001; 1 year 32% vs 47%, p=0.03). The occurrence of cardiac death and hospitalisation for cardiac cause was lower in the intervention group (7.5% vs 17%, p=0.04)., Conclusions: The proposed early, tailored, low-cost exercise intervention improves mobility, daily activities, quality of life and outcomes in older patients with ACS. Larger studies are needed to confirm the clinical benefit., Trial Registration Number: NCT03021044., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The number of older adults admitted to hospital for acute coronary syndrome (ACS) has increased worldwide. The aim of this study was to determine which scale of frailty or physical performance provides incremental improvements in risk stratification of older adults after ACS., Methods: A prospective cohort of 402 older (≥70 years) ACS patients were enrolled. Data about baseline characteristics, Global Registry of Acute Coronary Events (GRACE), and Thrombolysis in Myocardial Infarction (TIMI) risk scores were collected. Before hospital discharge, seven scales of frailty and physical performance were measured. The 1-year occurrence of adverse events (cardiac death, reinfarction, and cerebrovascular accident [MACCE] and all-cause mortality) was recorded., Results: Out of the 402 patients, 43 (10.5%) had a MACCE and 35 (8.7%) died. Following adjustment for confounding factors, scales of frailty and physical performance were associated with adverse events. Among the scales, the addition of short physical performance battery (SPPB) produced the highest incremental value over the initial model generated by baseline characteristics both for MACCE (ΔC-statistic 0.043, p = .04; integrated discrimination improvement (IDI) 0.054, p = .001; net reclassification improvement (NRI) 0.752, p < .001) and all-cause mortality (ΔC-statistic 0.063, p = .02; IDI 0.061, p < .001; NRI 1.022, p < .001). The addition of SPPB scale on top of GRACE or TIMI risk scores led to a considerable improvement in the prediction of MACCE and all-cause mortality (about 15% and 20%, respectively)., Conclusions: The assessment of the physical performance with SPPB scale before hospital discharge increases the ability to predict adverse events in older ACS patients and may be useful in the clinical decision-making process., Clinical Trial Registration: www.clinicaltrials.gov NCT02386124., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: The present analysis investigated the prevalence and the prognostic implication of nutritional status in older adults hospitalized for acute coronary syndrome (ACS)., Methods: The analysis is based on older ACS patients included in the FRASER and LONGEVO SCA studies. The Global Risk of Acute Coronary Events (GRACE) risk score was computed in all patients. Nutritional status was assessed with the Mini Nutritional Assessment-Short Form (MNA-SF, normal for values between 12 and 14, at risk of malnutrition for values between 8 and 11, and malnutrition for values ≤ 7). Physical performance was assessed with the Short Physical Performance Battery (SPPB). Primary outcome was all-cause mortality., Results: The study included 908 patients. Overall, 35 patients (4%) were malnourished and 361 (40%) were at risk of malnutrition. After a median follow-up of 288 [187-370] days, the primary endpoint occurred in 94 (10.5%) patients. The mortality rate was 31% in malnourished subjects, 19% in at-risk patients, 3% in patients with a normal nutritional status (p < 0.001). MNA-SF emerged as an independent predictor of all-cause mortality (HR 0.76, 95%CI 0.68-0.84 for single change unit). The MNA-SF score improved the GRACE score's ability to discriminate subjects at risk of death (ΔC-statistic = 0.076, p < 0.001; ΔBIC -28; IDI 0.052, p < 0.001; NRI 0.793, p < 0.001). The prognostic value of MNA-SF was maintained also by including the SPPB score in the predictive model., Conclusion: s: The MNA-SF helped to identify malnutrition in older ACS patients. Moreover, the MNA-SF value is an independent predictor of all-cause mortality and it improves the predictive value of the GRACE risk score., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: Hitherto, no study has yielded important information on whether the scales of frailty may improve the ability to discriminate the risk of haemorrhages in older adults admitted to hospital for acute coronary syndrome (ACS). The aim of this study is to investigate whether frailty scales would predict the 1-year occurrence of haemorrhagic events and if they confer a significant incremental prognostic value over the bleeding risk scores., Methods: The present study involved 346 ACS patients aged ≥ 70 years enrolled in the FRASER study. Seven different scales of frailty and PARIS, PRECISE-DAPT and BleeMACS bleeding risk scores were available for each patient. The outcomes were the 1-year BARC 3-5 and 2 bleeding events., Results: Adherence to antiplatelet treatment at 1, 6 and 12 months was 98%, 87% and 78%, respectively. At 1-year, 14 (4%) and 30 (9%) patients presented BARC 3-5 and 2 bleedings, respectively. Bleeding risk scores and four scales of frailty (namely Short Physical Performance Battery, Columbia, Edmonton and Clinical Frailty Scale) significantly discriminated the occurrence of BARC 3-5 events. The addition of the scales of frailty to bleeding risk scores did not lead to a significant improvement in the ability to predict BARC 3-5 bleedings. Neither the bleeding risk scores nor the scales of frailty predicted BARC 2 bleedings., Conclusions: Both the bleeding risk scores and the scales of frailty predicted BARC 3-5 haemorrhages. However, integrating the scales of frailty with the bleeding risk scores did not improve their discriminative ability., Clinical Trial Registration: www.clinicaltrials.gov: NCT02386124.

Objective: Grip strength is a well-characterised measure of weakness and of poor muscle performance, but there is a lack of consensus on its prognostic implications in terms of cardiac adverse events in patients with cardiac disorders., Methods: Articles were searched in PubMed, Cochrane Library, BioMed Central and EMBASE. The main inclusion criteria were patients with cardiac disorders (ischaemic heart disease, heart failure (HF), cardiomyopathies, valvulopathies, arrhythmias); evaluation of grip strength by handheld dynamometer; and relation between grip strength and outcomes. The endpoints of the study were cardiac death, all-cause mortality, hospital admission for HF, cerebrovascular accident (CVA) and myocardial infarction (MI). Data of interest were retrieved from the articles and after contact with authors, and then pooled in an individual patient meta-analysis. Univariate and multivariate logistic regression was performed to define predictors of outcomes., Results: Overall, 23 480 patients were included from 7 studies. The mean age was 62.3±6.9 years and 70% were male. The mean follow-up was 2.82±1.7 years. After multivariate analysis grip strength (difference of 5 kg, 5× kg) emerged as an independent predictor of cardiac death (OR 0.84, 95% CI 0.79 to 0.89, p<0.0001), all-cause death (OR 0.87, 95% CI 0.85 to 0.89, p<0.0001) and hospital admission for HF (OR 0.88, 95% CI 0.84 to 0.92, p<0.0001). On the contrary, we did not find any relationship between grip strength and occurrence of MI or CVA., Conclusion: In patients with cardiac disorders, grip strength predicted cardiac death, all-cause death and hospital admission for HF., Trial Registration Number: CRD42015025280., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Reperfusion therapy of the infarct-related artery (IRA) with primary percutaneous coronary intervention is the cornerstone for the treatment of patients with ST-elevation myocardial infarction (STEMI). However, up to 30% of STEMI patients present a multi-vessel coronary artery disease. Several methods are now available for the assessment of functional severity of a coronary stenosis both for IRA and non-culprit coronary lesions. The functional assessment of the IRA has mainly a prognostic implication in terms of major adverse cardiovascular events, recovery of left ventricular function and evaluation myocardial viability. Conversely, the functional assessment of the non-culprit coronary lesions has a fundamental role to guide staged revascularization. The aim of this review is to revise the most validated methods to perform the functional assessment of both culprit and non-culprit lesion in ST-elevation myocardial infarction.

Background: Reduced physical performance and impaired mobility are common in elderly patients after acute coronary syndrome (ACS) and they represent independent risk factors for disability, morbidity, hospital readmission and mortality. Regular physical exercise represents a means for improving functional capacity. Nevertheless, its clinical benefit has been less investigated in elderly patients in the early phase after ACS. The HULK trial aims to investigate the clinical benefit of an early, tailored low-cost physical activity intervention in comparison to standard of care in elderly ACS patients with reduced physical performance., Design: HULK is an investigator-initiated, prospective multicenter randomized controlled trial (NCT03021044). After successful management of the ACS acute phase and uneventful first 1 month, elderly (≥70 years) patients showing reduced physical performance are randomized (1:1 ratio) to either standard of care or physical activity intervention. Reduced physical performance is defined as a short physical performance battery (SPPB) score of 4-9. The early, tailored, low-cost physical intervention includes 4 sessions of physical activity with a supervisor and an home-based program of physical exercise. The chosen primary endpoint is the 6-month SPPB value. Secondary endpoints briefly include quality of life, on-treatment platelet reactivity, some laboratory data and clinical adverse events. To demonstrate an increase of at least one SPPB point in the experimental arm, a sample size of 226 patients is needed., Conclusions: The HULK study will test the hypothesis that an early, tailored low-cost physical activity intervention improves physical performance, quality of life, frailty status and outcome in elderly ACS patients with reduced physical performance., Trial Registration: Clinicaltrials.gov, identifier NCT03021044 , first posted January, 13th 2017.

Forty to 60% of ST-elevation myocardial infarction (STEMI) patients present with multivessel coronary artery disease, identified during primary percutaneous coronary intervention (pPCI) of the culprit lesion. At present, data about revascularization of non-culprit coronary lesions are conflicting. Nevertheless, patients with multivessel coronary artery disease have a worse outcome. Recently, several randomized controlled trials and meta-analyses compared a strategy of culprit-only revascularization vs complete revascularization (during pPCI or staged PCI of the non-culprit lesion). The majority of data show a potential benefit of complete revascularization, in particular a reduction in the composite endpoint of major adverse cardiac events, in absence of certain data regarding long-term mortality and reinfarction. Besides, it is still controversial the optimal timing of complete revascularization (during pPCI or staged PCI), as well as the best method for evaluating the lesions to be treated (angiographic vs functional assessment of ischemia). Considering all these data, the only tested and safe approach to treat multivessel coronary artery disease patients remains optimization of medical therapy with long-term prescription of newer antiplatelet agents (ticagrelor and prasugrel) and aggressive lipid-lowering therapy (LDL <70 mg/dl). At the same time, a complete coronary revascularization strategy with PCI, especially guided by ischemia and based on patient lesions and comorbidity, may further improve outcomes.

Background: Frailty has become a high-priority issue in cardiovascular medicine because of the aging of cardiovascular patients. Simple and reproducible tools to assess frailty in elderly patients are clearly on demand. Their application may help physicians in the selection of invasive and medical treatments and in the timing and modality of the follow-up. The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program is designed with the aim to validate the use of the short physical performance battery (SPPB) as prognostic tools in patients admitted to hospital for acute coronary syndrome (ACS)., Methods: The FRASER program is a multicenter prospective study involving 4 Italian cardiology units. The FRASER program enrolls only patients aged ≥70 years. The core of the FRASER program includes patients admitted to hospital for ACS. The aims are (1) to describe SPPB distribution before hospital discharge and (2) to investigate the prognostic role of SPPB score. The primary outcome is a composite of 1-year all-cause mortality and hospital readmission for any cause. Ancillary analyses will be focused on different study populations (patients hospitalized for arrhythmias or acute heart failure or symptomatic severe aortic stenosis) and on different tools to assess frailty (multidimensional prognostic index, clinical frailty score, grip strength)., Discussion: The FRASER program will fill critical gaps in the knowledge regarding the link between frailty, cardiovascular disease, interventional procedures and outcome and will help physicians in the generation of a more personalized risk assessment and in the identification of potential targets for interventions.

Background: Nuisance bleeding is a major determinant of quality of life and drug discontinuation in patients on dual antiplatelet therapy (DAPT). However, no randomized trial has been focused on the impact of nuisance bleeding on quality of life., Methods: BATMAN is an investigator-driven, randomized, controlled, single-center, open trial (NCT02554006). Four hundred and forty-eight consecutive patients with indication to at least 6 months of DAPT were randomized to: i) multimodal counseling program focused on nuisance bleedings (interventional arm); ii) usual discharge process (control arm). The primary endpoint was the one-month health-related quality of life assessed by the EuroQol-5 Dimension (EQ-5D) visual analog scale (VAS) score. Secondary endpoints were EQ-5D at 1 and 6 months, EQ-5D VAS at 6 months, DAPT withdrawal, need of information regarding DAPT and/or nuisance bleedings, 6-month ischemic and bleeding adverse events., Results: The EQ5D-VAS was significantly higher in the interventional arm compared to the control arm at 1 and 6 months (81[74-88] vs. 73[64-80], p < 0.001 at 1 month; 82[76-88] vs. 74[65-81], p < 0.001 at 6 months). Patients in the interventional arm had also significantly lower pain/discomfort and anxiety/depression at the EQ-5D both at 1 and 6 months. Patients in the control arm withdrew DAPT significantly more (7 (3%) vs. 1 (0.4%), p = 0.03) and looked for information regarding DAPT and/or about nuisance bleeding more frequently than those in the interventional arm (178 (79%) vs.19 (8%), p < 0.001)., Conclusions: The systematic utilization of a multimodal counseling program improved quality of life and reduced the DAPT withdrawal rate in patients on DAPT.

Background: In the last years bioresorbable vascular scaffold (BVS) become a new therapeutic option for interventional cardiologists, with the advantage of a scaffold inducing a possible vessel wall restoration. Nevertheless, several trials tried to prove the safety and efficacy profile of scaffolds, but with conflicting results., Methods: A systematic review and meta-analysis was performed. The search was carried out in PubMed, Google Scholar, Biomed Central and Cochrane Library between January and March 2017. Inclusion criteria: randomized clinical trials (RCT) comparing the Absorb BVS versus durable polymer cobalt-chromium Everolimus Eluting Stent. The outcomes analysed were all-cause mortality, cardiac death, ischemia-driven target lesion revascularization, target vessel myocardial infarction (MI), target lesion failure (TLF)/device oriented composite endpoints (DOCE), and device thrombosis. Fixed-effect meta-analysis was performed. Data were expressed as odds ratio (OR)., Results: Overall 5,674 patients were included (mean age 62.2±1.31 in drug eluting stents (DES) group vs. 62±1,47 in BVS group; P=0.942). DOCE (OR 1.16, 95% CI: 0.90-1.48; P=0.259, I2=0%), cardiac death (OR 0.86, 95% CI: 0.52-1.40; P=0.537, I 2 =0%) and all-cause death (OR 0.78, 95% CI: 0.53-1.15; P=0.205, I 2 =15%) did not differ between BVS and DES. Conversely, ischemia-driven target lesion revascularization was more frequent in the BVS group (OR 1.32, 95% CI: 1.01-1.73; P=0.039, I 2 =0%), as well as device thrombosis (2.2% vs. 0.6%, OR 2.94, 95% CI: 1.71-5.05, P=0.0001, I 2 =0%) and target-vessel MI (5.4% vs. 3%, OR 1.66, 95% CI: 1.25-2.21, P=0.001, I 2 =0%)., Conclusions: The implantation of BVS is associated with an increased risk of device thrombosis, ischemia-driven target lesion revascularization and target vessel MI. If longer follow-up or different implantation technique may change these findings should be addressed in future trials., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Dealing with bioresorbable vascular scaffolds (BVS) implantation in long lesions requiring device overlapping in this particular moment might seem a little provocative for several reasons. First, most studies testing BVS have focused on their safety and efficacy profile in simple patients with simple lesions. Second, ABSORB II did not meet its primary endpoint, while ABSORB III showed a higher rate of target vessel-myocardial infarction (TV-MI) at 2 years. Third, data on porcine model showed that overlapping zone has delayed but greater neointimal proliferation with consequent higher risk for scaffold thrombosis in the short-term and of in-scaffold restenosis in the long-term. Fourth, recently published data showed higher risk of TVF in patients treated with ≥60 mm BVS. Given all these premises, it may seem right to put aside this technology, while it may seem inappropriate to hypothesize the use of BVS in long lesions. The aim of the present review is precisely to critically review the available evidences regarding BVS with particular regard to overlapping BVS in order to understand whether this technology has a future per se and especially in long coronary lesions requiring overlap., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: No study has evaluated the clinical consequences of stent fracture (SF) detected during the index percutaneous coronary intervention (PCI). Thus, we sought to investigate the relationship between SF detected during PCI and clinical outcome.Methods and Results:We consecutively enrolled 832 patients with SF-predisposing factors undergoing 2nd-generation drug-eluting stent implantation and enhanced stent visualization (ESV) system evaluation to detect SF at index PCI. The primary endpoint was a 9-month device-oriented endpoint (DOCE, including cardiac death, target vessel myocardial infarction, and target lesion revascularization). We observed 136 SF in 115 patients (14% of study population). SF I-II was present in 78 patients (68% of patients with SF), and SF III-IV occurred in 37 patients (32%). DOCE at 9 months occurred in 135 patients (16% of the overall population). There was a significant difference in DOCE occurrence between the 3 groups (P=0.006 at log-rank), driven by the SF III-IV group (P=0.001 vs. no SF group, and P=0.01 vs. SF I-II group). In 23 cases of SF III-IV (62%) a further stent was implanted. DOCE occurrence was significantly higher in patients with "untreated" type III-IV SF as compared with the "treated" ones (9% vs. 79%, P<0.01)., Conclusions: The ESV system is helpful in detecting SF during the index PCI. Type III-IV SFs are associated with a higher incidence of DOCE.

Aims: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS., Methods and Results: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05-3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12-5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86-3.10, p = 0.131)., Conclusions: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.

Aims: Although acute heart failure (AHF) is a potential complication of acute aortic syndromes (AAS), its clinical details and management implications have been scarcely evaluated. This study aimed to assess prevalence, pathophysiological mechanisms, impact on treatment, and in-hospital mortality of AHF in AAS., Methods and Results: Data were collected from a prospective AAS registry (398 patients diagnosed between 2000 and 2013). Patients with AHF were identified by the presence of dyspnoea as the presentation symptom or radiological signs of pulmonary congestion or cardiogenic shock, including patients with cardiac tamponade (CT). AHF frequency was 28% (Stanford type A 32% vs. type B 20%, P = 0.01). Four mechanisms leading to AHF were identified, alone or in combination: CT (26%), aortic regurgitation (25%), myocardial ischaemia (17%), and hypertensive crisis (10%). In type A patients, aortic regurgitation and CT were the most frequent mechanisms, whereas myocardial ischaemia and hypertensive crisis were the most frequent in type B patients. Although no difference was noted for diagnostic times, AHF at presentation led to a longer surgical delay in type A AAS. In-hospital mortality was higher in patients with AHF compared with those without (34% vs. 17%, P < 0.001). After multivariable analysis, AHF was associated with increased risk of in-hospital death (adjusted odds ratio 1.97, 95% confidence interval 1.14-3.36, P = 0.014)., Conclusion: AHF occurs in more than a quarter of patients with AAS of both type A and type B, is due to a variety of pathophysiological mechanisms, and is associated with increased surgical delay and in-hospital mortality., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Aims: The use of high-sensitivity cardiac Troponin T (hs-cTnT) assay might lead to overdiagnosis and overtreatment of Acute Coronary Syndromes (ACS). This study assessed the epidemiological, clinical and prognostic impact of introducing hs-cTnT in the everyday clinical practice of an Emergency Department., Methods and Results: We compared all consecutive patients presenting with suspected ACS at the Emergency Department, for whom troponin levels were measured. In particular, we considered 597 patients presenting during March 2010, when standard cardiac Troponin T (cTnT) assay was used, and 629 patients presenting during March 2011, when hs-cTnT test was used. Patients with suspected ACS and troponin levels above the 99th percentile (Upper Reference Limit, URL) significantly increased when using an hs-cTnT assay (17.2% vs. 37.4%, p< 0.001). Accordingly, also the mean GRACE risk score increased (124.2 ± 37.2 vs. 136.7 ± 32.2; p< 0.001). However, the final diagnosis of Acute Myocardial Infarction (AMI) did not change significantly (8.7% vs. 6.8%, p=0.263) by using a rising and/or falling pattern of hs-cTnT (change ≥ 50% or ≥ 20% depending on baseline values). In addition, no significant differences were found between the two study groups with respect to in-hospital (2.7% vs. 1.9%, p=0.366) and 1-year mortality (9.8% vs. 7.6%, p=0.216)., Conclusions: We did not observe overdiagnosis and overtreatment issues in presenters with suspected ACS managed by appropriate changes in hs-cTnT levels, despite the increase in the number of patients presenting with abnormal troponin levels. This occurred without a rise in short-term and mid-term mortality., (© The European Society of Cardiology 2014.)

We sought to evaluate the rates, time course, and causes of death in the long-term follow-up of unselected patients with acute coronary syndromes (ACS). We enrolled 2046 consecutive patients hospitalized from January 2004 to December 2005 with an audited final diagnosis of ACS. The primary study end point was 5-year all-cause mortality. In our series, 896 patients had ST-segment elevation (STE) and 1,150 non-ST-segment elevation (NSTE). Mean age of the study population was 71.6 years. Primary percutaneous coronary intervention was performed in 86% of STE-ACS, and 70% of NSTE-ACS was managed invasively. The 5-year all-cause mortality was 36.4% for STE-ACS and 42.0% for NSTE-ACS, with patients with STE-ACS showing a trend boarding statistical significance toward a lower risk of mortality (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.76 to 1.02, p = 0.08). Landmark analysis demonstrated that patients with STE-ACS had a higher risk of 30-day mortality (STE-ACS vs NSTE-ACS HR = 1.53, 95% CI 1.16 to 2.06, p = 0.003) whereas the risk of NSTE-ACS increased markedly after 1 year (STE-ACS vs NSTE-ACS HR = 0.67, 95% CI 0.53 to 0.84, p = 0.001). The contribution of noncardiovascular (CV) causes to overall mortality increased from 3% at 30 days to 34% at 5 years, with cancer and infections being the most common causes of non-CV death both in STE-ACS and NSTE-ACS. In conclusion, long-term mortality after ACS is still too high both for STE-ACS and NSTE-ACS. Although patients with STE-ACS have a higher mortality during the first year, the mortality of patients with NSTE-ACS increases later, when non-CV co-morbidities gain greater importance., (Copyright © 2015 Elsevier Inc. All rights reserved.)