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Despite mounting evidence, the impact of the interplay between weather and pollution features on the risk of acute cardiac and cerebrovascular events has not been entirely appraised. The aim of this study was to perform a comprehensive cluster analysis of weather and pollution features in a large metropolitan area, and their association with acute cardiac and cerebrovascular events.Anonymized data on acute myocardial infarction (AMI) and acute cerebrovascular events were obtained from 3 tertiary care centers from a single large metropolitan area. Weather and pollution data were obtained averaging measurements from several city measurement stations managed by the competent regional agency for enviromental protection, and from the Metereological Center of Italian Military Aviation. Unsupervised machine learning was performed with hierarchical clustering to identify specific days with distinct weather and pollution features. Clusters were then compared for rates of acute cardiac and cerebrovascular events with Poisson models.As expected, significant pairwise correlations were found between weather and pollution features. Building upon these correlations, hierarchical clustering, from a total of 1169 days, generated 4 separate clusters: mostly winter days with low temperatures and high ozone concentrations (cluster 1, N.=60, 5.1%), days with moderately high temperatures and low pollutants concentrations (cluster 2, N.=419, 35.8%), mostly summer and spring days with high temperatures and high ozone concentrations (cluster 3, N.=673, 57.6%), and mostly winter days with low temperatures and low ozone concentrations (cluster 4, N.=17, 1.5%). Overall cluster-wise comparisons showed significant differences in adverse cardiac and cerebrovascular events (P0.001), as well as in cerebrovascular events (P0.001) and strokes (P=0.001). Between-cluster comparisons showed that cluster 1 was associated with an increased risk of any event, cerebrovascular events, and strokes in comparison to cluster 2, cluster 3 and cluster 4 (all P0.05), as well as AMI in comparison to cluster 3 (P=0.047). In addition, cluster 2 was associated with a higher risk of strokes in comparison to cluster 4 (P=0.030). Analysis adjusting for season confirmed the increased risk of any event, cerebrovascular events and strokes for cluster 1 and cluster 2.Unsupervised machine learning can be leveraged to identify specific days with a unique clustering of adverse weather and pollution features which are associated with an increased risk of acute cardiovascular events, especially cerebrovascular events. These findings may improve collective and individual risk prediction and prevention.

Cardiac stromal cells (CSCs) are the main players in fibrosis. Dysmetabolic conditions (metabolic syndrome-MetS, and type 2 diabetes mellitus-DM2) are strong pathogenetic contributors to cardiac fibrosis. Moreover, modulation of the oxidative state (OxSt) and autophagy is a fundamental function affecting the fibrotic commitment of CSCs, that are adversely modulated in MetS/DM2. We aimed to characterize CSCs from dysmetabolic patients, and to obtain a beneficial phenotypic setback from such fibrotic commitment by modulation of OxSt and autophagy. CSCs were isolated from 38 patients, stratified as MetS, DM2, or controls. Pharmacological modulation of OxSt and autophagy was obtained by treatment with trehalose and NOX4/NOX5 inhibitors (TREiNOX). Flow-cytometry and real-time quantitative polymerase chain reaction (RT-qPCR) analyses showed significantly increased expression of myofibroblasts markers in MetS-CSCs at baseline (GATA4, ACTA2, THY1/CD90) and after starvation (COL1A1, COL3A1). MetS- and DM2-CSCs displayed a paracrine profile distinct from control cells, as evidenced by screening of 30 secreted cytokines, with a significant reduction in vascular endothelial growth factor (VEGF) and endoglin confirmed by enzyme-linked immunoassay (ELISA). DM2-CSCs showed significantly reduced support for endothelial cells in angiogenic assays, and significantly increased Hsub2/subOsub2/subrelease and NOX4/5 expression levels. Autophagy impairment after starvation (reduced ATG7 and LC3-II proteins) was also detectable in DM2-CSCs. TREiNOX treatment significantly reduced ACTA2, COL1A1, COL3A1, and NOX4 expression in both DM2- and MetS-CSCs, as well as GATA4 and THY1/CD90 in DM2, all versus control cells. Moreover, TREiNOX significantly increased VEGF release by DM2-CSCs, and VEGF and endoglin release by both MetS- and DM2-CSCs, also recovering the angiogenic support to endothelial cells by DM2-CSCs. In conclusion, DM2 and MetS worsen microenvironmental conditioning by CSCs. Appropriate modulation of autophagy and OxSt in human CSCs appears to restore these features, mostly in DM2-CSCs, suggesting a novel strategy against cardiac fibrosis in dysmetabolic patients. © 2022 The Authors. The Journal of Pathology published by John Wileyamp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI.This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis.The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population.This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018.

Aims To develop a set of quality indicators (QIs) for the evaluation of the care and outcomes for atherosclerotic cardiovascular disease (ASCVD) prevention. Methods and results The Quality Indicator Committee of the European Society of Cardiology (ESC) formed the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with Task Force members of the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice and the European Association of Preventive Cardiology (EAPC). We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for ASCVD prevention by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. In total, 17 main and 14 secondary QIs were selected across six domains of care for ASCVD prevention: (i) structural framework, (ii) risk assessment, (iii) care for people at risk for ASCVD, (iv) care for patients with established ASCVD, (v) patient education and experience, and (vi) outcomes. Conclusion We present the 2021 ESC QIs for Cardiovascular Disease Prevention, which have been co-constructed with EAPC using the ESC methodology for QI development. These indicators are supported by evidence from the literature, underpinned by expert consensus and aligned with the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice to offer a mechanism for the evaluation of ASCVD prevention care and outcomes.

Transcatheter aortic valve implantation (TAVI) is an established management strategy for severe aortic valve stenosis. Percutaneous axillary approach for TAVI holds the promise of improving safety without jeopardizing effectiveness in comparison to surgical access. We aimed at appraising the comparative effectiveness of percutaneous vs surgical axillary approaches for TAVI.We performed an international retrospective observational study using de-identified details on baseline, procedural, and 1-month follow-up features. Valve Academic Research Consortium (VARC)-3 criteria were applied throughout. Outcomes of interest were clinical events up to 1 month of follow-up, compared with unadjusted and propensity score-adjusted analyses.A total of 432 patients were included, 189 (43.8%) receiving surgical access, and 243 (56.2%) undergoing percutaneous access. Primary hemostasis failure was more common in the percutaneous group (13.2% vs 4.2%, p0.001), leading to more common use of covered stent implantation (13.2% vs 3.7%, p0.001). Irrespectively, percutaneous access was associated with shorter hospital stay (-2.6 days [95% confidence interval: -5.0; -0.1], p=0.038), a lower risk of major adverse events (a composite of death, myocardial infarction, stroke, type 3 bleeding, and major access-site related complication; odds ratio=0.44 [0.21; 0.95], p=0.036), major access-site non-vascular complications (odds ratio=0.21 [0.06; 0.77], p=0.018), and brachial plexus impairment (odds ratio=0.16 [0.03; 0.76], p=0.021), and shorter hospital stay (-2.6 days [-5.0; -0.1], p=0.038).Percutaneous axillary access provides similar or better results than surgical access in patients undergoing TAVI with absolute or relative contraindications to femoral access.

Background: Coagulopathy, in the form of either venous or arterial thromboembolism, is one of the most severe sequelae of coronavirus disease (COVID-19) and has been associated with poorer outcomes. However, the role of therapeutic anticoagulation (tAC) or prophylactic anticoagulation (pAC) in COVID-19 patients has not been definitely established. Therefore, the aim of this systematic review and meta-analysis was to gather all the available real-world data in the field and to provide a reliable effect size of the effect on mortality of tAC compared to pAC in COVID-19 patients. Methods: Real-world studies (RWS) were identified by searching electronic databases from inception to 31th October 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively. Results: 10 RWS and 5541 patients were included in the analysis. Overall, tAC was associated with lower mortality (HR=0.62, 95% CI 0.54-0.71). There was asymmetry at the funnel plot suggesting publication bias, that was not confirmed at the Egger test (p=0.07). For the secondary endpoint, there was a non-statistically significant tendency for more bleedings in patients treated with tAC compared to pAC (RR=1.75, 95% CI 0.81-3.81). Conclusions: Our meta-analysis, based on RWS and adjusted estimates of risk, suggests a survival benefit of tAC over pAC in COVID-19 patients in the real world.

BACKGROUND: Collective risk factors such as climate and pollution impact on the risk of acute cardiovascular events, including ST-elevation myocardial infarction (STEMI). There is limited data however on the precise temporal and independent association between these factors and STEMI, and the potentially interacting role of government policies against Coronavrus Disease 2019 (COVID-19), especially for Latin America. METHODS: We retrospectively collected aggregate data on daily STEMI admissions at 10 tertiary care centers in the Buenos Aires metropolitan area, Argentina, from January 1, 2017 to November 30, 2020. Daily measurements for temperature, humidity, atmospheric pressure, wind direction, wind speed, and rainfall, as well as carbon monoxide (CO), nitrogen dioxide, and particulate matter

Aims We assessed the efficacy of add-on drugs in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD) already receiving neurohormonal inhibition (NEUi). Methods and results The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction Conclusions Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD. 633 Figure

Aims The impact of the interplay between weather and pollution features on the risk of acute cardiac and cerebrovascular events has not been entirely appraised. The aim of this study was to perform a comprehensive cluster analysis of weather and pollution features in a large metropolitan area, and their association with acute cardiac and cerebrovascular events. Methods and results Anonymized data on acute myocardial infarction (AMI) and acute cerebrovascular events were obtained from three tertiary care centre from a single large metropolitan area. Weather and pollution data were obtained averaging measurements from several city measurement stations managed by the competent regional agency for environmental protection, and from the Meteorologic Center of Italian Military Aviation. Unsupervised machine learning was performed with hierarchical clustering to identify specific days with distinct weather and pollution features. Clusters were then compared for rate of acute cardiac and cerebrovascular events with Poisson models. As expected, significant pairwise correlations were found between weather and pollution features. Building upon these correlations, hierarchical clustering, from a total of 1169 days, generated four separate clusters: Cluster 1, including 60 (5.1%) days, Cluster 2 with 419 (35.8%) days, Cluster 3 with 673 (57.6%) days, and Cluster 4 with 17 (1.5%) days, with significant between-cluster differences in weather and pollution features. Notably, Cluster 1 was characterized by low temperatures and high ozone concentrations (P Conclusions Unsupervised machine learning can be leveraged to identify specific days with a unique clustering of adverse weather and pollution features which are associated with an increases risk of acute cardiovascular events, especially cerebrovascular events.

The treatment of acute myocardial infarction is the early revascularization strategy. Heart failure and cardiogenic shock may complicate acute myocardial infarction nevertheless the best disposable strategy applied. Levosimendan is relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization of myocardial fibres. Levosimendan has a direct inotropic effect but also pleiotropic effects; through the K+ATP channels opening it has also a vasodilator effect with may participate concretely to the global effects of the drug. Literature has focused the attention on the anti-heart failure and anti-cardiogenic shock properties of Levosimendan, but it may have effects also preventing the development of myocardial insufficiency in the acute setting of acute myocardial infarction. Scope of the meta-analysis is to evaluate the effect of Levosimendan on acute myocardial infarction in placebo-controlled trials. Based on the eight studies selected we found a beneficial effect of Levosimendan on acute and long-term mortality of patients affected by acute myocardial infarction with no significative increase in adverse events (Figure 1). With caution in interpreting the results of this meta-analysis, our data support the idea that Levosimendan may already have a role in the treatment of acute ischaemic heart disease. Further studies, specifically designed to investigate the early role in the treatment of ischaemic heart failure, are needed.

Despite ongoing developments, prevention and treatment of atherothrombotic cardiovascular disease remains a common challenge. Antithrombotic options for cardiocerebrovascular disease prevention involves a choice between dual antiplatelet therapy (DAPT) and dual pathway inhibition (DPI), which includes an antiplatelet agent and a reduced dose anticoagulant agent. In selected patients at high risk of event and low risk of bleeding, especially those undergoing recent and complex coronary revascularization using drug-eluting stents (DES) ("revascularization-driven effect"), DAPT is superior to single antiplatelet therapy with aspirin. DPI involves a wider potential range of treatment and is superior to single antiplatelet therapy with aspirin, particularly in patients with atherothrombotic involvement in different vascular beds both previously revascularized and not ("no revascularization-driven effect"). After nearly thirty years of randomized trials and observational registries, we have sufficient data to customize antithrombotic therapy in patients at high cardiovascular risk. Therefore, "atherothrombosis stakeholders" must identify the right patient for the right therapy to ensure high levels of efficacy and safety with the best of current therapeutic opportunities.

Recurrence is the most frequent complication following acute pericarditis and may occur in 30% patients, rising to 50% in case of multiple recurrences, lack of colchicine treatment or use of glucocorticoids. Available treatments include aspirin or non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids, immunosuppressive agents, immunoglobulins, anti-interleukin-1 (IL-1) agents.This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the efficacy of pharmacological treatments for acute and recurrent pericarditis. Bibliographic databases were searched (PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library) using the terms "acute pericarditis" or "recurrent pericarditis" and "colchicine" or "NSAIDs" or "glucocorticoids" or "immunosuppressive agents" or "immunoglobulins" or "anti-IL1 agents." Random-effects meta-analysis was used to assess the risk of recurrent pericarditis. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.Eleven RCTs assessed the efficacy of pharmacological treatments for acute and recurrent pericarditis (colchicine and anti-interleukin-1 agents). Colchicine, assessed in nine RCTs, was effective in the reduction of recurrent pericarditis, compared with standard treatment (17% vs .34%, RR=0.50; 95% CI 0.42-0.60, P0.001), without any differences according to clinical setting (i.e. acute pericarditis, recurrent pericarditis, post-pericardiotomy syndrome; P=0.58). Anti-interleukin-1 agents (anakinra, rilonacept), assessed in two RCT, were effective in the reduction of recurrences, compared with placebo (10% vs.78%, RR=0.14; 95% CI 0.05-0.35, P0.001).A correct pharmacological management of pericarditis is key to prevent recurrences. Colchicine is the mainstay of treatment in acute and recurrent pericarditis, while anti-IL1 agents are a valuable option in case of recurrent pericarditis refractory to conventional drugs.

Background New messenger RNA (mRNA) and adenovirus-based vaccines (AdV) against Coronavirus disease 2019 (COVID-19) have entered large scale clinical trials. Since healthcare professionals (HCPs) and armed forces personnel (AFP) represent a high-risk category, they act as a suitable target population to investigate vaccine-related side effects, including headache, which has emerged as a common complaint. Methods We investigated the side-effects of COVID-19 vaccines among HCPs and AFP through a 38 closed-question international survey. The electronic link was distributed via e-mail or via Whatsapp to more than 500 contacts. Responses to the survey questions were analyzed with bivariate tests. Results A total of 375 complete surveys have been analyzed. More than 88% received an mRNA vaccine and 11% received AdV first dose. A second dose of mRNA vaccine was administered in 76% of individuals. No severe adverse effects were reported, whereas moderate reactions and those lasting more than 1 day were more common with AdV (P=0.002 and P=0.024 respectively). Headache was commonly reported regardless of the vaccine type, but less frequently, with shorter duration and lower severity that usually experienced by participants, without significant difference irrespective of vaccine type. Conclusions Both mRNA and AdV COVID-19 vaccines were safe and well tolerated in a real-life subset of HCPs and AFP subjects.

BackgroundEchocardiography (ECHO) is not widely available in primary care, the key structural (chamber enlargements) and functional abnormality are not easily available precluding the ability to diagnose HF other than through mainly symptomatic means. The opportunity for earlier detection of HF is lost.MethodsUsing a unique database, the etiology of HF is explored by prevalence analysis to unravel the diagnostic makeup of each HF category. Various relationships and patterns of comorbidities have been extracted between the Electrocardiogram (ECG) and ECHO parameters that contribute to HF, those relationships are then confirmed and categorized by a Principal Component Analysis (PCA). Finally, it was summarized what type of non-invasive ECG-like device should be used in primary care to better diagnose HF.ResultsThe sensitivity of abnormal ECHO reaches 92% over the abnormal ECG of 81% in the detection of HF. The first five PCA are discovered, which cover 49% of all the variance. Left atrial enlargement is the most representative finding in the overall comorbidity rate, which coincides with the probability direction of HF (3rdas input, 1stas finding in the coefficients), and reaches the highest (250%) prevalence increase in function of decreasing LVEF.ConclusionsThe core structural and functional abnormalities diagnosed by ECHO with the ECG interpretation provide sufficient information to diagnose “consider HF” in primary care. This paper overview of a novel bio-signal-based system supported by Artificial Intelligence, able to replicate Echo-findings, predict HF and indicates its phenotype, suitable for use in Primary Care.

The burden of chronic kidney disease (CKD) in patients with diabetes is high, and recent studies have highlighted the key role of perirenal fat (PRF) thickness in its pathophysiology (1,2). Indeed, increased PRF thickness has been associated with an unfavorable profile of inflammatory cytokines, atherosclerosis, dyslipidemias, metabolic syndrome, and unfavorable outcomes after nephrectomy (3–11). In this issue of Diabetes , …

Objectives: Non-ST-elevation acute coronary syndrome (NSTE-ACS) affects millions of patients. Although an invasive strategy can improve survival, the optimal treatment (i.e., percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) is not clear. We performed a meta-analysis of studies reporting outcomes between PCI and CABG in patients with NSTE-ACS.Methods: MEDLINE, EMBASE and Cochrane Library were assessed. The primary outcome was long-term mortality. Inverse variance method and random model were performed.Results: We identified 13 observational studies (48,891 patients). No significant difference was found in the primary endpoint (CABG vs. PCI, incidence rate ratio [IRR]= 0.93, 95% confidence interval [CI] 0.70; 1.23). CABG was associated with lower long-term major adverse cardiovascular events (MACE) (IRR= 0.64, 95% CI 0.54; 0.76) and lower long-term re-revascularization (IRR= 0.37, 95% CI 0.30; 0.47). There was no significant difference in long-term myocardial infarction (CABG vs. PCI, IRR= 0.96, 95% CI 0.50; 1.84) and peri-operative mortality (CABG vs. PCI, odds ratio [OR]= 1.36, 95% CI 0.94; 1.95).Conclusion: For the treatment of NSTE-ACS, CABG and PCI are associated with similar rates of long-term mortality and myocardial infarction. CABG is associated with lower rates of long-term MACE and re-revascularization. Randomized comparisons in this setting are necessary.

Non-ST-elevation acute coronary syndrome (NSTE-ACS) affects millions of patients. Although an invasive strategy can improve survival, the optimal treatment [i.e., percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] is not clear. We performed a meta-analysis of studies reporting outcomes between PCI and CABG in patients with NSTE-ACS. MEDLINE, EMBASE and Cochrane Library were assessed. The primary outcome was long-term mortality. Inverse variance method and random model were performed. We identified 13 observational studies (48,891 patients). No significant difference was found in the primary endpoint [CABG vs. PCI, incidence rate ratio (IRR) 0.93, 95% confidence interval (CI) 0.70; 1.23]. CABG was associated with lower long-term major adverse cardiovascular events (MACE) (IRR 0.64, 95% CI 0.54; 0.76) and lower long-term re-revascularization (IRR 0.37, 95% CI 0.30; 0.47). There was no significant difference in long-term myocardial infarction (CABG vs. PCI, IRR 0.96, 95% CI 0.50; 1.84) and peri-operative mortality (CABG vs. PCI, odds ratio 1.36, 95% CI 0.94; 1.95). For the treatment of NSTE-ACS, CABG and PCI are associated with similar rates of long-term mortality and myocardial infarction. CABG is associated with lower rates of long-term MACE and re-revascularization. Randomized comparisons in this setting are necessary.

The treatment of acute myocardial infarction is early revascularization. Heart failure and cardiogenic shock may complicate acute myocardial infarction despite applying the best available strategy. Levosimendan is a relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization of myocardial fibres. Levosimendan has a direct inotropic effect but also pleiotropic effects; through the K+ATP channel’s opening, it also has a vasodilator effect which may participate concretely in the global effects of the drug. The focus of the literature is on the anti-heart failure and anti-cardiogenic shock properties of Levosimendan, but it may have effects also preventing the development of myocardial insufficiency in acute myocardial infarction. The aim of the meta-analysis is to evaluate the effect of Levosimendan on acute myocardial infarction in placebo-controlled trials. Based on the eight studies selected, we found a beneficial effect of Levosimendan on acute and long-term mortality of patients affected by acute myocardial infarction. With caution in interpreting the results of this meta-analysis, our data support the idea that Levosimendan may already have a role in the treatment of acute ischemic heart disease. Further studies specifically designed to investigate the early role in the treatment of ischemic heart failure are needed.

The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that plays a major role in innate immunity. Following tissue injury, activation of the NLRP3 inflammasome results in cytokine production, primarily interleukin(IL)-1β and IL-18, and, eventually, inflammatory cell death - pyroptosis. While a balanced inflammatory response favors damage resolution and tissue healing, excessive NLRP3 activation causes detrimental effects. A key involvement of the NLRP3 inflammasome has been reported across a wide range of cardiovascular diseases (CVDs). Several pharmacological agents selectively targeting the NLRP3 inflammasome system have been developed and tested in animals and early phase human studies with overall promising results. While the NLRP3 inhibitors are in clinical development, multiple randomized trials have demonstrated the safety and efficacy of IL-1 blockade in atherothrombosis, heart failure and recurrent pericarditis. Furthermore, the non-selective NLRP3 inhibitor colchicine has been recently shown to significantly reduce cardiovascular events in patients with chronic coronary disease. In this review, we will outline the mechanisms driving NLRP3 assembly and activation, and discuss the pathogenetic role of the NLRP3 inflammasome in CVDs, providing an overview of the current and future therapeutic approaches targeting the NLRP3 inflammasome.

BACKGROUND The optimal management of patients with ST-elevation acute coronary syndromes and multivessel coronary artery disease is challenging. There is a growing body of evidence supporting invasive functional evaluation of multivessel disease with FFR or iFR, which it has been added to the literature. In this regard, the WAVE Study recently demonstrated the diagnostic accuracy of instantaneous wave-free ratio (iFR) functional assessment of non-culprit lesions in multivessel patients with STEMI. However, no studies have still verified the long-term clinical impact of an iFR-guided revascularization in this setting of patients. METHODS Patients undergoing primary PCI for STEMI and presenting multivessel disease will be enrolled. After the treatment of the culprit lesion, an iFR-guided functional assessment of non-culprit lesions will be done if iFR≤0.89 PCI will be performed during the index procedure or staged. Conversely, iFR>0.89 will direct the patient towards a conservative approach. RESULTS The study start date was May 1, 2018. The enrollment phase was completed on March 30, 2020. The primary endpoint is the occurrence of target lesion failure (TLF), a composite of cardiovascular death, non-fatal myocardial infarction, and ischemia-driven revascularization of the vessel previously assessed with iFR. Secondary endpoints include MACE (cardiovascular death, non-fatal MI, any revascularization). CONCLUSIONS The aim of the present study was to evaluate the long-term clinical impact of an iFR-guided revascularization of the non-culprit lesions in STEMI patients with multivessel coronary artery disease.

Long-term efficacy and safety of either surgical or percutaneous treatment left main coronary artery disease treatment is lacking.We conducted a systematic review and meta-analysis of the most updated randomized clinical trials that compared the efficacy of coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the Left Main Coronary Artery (LMCA) disease. It was also conducted a systematic search of PubMed, Google Scholar, reference lists of relevant articles, and Medline. The search utilized the following terms: "left main PCI versus CABG," "drug-eluting stents," "bypass surgery" and "left main stenting." The search of articles compatible with our inclusion and exclusion criteria was performed from inception through April 2020 and returned a combined total of 304 articles.We identified 6 studies, providing data on 5812 patients. The mean follow-up was 6.7 years. PCI was associated with an increased risk of major vascular events (MACE) (IRR 1.24, 95% CI [1.03-1.67], P0.01), and coronary revascularization (IRR 1.69, 95% CI [1.42-2.03], P0.01) compared to CABG. Furthermore, all-cause death, MI and stroke events were not statistically different between the two therapeutic revascularization methodologies (IRR 1.06, 95% CI [0.90-1.24], P=0.47, IRR 1.35, 95% CI [0.84-2.16], P=0.03 and IRR 0.66, 95% CI [0.43-1.01], P=0.05, respectively).LMCA PCI has an overall same survival compared to CABG in the long term follow-up. Nevertheless, MACE and revascularization events were more frequent in PCI compared to CABG.

Background: The aim was to determine the impact of diabetes mellitus (DM) on outcomes after percutaneous coronary intervention (PCI). There is limited data on the impact of DM and its subtypes among patients who underwent PCI during hospitalization. Methods: All PCI hospitalizations from the National Inpatient Sample (October 2015–December 2018) were stratified by the presence and subtype of DM. Multivariable logistic regression was performed to determine the adjusted odds ratios (aOR) of in-hospital adverse outcomes in type 1 DM (T1DM) and type 2 DM (T2DM) compared to no-DM. Results: Out of 1, 363, 800 individuals undergoing PCI, 12, 640 (0.9%) had T1DM and 539, 690 (39.6%) had T2DM. T1DM patients had increased aOR of major adverse cardiovascular and cerebrovascular events (MACCE) (1.26, 95%CI 1.17–1.35), mortality (1.56, 95%CI 1.41–1.72), major bleeding (1.63, 95%CI 1.45–1.84), and stroke (1.75, 95%CI 1.51–2.02), while T2DM patients had only increased aOR of MACCE (1.02, 95%CI 1.01–1.04), mortality (1.10, 95%CI 1.08–1.13) and stroke (1.22, 95%CI 1.18–1.27), compared to no-DM patients. However, both T1DM and T2DM had lower aOR of cardiac complications (0.87, 95%CI 0.77–0.97 and 0.87, 95%CI 0.85–0.89, respectively), in comparison to no-DM patients. When accounting for the indication, both DM subgroups had higher aOR of MACCE, mortality, and stroke compared to no-DM patients in the acute coronary syndrome setting (p < 0.001, for all), while only increased aOR of stroke (1.59, 95%CI 1.17–2.15 for T1DM and 1.12, 95%CI 1.05–1.20 for T2DM) persisted in the elective setting. Conclusions: Patients with DM who have undergone PCI during hospitalization are more likely to experience adverse in-hospital outcomes, and T1DM patients are a particularly high-risk cohort.

Background: Transcatheter aortic valve replacement (TAVR) has determined a paradigm shift in the treatment of patients with severe aortic stenosis. However, the durability of bioprostheses is still a matter of concern, and little is known about the management of degenerated TAV. We sought to evaluate the outcomes of patients with a degenerated TAV treated by means of a second TAVR. Methods: The TRANSIT is an international registry that included cases of degenerated TAVR from 28 centers. Among around 40 000 patients treated with TAVR in the participating centers, 172 underwent a second TAVR: 57 (33%) for a mainly stenotic degenerated TAV, 97 (56%) for a mainly regurgitant TAV, and 18 (11%) for a combined degeneration. Overall, the rate of New York Heart Association class III/IV at presentation was 73.5%. Results: Valve Academic Research Consortium 2 device success rate was 79%, as a consequence of residual gradient (14%) or regurgitation (7%). At 1 month, the overall mortality rate was 2.9%, while rates of new hospitalization and New York Heart Association class III/IV were 3.6% and 7%, respectively, without significant difference across the groups. At 1 year, the overall mortality rate was 10%, while rates of new hospitalization and New York Heart Association class III/IV were 7.6% and 5.8%, respectively, without significant difference across the groups. No cases of valve thrombosis were recorded. Conclusions: Selected patients with a degenerated TAV may be safely and successfully treated by means of a second TAVR. This finding is of crucial importance for the adoption of the TAVR technology in a lower risk and younger population. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04500964.

BACKGROUND: Invasive functional assessment is a mainstay in the management of patients with coronary artery disease (CAD), but there is uncertainty on the comparative accuracy of diagnostic indices of functional significance. We aimed to validate the diagnostic performance of a novel non-hyperemic diastolic pressure ratio (dPR).METHODS: We performed a retrospective analysis including two separate registries (VERIFY 2, Latina, Italy) of patients in whom functional indices were measured for lesions with angiographically moderate severity. On top of fractional flow reserve, distal coronary pressure (Pd)/aortic pressure (Pa) ratio, instantaneous wave-free ratio (iFR) and diastolic pressure ratio (dPR) were computed using a novel dedicated algorithm over 4 consecutive beats. Agreement/discrepancy between indexes was appraised Bland-Altman analysis, area under the receiver operating characteristic curve (AUC), and unsupervised machine learning.RESULTS: A total of 525 lesions from 479 patients were included. The novel dPR was highly correlated with iFR (R2=0.99, PCONCLUSIONS: This multicenter registry suggests this novel dPR algorithm provides results that are numerically equivalent to iFR. Pending further studies, physicians may consider using this novel dPR algorithm to gauge the functional significance of a coronary lesion.

We conducted a comprehensive and updated overview on complications occurring after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. Despite remarkable improvements in patient selection, devices, procedures, and ancillary management, complications may still occur in patients undergoing TAVI. On top of most commonly described adverse events such as death, myocardial infarction, stroke, bleeding, vascular complication, renal failure, pacemaker implantation and residual valve regurgitation, other less common but similarly severe complications may still occur. These may include events ranging from acute delirium to valve compression during cardiopulmonary resuscitation. Meticulous care should be applied to all screening and procedural steps for TAVI, and attentive follow-up should be implemented afterwards, especially in suboptimal TAVI candidates or those otherwise at high operative risk. Despite recent remarkable improvements, additional research is warranted in order to further improve early and late outlook of TAVI, identify predictors of complications, and the best way to handle them.

AIMS: To evaluate the associations of blood pressure (BP) categorization based on the 2017 American Heart Association and the American College of Cardiology guideline with the risk of peripheral artery disease (PAD). METHODS: Among 13,113 middle-aged participants, we investigated the associations of 2017 BP categories (systolic

We aim to compare Polymer-Free Biolimus-Eluting Stent (PF-BES) with Durable Polymer Everolimus-Eluting stent (DP-EES) in unselected patients. PF-BES showed a favorable profile in high-bleeding risk patients who underwent percutaneous coronary intervention. Limited data are available on PF-BES compared with second-generation durable polymer-coated drug-eluting stents in patients eligible for standard dual antiplatelet therapy. A total of 848 consecutive patients were enrolled: 306 patients were treated with PF-BES and 542 with DP-EES. Stent performance was tested in a propensity score-matched population and in a Complex Higher-Risk and Indicated Patients (CHIP) subpopulation. A per-lesion analysis on 1,204 lesions (PF-BES = 424 vs DP-EES = 780) was also performed. At a medium follow-up of 18.5 ± 5.0 months, no differences in the matched population were found in terms of major adverse cardiac events (PF-BES 9.0% vs DP-EES 4.5%; p 0.091), myocardial infarction (PF-BES 6.2% vs DP-EES 2.3%; p 0.111), stent restenosis (PF-BES 2.3% vs DP-EES 0.0%; p 0.123), definite or probable stent thrombosis (PF-BES 2.8% vs DP-EES 1.1%; p 0.448). A significant inferior rate of restenosis was observed in the DP-EES arm in the whole (PF-BES 2.3% vs DP-EES 0.6%; p 0.041) and CHIP populations (PF-BES 4.3% vs DP-EES 0.5%; p 0.023), as well as in the per-lesion analysis (DP-EES 0.4% vs PF-BES 1.7%; p 0.039). In conclusion, in a real-world cohort PF-BES performed similarly to DP-EES in terms of restenosis and stent thrombosis in the matched population. Nonetheless, in the whole and CHIP populations, as well as in the per-lesion analysis, restenosis occurrence resulted higher in the PF-BES group.

Transcatheter aortic valve implantation has become an established treatment for severe aortic stenosis, thanks to key improvements achieved by new-generation devices. Their comparative effectiveness and safety are, however, still uncertain.We queried a prospective registry on transcatheter aortic valve implantation to compare Evolut and Portico devices, focusing on procedural, in-hospital, and mid-term outcomes. Unadjusted and propensity-adjusted analyses were carried out.In all, 233 patients were included, 119 (51.1%) receiving Evolut and 114 (48.9%) Portico. Several differences in baseline and procedural features were evident, including comorbidities, device size, and postdilation (all P 0.05). Unadjusted analysis for procedural results showed significant differences in fluoroscopy time, left ventricular ejection fraction, and aortic regurgitation (all P 0.05), whereas device and procedural success rates were not significantly different (both P 0.05). In-hospital outcomes were not significantly different (all P 0.05). Survival analysis for mid-term follow-up (6 ± 7 months) outcomes showed no significant differences in death, stroke, myocardial infarction, major vascular complication, or major bleeding (all P 0.05). Conversely, Evolut appeared associated with lower peak and mean aortic gradients (both P 0.05), but higher rate of permanent pacemaker implantation (P = 0.043). Propensity-score-adjusted analysis largely confirmed the similar performance of the two devices, including peak and mean aortic gradients (both P 0.05). However, Evolut continued to be associated even at adjusted analysis with an increased risk of pacemaker implantation (P = 0.018).The acute and mid-term comparative safety and effectiveness of Evolut and Portico in experienced hands are similar, with the notable exception of a lower risk of permanent pacemaker implantation with Portico.

To examine the effectiveness of telemonitoring and hemodynamic monitoring devices in reducing mortality rates in heart failure. PubMed and Cochrane Library were searched to 1 May 2017 for randomized controlled trials and real-world studies investigating the effects of telemonitoring or hemodynamic monitoring on mortality in heart failure. Heart failure is associated with increased mortality. Telemonitoring and hemodynamic monitoring have been shown to reduce mortality rates in some studies but not others. Fifty-two and five publications on telemonitoring and hemodynamic monitoring were included. In 23,233 patients (mean age 70 years, mean follow-up 12 ± 10 months), telemonitoring reduced all-cause mortality by 22% (HR = 0.78; 95% confidence interval (CI), 0.74–0.83; P 0.05). Overall, telemonitoring but not hemodynamic monitoring reduced mortality in heart failure.

Relative benefits of coronary artery bypass (CABG) using single and multiple arterial grafting (SAG, MAG) and drug eluting stent (DES) in multivessel coronary disease remain uncertain. We compared SAG, MAG, and DES in a pairwise and network meta-analysis. Randomized trials and adjusted observational studies comparing CABG versus DES were included (primary end point: long-term mortality; secondary end points: operative mortality, perioperative stroke, and follow-up repeated revascularization [RR]). Studies with ≥1.7 arterial grafts and/or patient were classified as MAG. Bayesian network meta-analyses and random-model pairwise meta-analyses were performed. A total of 53,239 patients (8 randomized, 17 observational studies) were included (26,306 DES; 26,933 CABG). In pairwise comparison (mean follow-up: 5.42 years), CABG (MAG + SAG) was associated with lower long-term mortality (incident rate ratio [IRR] 0.77, 95% confidence interval [CI] 0.66 to 0.90), lower RR (IRR 0.37, 95% CI 0.27 to 0.51), increased perioperative stroke (odds ratio [OR] 3.18, 95% CI 1.70 to 5.97), and similar operative mortality (OR 1.04, 95% CI 0.64 to 1.70) compared with DES. There was a nonsignificant trend toward lower long-term mortality for studies with higher mean number of arterial grafts. In network meta-analyses, compared with DES, MAG was associated with lower long-term mortality (IRR 0.72, 95% credible interval [CrI] 0.57 to 0.92) and late RR (IRR 0.32, 95% CrI 0.21 to 0.49), SAG was associated with lower long-term mortality and RR (IRR 0.80, 95% CrI 0.66 to 0.97 and IRR 0.42, 95% CrI 0.29 to 0.61, respectively). In conclusion, CABG was associated with reduced 5-year mortality and need for RR compared with DES. MAG was ranked as the best treatment for the primary and all secondary outcomes.

Transcatheter aortic valve implantation (TAVI) is a safe and beneficial treatment for patients with severe symptomatic aortic stenosis at high and intermediate surgical risk. Success rates for TAVI continue to increase due to more refined procedural approaches and devices, and above all, to the improvements in procedural knowledge by TAVI operators. The development of a new delivery system represents an important evolutionary process in the TAVI procedure, both for the type of device and for the operators, as it may substantially expand indications, success rates, and safety. FlexNav (Abbott Cardiovascular) is a novel delivery system designed to improve ease and precision of TAVI using the Abbott Portico valve. Despite limited results on its advantages, such as those provided in the PORTICO investigational device exemption substudy, uncertainty persists on the actual role of FlexNav in real-world practice.We hereby present our preliminary experience with FlexNav in a consecutive series of 18 patients undergoing TAVI with Portico valve in early 2020 (3 with axillary access). Procedural results were excellent, as shown by the absence of deaths, strokes, and major vascular complications (95% confidence interval, 0%-18.5%), and pacemaker implantation in 3 subjects (21.4%; 95% confidence interval, 4.7%-50.8%).Despite the small sample size, the present case series suggests that adoption of the FlexNav novel delivery system for TAVI with Portico valve is feasible and safe, and holds the promise of further improving early and long-term results of this procedure.