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Dual antiplatelet therapy (DAPT) is the gold standard after acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Because local and systemic ischemic complications can occur particularly in the early phase (i.e. 1-3 months) after ACS or PCI, the synergistic platelet inhibition of aspirin and a P2Y

Preserving coronary artery access is a crucial goal during transcatheter aortic valve replacement (TAVR) procedures, especially in case of self-expandable transcatheter heart valve (SE-THV) implantation. In this light, a proper commissural alignment is needed to avoid the risk of coronary obstruction and to permit easy vessels re-cannulation for diagnostic and interventional purposes. New-generation SE-THVs have been furnished of different markers, able to guide operators to perform a correct commissural alignment. In this case series, we describe key procedural aspects of commissural alignment for the different available SE-THVs, providing a step-by-step tutorial for each device. Lastly, we illustrate a commissural alignment in a contrast-zero TAVR.

Aims The effect of the COVID-19 pandemic on care and outcomes across non-COVID-19 cardiovascular (CV) diseases is unknown. A systematic review and meta-analysis was performed to quantify the effect and investigate for variation by CV disease, geographic region, country income classification and the time course of the pandemic. Methods and results From January 2019 to December 2021, Medline and Embase databases were searched for observational studies comparing a pandemic and pre-pandemic period with relation to CV disease hospitalisations, diagnostic and interventional procedures, outpatient consultations, and mortality. Observational data were synthesised by incidence rate ratios (IRR) and risk ratios (RR) for binary outcomes and weighted mean differences for continuous outcomes with 95% confidence intervals. The study was registered with PROSPERO (CRD42021265930). A total of 158 studies, covering 49 countries and 6 continents, were used for quantitative synthesis. Most studies (80%) reported information for high-income countries (HICs). Across all CV disease and geographies there were fewer hospitalisations, diagnostic and interventional procedures, and outpatient consultations during the pandemic. By meta-regression, in low-middle income countries (LMICs) compared to HICs the decline in ST-segment elevation myocardial infarction (STEMI) hospitalisations (RR 0.79, 95% confidence interval [CI] 0.66–0.94) and revascularisation (RR 0.73, 95% CI 0.62–0.87) was more severe. In LMICs, but not HICs, in-hospital mortality increased for STEMI (RR 1.22, 95% CI 1.10–1.37) and heart failure (RR 1.08, 95% CI 1.04–1.12). The magnitude of decline in hospitalisations for CV diseases did not differ between the first and second wave. Conclusions There was substantial global collateral CV damage during the COVID-19 pandemic with disparity in severity by country income classification.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were individually proven to reduce major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients, but the relative magnitude of benefits from these two drug classes is debated. We aimed to review current available data on GLP1-RA and SGLT2i in T2DM patients and compare their efficacy and safety in this population.We systematically searched MEDLINE/PubMed, the Cochrane Library, Google Scholar, Embase, www.tctmd.com, www.clinicaltrials.gov, www.clinicaltrialresults.org, from inception to September 17, 2020 for randomized controlled trials (RCTs) comparing the effects of GLP1-RA vs SGLT2i vs optimal medical therapy (OMT) in adult T2DM patients. Three authors independently screened references and extracted data using a predefined data collection form. Outcomes were analyzed using an indirect comparison meta-analysis of aggregate study-level data. The primary combined efficacy outcome comprised cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. Secondary efficacy outcomes included all-cause mortality, cardiovascular mortality, non-fatal MI, non-fatal stroke, heart failure hospitalizations (HFH), and worsening renal function (WRF).11 RCTs enrolling a total of 98572 patients were included; 56004 (57%) patients were derived from GLP1-RA RCTs and 42568 (43%) from SGLT2i RCTs. At a median follow-up of 3.0±1.3 years, compared with OMT, both GLP1-RA and SGLT2i similarly reduced the rate of the composite primary outcome (risk ratio [RR] 0.88; 95% confidence interval [95%CI] 0.83-0.93 and RR 0.88, 95%CI 0.82-0.95, respectively) with no difference between the drug classes (RR 1.00, 95%CI 0.92-1.10). Both classes similarly reduced MI rate, cardiovascular and all-cause mortality compared with OMT; stroke reduction was only observed with GLP1-RA with no difference in the indirect comparison with SGLT2i; conversely, only SGLT2i were effective in preventing HFH. Both GLP1-RA and SGLT2i were protective against WRF, with a major efficacy of SGLT2i in the indirect comparison.This meta-analysis report that GLP1-RA and SGLT2i reduced with a similar efficacy not only MACE as MI, but also cardiovascular mortality and all-cause mortality at a median 3 years follow-up. SGLT2i were more protective in HFH and WRF than GLP1RA. These new data highlight the efficacy of SGLT2i not only in HF and chronic kidney disease (CKD) but also in ischemic heart diseases (IHD), with a homogeneity among the class, whereas the results observed with GLP1-RA are heterogenous. These findings will help clinical's decisions to optimize therapeutic strategies for diabetic patients.

Acute aortic dissection (AAD) is the most common acute aortic syndrome. It is a life-threatening condition and surgical emergency associated with high mortality if not treated promptly. While it is well established that cardiovascular disease recognises different pathophysiological pathways between men and women, there is limited evidence of sex differences in AAS, especially in type A AAD. According to a recent synthesis of clinical studies on gender differences in type A AAD, women were found to have different baseline characteristics, presentation and outcomes, and thus sex should be considered relevant for diagnosis, risk-stratification and management of type A AAD.

Recent trials demonstrated the clinical efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF), regardless of the presence or absence of type 2 diabetes. These data may allow the use of this innovative drug class in clinical routine for treating these patients.We aimed at further clarifying the role of SGLT2i in patients with diagnosis of HF, capitalizing on pooled sample size and heightened power for clinically relevant safety and efficacy outcomes.We conducted a systematic search of PubMed, reference lists of relevant articles, and Medline database from inception until March 1, 2021.This meta-analysis was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for randomized trials that evaluated the cardiovascular effects of SGLT2i in patients with HF. Three investigators independently assessed study eligibility, extracted the data, and assessed risk of bias. Hazard ratios and 95% confidence intervals (CIs) were pooled and meta-analyzed using a random-effect model. Numbers needed to treat (NNT) with the relative 95% CIs were also calculated. The primary outcome was a composite of HF hospitalization or an urgent visit for worsening HF and cardiovascular death.Three trials were included in the study. Overall, treatment with SGLT2i was associated with a lower risk of the primary composite outcome [hazard ratios 0.73, 95% CI (0.67-0.80), NNT = 11.3]. Similarly, there was a significantly reduced risk of cardiovascular death, all-cause death, HF hospitalization and need for urgent treatment for HF, and HF hospitalization.Therefore, the available evidence supports the routine use of these drugs as standard-of-care, also given the highly favorable NNTs.

Background: Cangrelor, the first intravenous P2Y12 inhibitor (P2Y12-I), has been approved on the basis of three large RCTs from the CHAMPION program which nevertheless have been criticized for the low bleeding risk of the enrolled patients, the large quote of chronic coronary syndromes (CCS), and the use of Clopidogrel as control arm even in the setting of acute coronary syndromes (ACS). We sought to investigate, in the setting of ACS, the comparative performance of Cangrelor in terms of in-hospital ischemic and haemorrhagic outcomes compared with the current gold-standard of oral P2Y12-I. Methods: The study retrospectively enrolled 686 consecutive patients admitted to the Divisions of Cardiology of Policlinico of Bari and L. Bonomo Hospital of Andria for ACS and treated with percutaneous coronary intervention (PCI). The study population was divided according to the P2Y12-I treatment strategy in two groups: patients given an oral P2Y12-I and patients receiving Cangrelor in the CathLab followed by an oral P2Y12-I. Clinical endpoints included death, ischemic and bleeding events occurring during hospital stay. Results: Cangrelor treated patients presented higher clinical risk profile at presentation and faced higher death rate. However, after PS matching, in-hospital mortality resulted comparable between the groups and Cangrelor use was associated with reduced in-hospital definite stent thrombosis (p=0.03). Conclusions: Data from our real-world registry highlight that, in the setting of ACS, Cangrelor is prevalently used in patients with very challenging clinical presentations. The adjusted analysis provides for the first time promising data on stent thrombosis reduction associated with Cangrelor use.

Background Acute coronary syndromes (ACS) are a common cause of morbidity and mortality, irrespective of sex. While several studies have focused on ACS at admission or long-after the acute event, limited if any research is available on sex-based comparison of patients discharged after ACS. We aimed at appraising the outlook of women discharged after ACS, exploiting a large multinational registry. Methods Details on women enrolled in the PRAISE multicenter registry, a large database spanning 23,702 patients included between 2003 and 2019, were systematically collected. We focused on patient and procedural features, medications at discharge, and 1-year outcomes. The primary endpoint was the composite of death, myocardial infarction, or major bleeding after discharge. Secondary outcomes were the individual components of the primary endpoint. Results Characteristics of 17,804 men and 5,466 women discharged after ACS were collected. Several baseline differences were found, including risk factors and history of prior revascularization (all p Conclusions Women are treated less aggressively with apparently worst outcomes 2 years after discharge for ACS managed invasively. On the basis of these findings, we should change our approach and adopt a more aggressive management of women with ACS. Figure 1. Sex-based comparison of clinical outcomes 2 years after discharge for an invasively managed acute coronary syndrome (ACS) (all p

Background The use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. Objective To investigate the effects of circulating molecules in HNBC chronic smokers on the fibrotic specification and paracrine function of cardiac stromal cells (CSCs). Methods Resident CSCs were isolated from the atrial tissue of non-smokers patients with cardiovascular diseases, and exposed to the serum pools derived from 60 young healthy subjects, stratified in exclusive HNBC smokers, traditional combustion cigarette (TCC) smokers, or non-smokers (NS) as reference. Results CSCs treated with TCC serum versus NS displayed impaired 3D growth (NS 568±24 vs. TCC 442±27 spheroids/well, p≤0,01) and reduced migration after 6h (NS 0,62±0,04 vs. TCC 0,80±0,03 normalized scratch area versus t0, p≤0,01) and 10h (NS 0,49±0,03 vs. TCC 0,36±0,03 normalized scratch area versus t0, p≤0,05), as well as significantly increased expression (IL-6, IL-8) and/or release of pro-inflammatory (e.g CRP, PAI-1, CD40L, CXCL4) and pro-fibrotic cytokines (PDGFA, MMP1). CSCs cultured with HNBC serum showed significantly increased mRNA levels of pro-fibrotic genes (PDGFA, THY1, COL1A1, p Conclusion The circulating molecules in the serum of chronic HNBC smokers induce fibrotic specification in CSCs. They also reduce the beneficial paracrine effects of stromal cells on endothelial cells and cardiomyocytes, albeit to a reduced extent for some features. These results point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.

Background Characterization and management of patients with acute coronary syndromes (ACS) remain challenging, and it is unclear whether currently available clinical and procedural features can suffice to inform adequate decision making. Methods Details on patients discharged after an ACS were obtained by querying an extensive multicenter registry, detailing patient features as well as management details. Clinical outcomes included fatal and non-fatal cardiovascular events at 1-year follow-up. After missing data imputation, two unsupervised machine learning approaches (k-means and Clustering Large Applications [CLARA]) were used to generate separate clusters with different features. Bivariate and multivariable-adjusted analyses were performed to compare different clusters for clinical outcomes. Findings: 23,270 patients discharged after ACS were included. Two clusters were identified by k-mean algorithm (k1 and k2), and two clusters by CLARA algorithm (C1 and C2). Differences in 2-years outcomes between k1 and k2 and between C1 and C2 were substantial. K2 cluster (N=21,988) in comparison with k1 cluster (N=1,282) had significantly higher occurrence of death (9.5% vs 3.8%, p Conclusions A machine-learning based clustering approach is effective at face value to inform on the prognosis of patients with ACS managed invasively. These findings can be leveraged to inform decision-making in this setting, but also highlight the potential role of cluster analysis in first-in-man, and preapproval studies of medical devices.

Background It is unclear which diagnostic strategy for detecting coronary artery disease (CAD) yields better outcomes. We aimed to compare the clinical accuracy and efficacy of non-invasive and invasive diagnostic strategies for the initial assessment of patients with suspected stable CAD. Methods On March 16, 2022, we searched PubMed, Embase, and CENTRAL databases for randomised controlled trials comparing diagnostic strategies for CAD detection among patients with symptoms suggestive of stable CAD. Diagnostic modalities included coronary computed tomographic angiography (CCTA), cardiovascular magnetic resonance (CMR), exercise electrocardiography, invasive coronary angiography (ICA), single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI), and stress echocardiography. Functional tests were grouped into a single node for the primary analyses, while being analysed as separate nodes for the secondary analyses. Frequentist random-effect network meta-analyses were conducted to summarise the evidence. GRADE frameworks were applied to rate the certainty of findings. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE) and the primary accuracy outcome was the rate of unnecessary angiography. The study was registered with PROSPERO (CRD42022329635). Results Twenty trials (n=27753 participants) were included. Compared with direct-ICA referral, CCTA and functional testing provided no significant difference in the risk of MACE (incidence rate ratios [IRRs] 0·87 [95% CI 0·65-1·17] and 1·19 [95% CI 0·87-1·62], respectively; moderate certainty) and a large reduction in the rate of unnecessary angiography (odds ratios 0·04 [95% CI 0·02-0·09] and 0·08 [95% CI 0·03-0·18], respectively; high certainty). Among non-invasive diagnostic strategies, CCTA significantly reduced the risk of MACE compared with functional testing (IRR 0·73, 95% CI 0·57-0·95; high certainty). The worse prognostic performance of functional testing was mainly driven by the poor efficacy of exercise electrocardiography (high certainty) and stress echocardiography (moderate to low certainty), whose risk of MACE was significantly reduced by CCTA (IRRs 0·56 [95% CI 0·42-0·75] and 0·59 [95% CI 0·42-0·81], respectively), SPECT-MPI (IRRs 0·56 [95% CI 0·41-0·77] and 0·59 [95% CI 0·43-0·81], respectively), and direct-ICA referral (IRRs 0·64 [95% CI 0·45-0·91] and 0·67 [95% CI 0·48-0·92], respectively), while non-significantly reduced by CMR (IRRs 0·71 [95% CI 0·47-1·06] and 0·74 [95% CI 0·53-1·04], respectively). Conclusion In patients with suspected stable CAD, an initial assessment with non-invasive diagnostic strategies is safe and addresses the low diagnostic yield of direct-ICA referral. CCTA is among the most effective strategies in terms of both clinical accuracy and efficacy. Among functional non-invasive tests, exercise electrocardiography and stress echocardiography may not be deemed effective diagnostic alternatives, while SPECT-MPI and CMR are valuable and feasible options, respectively.

Radial artery occlusion after transradial procedures is a frequent iatrogenic thrombotic process. The impact on prognosis has not been investigated. This study sought to investigate whether radial artery occlusion is related to increased risk of major adverse cardiac and cerebrovascular events, defined as death, myocardial infarction, stroke and coronary revascularization.Eight hundred thirty-seven consecutive patients who underwent a transradial coronary procedure had patency of radial artery checked at 24 hours. Radial artery occlusion occurred in 41 over 837 patients (4.8%); 764 (91.2%) were available for planned follow-up at 1 year and were included in the analysis. Event-free survival rate between patients with and without radial artery occlusion was calculated using Kaplan-Meier estimates, and Cox proportional-hazards models were used to identify independent risk factors.At a median 370-day follow-up (IQR: 366-375 days), adverse events occurred in 37 patients (4.8%), 2 in patients with radial artery occlusion and 35 in patients without. One-year survival rate was 94.9% vs. 95% (unadjusted HR=1.026, 95% CI: 0.24 to 4.6, P=0.9). After multivariable modeling, age and coronary artery disease extension was associated with increased risk of adverse events.Age and coronary artery disease extension were independent predictors of adverse events at follow-up. RAO had no prognostic impact. (NCT02762344).

Conventional angioplasty balloon catheter, drug coated balloon (DCB), or angioplasty with drug eluting stent (DES) have been used on the percutaneous treatment of erectile dysfunction (ED). Currently available DCBs are paclitaxel eluting balloon (PEB), very recently, sirolimus eluting balloon (SEB). Although endovascular revascularization with balloon resulted in improvement of ED, there have been no prior reports on the feasibility of SEB treatment for ED.We present an observational, retrospective-prospective multicentre registry in patients evaluating the use of SEB for the treatment of de novo stenosis in native internal pudendal arteries. We will include 100 patients affected by vasculogenic ED non responder to PDE5i with up to two lesions requiring treatment. ED patients should present a IIEF-5 Score15, positive dynamic doppler (PSV25 cm/s) and/or evidence at basal CT angiography. At 30 days, 180, 240, and 365 days following the index procedure, IIEF-5 score will be assessed, and medication regimen and adverse event monitoring will be assessed. At 8 months a dynamic Doppler will be performed. Patients will be followed up for 2 years. The primary endpoints are the Delta IIEF-5 Score and a Delta PSV between basal and 8 months follow up. The secondary endpoint is the incidence of major adverse event (MAE), binary restenosis and late loss in patients who will repeat control angiography if clinically indicated.Considering the limitations and safety concerns of PEB, POBA and DES used so far in ED clinical investigations, we hypothesize that sirolimus nanocarriers-coated balloon can potentially be an improved next-generation treatment for ED patients.

Aims ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). In this study, we sought to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF. Methods and results We performed a pooled analysis of three early phase randomized clinical trials. The endpoints included the composite of all-cause death and new-onset HF, and the composite of all-cause death and hospitalization for HF at 1-year follow-up. Safety events, including injection site reaction and serious infections, were also recorded. We analysed 139 patients with STEMI from three separate trials: VCUART (N = 10), VCUART2 (N = 30), and VCUART3 (N = 99). Of these, 84 (60%) patients were randomized to anakinra and 55 (40%) to placebo. Treatment with anakinra significantly reduced the incidence of all-cause death or new-onset HF (7 [8.2%] vs. 16 [29.1%], log-rank P = 0.002) and of all-cause death or HF hospitalization (0 [0] vs. 5 [9.1%], log-rank P = 0.007). Patients treated with anakinra had significantly higher injection site reactions (19 [22.6%] vs. 3 [5.5%], P = 0.016) without a significant difference in the incidence of serious infections (11 [13.1%] vs. 7 [12.7%], P = 0.435). Treatment with anakinra significantly reduced the area under the curve for high-sensitivity C-reactive protein between baseline and 14 days (75.48 [41.7–147.47] vs. 222.82 [117.22–399.28] mg day/L, P Conclusion IL-1 blockade with anakinra for 14 days in patients with STEMI reduces the incidence of new-onset HF or hospitalization for HF at 1 year following STEMI.

Renal denervation (RDN) is a therapeutic strategy for patients with uncontrolled arterial hypertension characterized by considerable fluctuations during its progression. After initial strong enthusiasm, the procedure came to an abrupt halt following the publication of the Symplicity HTN-3 study results. The results of recently published studies highlight the reduction in blood pressure values after RDN and justify the inclusion in the Guidelines of new recommendations for the use of RDN in clinical practice, in selected patients. Additionally, RDN findings are summarized in view of other potential indications such as atrial fibrillation. Six prospective, randomized studies are presented that evaluated RDN as an adjunct therapy to pulmonary vein isolation for the treatment of atrial fibrillation. In five studies, patients had uncontrolled hypertension despite therapy with three antihypertensive drugs. The analysis of these studies showed that RDN reduced the recurrence of atrial fibrillation (AF) by 57% compared to patients with pulmonary vein isolation (PVI) only. Modulation of the autonomic nervous system by RDN has been shown not only to reduce blood pressure but also to have an antiarrhythmic effect in symptomatic AF patients when the strategy is combined with PVI, thus opening up new therapeutic scenarios.

Transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis. We aimed at appraising effectiveness of a new self-expandable TAVI device.We retrospectively analyzed our institutional experience with Allegra (Biosensors, Morges, Switzerland) for TAVI, focusing on procedural outcomes and 1-month adverse events. We explored the impact of operator experience with this device, dividing patients according to their time of intervention.Between 2018 and 2021, a total of 50 patients underwent TAVI with Allegra, with average age of 81 years, 80% women, and 50% at low or intermediate surgical risk. No major significant difference in baseline patient features were found when comparing the Phase 1 and Phase 2, except for baseline left ventricular ejection fraction and New York Heart Association, which were worse in Phase 1. All procedures were performed transfemorally and percutaneously, with predilation in 94% and postdilation in 36%, yielding device success in 98%, and procedural success in 96%. No significant differences in procedural features were found when comparing Phase 1 vs. Phase 2 (all P0.05). One-month follow-up was also favorable, with no significant difference in adverse outcomes according to phase, and a total of 1 (4%) death, 1 (4%) myocardial infarction, 1 (4%) minor vascular complication, and 4 (8%) permanent pacemaker implantations. Consistent findings were obtained at 6-month follow-up.The Allegra TAVI device is associated with favorable short-to-midterm outcomes in experienced hands. Operators already proficient with other devices can achieve satisfactory results even in the early phase of adoption of Allegra.

Since its outbreak, the Coronavirus disease 2019 (COVID-19) has profoundly changed the world we were acquainted with. After the first known contact with humankind in Wuhan, China, in December 2019, the reckless spread of such pathogen put the healthcare system to the test, leading to harmful consequences affecting human lives in every aspect. As of February 2022, the death toll amounts to almost 6 million deaths, but the pathogenic profile of SARS-CoV2 goes way beyond the mere biological interaction between the viral particle and our organism. People had to deal with the severe psychological impact caused by the only available weapon to fight this infection, i.e., social distancing. The human psychological profile has been strained with repercussions we still are unaware of nowadays. Healthcare professionals were among the most hit categories, not only because of the quarantine but above all for the situations they had to bear every day, constantly facing desperation, death, isolation, and rage. In such circumstances, social media represented a powerful shelter, giving people the ability to keep in contact and to feel connected even if miles apart. In our country, the power of communication was strongly emphasized by launching an Italian Facebook group called Memedical, where members can share ironic memes to feel closer and give a glimmer of happiness in such a challenging moment. Our review highlights the severity of this pandemic's impact, deteriorating the global population's physical and mental health, and shows how wise use of social media can benefit the quality of life.

Despite unanimous calls for more equitable access and support to female researchers, there are persistent barriers to women's career progression and professional fulfillment. These discriminative hurdles undermine female gender in science and have detrimental effects on research activities and female professionals and patients. There is no data on women's outlook in cardiovascular research in Italy, which limits appropriate remedial actions. We aimed at providing an updated perspective on top Italian cardiovascular researchers, focusing on women versus men comparisons.Top Italian cardiovascular researchers were retrieved from a dedicated and validated Scopus query. Researchers' sex was assigned according to the given name with a consensus process. Several metrics were compared, including global rank, total cites, total cites adjusted by academic age, H-index, and self-citation percentage. Bivariate and propensity score-adjusted analyses were used for inferential purposes.Our analysis shows the existence of a gender gap: the number of scientific articles published by Italian male researchers in their careers is significantly higher than their female counterparts (P=0.002). For men, the year of first publication is earlier (P=0.001); they also published more articles as a single author, or single + first author or single + first + last author. Men's papers cited at least once were more than those of women (P≤0.001), and the total number of citations was significantly higher for men (P=0.002). These results remain significant both in the analysis excluding self-citations as well as in the analysis including self-citations. The single-year analysis (2019) confirms the significance of the career analysis, adding that men have a higher rank based on composite score (P=0.041, or P=0.005 if including self-citation). Finally, men have a higher percentage of self-citation in 2019 than women (P=0.008).The gender disparity is still a limiting factor in Italian cardiovascular research. Despite career advancement, women continue to be underrepresented. Men retain more leadership positions in academia and maintain the edge for scientific work productions. More efforts are needed to ensure equity between men and women.

BackgroundDyslipidaemia is associated with increased cancer risk. However, the prognostic value of visit-to-visit lipid variability (VVLV) is unexplored in this regard.ObjectiveTo investigate the associations between VVLV and the risk of incident cancer.DesignRetrospective cohort study.SettingFamily medicine clinics.PatientsAdults attending a family medicine clinic in Hong Kong during 2000-2003, excluding those with MeasurementsVisit-to-visit LDL-C, HDL-C, TC, and triglycerides variabilities were measured by the coefficient of variation (CV). Patients were followed up until 31st December 2019 for the primary outcome of incident cancer.ResultsAltogether, 69,186 patients were included (26,679 males (38.6%); mean age 60±13 years; mean follow-up 16±3 years); 7958 patients (11.5%) had incident cancer. Higher variability of LDL-C, HDL-C, TC, and TG was associated with higher risk of incident cancer. Patients in the third tercile of the CV of LDL-C (adjusted hazard ratio (aHR) against first tercile 1.06 [1.00, 1.12], p=0.049), HDL-C (aHR 1.37 [1.29, 1.44], pLimitationsDue to the observational nature of this study, there may be residual and unmeasured confounders. Patient data could not be individually adjudicated, implying that coding errors may be possible.ConclusionHigher VVLV was associated with significantly higher long-term risks of incident cancer. VVLV may be a clinically useful tool for cancer risk stratification.

BackgroundThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain.ObjectiveTo investigate the effects of circulating molecules in HNBC chronic smokers on the fibrotic specification and paracrine function of cardiac stromal cells (CSCs).MethodsResident CSCs were isolated from the atrial tissue of patients with cardiovascular diseases, and exposed to the serum of 60 young healthy subjects, stratified in exclusive HNBC smokers, traditional combustion cigarette (TCC) smokers, or non-smokers (NS) as reference.ResultsCSCs treated with TCC serum displayed impaired 3D growth and migration, as well as increased expression and/or release of pro-inflammatory and pro-fibrotic cytokines. Cells cultured with HNBC serum showed increased mRNA levels of pro-fibrotic genes, and reduced expression of the gap junction protein CX43. Nonetheless, both TCC and HNBC sera reduced the release of angiogenic and protective factors from CSCs. In fact, their paracrine support to tube-formation by endothelial cells and to preserved cell viability of cardiomyocytes in culture was significantly impaired. Treatment with the sera of both types of smokers also increased the expression of NOX isoforms and the release of H2O2 by CSCs.ConclusionThe circulating molecules in the serum of chronic HNBC smokers induce fibrotic specification in CSCs. They also reduce the beneficial paracrine effects of stromal cells on endothelial cells and cardiomyocytes, albeit to a reduced extent for some features. These results point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.CONDENSED ABSTRACTThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. We isolated human stromal cells from the atrial tissue of patients with cardiovascular diseases, and exposed them to the serum of young healthy subjects, that are exclusive HNBC smokers. Results showed significant alterations in the phenotype of CSCs exposed to HNBC serum, suggesting a specification towards fibrosis, reduced support to parenchymal cells, and increased oxidative stress production. Data point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.

Background: The mismatch between in-stent minimum lumen area (sMLA) and reference vessel lumen area, defined as stent underexpansion (SU), could be an important determinant of stent failure. We tested the clinical predictive value of absolute sMLA in comparison to relative SU in the context of the CLI-OPCI (Centro Per La Lotta Contro L’Infarto-Optimisation of Percutaneous Coronary Intervention) project registry. Methods: We retrospectively analyzed end procedural optical coherence tomography findings in 1211 patients (1422 lesions) undergoing percutaneous coronary intervention, assessing the prevalence and magnitude of residual SU and exploring correlation with outcome in comparison with sMLA. Results: In our series, both sMLA and SU were related to vessel size and anatomic lesion complexity. When compared with patients without adverse event at follow-up, those experiencing device-oriented cardiovascular events (composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis) showed a lower sMLA (5.6±2.1 versus 6.1±2.1 mm 2 ; P =0.011) but a comparable degree of SU (11.6±14.1% versus 11.2±13.3%; P =0.734). The prespecified cutoff value of sMLA 2 , documented in 23.8% of cases, was confirmed as independent outcome predictor for device-oriented cardiovascular events (hazard ratio [HR], 2.05 [95% CI, 1.5–2.9]) including target lesion revascularization (HR, 2.43 [95% CI, 1.7–3.5]) and stent thrombosis (HR, 3.23 [95% CI, 1.7–6.3]). A residual SU of 10%, 20%, and 30% was observed in 38.0%, 18.2%, and 7.6% of cases, respectively. No grade of residual SU significantly increased the risk of stent failure, unless if an SU >20% was associated with an sMLA 2 (HR, 3.11 [95% CI, 1.7–5.6]). Finally, an association between stent overexpansion (ie, >110%) and device-oriented cardiovascular events was also observed (HR, 1.60 [95% CI, 1.1–2.3]). Conclusions: Final absolute sMLA and not relative SU was associated with an increased risk of stent failure. A variable grade of SU was common, but it resulted in being clinically relevant only when associated with an sMLA 2 .