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Stroke has a deleterious impact on human health due to its high incidence, degree of disabling sequelae and mortality, constituting one of the main causes of death and disability worldwide.This study aimed to assess the efficacy and safety of very early mobilization (VEMG) after thrombolysis in functional recovery in patients with acute ischemic stroke.The present study was an open, prospective, randomized study, with no blinded outcome, carried out in the stroke unit of a tertiary referral hospital located in Salvador-Bahia, Brazil. The primary outcome was the level of functional independence. Secondary outcomes were functional mobility, balance, complications within 7 days of hospitalization and 90 days after hospital discharge, and length of stay.A total of 104 patients with ischemic stroke who received thrombolytic treatment between August 2020 and July 2021 were prospectively recruited to the study. Of these, 51 patients received VEMG within 24 h of the ictus and another 53 patients receiving usual care (UCG) with mobilization 24 h after the ictus. When compared to the usual care, the VEMG group was not associated with a significant reduction in the risk of the primary outcome (relative risk [95% confidence intervals]: 0.74 [0.339-1.607]) or any of the secondary outcomes.In this study, the strategy of early mobilization after thrombolysis in ischemic stroke was safe, but without evidence of short-term benefit. Brazilian Registry of Clinical Trials under the registry (registry number: RBR-8bgcs3).

BACKGROUND: On March 9, 2020, the Italian government imposed a national lockdown to tackle the COronaVIrus Disease 19 (COVID-19) pandemic, including stay at home recommendations. The precise impact of COVID-19 scare and lockdown on emergency access for acute myocardial infarction (MI) is still subject to debate. METHODS: Data on all patients undergoing invasive coronary angiography at 9 hospitals in the greater area of Rome, Italy, between February 19, 2020 and March 29, 2020, 9, 2020, were retrospectively collected. Incidence of ST-elevation MI (STEMI), and non-ST-elevation MI (NSTEMI), as well as corresponding percutaneous coronary intervention (PCI), was compared distinguishing two different 20-day time periods (before vs on or after March 10, 2020). RESULTS: During the study period, 1,068 patients underwent coronary angiography, 142 (13%) with STEMI and 169 (16%) with NSTEMI. The average daily number of STEMI decreased from 4.3 before the lockdown to 2.9 after the lockdown (p=0.021). Similarly, the average daily number of NSTEMI changed from 5.0 to 3.5 (p=0.028). The average daily number of primary PCI changed from 4.2 to 2.9 (p=0.030), while the average daily number of PCI for NSTEMI changed from 3.5 to 2.5 (p=0.087). For STEMI patients, the time from symptom onset to hospital arrival (onset-to-door time less than three hours) showed a significant increase after the lockdown (p=0.018), whereas door-to-balloon time did not change significantly from before to after the lockdown (p=0.609). CONCLUSIONS: The present study, originally reporting on the trends in STEMI and NSTEMI in the Rome area, highlights that significant decreases in the incidence of both acute coronary syndromes occurred between February 19, 2020 and March 29, 2020, together with increases in time from symptom onset to hospital arrival, luckily without changes in door-to-balloon time.

The continuous progress in cardiovascular (CV) risk prevention strategies has led to an impressive reduction in mortality and recurrent ischemic events in patients with coronary artery disease (CAD). However, the control of several CV risk factors remains suboptimal in many CAD patients, with a high rate of recurrent events, underlying the need for more new prevention strategies. The GAPS-I (GLP1 analogues, Antithrombotic agents, PCSK9 inhibitors, SGLT2 inhibitors and Immunomodulators) strategy offers a promising potential in patients with a high-residual CV risk, who are frequently encountered in daily practice, by offering an individualised and structured approach to addressing their individual risk factors. The current review summarises the evidence to date on each of its components, with respect to clinical outcomes and economic feasibility. The current evidence points to an efficacy of GAPS-I in reducing MACE and mortality, without a compromise on safety, albeit with the need for longer follow-up data. Key Points: - Secondary prevention remains suboptimal in many CAD patients, highlighting the need for innovative prevention strategies. - The present review discusses the current evidence on efficacy of the GAPS-I strategy in reducing MACE and mortality in patients with CAD. - The GAPS-I strategy, if widely adopted, provides a promising potential to assist cardiologists in managing patients at a heightened risk for further CV events.

To establish the relationship between AH and hemodynamically significant atherosclerotic stenosis of carotid bifurcation and study the effect of carotid endarterectomy (CEA) on the course of AH.In our investigation we included 320 patients: 243 (75,9%) men and 77 (24,1%), the mean age - 59,6 ± 8,2. All patients underwent CEA operation. Patients were divided into groups: I (320) - before CEA surgery and AH; II (320) - the same patients after CEA operation. All patients underwent laboratory tests, ECG, chest X-ray, ultrasound of the kidneys, thyroid gland, computer tomography (CT) of adrenal glands, of the brain, echocardiography, ultrasound or angiography of the renal arteries. Before and after the CEA, there were made Doppler ultrasound of brachiocephalic arteries, 24 hours blood pressure (BP) monitoring. Additional visits were made by 73 patients in 3, 6 and 12 months after the CEA.Most of the patients had significant decrease of BP in the postoperative period, which was observed in 257 (80,3%) patients on days 2-7, in 58 (18,1%) - did not change significantly, and only 5 (1,6%) had the increasing of BP. In 29 (39,7%) patients 1 year after CEA, there was no need to use antihypertensive therapy due for the normalization of BP after the surgery.It is necessary to highlight the cerebrovascular AH into a separate form of the secondary AH. The CEA has prominent, stable anti-hypertensive effect on these patients.

The ACC/TVT score is a specific predictive model of in-hospital mortality for patients undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to test its predictive accuracy in comparison with standard surgical risk models (Logistic Euroscore, Euroscore II, and STS-PROM) in the population of TAVI patients included in the multicenter RISPEVA (Registro Italiano GISE sull'impianto di Valvola Aortica Percutanea) registry. The study cohort included 3293 patients who underwent TAVI between 2008 and 2019. The 4 risk scores were calculated for all patients. For all scores, the capability to predict 30-day mortality was assessed by means of several analyses testing calibration and discrimination. The ACC/TVT score showed moderate discrimination, with a C-statistics for 30-day mortality of 0.63, not significantly different from the standard surgical risk models. The ACC/TVT score demonstrated, in contrast, better calibration compared with the other scores, as proved by a greater correspondence between estimated probabilities and the actual observations. However, when the ACC/TVT score was tested in the subgroup of patients treated in a more contemporary period (from 2016 on), it revealed a slight tendency to lose discrimination and to overestimate mortality risk. In conclusion, in comparison with the standard surgical risk models, the ACC/TVT score demonstrated better prediction accuracy for estimation of 30-day mortality in terms of calibration. Nevertheless, its predictive reliability remained suboptimal and tended to worsen in patients treated more recently.

In the era of evidence-based medicine, systematic reviews and meta-analyses are considered at the top of evidence hierarchy. Despite the almost exponential increase in the number of published meta-analyses over the course of the last decades, only a small minority of them are of high quality, with major flaws involving every aspect of the meta-analytic process. The strength of a meta-analysis is closely linked to the quality of the included studies. Once preliminary phases are completed, it is vital that selected papers undergo a thorough quality assessment, using the most appropriate tools among those available. Analytical approaches must be tailored to the nature of the extracted data and the specific purpose of the meta-analysis. Appraisal of heterogeneity is a key step to inform subgroup or meta-regression analyses. The solidity of the results of the main analysis (especially in meta-analyses of observational studies or studies with high heterogeneity) should be tested by means of pertinent sensitivity analyses. Finally, the investigators should be aware of the possibility of publication bias and make efforts to assess it using qualitative and quantitative methods. The aim of the second part of this expert review is to provide guidance on how to appropriately perform trial level meta-analyses, with particular focus on the quality assessment of the included studies, the choice of the appropriate statistical approach, the methods to deal with heterogeneity (including subgroup, meta-regression, and sensitivity analyses), and the appraisal of publication bias.

In the era of evidence-based medicine, systematic reviews and meta-analyses are considered at the top of evidence hierarchy. Despite the almost exponential increase in the number of published meta-analyses over the course of the last decades, only a small minority of them are of high quality, with major flaws involving every aspect of the meta-analytic process. The strength of a meta-analysis is closely linked to the quality of the included studies. Once preliminary phases are completed, it is vital that selected papers undergo a thorough quality assessment, using the most appropriate tools among those available. Analytical approaches must be tailored to the nature of the extracted data and the specific purpose of the meta-analysis. Appraisal of heterogeneity is a key step to inform subgroup or meta-regression analyses. The solidity of the results of the main analysis (especially in meta-analyses of observational studies or studies with high heterogeneity) should be tested by means of pertinent sensitivity analyses. Finally, the investigators should be aware of the possibility of publication bias and make efforts to assess it using qualitative and quantitative methods. The aim of the second part of this expert review is to provide guidance on how to appropriately perform trial level meta-analyses, with particular focus on the quality assessment of the included studies, the choice of the appropriate statistical approach, the methods to deal with heterogeneity (including subgroup, meta-regression, and sensitivity analyses), and the appraisal of publication bias.

Objectives The evidence supporting the use of the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) score for risk stratification is controversial. We performed a systematic review and meta-analysis of all the randomized controlled trials comparing percutaneous coronary intervention versus coronary artery bypass grafting that reported their outcomes stratified by SYNTAX score, focusing on between-strata comparisons. Methods A systematic review of MEDLINE, EMBASE, Cochrane Library databases was performed. Incidence rate ratios were pooled with a random effect model. Between-group statistical heterogeneity according to accepted SYNTAX score tertiles was computed in the main analysis. Ratios of incidence rate ratios were computed to appraise between-strata effect, as sensitivity analysis. Primary and secondary outcomes were major adverse cardiac and cerebrovascular events and all-cause mortality, respectively. Separate sub-analyses were performed for left main and multivessel disease. Results From 425 citations, 6 trials were eventually included (8269 patients [4134 percutaneous coronary interventions, 4135 coronary artery bypass graftings]; mean follow-up: 6.2 years [range: 3.8-10]). Overall, percutaneous coronary intervention was associated with a significant increase in major adverse cardiac and cerebrovascular events (incidence rate ratio, 1.39, 95% confidence interval, 1.27-1.51) and nonsignificant increase in all-cause mortality (incidence rate ratio, 1.17, 95% confidence interval, 0.98-1.40). There was no significant statistical heterogeneity of treatment effect by SYNTAX score for major adverse cardiac and cerebrovascular events or mortality (P = .40 and P = .34, respectively). Results were consistent also for patients with left main and multivessel disease (major adverse cardiac and cerebrovascular events: P = .85 in left main, P = .78 in multivessel disease 0.78; mortality: P = .12 in left main; P = .34 in multivessel disease). Results of analysis based on ratios of incidence rate ratios were consistent with the main analysis. Conclusions No significant association was found between SYNTAX score and the comparative effectiveness of percutaneous coronary intervention and coronary artery bypass grafting. These findings have implications for clinical practice, future guidelines, and the design of percutaneous coronary intervention versus coronary artery bypass grafting trials.

Summary Background The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. Methods Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). Findings The PRAISE score showed an AUC of 0·82 (95% CI 0·78–0·85) in the internal validation cohort and 0·92 (0·90–0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70–0·78) in the internal validation cohort and 0·81 (0·76–0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66–0·75) in the internal validation cohort and 0·86 (0·82–0·89) in the external validation cohort for 1-year major bleeding. Interpretation A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. Funding None.

Background: The T2238C variant of the atrial natriuretic peptide (ANP) gene has emerged as a novel risk factor for the incidence of cardiovascular events. However, the impact of this variant on cardiovascular outcome in patients with atrial fibrillation (AF) is unknown. Methods: We included 557 anticoagulated patients with non-valvular AF randomly selected from the prospective ATHERO-AF cohort. Patients underwent genetic analysis for the T2238C/ANP variant and were grouped as wild type or heterozygous or homozygous for C2238 variant allele. Primary endpoint was a composite of cardiovascular events (CVEs) including cardiovascular death, fatal/non-fatal ischemic stroke and myocardial infarction. Overall, 429 patients carried the TT wild type genotype, 110 patients (19.7%) were heterozygous (T/C) and 18 patients (3.2%) were homozygous (CC). Results: Incidence of CVEs was higher in homozygous patients for C2238 allele at unadjusted analysis (log-rank test, p = 0.042 for additive model, p = 0.043 for recessive model). The multivariable Cox proportional hazards regression analysis confirmed that C2238 ANP allele was associated with CVEs in the additive (p = 0.008) and recessive models (p = 0.005). Conclusions: Carrier status for the C2238/ANP variant allele is associated with an increased risk of CVEs in anticoagulated AF patients.

Transcatheter aortic valve implantation (TAVI) is a safe and beneficial treatment for patients with severe symptomatic aortic stenosis at high and intermediate surgical risk. The safety of the procedure continues to improve thanks to more refined procedural approaches and devices but, also and above all, to the accrual of the procedural knowledge and expertise by the operators. The diversification of the approaches and the possibility to tailor the treatment on the individual needs and anatomical features of the patients allows a rapid learning curve in the management of even complications. Indeed, there are several approaches with which TAVI can be carried out: transfemoral arterial, subclavian, transcarotid, transaortic, transaxillary, transapical, and through right anterior thoracotomy. Although transfemoral venous TAVI is less common, it has already have been carried out using caval-aortic punctures. This field is rapidly evolving, and it will be of paramount importance for interventional cardiologists and cardiothoracic surgeons to keep up to date with further developments. This review intends to give an in-depth and update overview of both conventional and innovative TAVI approaches, with the scope to highlight the relevant advantages, major disadvantages, safety aspects and techniques.

The differential outcomes between pure/predominant aortic stenosis (AS) and mixed aortic valve disease (MAVD) in patients undergoing transcatheter aortic valve implantation (TAVI) are still debated.To evaluate the comparative clinical outcomes of patients with MAVD and AS undergoing TAVI using data from the RISPEVA registry.A total of 3263 patients were included. Of the 3263 patients, 656 with concomitant moderate/severe aortic regurgitation constituted the MAVD group and 2607 constituted the AS cohort. Primary endpoints were 30-day mortality and 1-year survival. Postprocedural paravalvular regurgitation (PPVR), cerebrovascular events, bleeding, and vascular complications were assessed at 30 days.In the overall population, 30-day mortality in the MAVD group was higher than in AS patients (4.3% vs 2.6%;P=.02); however, no differences were detected after propensity-score matching (4.1% vs 3.5%; P=.62). One-year survival was comparable between MAVD and AS patients in both unmatched and matched cohorts. Left ventricular ejection fraction, pulmonary artery systolic pressure, and PPVR, but not baseline MAVD, were predictors of 30-day mortality. The incidence of PPVR was higher in the MAVD group vs the AS group; this difference was not confirmed in patients implanted with a balloon-expandable device.MAVD per se did not negatively affect patients' prognoses, but appears to identify a more complex cohort of patients with a worse clinical and functional status, probably referred to TAVI in a later stage of the disease. Patients with MAVD had a greater propensity to develop PPVR, which is a known predictor of worse outcome; this tendency seems to be mitigated by the implantation of balloon-expandable valves.

Physical activity (PA) is an established modifiable factor for the prevention of cardiovascular disease. Our objective was to assess the association of PA with mortality rates in a national sample of patients with diabetes.We analyzed a nationally representative sample from The National Health and Nutrition Examination Survey (NHANES, periods 2003-2004 and 2005-2006) that used Physical Activity Monitors. Individuals were matched for BMI, number of steps/ per day and age. Three groups were created: subjects with less than 5000/steps per day (low), 5000-7500/steps per day (moderate) and more than 7500/steps per day (high levels of physical activity). All-cause mortality was ascertained through December 2015.A sample of 3,072 individuals (1018 with diabetes) was analyzed. Patients with diabetes had 30% increased risk of mortality of all causes (RR: 1,298, 95% CI [1,162-1,451], p0,001), Higher levels of physical activity (7500 steps/day) provided similar relative risk for subjects with diabetes compared to their controls [RR:1,256 (95% CI 0,910-1,732)]. In a Poisson model adjusted for sex, history of previous cardiovascular event or cancer, ethnicity, Hb1ac, SBP, and total cholesterol to HDL ratio, patients with diabetes and moderate or high PA had an associated 44% to 80% lower risk of all-cause mortality compared to those with low PA.The subgroup of patients with diabetes and high PA had no excess of mortality compared to the general population. PA can reduce the gap for all-cause mortality, used as an index of cardiovascular fitness and a clinical tool for the assessment of mortality risk.

It is unclear whether coronary artery bypass grafting (CABG) improves survival compared with medical therapy (MT) in patients with stable coronary artery disease (CAD). The aim of this analysis was to perform an individual-patient data-pooled meta-analysis of contemporary randomized controlled trials that compared CABG and MT in patients with stable CAD.A systematic search was performed in January 2021 to identify randomized controlled trials enrolling adult patients with stable CAD, randomized to CABG or MT. Only trials using at least aspirin, beta-blockers, and statins in the MT arm were included. Individual patient data were obtained from all eligible studies and pooled. The primary outcome was all-cause mortality.Four trials involving 2523 patients (1261 CABG; 1262 MT) were included with a median follow-up of 5.6 (4.0-9.2) years. CABG was associated with increased risk of all-cause mortality within 30 days (hazard ratio [HR], 4.81; 95% confidence interval [CI], 1.95-11.83) but subsequent reduction in the long-term risk of death (HR, 0.79; 95% CI, 0.69-0.89). As such, the cumulative 10-year mortality rate was lower in patients treated with CABG compared with MT (45.1% vs 51.7%, respectively; odds ratio, 0.70; 95% CI, 0.58-0.85). Age and race were significant treatment effect modifier (interaction P = .003 for both).In patients with stable CAD, initial allocation to CABG was associated with greater periprocedural risk of death but improved long-term survival compared with MT. The survival advantage for CABG became significant after the fourth postoperative year and was particularly pronounced in younger and non-White patients.

Complete revascularization (CR) of nonculprit lesions (NCL) is strongly recommended in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), but no definitive evidence is available regarding which diagnostic strategy should be preferred. Instantaneous wave-free ratio (iFR) has never been investigated in this setting. We aimed to describe clinical outcomes of a cohort of patients undergoing iFR-guided CR.Following primary percutaneous coronary intervention (PCI), consecutive patients with STEMI and intermediate NCL were enrolled and destinated to an iFR-guided CR. NCL with iFR ≤ 0.89 underwent PCI while NCL with iFR 0.89 were deferred. The primary endpoint was NC target lesion failure (NC-TLF) and the secondary endpoint was major adverse cardiovascular events (MACE), at 1-year follow-up.Overall, 209 patients were enrolled (ischemic iFR = 83; nonischemic iFR = 126). Patients with ischemic iFR showed a higher prevalence of traditional cardiovascular risk factors and angiographically determined three-vessel disease. In the entire cohort, NC-TLF and MACE occurred in 6.7% and 10.5% of patients, respectively. Compared to the deferred group, patients with ischemic iFR experienced significantly higher rates of both NC-TLF (3.2% vs. 12.1%; p = 0.021) and MACE (7.1% vs. 16.9%; p = 0.041). These results were mostly driven by increased rates of NC-TLF PCI and further revascularizations in this latter group, while no differences were evident in terms of nonfatal myocardial infarction or death. At multivariable analysis, the strongest predictor of MACE was symptom onset to balloon time (HR = 1.17 [95% CI: 1.04-1.31], p = 0.008).In our study enrolling STEMI patients with MVD, iFR assessment was feasible and safe. PCI-deferring according to iFR evaluation of NCL was associated with low rates of adverse events. Further randomized studies are needed to investigate the effectiveness of iFR-guided revascularization compared to current practice in this setting.

The microbiota of the gastrointestinal tract (GIT) is an extremely diverse community of microorganisms, and their collective genomes (microbiome) provide a vast arsenal of biological activities, particularly enzymatic ones, which are far from being fully elucidated. The study of the microbiota (and the microbiome) is receiving great interest from the biomedical community because it carries the potential to improve risk prediction models, refine primary and secondary prevention efforts, and also design more appropriate and personalized therapies, including pharmacological ones. A growing body of evidence, although sometimes impaired by the limited number of subjects involved in the studies, suggests that GIT dysbiosis, that is, the altered microbial composition, has an important role in causing and/or worsening cardiovascular disease (CVD). Bacterial translocation and the alteration of levels of microbe-derived metabolites can thus be important to monitor and modulate because they may lead to initiation and progression of CVD and to its establishment as chronic state. We hereby aim to provide readers with details on available resources and experimental approaches that are used in this fascinating field of biomedical research and on some novelties on the impact of GIT microbiota on CVD.

The next iteration of drug-eluting stents (DESs) for percutaneous coronary intervention (PCI) has focused on bioresorbable polymers and thin struts. The Alex Plus DES is a new-generation sirolimus-eluting device with 70-μm cobalt chromium struts, a 5-μm bioresorbable polymer and a very small profile. Despite such favorable features, limited data are available to estimate the risk-benefit profile of Alex Plus. We aimed at comparing the effectiveness of Alex Plus in real-world practice.Retrospective clinical data on patients treated with Alex Plus at our institutions were collected and clinical outcome data over follow-up were obtained, comparing them with those of subjects receiving Xience, a leading DES with permanent polymer.A total of 100 patients (126 lesions) treated with Alex Plus and 753 subjects (1020 lesions) receiving Xience were included. Baseline and procedural features were largely similar in the 2 groups, with the notable exception of age, sex, and left circumflex coronary artery as the target vessel. Clinical follow-up showed that patients with Alex Plus had a significantly higher risk of major adverse clinical event (MACE), mainly driven by an excess in repeat PCI (hazard ratio, 4.81; 95% confidence interval, 2.83-8.20; P.001). Even after propensity-score matching, Alex Plus was associated with an increased risk of MACE (P.001).Our clinical experience to date with Alex Plus has been disappointing, despite the favorable promises. Further improvements are likely needed in the Alex Plus DES, most likely in drug delivery, before this device is considered for routine clinical use in complex patients or lesions.

We aimed to assess which bifurcation technique performs best in unprotected left-main (LM) percutaneous coronary intervention (PCI).Provisional stenting was considered the preferred technique for LM bifurcation PCI due to the supposed lower risks of thrombosis and restenosis. However, recent studies showed potential advantages of double kissing (DK)-crush technique over the other strategies.We performed a frequentist network meta-analysis comparing different stenting techniques in the setting of LM bifurcation. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched. Both randomized clinical trials and non-randomized clinical trials were considered eligible for inclusion. Incidence rate ratios (IRRs) were computed using a random-effects model for death, cardiac death, myocardial infarction, target-vessel revascularization, target-lesion revascularization, and stent thrombosis, including 95% confidence intervals (CIs).A total of 10 studies (2364 patients) were included. Compared with provisional stenting, DK-crush was associated with fewer cardiac deaths (IRR, 0.34; 95% CI, 0.17-0.70; P.01), myocardial infarctions (IRR, 0.19; 95% CI, 0.08-0.44; P.001), stent thromboses (IRR, 0.31; 95% CI, 0.14-0.69; P.01), target-vessel revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P.001), and target-lesion revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P.001). DK-crush was also associated with a lower risk of myocardial infarction (IRR, 0.19; 95% CI, 0.05-0.76; P=.02) when compared with standard crush and lower risk of target-lesion revascularization when compared with culotte (IRR, 0.32; 95% CI, 0.12-0.83; P=.02) and crush (IRR, 0.07; 95% CI, 0.02-0.28; P.001).DK-crush is the best technique for unprotected LM bifurcation PCI.

Transcatheter aortic valve implantation (TAVI) is emerging a an appealing management strategy for patients with severe aortic stenosis at intermediate, high or exceedingly high risk, but its risk-benefit profile in younger patients is less certain. We aimed at exploring the outlook of patients aged 70 years or less and undergoing TAVI at 2 high-volume Italian institituions.We retrospectively collected baseline, imaging, procedural and outcome features of patients with age ≤70 years in whom TAVI was attempted at participating centers between 2012 and 2021. Non-parametric tests and bootstrap resampling were used for inferential purposes.A total of 39 patients were included, out of3,000 screened with heart team involvement and1,500 receiving TAVI. Most common or relevant indications for TAVI were reduced life expectancy (eg cardiogenic shock or severe left ventricular systolic dysfunction), chronic obstructive pulmonary disease, morbid obesity, active or recent extra-cardiac cancer, porcelain aorta, neurologic disability, cirrhosis, or prior surgical aortic valve replacement, as well as extreme cachexia, and Hutchinson-Gilford progeria. At least two contemporary high-risk features were present in most cases. Transapical access was used in 5 (12.8%) cases, and a sheathless approach in 15 (38.5%). A variety of devices were used, including both balloon- and selfexpandable devices. Clinical outcomes were satisfactory, despite the high risk profile, at both shortand mid-term, with no in-hospital death, and 5.1% (95% confidence interval 0-12.8%) mortality at a median follow-up of 15 months (minimum 1; maximum 85). Notably, no case of significant valve deterioration requiring reintervention occurred.In carefully selected patients with 70 years or less of age and prohibitive risk for surgery or reduced life expectancy, TAVI represents a safe option with a favorable mid-term survival and low rate of adverse events.

Aims Little is known about the outcomes and processes of care of patients with non-ST-segment myocardial infarction (NSTEMI) who present with ‘polyvascular’ disease. Methods and results We analysed 287 279 NSTEMI patients using the Myocardial Ischaemia National Audit Project registry. Clinical characteristics and outcomes were analysed according to history of affected vascular bed—coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral vascular disease (PVD)—with comparison to a historically disease-free control group, comprising 167 947 patients (59%). After adjusting for demographics and management, polyvascular disease was associated with increased likelihood of major adverse cardiovascular events (MACEs) [CAD odds ratio (OR): 1.06; 95% confidence interval (CI): 1.01–1.12; P = 0.02] (CeVD OR: 1.19; 95% CI: 1.12–1.27; P Conclusion Polyvascular disease patients had a higher incidence of in-hospital mortality and MACEs. Patients with no history of vascular disease were less likely to receive statins or ACE inhibitors/ARBs, but more likely to receive DAPT.

Transcatheter aortic valve implantation (TAVI) has proved beneficial in patients with severe aortic stenosis, especially when second-generation devices are used. We aimed at reporting our experience with Navitor, a third-generation device characterized by intrannular, large cell, and cuffed design, as well as high deliverability and minimization of paravalvular leak. Between June and December 2021, a total of 39 patients underwent TAVI with Navitor, representing 20% of all TAVI cases. Mean age was 80.0 ± 6.7 years, and 14 (36.8%) women were included. Severe aortic stenosis was the most common indication to TAVI (37 [97.4%] cases), whereas 2 (5.3%) individuals were at low surgical risk. Device and procedural success was obtained in all patients, with a total hospital stay of 6.6 ± 4.5 days. One (2.9%) patient required permanent pacemaker implantation, but no other hospital events occurred. At 1-month follow-up, a cardiac death was adjudicated in an 87-year-old man who had been at high surgical risk. Echocardiographic follow-up showed no case of moderate or severe aortic regurgitation, with mild regurgitation in 18 (47%), and none or trace regurgitation in 20 (53%). The Navitor device, thanks to its unique features, is a very promising technology suitable to further expand indications and risk-benefit profile of TAVI.

Despite mounting evidence, there is uncertainty on the impact of the interplay between weather and pollution features on the risk of acute cerebrovascular events (CVE). We aimed at appraising role of weather and pollution on the daily risk of CVE.Anonymized data from a hub CVE center in a large metropolitan area were collected and analyzed according to weather (temperature, pressure, humidity, and rainfall) and pollution (carbon monoxide [CO], nitrogen dioxide [NO2], nitrogen oxides [NOX], ozone [O3], and particulate matter [PM]) on the same and the preceding days. Poisson regression and time series analyses were used to appraise the association between environmental features and daily CVE, distinguishing also several subtypes of events.We included a total of 2534 days, with 1363 days having ≥1 CVE, from 2012 to 2017. Average daily rate was 1.56 (95% confidence interval: 1.49; 1.63) for CVE, with other event rates ranging between 1.42 for stroke and 0.01 for ruptured intracranial aneurysm. Significant associations were found between CVE and temperature, pressure, CO, NO2, NOX, O3, and PM10 µm (all P0.05), whereas less stringent associations were found for humidity, rainfall, and PM2.5 µm. Time series analysis exploring lag suggested that associations were stronger at same-day analysis (lag 0), but even environmental features predating several days or weeks were significantly associated with events. Multivariable analysis suggested that CO (point estimate 1.362 [1.011; 1.836], P=0.042) and NO2 (1.011 [1.005; 1.016], P0.001) were the strongest independent predictors of CVE.Environmental features are significantly associated with CVE, even several days before the actual event. Levels of CO and NO2 can be potentially leveraged for population-level interventions to reduce the burden of CVE.

Background Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and oral P2Y12 inhibitor (P2Y12-I) represents the standard of care for patients with acute coronary syndromes (ACS) or with chronic coronary syndromes (CCS) treated with percutaneous coronary intervention (PCI). Cangrelor, the first intravenous P2Y12-I, is deemed to overcome the drawbacks of the oral administration; nevertheless real world data on this new drug are scanty. We sought to investigate routine clinical use of cangrelor in four interventional centers of Italy. Methods We enrolled 241 consecutive patients (196 ACS, 45 CCS) treated with cangrelor during PCI. Drug administration modalities and in-hospital clinical outcomes were evaluated. A subanalysis in patients selected on the basis of the CHAMPION Phoenix trial inclusion/exclusion criteria (CHAMPION-like subpopulation) was also performed. Results Cangrelor was mainly utilized in ACS patients, who presented poorer clinical conditions and higher bleeding risk. Cangrelor was given only in P2Y12-I naive patients; switch to clopidogrel was always done at the end of the infusion, while ticagrelor or prasugrel were prevalently given 30 minutes before. In-hospital mortality was 10.0% and GUSTO moderate/severe bleeding was 2.5%. Bleeding data showed nevertheless to be in line with the CHAMPION Phoenix results in the "CHAMPION-like" subpopulation. Conclusions Cangrelor was predominantly used in ACS with modalities substantially in accord with the label indications. Poor clinical outcomes are due to the prevalent utilization in highly challenging clinical settings, nevertheless the rate of bleeding and stent thrombosis are in line with the randomized trials if analyzed in a subpopulation of comparable risk profile.

Initial studies on renal denervation (RDN) for the treatment of non-controlled arterial hypertension (HTN) through radiofrequency ablation of renal arteries demonstrated that RDN is an effective therapeutic strategy to reduce arterial blood pressure (BP). Nonetheless, the first randomized study, SYMPLICITY-HTN-3, failed to demonstrate a clear benefit for RND over the control group. Technologic evolution, with the introduction of new second generation multi-electrode devices, allowed deep energy delivery along the full circumference of the vessel. Two recent randomized studies involving patients assuming (SPYRAL HTN-ON MED) or not (SPYRAL HTN-OFF MED) antihypertensive pharmacologic treatment, demonstrated the efficacy and safety of RDN using second generation systems for radiofrequency ablation. Another recent randomized study demonstrated that RDN with ultrasounds (RADIANCE-HTN SOLO) of the main renal arteries led to a significant BP reduction compared to the control group. These studies have once again raised the interest of the scientific community towards attempting to define the appropriate role of RDN in the treatment of hypertension. Nonetheless, larger and longer clinical trials will be necessary to draw further conclusions.

The differential outcomes across the age spectrum of transcatheter aortic valve implantation (TAVI) recipients are still debated. Aim of the study was to evaluate the clinical outcomes of oldest-old patients undergoing TAVI in the large "Registro Italiano GISE sull'impianto di Valvola Aortica Percutanea (RISPEVA)" registry. A total of 3,507 patients were stratified according to age: 1,381 were ≥85 years, 2,126 were85 years. Primary endpoints were death at 30-days and complete follow-up (FU) (medium 368 days). Cerebrovascular events, myocardial infarction, bleedings, vascular complications at 30-days and complete FU were considered. In the unadjusted analysis, 30-days mortality in the oldest-old group was higher than in younger patients (4.2% vs 2.4%; p = 0.007); this difference kept true also at complete FU (19.6% vs 15.9%; p = 0.014). After propensity score (PS) matching, the oldest-old population showed a higher mortality solely at 30-days (4.7% vs 2.4%; p = 0.016), while the survival at complete FU was similar to that of younger patients (20.1% vs 18.0%; p = 0.286). The incidence of non-fatal outcomes resulted comparable between the 2 groups, also after propensity score matching. At the multivariate logistic regression analysis procedural major or disabling bleedings, cerebrovascular events, cardiogenic shock resulted predictors of 30-days death in the oldest-old cohort. In conclusion, patients ≥85 years can safely undergo TAVI being not more exposed to procedural complications than those85 years; nevertheless they showed worse 30-days mortality, probably driven by reduced tolerance to complications. Passed the critical periprocedural phase, patients ≥85 years had a similar survival to those85 years with comparable risk profile.

According to previous epidemiological studies, we can reduce the thickness of epicardial fat and improve cardiovascular risk factors through exercise, and the changes may depend on the form of exercise. We systemically reviewed published studies that evaluated exercise intervention on epicardial adipose tissue (EAT) levels. We included randomized controlled trials (RCTs) comparing one exercise with another exercise or diet for the treatment to reduce EAT. We used fixed effects models for meta-analyses; effects of exercise on outcomes were described as mean differences (MD) or standardized difference of means (SMD) was used, their 95% confidence intervals (CI). Five RCTs were included (n = 299), 156 in exercise group and 143 in the control. In comparison to the control group, exercise significantly reduced EAT (SMD − 0.57, 95%CI − 0.97 to − 0.18) and waist circumference (MD − 2.95 cm, 95%CI − 4.93 to − 0.97). Exercise did not have an effect on BMI (MD − 0.23 kg/m2, 95%CI − 0.73 to 0.27), weight (MD − 0.06 kg, 95%CI − 1.46 to 1.34), or HDL (SMD 0.26, 95%CI − 0.06 to 0.57).VO2 was significantly increased by exercise (SMD 1.58, 95%CI 1.17 to 1.99). Risk of bias was high for 3 studies, and GRADE quality of evidence was very low to moderate. Exercise reduced epicardial adipose tissue and waist circumference, and did not have effect on weight, BMI, or HDL. Newer trials with better design and methods are necessary to improve the quality of the evidence. PROSPERO registration number (CRD42018096581)

Fractional flow reserve (FFR) provides an objective measurement of the severity of ischemia caused by coronary stenoses in downstream myocardial regions. Data from the interventional cardiology realm have suggested benefits of a FFR-guided percutaneous coronary intervention (PCI) strategy. Limited evidence is available on the use of FFR to guide coronary artery bypass grafting (CABG). The most recent data have shown that FFR might simplify CABG procedures and optimize patency of arterial grafts without any clear impact on clinical outcomes. The aim of this review was to summarize the available data on FFR-based CABG and discuss the rationale and potential consequences of a switch toward FFR-based surgical revascularization strategy.

Percutaneous coronary intervention has become a mainstay in the management of coronary artery disease. While initially advanced age was considered a relative contraindication to invasive management of coronary artery disease, current cardiovascular practice stands solidly on an early invasive approach for elderly patients, typically based on radial access and drug-eluting stent implantation. Since the advent of coronary stents, oral antiplatelet therapy has proved crucial to maximize the benefits and minimize the risks of stenting, and this holds even truer in older patients rather than in younger ones. Indeed, the elderly is typically at higher risk of thrombotic events as well as bleeding complications, and thus careful decision making must be exercised to prescribe the most appropriate antiplatelet regimen. We thus conducted an umbrella review with scoping purposes on oral antiplatelet therapy in elderly patients undergoing percutaneous coronary intervention, retrieving 8 pertinent systematic reviews. We found that, while several drugs are available, ranging from aspirin to cilostazol, clopidogrel, dipyridamole, prasugrel, ticagrelor, and ticlopidine, most commonly a dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor is recommended, with subtle adjustments for pretreatment, loading, dose, duration, escalation or de-escalation, with the potential adjunct in selected patients of novel oral anticoagulants. Indeed, a flexible and individualized approach to oral antiplatelet therapy in elderly patients undergoing percutaneous coronary intervention is paramount, factoring patient features (exploiting thrombotic, bleeding and frailty scores), triage (including when appropriate non-invasive assessment of anatomic and functional significance of coronary artery disease), angiographic and other invasive imaging features, interventional technique, stent choice, rehabilitation, and secondary prevention.

Despite significant efforts during the last decades, cigarette smoking still remains prevalent. Discouraging the use of all tobacco products, it is certainly the most effective mean to enhance public health, but complete prohibition is unlikely to succeed. The greatest challenge is the approach to chronic smokers, particularly those affected with cardiovascular conditions. To better support these patients during the difficult process leading to complete smoke cessation, it is important to characterize each patient from a clinical and psychological perspective, introducing the most reliable approaches to incentivize and support abstinence, such as varenicline and nicotine replacement therapy, thus providing a personalized recommendation. The recent introduction of electronic systems for nicotine release or tobacco heating (electronic cigarettes), offers an important challenge. These devices are reasonably considered as lower risk tools, thus providing a useful alternative which unable the patient a smoother transition toward smoking cessation, also presenting an array of choices among which a personalized selection could be made. This technology, though, should not be overemphasized, considering also its potential harmful effects, and certainly its use should be strongly discouraged in non-smokers, particularly at young age. This approach, cautious and pragmatic, aside from demonization or over-enthusiastic appraisal, could provide favourable results in the constant struggle against cigarette smoking.

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

The majority of stent-related major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) are believed to occur within the first year. Very-late (1-year) stent-related MACE have not been well described.The purpose of this study was to assess the frequency and predictors of very-late stent-related events or MACE by stent type.Individual patient data from 19 prospective, randomized metallic stent trials maintained at a leading academic research organization were pooled. Very-late MACE (a composite of cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]), and target lesion failure (cardiac death, target-vessel MI, or ID-TLR) were assessed within year 1 and between 1 and 5 years after PCI with bare-metal stents (BMS), first-generation drug-eluting stents (DES1) and second-generation drug-eluting stents (DES2). A network meta-analysis was performed to evaluate direct and indirect comparisons.Among 25,032 total patients, 3,718, 7,934, and 13,380 were treated with BMS, DES1, and DES2, respectively. MACE rates within 1 year after PCI were progressively lower after treatment with BMS versus DES1 versus DES2 (17.9% vs. 8.2% vs. 5.1%, respectively, p 0.0001). Between years 1 and 5, very-late MACE occurred in 9.4% of patients (including 2.9% cardiac death, 3.1% MI, and 5.1% ID-TLR). Very-late MACE occurred in 9.7%, 11.0%, and 8.3% of patients treated with BMS, DES1, and DES2, respectively (p 0.0001), linearly increasing between 1 and 5 years. Similar findings were observed for target lesion failure in 19,578 patients from 12 trials. Findings were confirmed in the network meta-analysis.In this large-scale, individual patient data pooled study, very-late stent-related events occurred between 1 and 5 years after PCI at a rate of ∼2%/year with all stent types, with no plateau evident. New approaches are required to improve long-term outcomes after PCI.

Optimal timepoint for the discontinuation of dual antiplatelet therapy (DAPT) after an acute coronary syndrome is still debated. In fact, despite a shortening of DAPT duration should be advocated, based on the negligible risk of thrombotic complications observed with newer generations of drug-eluting stents (DES), in order to reduce the hemorrhagic risk, a more prolonged anti-ischemic protection would be suitable for certain higher-risk patients, rendering the traditional 12 months strategy outdated. We performed an updated meta-analysis and indirect comparison of randomized trials comparing shorter vs extended DAPT duration in ACS patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched for studies comparing 3–6 (short-term) or prolonged (> 12 months) DAPT vs traditional 12 months in ACS patients treated with DES. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stent thrombosis. We included three randomized clinical trials and six study sub-analysis comparing alternative (short-term or prolonged) DAPT vs 12 months in post-ACS, with a total of 15,738 patients. Mortality occurred in 1.8% of patients, with no difference according to DAPT duration (short-term vs standard DAPT: OR [95% CI] 1.00 [0.72–1.39], p = 0.99; > 12 vs 12 months: OR [95% CI] 0.87 [0.61–1.22], p = 0.41). No difference in the risk of recurrent myocardial infarction and stent thrombosis was observed between short-term and standard DAPT, while a significant reduction was achieved only when extending the duration beyond 12 months (MI: OR [95% CI] 0.49 [0.36–0.67], p

Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. However, there are very limited data on the efficacy of sacubitril/valsartan in the prevention and treatment of cardiotoxicity. This systematic review aimed to evaluate the potential benefit of sacubitril/valsartan in patients with CTRCD.The databases included MEDLINE, Embase, LILACS, Scopus and Cochrane Central up to January 20, 2022. All pre-clinical and clinical studies including observational studies (cohorts, case-control, cross-sectional and case reports) that used sacubitril/valsartan for prevention or treatment of CTRCD. The primary effectiveness endpoints was CTRCD, defined as a clinically significant change in left ventricular ejection fraction (LVEF) at the end of the follow-up.And after applying the eligibility criteria, 12 articles (9 in humans and 3 preclinical studies) were included in this systematic review. The 3 preclinical studies demonstrated beneficial effects in preventing, attenuating and/or delaying the onset of myocardial damage at the cellular level, ventricular dysfunction and remodeling. Regardind human studies, most of them were composed of case reports. The largest study consisted of a retrospective multicentric cohort with 64 patients.All clinical studies have demonstrated that used Sac/Val in human showed a significant increase in LVEF, and when reported, a reduction in left ventricular volume and NT-proBNP (or BNP). Randomized clinical trials are needed to confirm this hypothesis.