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Background: The aim of this study was the creation of an optimal model for predicting arterial vascular complications in patients with extrasystolic arrhythmia., Methods: A single-center prospective study was performed with involving 634 patients with supraventricular or ventricular extrasystoles (ES) of 700 or more per 24 hours. The control group consisted of 106 people with ES less than 700 per 24 hours. The main and control groups were initially equivalent in anthropometric criteria and concomitant pathology. The list of examinations included laboratory methods (including lipid profile, coagulograms), as well as instrumental studies (transthoracic and/or transesophageal echocardiography (EchoCG), Doppler ultrasound of the brachiocephalic arteries and arteries of the lower extremities, 24-hours ECG monitoring, according to the indications - computed tomography or magnetic resonance imaging of the brain, coronary angiography, stress echocardiography. Prospective observation of patients performed for 1 year after the initial examination. Combined end points: development of arterial vascular complications - stroke, myocardial infarction, distal arterial embolism of other locations. We studied the data on identified complications. Next, we built models for predicting complications in various ways: Decision Tree; Bootstrap Forest; Boosted Tree; Neural Boosted; Support Vector Machines; Fit Stepwise; Nominal Logistic; Generalized Regression Lasso; Generalized Regression Forward Selection; Generalized Regression Pruned Forward Selection; Generalized Regression Elastic Net; Generalized Regression Ridge. To assess the quality of the models and compare them we used cross-validation with 30 replications., Results: The highest profit values with minimal values of false positive results were obtained for the Bootstrap Forest model. Basing on this model, we created arterial vascular complications predictive score in extrasystolic arrhythmia "EX-prognosis" that included the following parameters: atheroma type III in carotid arteries - 3 points; age 69+ years old - 2 points; ES appearing before transmitral blood flow peak in cardiac cycle 700 and more per 24 hours - 1 point; carotid arteries stenosis, non-significant - 1 point. If total number is 3 and more points, the risk of arterial vascular complications within 1 year is high., Conclusions: We recommend to use the scale "EX-prognosis" in the clinical practice. For a quick assessment of the total risk, it is optimal to implement the risk14.exe program - calculator - developed by us for a personal computer, based on this scale.

This tutorial provides a comprehensive guide on leveraging ChatGPT for systematic literature reviews, leveraging actual applications in cardiovascular research. Systematic reviews, while essential, are resource-intensive, and ChatGPT offers a potential solution to streamline the process. The tutorial covers the entire review process, from preparation to finalization. In the preparation phase, ChatGPT assists in defining research questions and generating search strings. During the screening phase, ChatGPT can efficiently screen titles and abstracts, processing multiple abstracts simultaneously. The tutorial also introduces an intermediate step of generating study summaries that leads to the generation of reliable data extraction tables. For assessing the risk of bias, ChatGPT can be prompted to perform these tasks. Using each tool's explanation document to generate an appropriate prompt is an efficient method of reliable risk of bias assessments using ChatGPT. However, users are cautioned about potential hallucinations in ChatGPT's outputs and the importance of manual validation. The tutorial emphasizes the need for vigilance, continuous refinement, and gaining experience with ChatGPT to ensure accurate and reliable results. The methods presented have been successfully tried in several projects, but they remain in nascent stages, with ample room for improvement and refinement.

Background: Atrial fibrillation is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. Despite the effectiveness of catheter-based ablation, periprocedural complication and recurrences remain a concern. In this context, we aim to appraise the potential impact of brain-derived neurotrophic factor (BDNF) on reducing episodes of paroxysmal atrial fibrillation (PAF)., Methods: 22 patients with an established diagnosis of PAF and without structural heart disease were considered. Every patient received 20 drops of GUNA-BDNF administered in the morning. During the 24 months of follow-up, the arrhythmic burden was measured by the average monthly duration of PAF episodes., Results: At the end of the follow-up period (24 months), data from 22 patients, of whom 17 men and five women, were analyzed. The arrhythmic burden, measured in terms of average monthly duration of PAF episodes, was found significantly reduced after the administration of low dose BDNF (9.5 vs. 65.3 minutes per month, P<0.001). A total of 17 out of 22 patients saw their arrhythmic burden eliminated or consistently reduced, furthermore two patients underwent a drastic reduction of the average monthly duration of AF (more than 200 minutes compared to the baseline). Only four patients, despite the administration of BDNF, still experienced an arrhythmic burden of 20 minutes or more. Considering the age groups, the major reduction was observed in people aged 70 or more, who were also the most represented in the sample. These results are coherent with the poor literature currently available., Conclusions: BDNF low dose therapy has shown to have an impacting role in reducing the arrhythmic burden and recurrences of AF, with a particular effectiveness in patients over 70 and without structural heart disease. We should welcome this work, despite it limitations. Further clinical and molecular studies are needed before-considering BDNF low dose as a tool against PAF.

Background: Fast acting insulin analogues are known to improve arterial stiffness. The combination of metformin with insulin represents a widely used therapeutic strategy in diabetes. We hypothesized that insulin treatment in patients with type 2 diabetes (T2D) with long-acting, fast-acting or basal bolus insulin as an add-on to metformin would provide additional improvement of arterial stiffness., Methods: The INSUlin Regimens and VASCular Functions (INSUVASC) study is a pilot, randomized, open label three-arms study that included 42 patients with type 2 diabetes (T2D) in primary prevention, after a failure to oral antidiabetic agents. Arterial stiffness measurements were performed at fasting and after a standardized breakfast. During the first visit (V1) pre-randomization, participants took only metformin to perform the tests. The same tests were repeated after 4 weeks of insulin treatment during the second visit (V2)., Results: Data were available for final analysis in 40 patients, with a mean age of 53.6±9.7 years and a mean duration of diabetes of 10.6±5.6 years. Twenty-one were females (52.5%), hypertension and dyslipidemia were present in 18 (45%) and 17 patients (42.5%), respectively. After insulin treatment, the metabolic control was associated to a decrease in oxidative stress and improvement of endothelial functions, with a post prandial diastole duration increased and a decrease of the peripheral arterial stiffness, with a better post prandial pulse pressure ratio and ejection duration after insulin. In hypertensive patients, insulin treatment provided positive effects by decreasing the pulse wave velocity and improving reflection time., Conclusions: A short time treatment by insulin in addition to metformin improved myocardial perfusion. Moreover, insulin treatment in hypertensive patients provides a better hemodynamic profile in large arteries.

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-CoV-2 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.

Introduction: The association of coronary stent malapposition (SM) and adverse clinical outcomes after percutaneous coronary intervention (PCI) remains unclear. We aimed to perform a systematic review and meta-analysis of randomized and observational studies to assess the association between acute and persistent SM detected using intravascular ultrasound (IVUS) or optical coherence tomography (OCT) and adverse cardiovascular outcomes., Evidence Acquisition: Available studies were identified through a systematic search of PubMed, reference lists of relevant articles, and Medline. Main efficacy outcomes of interest were: device-oriented composite endpoint (DoCE, including cardiac death, myocardial infarction [MI], target lesion revascularization [TLR], and stent thrombosis [ST]), major safety events (MSE, including cardiac death, MI and ST), TLR, and ST. A sensitivity analysis regarding the impact of major malapposition was also performed., Evidence Synthesis: A total of 9 studies enrolling 6497 patients were included in the meta-analysis. After a mean follow-up of 24±14 months, overall acute and/or persistent malapposition was not significantly associated with the occurrence of all the outcomes of interest, including DoCE (risk ratio [RR] 1.00, 95% confidence interval [CI, 0.79-1.26], P=0.99), MSE (RR 1.42, 95%CI [0.81-2.50], P=0.22), TLR (RR 0.84, 95%CI [0.59-1.19], P=0.33), and ST (RR 1.16, 95%CI [0.48-2.85], P=0.74). In the sensitivity analysis, we found a significant increase of MSE in patients with major malapposition (RR 2.97, 95%CI [1.51-5.87], P=0.001)., Conclusions: Acute and persistent SM were not overall associated with adverse cardiovascular clinical outcomes at follow-up. However, major malapposition was associated with an increased risk of major safety events, including cardiac death, MI and ST. These findings should be taken into account during stent implantation and PCI optimization.

Background: 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., Methods: 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., Results: 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., Conclusions: Age and coronary artery disease extension were independent predictors of adverse events at follow-up. RAO had no prognostic impact.

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.

Background: 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., Methods: 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 Score<15, positive dynamic doppler (PSV <25 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., Conclusions: 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.

Background: Transcatheter aortic valve implantation (TAVI) is emerging as 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 to explore the outlook of patients aged 70 years or less and undergoing TAVI at 2 high-volume Italian institutions., Methods: 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., Results: A total of 39 patients were included, out of >3000 screened with heart team involvement and >1500 receiving TAVI. Most common or relevant indications for TAVI reduced life expectancy (e.g. 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 self-expandable devices. Clinical outcomes were satisfactory, despite the high-risk profile, at both short- and 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., Conclusions: 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.

Introduction: 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., Evidence Acquisition: 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)., Evidence Synthesis: Eleven 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., Conclusions: 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-year 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.

Introduction: 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., Evidence Acquisition: Real-world studies (RWS) were identified by searching electronic databases from inception to 31 st October, 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively., Evidence Synthesis: 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: Transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis. We aimed at appraising effectiveness of a new self-expandable TAVI device., Methods: 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., Results: 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 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 P>0.05). 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 exploratory 6-month follow-up., Conclusions: 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.

Introduction: The impact of the International Criteria for ECG interpretation in athletes has further improved the diagnostic accuracy of the 12-lead ECG use for preparticipation screening (PPS); moreover, these criteria have been evaluated in different populations of athletes and settings proving good results., Evidence Acquisition: We aimed to perform a comprehensive review of the use of the International Criteria for ECG interpretation in athletes, stemming from a systematic review to diagnostic meta-analysis, limiting our inclusion only to observational studies to determine the diagnostic accuracy of ECG for detecting cardiac anomalies related to sudden cardiac death in athletes., Evidence Synthesis: This meta-analysis is expected to include several important studies related to PPS on different populations of athletes comparing different ECG criteria and detail important data on the diagnostic accuracy of ECG in PPS. Furthermore, we intend to highlight the advantage of using ECG in PPS., Conclusions: The present diagnostic meta-analysis results will aid sports medicine physicians and cardiologist in adhering to the most accurate criteria for ECG evaluation in athletes and it may help to solve controversies aroused regarding the excess cost of ECG in PPS related to the amount of false positive cases.

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 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, 1068 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.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has rapidly spread globally. Due to different testing strategies, under-detection of positive subjects and COVID-19-related-deaths remains common. Aim of this analysis was to assess the real impact of COVID-19 through the analysis of 2020 Italian all-cause mortality data compared to historical series., Methods: We performed a retrospective analysis of 2020 and 2015-2019 all-cause mortality data released by the Italian National Institute for Statistics (ISTAT) for the time period January 1 st -March 21 st . This preliminary sample included 1084 Italian municipalities showing at least 10 deaths during the above-mentioned timeframe and an increase in mortality of more than 20% as compared to the previous five years (2015-2019), with a resulting coverage of 21% of Italian population. The difference between 2020 observed and expected deaths (mean of weekly deaths in 2015-2019) was computed, together with mortality rate ratio (MRR) for each of the four weeks following detection of the first autochthonous COVID-19 case in Italy (February 23 rd , 2020 - March 21 st , 2020), as well as for this entire timeframe. Subgroup analysis by age groups was also performed., Results: Overall MRR was 1.79 [1.75-1.84], with an observed excess mortality of 8750 individuals in the investigated sample, which in itself outweighs Italian Civil Protection report of only 4,825 COVID-19-related deaths across Italy, as of March 21. Subgroup analysis did not show any difference in mortality rate in '0-14 years' age group, while MRRs were significantly increased in older age groups, in particular in patients >75 years (MRR 1.84 [1.79-1.89]). In addition, week-by-week analysis showed a progressive increase in MRR during this period, peaking in the last week (March 15 th , 2020 - March 21 st , 2020) with an estimated value of 2.65 [2.53-2.78]., Conclusions: The analysis of all-cause mortality data in Italy indicates that reported COVID-19-related deaths are an underestimate of the actual death toll. All-cause death should be seen as the epidemiological indicator of choice to assess the real mortality impact exerted by SARS-CoV-2, given that it also best reflects the toll on frail patient subsets (e.g. the elderly or those with cardiovascular disease).

Cardiovascular medicine is facing several challenges in the current era, dominated by the rapid spread of a previously unknown virus around the world. Indeed, the 2020 COVID-19 pandemic set the course of cardiovascular science and education in an extraordinary way, hogging the attention of the medical community. Notably, while COVID-19 impacted research progress, there has been considerable effort in exploring topics of great interest, from the management of acute coronary syndromes to new horizons in the treatment of heart failure, from novelties in the surgical treatment of cardiovascular disease to new data on implantable cardiac devices, and from new diagnostic applications of multimodal imaging techniques to relevant basic science findings. Minerva Cardiology and Angiology, formerly Minerva Cardioangiologica, has strived to inform its readers on these topics and novelties, aiming for a succinct yet poignant melding of timeliness and accuracy. Accordingly, the purpose of this narrative review is to highlight and summarize the major research and review articles published during 2020. In particular, we provide a broad overview of the novelties identifying six major areas of interest in the field of cardiovascular sciences in which new evidences have contributed to improving prevention, diagnosis and treatment of heart and vessels diseases.

Background: The management of patients with unprotected left main (LM) coronary artery disease remains challenging, with recent data casting a shadow of doubt on the safety of percutaneous coronary intervention. We aimed at describing the features of patients undergoing myocardial perfusion imaging (MPI) subsequently found to have LM disease., Methods: We queried our institutional database for subjects without prior revascularization or myocardial infarction (MI), who had undergone MPI followed by invasive coronary angiography within 6 months, comparing those with evidence of angiographically significant LM disease (i.e. diameter stenosis ≥50%) to those without significant coronary artery disease (CAD), or those with CAD not involving LM. Baseline, stress and imaging features were systematically collected and analyzed, and clinical outcomes (death, myocardial infarction, revascularization) sought., Results: We included a total of 74 patients with LM disease, which were compared with 70 without CAD, and 920 with significant CAD not involving LM. MPI was remarkably safe in all subjects, and significant differences were found for several features, but particularly so for ST change, rate pressure product, and left ventricular ejection fraction (all P<0.05). Most patients with LM disease had moderate or severe ischemia, and the apical, lateral and inferior regions were the most sensitive ones. Clinical outcomes after an average of 35 months were worse in patients with LM disease than in subjects with significant CAD not involving LM, albeit non-significantly, possibly in light of the higher use of coronary artery bypass grafting., Conclusions: MPI is safe and informative in patients with LM disease, and multidimensional appraisal of MPI results may guide decision-making on top of providing prognostic detail and warranty period.

Introduction: The optimal choice of oral P2Y12 receptor inhibitors has the potential to significantly influence outcomes. We seek to compare the safety and efficacy of the three most commonly used oral P2Y12 receptor inhibitors (clopidogrel, prasugrel, and ticagrelor) in acute coronary syndromes (ACS) via a comprehensive systematic review and network meta-analysis., Evidence Acquisition: In line with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, we performed a comprehensive search for RCTs which compared cardiovascular and hemorrhagic outcomes after use of at least two of the distinct oral P2Y12 receptor inhibitors (i.e. clopidogrel, prasugrel, and ticagrelor). A search strategy has been designed to systematically search multiple databases, including MEDLINE with PubMed interface, The Cochrane Central Register of Controlled Trials, and Embase. In addition, key inclusion criteria will be trial size of at least 100 patients and at least 1 month of follow-up time. Several prespecified subgroups will be explored, including Asian patients, patients presenting with ST-elevation myocardial infarction, patients of advanced age, and others., Evidence Synthesis: Exploratory frequentist pairwise meta-analyses will be based primarily on a random-effects method, relying on relative risks (RR) for short-term outcomes and incidence rate ratios (IRR) for long-term outcomes. Inferential frequentist network meta-analysis will be based primarily on a random-effects method, relying on RR and IRR as specified above. Results will be reported as point summary of effect, 95% CI, and P values for effect, and graphically represented using forest plots., Conclusions: An international collaborative network meta-analysis has begun to comprehensively analyze the safety and efficacy of prasugrel, ticagrelor and clopidogrel, each on a background of aspirin, for management of patients with ACS. It is our hope that the rigor and breadth of the undertaking described herein will provide novel insights that will inform optimal patient care for patients with ACS treated conservatively, or undergoing revascularization.

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.

Introduction: Long-term efficacy and safety of either surgical or percutaneous treatment left main coronary artery disease treatment is lacking., Evidence Acquisition: 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., Evidence Synthesis: 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], P<0.01), and coronary revascularization (IRR 1.69, 95% CI [1.42-2.03], P<0.01) 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)., Conclusions: 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: Cardiovascular disease (CVD) is still the leading cause of death worldwide, responsible for an estimated 17.8 million deaths globally in 2017, accounting for 31.8% of all deaths. In this review, we aim to provide an updated overview of CVD burden from an Italian and a global perspective., Methods: Crude and age-standardized incidence and prevalence, as well as age-standardized mortality rate and morbidity rate (expressed as disability-adjusted life years - DALYs), of different cardiovascular conditions, derived from the Global Burden of Disease Injuries, and Risk Factors Study (GBD) 2017, were reported and compared between Italy and the world., Results: Crude prevalence of CVD in Italy is nearly twofold higher than global prevalence (12.9% vs. 6.6%), while age-standardized estimates are similar (6.2% vs. 6.3%). Mortality and morbidity from CVD are reduced in Italy, as compared to worldwide estimates (age-standardized mortality rate 113/100,000 vs. 233/100,000; age-standardized rate of DALYs lost 1764/100,000 vs. 4598/100,000). Of the evaluated cardiovascular conditions, the most important CVD burden is due to ischemic heart disease, which show a crude prevalence of 3.6% in Italy (age-standardized: 1.7%), doubling the corresponding crude global estimate (1.7%; age-standardized: 1.6%)., Conclusions: This latest update on the epidemiology of CVD within Italy and the world summarizes the burden of major cardiovascular conditions. CVD, especially ischemic heart disease, is still an important cause of mortality and morbidity. The impact of increasing life-expectancy is a key determinant of CVD epidemiology in Italy, if compared to worldwide data, since older age is one of the major risk factors for CVD.

Introduction: The concomitant presence of myocardial necrosis with myocardial ischemia, stunning or hibernation may complicates appraisal of left ventricular (LV) function and patient management. Several imaging modalities have been proposed for the accurate assessment of myocardial necrosis, viability, stunning and hibernation, with mixed results. We aimed to review the evidence base on myocardial necrosis, stunning and hibernation by conducting an umbrella review (i.e. overview of systematic reviews)., Evidence Acquisition: We searched PubMed and The Cochrane Library for meta-analyses focusing on the diagnostic, prognostic, or management appraisal of myocardial necrosis, viability, stunning and hibernation. Diagnostic test accuracy, prognostic yield, and clinical outcomes were systematically abstracted from shortlisted reviews., Evidence Synthesis: From an initial set of 6069 citations, 12 systematic reviews were finally included, encompassing 286 studies and 201,680 patients. Cardiac magnetic resonance imaging (CMR) had favorable results in 4 reviews that focused on the diagnosis of myocardial stunning or hibernation in patients followed for 6±4 months after coronary revascularization (sensitivity 96% and specificity 91%). Positron emission tomography (PET), single photon emission tomography (SPECT) and CMR in 6 meta-analyses had each a significant and independent prognostic role for the prediction of fatal and non-fatal cardiovascular events in patients with follow-up of 2.8±1.7 years. Finally, 2 reviews with 2.3±1.1 years of follow-up showed moderate quality evidence in favor of coronary revascularization in patients with objective signs of myocardial viability., Conclusions: The appraisal of myocardial necrosis and residual viability remains a cornerstone of the modern management of patients with CAD. Current imaging modalities (echocardiography, PET, SPECT and CMR) are widely used. Further trials using contemporary methods are warranted to further clarify the impact of viability assessment on patient management, and the cumulative risk of morbidity and mortality.