Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

[Ten questions about myocardial infarction with non-obstructed coronary arteries]. / Dieci quesiti in tema di infarto miocardico in assenza di coronaropatia ostruttiva.

The term "MINOCA" refers to myocardial infarction with non-obstructed coronary arteries and has been used to define acute myocardial infarction with no angiographic evidence of significant epicardial coronary artery stenosis. Patients with MINOCA represent a rather heterogeneous group of acute coronary syndrome, and this may account for the wide variation in the incidence of MINOCA in different studies. Several pathogenic mechanisms have been suggested to underlie MINOCA, but the condition continues to represent a diagnostic and therapeutic challenge for the cardiologist. Therefore, an adequate diagnostic assessment, carefully characterizing the pathogenic mechanisms, and a selection of more targeted treatments are needed to improve clinical outcomes. In this focused review, we will try to provide answers to the most common questions on the causes, diagnosis, treatment, and outcomes of MINOCA.

Impact of Contrast-Associated Acute Kidney Injury on One-Year Outcomes in Very Elderly STEMI Patients: Insights From a Multicenter Registry in Northern Italy.

Data about contrast-associated acute kidney injury (CA-AKI) in oldest old (age ≥85 years) ST-elevation myocardial infarction (STEMI) patients are scarce. We evaluated the incidence and the 1-year prognostic impact of CA-AKI in this population. Patients were included in a multicenter real-world registry, and CA-AKI was defined according to KDIGO (Kidney Disease Improving Global Outcomes) criteria. Major adverse cardiac and cerebrovascular events (MACCEs) were defined as the composite of all-cause death, stroke, unplanned coronary revascularization, and heart failure hospitalization. The primary outcome was the incidence and impact of CA-AKI on MACCEs at 1 year follow-up. Out of 461 STEMI patients (mean age 88.6 ± 2.9 years), 102 (22.1%) patients developed CA-AKI. Chronic kidney disease was the strongest predictor of CA-AKI (odds ratio [OR]: 4.52, 95% CI: 2.81-7.30, P < .01). The CA-AKI cohort showed a higher risk of MACCEs (adjusted HR: 1.75, 95% CI: 1.13-2.71, P = .01), driven mainly by all-cause death (adjusted hazard ratio [HR]: 2.39, 95% CI: 1.41-4.07, P = .01) and followed by heart failure hospitalization (adjusted HR: 2.01, 95% CI: 1.08-3.76, P = .01). Among oldest old STEMI, CA-AKI was frequent and associated with a higher incidence of MACCEs at 1-year follow-up.

Comprehensive diagnostic workup in patients with suspected heart failure and preserved ejection fraction.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging and it could require different tests, some of which are affected by limited availability. Nowadays, considering that new therapies are available for HFpEF and related conditions, a prompt and correct diagnosis is relevant. However, the diagnostic role of biomarker level, imaging tools, score-based algorithms and invasive evaluation, should be based on the strengths and weaknesses of each test. The aim of this review is to help the clinician in diagnosing HFpEF, overcoming the diagnostic uncertainty and disentangling among the different underlying causes, in order to properly treat this kind of patient.

Working in interventional cardiology laboratories: The perceived impact of radiation exposure as a health and gender hazard. A NEXT generation ANMCO initiative.

BACKGROUND: Gender-related discrepancies in personal and professional life have been reported among radio-exposed workers. We assessed this topic among cardiac catheterization workers in Italy, with a focus on gender and working position. METHODS: Radio-exposed workers affiliated with the Italian Association of Hospital Cardiologists were invited to answer an online survey, which included 41 questions formatted as multiple choice. RESULTS: Overall, 237 workers responded. The proportion of males was significantly higher than that of females in the population aged >50 years. A greater portion of females than males perceived female-gender discrimination regarding career advancement (77.2% vs 30.9%, p < 0.001) and work compensation (49.1% vs. 17.1%, p < 0.001). There was no difference in perceived gender- discrimination in terms of career advancement opportunities between physician and non-physicians. A larger portion of females than males experienced workplace discrimination (51.8% of females vs. 8.1% of males, p < 0.0001). Non-physician responders made up 38.8% of all respondents and reported a lower yearly radiation exposure than physicians. Non-physicians were more aware of the laws regulating lab access during pregnancy than physicians (93.5% vs. 48.3%, p < 0.0001). A greater percentage of female nurses than physicians communicate without hesitation the pregnancy status to their employers (45.6% vs 20%, p < 0.001). CONCLUSIONS: Gender-based career disparities were perceived among physicians and non-physician staff of cardiology interventional laboratories. Strategies should be implemented to ensure gender equality in career opportunities and to increase knowledge of radioprotection and the laws regulating access to laboratories during pregnancy.

Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review.

Cardiovascular conditions in the spectrum of acute coronary syndromes are characterized by sex differences with regard to pathophysiology, risk factors, clinical presentation, invasive and pharmacologic treatment, and outcomes. This review delves into these differences, including specific subsets like myocardial infarction with non-obstructed coronary arteries or Spontaneous Coronary Artery Dissection, and alternative diagnoses like Takotsubo cardiomyopathy or myocarditis. Moreover, practical considerations are enclosed, on how a sex-specific approach should be integrated in clinical practice: in fact, personal history should focus on female-specific risk factors, and hormonal status and hormonal therapy should be assessed. Moreover, physical and psychological stressors should be investigated, particularly in the event of Spontaneous Coronary Artery Dissection or Takotsubo cardiomyopathy.

[Drug-eluting stents in contemporary interventional practice: the STENT PANORAMA project (Part I)]. / Gli stent coronarici a rilascio di farmaco nella pratica interventistica contemporanea: progetto STENT PANORAMA (Parte I).

STENT PANORAMA is a project carried out by the Young Interventional Cardiologists of Triveneto coordinated by the Italian Society of Interventional Cardiology (GISE) Veneto delegation. The project includes two parts: the first, here reported, is aimed at describing in a standardized and easily usable way the main technological characteristics of the latest generation of the drug eluting stents (DES) that are most widely used in the Italian cath-labs. The second, to follow, will aim to summarize the main scientific evidence regarding the performance of individual devices with particular reference to subgroups of clinical interest. The ambitious goal of the STENT PANORAMA working group is to provide the interventional cardiologist with a thorough, practical, and functional knowledge of the DES currently available in the modern therapeutic armamentarium to promote a therapeutic strategy tailored to the patient.

[ANMCO Position paper: States General 2023 - Scientific societies and training: the role of ANMCO]. / Position paper ANMCO: Stati Generali 2023 ­ Società scientifiche e formazione: il ruolo dell'ANMCO.

Scientific societies promote numerous activities, including the training of professionals. With the continuous growing of knowledge and the availability of new evidence in the cardiological field, the achievement and maintenance of knowledge and know-how is difficult. The evolving educational needs of professionals in cardiology have been analyzed during the 2023 ANMCO General States. Furthermore, the initiatives implemented to meet professionals' needs after the university medical training have been discussed. In this document, we report the main and most innovative training activities promoted by ANMCO, from distance training to simulation training, including courses for master's degree, training to and through clinical research and the potential role of teaching hospitals.

[ANMCO Position paper: States General 2023 - Role of ANMCO in the setting of clinical research in Cardiology in Italy: current state and future perspectives]. / Position paper ANMCO: Stati Generali 2023 ­ Ruolo dell'ANMCO nella ricerca clinica cardiologica in Italia: attualità e prospettive.

For over 40 years, clinical research has been one of the most important aims of the Italian Association of Hospital Cardiologists (ANMCO), being an essential tool in pursuing promotion and fulfillment of good clinical practices in prevention, treatment and rehabilitation of cardiovascular diseases. Since 1992, with the creation of the Research Center (now part of the Heart Care Foundation), ANMCO is capable of independently and professionally managing all the aspects related to planning, management, and publication of the results of clinical studies. The other strength of ANMCO is the network built in Cardiology Departments on the whole territory of Italy, a human capital that allows ANMCO to deal with the new scientific challenges, in a context of profound changes in the social, economic, technological, and methodological setting. This document is based on the debate about the state of clinical research in Italy and the role of ANMCO in this setting that took place during the 2023 ANMCO States General.

[ANMCO Position paper - 2023 ANMCO States General: The shortage of healthcare personnel in the cardiology field]. / Position paper ANMCO ­ Stati Generali ANMCO 2023: La carenza del personale sanitario in ambito cardiologico.

Over the latest years, a worrying progressive reduction of medical specialists has been observed in Italy and in other European and non-European countries. This trend is assuming alarming proportions, especially considering the continuous population aging and the concomitant increase in the prevalence of chronic cardiovascular disease. The underlying reasons are complex and multifactorial. The purpose of this document, derived from the collegial discussion held during the 2023 ANMCO States General is to highlight the current critical issues regarding the lack of healthcare personnel in the cardiology field, examining the current and future Italian situation and proposing some potential strategies to counteract this alarming phenomenon.

[ANMCO Position paper - 2023 ANMCO States General: Towards a modern Cardiological Community Care]. / Position paper ANMCO ­ Stati Generali ANMCO 2023: Verso una moderna Cardiologia Territoriale.

Over the last two decades, cardiovascular diseases have become the leading cause of chronic disease morbidity and mortality in Italy. Therefore, the chronic cardiovascular care landscape has evolved rapidly in an era of unprecedented demand. Furthermore, the COVID-19 pandemic has highlighted significant deficiencies in existing health and social care systems, especially in the management of chronic cardiovascular disease. In this scenario, the National Reform for Recovery and Resilience (PNRR) may represent a unique opportunity for the development of a new integrated care system between hospital and community. The Italian Association of Hospital Cardiologists (ANMCO) recognizes the need for a statement on the integrated cardiological community care to guide health professionals caring for people with chronic cardiovascular conditions. The aim of the present statement is to outline the evidence for a modern integrated cardiological community care identifying challenges and offering advice for a future transdisciplinary and multi-organizational approach to ensure best practice in the management of chronic cardiovascular disease.

[ANMCO Position paper: States General 2023 - Digital medicine in cardiology: evidence and state of progress in Italy]. / Position paper ANMCO: Stati Generali 2023 ­ La medicina digitale in cardiologia: evidenze e stato di avanzamento in Italia.

Technological innovation provides easily accessible tools capable of simplifying healthcare processes. Notably, digital technology application in the cardiology field can improve prognosis, reduce costs, and lead to an overall improvement in healthcare. The digitization of health data, with the use of electronic health records and of electronic health files in Italy, represents one of the fields of application of digital technologies in medicine. The 2023 States General of the Italian Association of Hospital Cardiologists (ANMCO) provided an opportunity to focus attention on the potential benefits and critical issues associated with the implementation of the aforementioned digital tools, artificial intelligence, and telecardiology. This document summarizes key aspects that emerged during the event.

[Definition, classification and diagnosis of myocardial infarction with non-obstructive coronary artery disease: where do we stand?] / Definizione, classificazione e diagnosi di infarto miocardico in assenza di coronaropatia ostruttiva: a che punto siamo?

The systematic use of coronary angiography and the availability of increasingly sensitive biomarkers of myocardial cytolysis have determined an increase in the diagnosis of myocardial infarction with non-obstructed coronary arteries (MINOCA), which is currently reported in 5-20% of patients with acute myocardial infarction. The first diagnostic criteria of MINOCA were reported by a position paper of the European Society of Cardiology in 2017; since then, these criteria have been revised several times until the current version. The diagnosis of MINOCA requires not only the presence of myocardial damage, indicated by the detection of a rise or fall in cardiac troponin with at least one value above the 99th percentile upper reference limit, but also the clinical evidence of acute myocardial infarction as shown by symptoms, ECG, or imaging. This definition resulted in the exclusion from the umbrella group of MINOCA of certain conditions, such as takotsubo syndrome and myocarditis, that do not have a clear ischemic etiology. The term MINOCA encompasses heterogeneous conditions from a pathophysiological, clinical and therapeutic perspective. For this reason, MINOCA should be used to identify a "working diagnosis", which is the first step of a diagnostic work-up aimed at clarifying the mechanisms and identifying the most appropriate therapy for the individual patient. The aim of this review is to describe the state of the art regarding the definition, classification, and diagnosis of MINOCA, providing an excursus on the principal documents proposed by scientific societies or experts in the field in recent years.

Drug Coated Balloon in the Treatment of De Novo Coronary Artery Disease: A Narrative Review.

Drug coated balloons (DCBs) are currently indicated in guidelines as a first choice option in the management of instant restenosis, whereas their use in de novo lesions is still debated. The concerns raised after the contrasting results of the initial trials with DCBs in de novo lesions have been more recently overcome by a larger amount of data confirming their safety and effectiveness as compared to drug-eluting stents (DES), with potentially greater benefits being achieved, especially in particular anatomical settings, as in very small or large vessels and bifurcations, but also in selected subsets of higher-risk patients, where a 'leave nothing behind' strategy could offer a reduction of the inflammatory stimulus and thrombotic risk. The present review aims at providing an overview of current available DCB devices and their indications of use based on the results of data achieved so far.

[Managing patients with left ventricular thrombosis after acute myocardial infarction: current evidence, uncertainties, and future perspectives]. / Il paziente con trombosi ventricolare sinistra dopo infarto miocardico acuto: tra evidenze disponibili, incertezze e prospettive future.

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

Prognostic Impact of Drug-Coated Balloons in Patients With Diabetes Mellitus: A Propensity-Matched Study.

Patients with diabetes mellitus (DM) are at higher risk of restenosis and stent thrombosis after percutaneous coronary intervention (PCI) and drug-eluting stent (DES) positioning. Whether drug-coated balloons (DCB) can offer any benefit in this subset of patients has been seldom cleared out and was the aim of the present propensity-matched cohort study, that compared the prognostic impact of DCB versus DES in patients with DM who underwent PCI. Patients with DM enrolled in the NOvara-BIella-TREnto (NOBITRE) Registry were identified and matched according to propensity score, to a control population of patients with DM treated with DES. The primary study end point was the occurrence of major adverse cardiovascular events (MACEs). A total of 150 patients were identified in the DCB group and matched with 150 DES-treated patients. Patients treated with DCB displayed more often a previous cardiovascular history and received a more complete pharmacological therapy. Target vessel diameter and the percentage of stenosis were lower in patients with DCB, whereas binary in-stent restenosis was more common (p <0.001, p = 0.003, and p <0.001, respectively). Paclitaxel-eluting balloon represented the most common strategy in the DCB group, whereas Zotarolimus-eluting stents were used in half of the DES population. At a median follow-up of 545.5 days, MACE occurred in 54 (19.4%) of patients, with no difference according to the PCI strategy (21.6% vs 17.3%, adjusted hazard ratio [95% confidence interval] 1.51 [0.46 to 4.93], p = 0.50). Major ischemic end points were slightly increased in patients treated with DCB, whereas overall death was significantly reduced (3.6% vs 10.9%; adjusted hazard ratio [95% confidence interval] 0.27 [0.08 to 0.91], p = 0.03). In conclusion, the present propensity-matched study shows that, in patients with DM who underwent PCI for in-stent restenosis or de novo lesions, the use of DCB is associated with a similar rate of MACE and a modest increase in target lesion failure, but a significantly improved survival as compared with DES.

Long-Term Outcomes With Drug-Eluting Balloon for the Treatment of In-Stent Restenosis and De Novo Lesions: The Novara-Biella-Trento (NOBITRE) Registry.

Drug-coated balloons (DCBs) have emerged for percutaneous coronary interventions (PCI) of in-stent restenosis or particular anatomical subsets. We provide a real-world analysis of the prognostic determinants and long-term outcomes of patients treated with DCB for any lesion in a comprehensive multicenter registry. The primary study endpoint was the occurrence of major cardiovascular events (MACE: composite of all-cause death, myocardial infarction, and target vessel revascularization) at the longest available follow-up. We included 267 patients (196 treated for in-stent restenosis and 71 for de novo lesions), with a median follow-up of 616 [368-1025] days. MACE occurred in 70 (26.2%) of the patients and related with higher rates of in-stent restenosis (P = .04), longer and more type C lesions (P = .05 and P = .04). At multivariate Cox-regression, type C lesions emerged as the only independent predictor of MACE (adjusted OR [95% CI] = 1.83[1.13-2.97], P = .014), mainly driven by target vessel revascularization (adjusted OR[95% CI] = 1.78[1.05-2.95], P = .03) not conditioning survival. In-stent restenosis emerged as major determinant of TLF (adjusted OR[95% CI] = 2.59[1.17-5.75], P = .02). DCBs represent a treatment option for any lesion; however, type C and restenotic lesions are associated with an increased risk of MACE and target lesion failure, where the optimal strategies for patients' selection and lesion preparation are still undefined.

Characteristics of patients with recurrent acute myocardial infarction after MINOCA.

BACKGROUND: Myocardial infarction (MI) with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Some MINOCA patients ultimately experience recurrent acute MI (re-AMI) during follow-up; however, clinical and angiographic factors predisposing to re-AMI are still poorly defined. METHODS: In this retrospective multicenter cohort study we enrolled consecutive patients fulfilling diagnostic criteria of MINOCA according to the IV universal definition of myocardial infarction; characteristics of patients experiencing re-AMI during the follow-up were compared to a group of MINOCA patients without re-AMI. RESULTS: 54 patients (mean age 66 ± 13) experienced a subsequent re-AMI after MINOCA and follow-up was available in 44 (81%). Compared to MINOCA patients without re-AMI (n = 695), on first invasive coronary angiography (ICA) MINOCA patients with re-AMI showed less frequent angiographically normal coronaries (37 versus 53%, p = 0.032) and had a higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p = 0.049). Twenty-four patients (44%) with re-AMI underwent a new ICA: 25% had normal coronary arteries, 12.5% had mild luminal irregularities (<30%), 20.8% had moderate coronary atherosclerosis (30-49%), and 41.7% showed obstructive coronary atherosclerosis (≥50% stenosis). Among patients undergoing new ICA, atherosclerosis progression was observed in 11 (45.8%), 37.5% received revascularization, only 4.5% had low-density lipoprotein cholesterol (LDL_C) under 55 mg/dL and 33% experienced a new cardiovascular disease (CVD) event (death, AMI, heart failure, stroke) at subsequent follow-up. CONCLUSIONS: In the present study, only a minority of MINOCA patients with re-AMI underwent a repeated ICA, nearly one out of two showed atherosclerosis progression, often requiring revascularization. Recommended LDL-C levels were achieved only in a minority of the cases, indicating a possible underestimation of CVD risk in this population.

Symptoms-to-emergency-call timing delay in acute coronary syndrome before and during COVID-19: independent predictors and their impact on mortality.

BACKGROUND: The COVID-19 pandemic severely impacted global health. The aim of this study was to compare predictors of symptoms-to-emergency-call timing delay in acute coronary syndrome (ACS) and their impact on mortality before and during the COVID-19 outbreak. METHODS: We collected sociodemographic, clinical data, procedural features, preadmission and intra-hospital outcomes of consecutive patients admitted for ACS in seventeen Italian centers from March to April 2018, 2019, and 2020. RESULTS: In 2020, a 32.92% reduction in ACS admissions was observed compared to 2018 and 2019. Unstable angina, typical and atypical symptoms, and intermittent angina were identified as significant predictors of symptoms-to-emergency-call timing delay before and during the COVID-19 pandemic (P<0.005 for all the items). Differently from 2018-2019, during the pandemic, hypertension and dyspnea (P=0.002 versus P=0.490 and P=0.001 vs. P=0.761 for 2018-2019 and 2020, respectively) did not result as predictors of delay in symptoms-to-emergency-call timing. Among these predictors, only the atypical symptoms (HR 3.36; 95% CI: 1.172-9.667, P=0.024) in 2020 and the dyspnea (HR 2.64; 95% CI: 1.345-5.190, P=0.005) in 2018-2019 resulted significantly associated with higher mortality. Finally, the family attendance at the onset of the symptoms resulted in a reduction in symptoms-to-emergency-call timing (in 2020 P<0.001; CI: -1710.73; -493.19) and in a trend of reduced mortality (HR 0.31; 95% CI: 0.089-1.079, P=0.066) in 2020. CONCLUSIONS: During the COVID-19 outbreak, atypical symptoms and family attendance at ACS onset were identified, respectively, as adverse and favorable predictors of symptoms-to-emergency-call timing delay and mortality.