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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.

Objectives To investigate outcomes with selective, clopidogrel-based therapies versus conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome. Background Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established. Methods We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation, N = 3,473; three on guided clopidogrel therapy, N = 7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints were major bleeding, any bleeding, major adverse cardiovascular events (MACE), and net clinical endpoint. Results The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51–1.01, p = 0.06; OR: 0.93, 0.72–1.20, p = 0.58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based therapy versus conventional treatment group (OR: 0.57, 95% CI: 0.40–0.80, p = 0.001); this greater safety was significant for unguided de-escalation (OR: 0.43, 95% CI: 0.32–0.58, p = 0.00001) and nonsignificant for guided clopidogrel therapy (OR: 0.72, 95% CI: 0.51–1.02, p = 0.07; p for interaction: 0.03). The incidence of the net clinical endpoint was fewer in the selective, clopidogrel-based therapy versus the conventional treatment arm (OR: 0.59, 95% CI: 0.41–0.85, p = 0.004); this benefit was significant for unguided de-escalation (OR: 0.50, 95% CI: 0.39–0.64, p Conclusion As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding, and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.

Background A polymer-free biolimus-eluting stent (PF-BES) and a zotarolimus-eluting stent (ZES) recently showed similar clinical profiles and appear to be competing options in specific clinical settings of patients undergoing percutaneous coronary intervention (PCI). Whether they perform similarly also in complex procedural settings as coronary bifurcation lesions remains unaddressed. Methods All consecutive patients undergoing coronary bifurcation PCI with PF-BES or the new iteration of the ZES from three large multicenter real-world registries were included. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis (ST). Multiple analyses to adjust for baseline differences were carried out including propensity-score matching, propensity-score stratification and inverse-probability-weighting. Outcomes are reported according to Cox proportional hazard models censored at 400-day follow-up. Results 1169 patients treated with PF-BES (n = 440) or ZES (n = 729) on the main branch of a coronary bifurcation lesion were included (mean age 69 ± 11 years, 75.4% male, 53.8% acute coronary syndrome at presentation, 26.6% left main bifurcation, median dual antiplatelet therapy duration 12 [range 12–12] months). MACE, all-cause death, TLR and ST tended towards non-statistically higher rates with the PF-BES as compared to the ZES. Higher MI and target vessel revascularization occurrence was observed with PF-BES. Conclusions In this large contemporary cohort of patients undergoing coronary bifurcation PCI, the occurrence of MACE was non-statistically different with the use of PF-BES and ZES devices. However, differences favoring the ZES device that may entail clinical relevance were observed. Further studies are needed to confirm these findings and explore whether they remain valid when a short dual antiplatelet therapy is adopted.

Background: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. Methods: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. Findings: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. Interpretation: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

Patient presentation. We present the case of an 85-years old woman, hypercholesterolemic, with a previous history of microvascular angina treated with nitrates, ASA and ranolazine. She presented in our emergency department for repeated episodes of seizure and “drop attacks” and she underwent neurological and cardiological evaluation. ECG showed sinus tachycardia, 110/min, left anterior hemiblock. Transthoracic echocardiogram was normal. Head CT-scan and cerebral magnetic resonance documented mild hyperintense areas in the subcortical part of white matter suggestive for chronic cerebrovascular disease. Carotid Doppler was negative for significant stenosis. Thus, suspecting an unexplained syncope, she underwent loop recorder implantation. One month later she was admitted to the emergency room for dysarthria, left hemiparesis and ataxia, that completely regressed after 24-hours, posing the diagnosis of transient ischemic stroke. Physical examination was normal. During in-hospital stay, the patient progressively developed dyspnoea and oxygen desaturation (SpO2 < 90%). Initial work-up. Due to oxygen desaturation non-invasive ventilation with Venturi mask (60%) was started. Blood tests were normal. The arterial blood gas analysis in Venturi mask showed: pH 7.47, pCO2 48 mmHg, pO2 136 mmHg, P/F 226. Despite non-invasive ventilation with Venturi mask, P/F remained low and so continuous positive airway pressure (CPAP) was started. A repeated echocardiogram showed a mild reduction of ejection fraction (45-50%) due to hypokinesia of the septum, secondary to right ventricular overload and compression. Pulmonary embolism was excluded by angio-CT. Medical management with vasodilators and diuretics finally allowed to wean off the non-invasive ventilation, still maintaining oxygen support with nasal cannulas. However, surprisingly, the mobilization of the patient in a sitting position resulted impossible, due to the occurrence of sudden desaturation. Diagnosis and Management. Suspecting a manifestation of platypnea-orthodeoxia syndrome (POS) a transoesophageal echocardiogram was performed. It revealed a wide patent foramen ovale (PFO), maximum diameter 1.5 cm, with a baseline mild right-to-left shunt, confirmed with sonicated contrast, that increased in the sitting position. Therefore, the diagnosis of POS syndrome and paradoxical cerebral embolization was posed. Elective PFO closure with the percutaneous positioning of an atrial septal defect (ASD) Occluder n.15 was successfully performed. Conclusions The platypnea-orthodeoxia syndrome is a rare cause of hypoxemia. The most common structural abnormality associated with this syndrome is the PFO, which can remain asymptomatic for decades. A shift in the relationship between right-and left intra-cardiac pressures, a change in the anatomy of the adjoining structures with age, stretching the atrial septum and favouring the blood inflow into the PFO (as ascending aorta dilatation or Thoracic Kyphosis) can lead to POS. The closure of the atrial defect is generally resolutive. However, the heterogeneous clinical presentations, the rarity of the disease and the confounding role of comorbidities can often result misleading, especially in advanced age.

Background and Aims The pandemic proportion of vitamin D deficiency has raised particular concerns on its association with mortality and cardiovascular disease (CVD). However, the independent and causative role of hypovitaminosis D in CVD is still debated. Few data have been reported, so far, among STEMI patients undergoing primary percutaneous coronary intervention (pPCI), that was therefore the aim of the present study. Methods A consecutive cohort of patients admitted for STEMI treated with pPCI were included. The levels of 25(OH)D were assessed at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Hypovitaminosis D was defined for 25(OH)D < 10 ng/ml. The primary study endpoint was net adverse cardiovascular events (a composite of death, recurrent MI and target vessel revascularization) at the longest available follow-up. Secondary endpoints were overall mortality, major bleedings or the individual components of the primary endpoint. Results We included 136 patients divided according to tertiles values of 25(OH)D (< 12.98 ng/ml, n=44; 12.98-22.1 ng/ml, n=41; ≥ 22.1 ng/ml, n=51). The prevalence of renal failure (p=0.047) and coronary calcifications inversely related with vitamin D. Lower vitamin D levels were associated with “no reflow” (10.3% vs 6.7% vs 0%, p=0.04), with increased use of adenosine. At a mean follow-up of 305± 217 days (mean + SD), the primary endpoint (NACE) was slightly increased in patients with lower vitamin D values (adjusted HR [95% CI] = 3.07 [0.85-11.1], p = 0.09). Similar results were observed for ischemic events (MACE: adjusted HR [95% CI] = 2.78 [0.68-11.48], p = 0.16). However, when considering separately patients with severe hypovitaminosis D ( Conclusion The present study shows that among patients with STEMI undergoing pPCI, extremely low levels of vitamin D are independently associated with impaired outcomes. Future dedicated studies will shed light on the prognostic implications of hypovitaminosis D in these patients and the potential therapeutic perspectives.

Patient-related and lesion-related factors may influence instantaneous wave-free ratio (iFR)/fractional flow reserve (FFR) concordance, potentially affecting the safety of revascularization deferral.Consecutive patients with at least an intermediate coronary stenosis evaluated by both iFR and FFR were retrospectively enrolled. The agreement between iFR and FFR at their diagnostic cut-offs (FFR 0.80, iFR 0.89) was assessed. Predictors of discordance were assessed using multivariate analyses. Tailored iFR cut-offs according to predictors of discordance best matching an FFR of 0.80 were identified. The impact of reclassification according to tailored iFR cut-offs on major cardiovascular events (MACE: cardiovascular death, myocardial infarction or target-lesion revascularization) among deferred lesions was investigated.Two hundred and ninety-nine intermediate coronary stenosis [FFR 0.84 (0.78-0.89), iFR 0.91 (0.87-0.95), 202 left main/left anterior descending (LM/LAD) vessels, 67.6%] of 260 patients were studied. Discordance rate was 23.4% (n = 70, 10.7% iFR-negative discordant, 12.7% iFR-positive discordant). Predictors of discordance were LM/LAD disease, multivessel disease, non-ST-elevation myocardial infarction, smoking, reduced eGFR and hypertension. Lesion reclassification with tailored iFR cut-offs based on patient-level predictors carried no prognostic value among deferred lesions. Reclassification according to lesion location, which was entirely driven by LM/LAD lesions (iFR cut-offs: 0.93 for LM/LAD, 0.89 for non-LM/LAD), identified increased MACE among lesions deferred based on a negative FFR, between patients with a positive as compared with a negative iFR (19.4 vs. 6.1%, P = 0.044), whereas the same association was not observed with the conventional 0.89 iFR cut-off (15 vs. 8.6%, P = 0.303).Tailored vessel-based iFR cut-offs carry prognostic value among FFR-negative lesions, suggesting that a one-size-fit-all iFR cut-off might be clinically unsatisfactory.

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.We collected sociodemographic, clinical data, procedural features, pre-admission and intra-hospital outcomes of consecutive patients admitted for ACS in seventeen Italian centers from March to April 2018, 2019, and 2020.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 (p0.005 for all the items). Differently from 2018-2019, during the pandemic, hypertension and dyspnea (p=0.002 versus [vs] 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 p0.001; 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.During the COVID-19 outbreak, atypical symptoms and family attendance at ACS onset were identified, respectively, as adverse and favorable predictors of symptoms-to-emergencycall timing delay and mortality.

No study has so far evaluated the impact of chronic kidney disease (CKD) on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were therefore the aim of the present study.Patients on dual antiplatelet therapy with ASA+ticagrelor (90mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome (MI), target vessel revascularization) at the longest available follow-up.We included 396 patients, that were divided according to CKD (eGFRor≥ 60 m l/min). Mean platelet reactivity was comparable irrespective of renal function Prevalence of high platelet reactivity (HRPR) on Ticagrelor was similar among patients with or without CKD (9.7% vs. 11.8%, P=0.84). At a mean follow-up of 939±581.4 days, 21.2% of the patients experienced the primary composite endpoint, with a similar rate of events in patients CKD or normal renal function (22.2% vs. 21.2% HR [95%CI]= 0.92[0.52-1.61], P=0.77), and no difference in survival, ischemic and bleeding endpoints. After correction for baseline differences CKD did not emerge as an independent predictor of either HRPR (adjusted OR [95%CI]=0.47 [0.18;1.25], P=0.13) or MACE (adjusted HR [95%CI]=0.66 [0.34-1.29] P=0.18).In the present study we demonstrated that among ACS patients on DAPT with ASA and ticagrelor after PCI, renal failure is not associated with a higher rate of HRPR or to an increased risk of mortality or major ischemic and bleeding events.

Purpose: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. Methods: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients

Recent evidence on ischemia, rather than coronary artery disease (CAD), representing a major determinant of outcomes, has led to a progressive shift in the management of patients with ischemic heart disease. According to most recent guidelines, myocardial revascularization strategies based on anatomical findings should be progressively abandoned in favor of functional criteria for the guidance of PCI. Thus, emerging importance has been assigned to the assessment of coronary physiology in order to determine the ischemic significance of coronary stenoses. However, despite several indexes and tools that have been developed so far, the existence of technical and clinical conditions potentially biasing the functional evaluation of the coronary tree still cause debates regarding the strategy of choice. The present review provides an overview of the available methods and the most recent acquirements for the invasive assessment of ischemia, focusing on the most widely available indexes, fractional flow reserve (FFR) and instant-wave free ratio (iFR), in addition to emerging examples, as new approaches to coronary flow reserve (CFR) and microvascular resistance, aiming at promoting the knowledge and application of those “full physiology” principles, which are generally advocated to allow a tailored treatment and the achievement of the largest prognostic benefits.

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 COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). Aim: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. Methods: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March–April 2020) and in the same period in the previous two years. Results: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. Conclusions: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients.

The association between vitamin D and the prevalence and severity of coronary artery disease (CAD), major established cardiovascular risk factors, and acute ischemic events has been consistently demonstrated in large-scale observational studies and meta-analyses, with relevant prognostic implications. The rise in prevalence of hypovitaminosis D in recent years, reaching pandemic pro-portions, has pointed to the importance of the identification and optimization of the indications and strategies for the therapeutic use of vitamin D, with particular relevance for cardiovascular health. However, vitamin D supplementation has provided so far inconsistent results in primary prevention, with even fewer data reported in patients with established CAD. The present review aims to provide an updated overview of the available evidence and potential therapeutic applications of vitaminD in patients with CAD.

Background Although oral P2Y12 inhibitors are key in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS), the optimal timing of their administration is not well defined. Objective to compare downstream and upstream oral P2Y12 inhibitors administration strategies in NSTE-ACS patients undergoing invasive management. Methods We performed a randomized, adaptive, open-label, multi-center, clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention (PCI) were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was superiority of the downstream over the upstream strategy on the combination of efficacy and safety events (net clinical benefit). Results We randomized 1449 patients to downstream or upstream oral P2Y12 inhibitor administration. A prespecified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes, non-fatal myocardial infarction or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4 and 5 bleedings through day 30, did not differ significantly between the downstream and upstream groups (Absolute Risk Reduction (ARR%) -0.46 [-2.90; 1.90]).These results were confirmed among patients undergoing PCI (72% of population) and regardless of the timing of coronary angiography (within or after 24 hours from enrolment). Conclusions Downstream and upstream oral P2Y12 inhibitors administration strategies were associated with low incidence of ischemic and bleeding events and minimal numerical difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of one strategy over the other. [Funded by the Italian Society of Interventional Cardiology (SICI-GISE)]

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.

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01–1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05–6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19–10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13–8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered.

Background The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population. Methods Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months. Results After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women. Conclusions In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.

Patients with Coronavirus Disease-2019 (COVID‐19) have haemostatic dysfunction and are at higher risk of thrombotic complications. Although age is a major risk factor for outcome impairment in COVID-19, its impact on coagulative patterns here is still unclear. We investigated the association of Endogenous Thrombin Potential (ETP) with thrombotic and haemorrhagic events according to different ages in patients admitted for COVID-19. A total of 27 patients with COVID‐19-related pneumonia, without need for intensive care unit admission or mechanical ventilation at hospital presentation, and 24 controls with non-COVID-19 pneumonia were prospectively included. ETP levels were measured on admission. Patients were evaluated for major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, transient ischemic attack, venous thromboembolism) and bleeding complications [according to Bleeding Academic Research Consortium (BARC) definition] during in-hospital stay. COVID-19 patients had similar ETP levels compared to controls (AUC 93 ± 24% vs 99 ± 21%, p = 0.339). In the COVID-19 cohort, patients with in-hospital MACE showed lower ETP levels on admission vs those without (AUC 86 ± 14% vs 95 ± 27%, p = 0.041), whereas ETP values were comparable in patients with or without bleeding (AUC 82 ± 16% vs 95 ± 26%, p = 0.337). An interaction between age and ETP levels for both MACE and bleeding complications was observed, where a younger age was associated with an inverse relationship between ETP values and adverse event risk (pint 0.018 for MACE and 0.050 for bleeding). Patients with COVID-19 have similar thrombin potential on admission compared to those with non-COVID-19 pneumonia. In younger COVID-19 patients, lower ETP levels were associated with a higher risk of both MACE and bleeding. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02497-1.

Introduction and objectives There is little evidence on rates of stent thrombosis (ST) in patients receiving dual antiplatelet therapy (DAPT) with ticagrelor or prasugrel . The aim of this study was to analyze the incidence and predictors of ST after an acute coronary syndrome among patients receiving DAPT with ticagrelor vs prasugrel. Methods We used data from the RENAMI registry (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), analyzing a total of 4123 acute coronary syndrome patients discharged with DAPT with ticagrelor or prasugrel in 11 centers in 6 European countries. The endpoint was definite ST within the first year. A competitive risk analysis was carried out using a Fine and Gray regression model, with death being the competitive event. Results A total of 2604 patients received DAPT with ticagrelor and 1519 with prasugrel; ST occurred in 41 patients (1.10%), with a similar cumulative incidence between ticagrelor (1.21%) and prasugrel (0.90%). The independent predictors of ST were age (sHR, 1.03; 95% C I, 1.01-1.06), ST segment elevation (sHR, 2.24; 95%CI, 1.22-4.14), previous myocardial infarction (sHR, 2.56; 95%CI, 1.19-5.49), and serum creatinine (sHR, 1.29; 95%CI, 1.08-1.54). Conclusions Stent thrombosis is infrequent in patients receiving DAPT with ticagrelor or prasugrel. The variables associated with an increased risk of ST were advanced age, ST segment elevation, previous myocardial infarction, and serum creatinine.

Resumen Introduccion y objetivos Hay muy poca evidencia sobre las tasas de trombosis del stent (TS) en pacientes que reciben tratamiento antiagregante plaquetario doble (TAPD) con ticagrelor o prasugrel. El objetivo de este estudio es analizar la incidencia y predictores de la TS tras un sindrome coronario agudo en pacientes que reciben TAPD con ticagrelor frente a prasugrel. Metodos Se utilizaron datos del registro RENAMI (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), y se analizo en total a 4.123 pacientes con sindrome coronario agudo dados de alta con TAPD con ticagrelor o prasugrel en 11 centros de 6 paises europeos. Se considero como evento la TS confirmada en el primer ano. Se realizo un analisis de riesgos competitivos mediante un modelo de regresion de Fine y Gray, siendo la muerte el evento competitivo. Resultados Recibieron TAPD con ticagrelor 2.604 pacientes y con prasugrel, 1.519; 41 pacientes (1,10%) presentaron TS, con incidencias acumuladas similares entre ticagrelor (1,21%) y prasugrel (0,90%). Los predictores independientes de la TS fueron: la edad (sHR = 1,03; IC95%, 1,01-1,06), la elevacion del segmento ST (sHR = 2,24; IC95%, 1,22-4,14), el antecedente de infarto de miocardio (sHR = 2,56; IC95%, 1,19-5,49) y la creatinina serica (sHR = 1,29; IC95%, 1,08-1,54). Conclusiones La TS es infrecuente en pacientes que reciben TAPD con ticagrelor y prasugrel. La edad avanzada, la elevacion del segmento ST, el antecedente de infarto y la creatinina serica son las variables que se asocian con mayor riesgo de TS.

Resumen Introduccion y objetivos La puntuacion PARIS permite una estratificacion combinada de los riesgos isquemico y hemorragico de los pacientes con cardiopatia isquemica tratados con stent coronario y tratamiento antiagregante plaquetario doble (TAPD). Se desconoce su utilidad en pacientes con sindrome coronario agudo (SCA) tratados con ticagrelor o prasugrel. Se investiga este aspecto en un registro internacional. Metodos Estudio retrospectivo multicentrico con participacion voluntaria de 11 centros de 6 paises europeos. Se estudio a 4.310 pacientes con SCA dados de alta en TAPD con ticagrelor o prasugrel. Se definio evento isquemico como trombosis de stent o infarto de miocardio espontaneo, y evento hemorragico segun BARC (Bleeding Academic Research Consortium) tipo 3 o 5. Se calculo la discriminacion y la calibracion para ambas vertientes de la puntuacion PARIS (PARISisquemico y PARIShemorragico). El beneficio neto isquemico-hemorragico se obtuvo mediante la diferencia entre las probabilidades predichas de eventos isquemicos y hemorragicos. Resultados Durante 17,2 ± 8,3 meses, hubo 80 eventos isquemicos (el 1,9% anual) y 66 eventos hemorragicos (el 1,6% anual). PARISisquemico y PARIShemorragico se asociaron con el riesgo de eventos isquemicos (sHR = 1,27; IC95%, 1,16-1,39) y hemorragicos (sHR = 1,14; IC95%, 1,01-1,30) respectivamente. La discriminacion de eventos isquemicos fue discreta (indice C = 0,64) y la de eventos hemorragicos, pobre (indice C = 0,56), con buena calibracion para ambos. El beneficio neto isquemico-hemorragico resulto negativo (mas eventos hemorragicos) en pacientes con alto riesgo hemorragico y positivo (mas eventos isquemicos) en pacientes con alto riesgo isquemico. Conclusiones En pacientes con SCA tratados con TAPD con ticagrelor o prasugrel, la escala PARIS ayuda a establecer un equilibrio apropiado del riesgo isquemico-hemorragico.

BACKGROUND Among patients with acute coronary syndrome following transcatheter aortic valve replacement (TAVR), those presenting with ST-segment elevation myocardial infarction (STEMI) are at highest risk. OBJECTIVES The goal of this study was to determine the clinical characteristics, management, and outcomes of STEMI after TAVR.METHODS This was a multicenter study including 118 patients presenting with STEMI at a median of 255 days (inter quartile range: 9 to 680 days) after TAVR. Procedural features of STEMI after TAVR managed with primary percutaneous coronary intervention (PCI) were compared with all-comer STEMI: 439 non-TAVR patients who had primary PCI within the 2 weeks before and after each post-TAVR STEMI case in 5 participating centers from different countries.RESULTS Median door-to-balloon time was higher in TAVR patients (40 min [interquartile range: 25 to 57 min] vs. 30 min [interquartile range: 25 to 35 min]; p = 0.003). Procedural time, fluoroscopy time, dose-area product, and contrast volume were also higher in TAVR patients (p < 0.01 for all). PCI failure occurred more frequently in patients with previous TAVR (16.5% vs. 3.9%; p < 0.001), including 5 patients in whom the culprit lesion was not revascularized owing to coronary ostia cannulation failure. In-hospital and late (median of 7 months [interquartile range: 1 to 21 months]) mortality rates were 25.4% and 42.4%, respectively (20.6% and 38.2% in primary PCI patients), and estimated glomerular filtration rate < 60 ml/min (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.42 to 6.43; p = 0.004), Killip class $2 (HR: 2.74; 95% CI: 1.37 to 5.49; p = 0.004), and PCI failure (HR: 3.23; 95% CI: 1.42 to 7.31; p = 0.005) determined an increased risk.CONCLUSIONS STEMI after TAVR was associated with very high in-hospital and mid-term mortality. Longer door-to balloon times and a higher PCI failure rate were observed in TAVR patients, partially due to coronary access issues specific to the TAVR population, and this was associated with poorer outcomes. (J Am Coll Cardiol 2021;77:2187-99)(c) 2021 by the American College of Cardiology Foundation.

Background The optimal pharmacological therapy after transcatheter aortic valve implantation (TAVI) remains uncertain. We compared efficacy and safety of various antiplatelet and anticoagulant approaches after TAVI by a network meta-analysis. Methods A total of 14 studies (both observational and randomized) were considered, with 24,119 patients included. Primary safety endpoint was the incidence of any bleeding complications during follow-up. Secondary safety endpoint was major bleeding. Efficacy endpoints were stroke, myocardial infarction, and cardiovascular mortality. A frequentist network meta-analysis was conducted with a random-effects model. The following strategies were compared: dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), oral anticoagulation (OAC), and OAC + SAPT. The mean follow-up was 15 months. Results In comparison to DAPT, SAPT was associated with a 44% risk reduction of any bleeding (odds ratio [OR]: 0.56 [95% confidence interval, CI: 0.39–0.80]). SAPT was ranked as the safest strategy for the prevention of any bleeding (p-score: 0.704), followed by OAC alone (p-score: 0.476) and DAPT (p-score: 0.437). Consistent results were observed for major bleeding. The incidence of cardiovascular death and secondary ischemic endpoints did not differ among the tested antithrombotic approaches. In patients with indication for long-term anticoagulation, OAC alone showed similar rates of stroke (OR: 0.92 [95% CI: 0.41–2.05], p = 0.83) and reduced occurrence of any bleeding (OR: 0.49 [95% CI: 0.37–0.66], p Conclusion The present network meta-analysis supports after TAVI the use of SAPT in patients without indication for OAC and OAC alone in those needing long-term anticoagulation.

International audience; Background: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed.Methods: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents.Results: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI.Conclusions: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49–0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Background The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. Methods and results All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 μm (n = 206) versus 81 μm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 μm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). Conclusion In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Background: Selective, clopidogrel-based therapies after percutaneous coronary intervention (PCI) have been investigated to reduce the bleeding risk while maintaining an adequate anti-ischemic protection. However, single studies may be underpowered for events at low incidence, mainly major bleeding or ischemic complications. Methods: We performed an updated meta-analysis and meta-regression of randomized trials comparing outcome with unguided de-escalation to clopidogrel or guided clopidogrel therapy vs conventional treatment with potent oral P2Y12 inhibitors in patients undergoing PCI, especially for acute coronary syndrome (ACS). The primary safety endpoint was major bleeding. The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE, cardiovascular death, myocardial infarction, stroke). Stent thrombosis was also an outcome measure. Findings: We considered six randomized trials, three on unguided de-escalation (N=3473) and three on guided clopidogrel therapy (N=7533). Control groups received conventional treatment with ticagrelor/prasugrel in all studies. The incidence of major bleeding was significantly lower with unguided de-escalation (1·0% vs 2·0% with conventional treatment; OR 0·53, 95% CI 0·30-0·95, p=0·03) and non-significantly reduced with guided de-scalation clopidogrel therapy (2·2% vs 3·6%; OR 0·79, 95% CI 0·49-1·27, p=0·33). Both unguided (3·3% vs 4·4%; OR 0·74, 95% CI 0·52-1·05, p=0·09) and guided clopidogrel therapy (2·8% vs 2·7%; OR 1·09, 95% CI 0·79-1·51, p=0·61) were associated with similar incidence of MACE vs conventional treatment. A trend towards an increased risk of stent thrombosis was observed in studies on guided clopidogrel therapy (OR 2·27, 95% CI 0·72-7·16, p=0·16). Meta-regression indicated greater safety and similar ischemic protection of the two alternatives clopidogrel-based therapies, regardless of baseline bleeding and ischemic risk. Interpretation: As compared with prasugrel/ticagrelor treatment, unguided de-escalation to clopidogrel, but no a guided clopidogrel therapy, decreases bleeding complications among patients with ACS undergoing PCI. Both unguided de-escalation and guided clopidogrel therapy appear as effective as in preventing MACE. Funding Information: None. Declaration of Interests: G.P.: speaker/consultant fee from Abbott, Astra Zeneca, Sanofi, Amgen, Menarini, Bayer, Pfizer, BMS, Daiichi Sankyo, PIAM, Malesci, Sigma Tau, Chiesi, Medtronic, MSD, Boehringer Ingelheim, Servier. L.G., E.G.S., A.R., M.M.: none.

Background COronaVIrus Disease 19 (COVID-19) led to the reorganization of Cardiology Units in terms of working spaces and healthcare personnel. In this scenario, both outpatient visits and elective interventional cardiology procedures were suspended and/or postponed. We aimed to report the impact of COVID-19 on interventional coronary and structural procedures in Piedmont, Italy. Methods The number of coronary angiographies (CAG), percutaneous coronary interventions (PCI), primary PCI (pPCI), transcatheter aortic valve replacements (TAVR) and Mitraclip performed in Piedmont between March 1st and April 20th, 2020 (CoV-time) were collected from each catheterization laboratory and compared to the number of procedures performed the year before in the same months (NoCoV-time). Results Procedural data from 18 catheterization laboratories were collected. Both coronary (5498 versus 2888: difference: −47.5%; mean 305.4 VS 160.4; p = 0.002) and structural (84 versus 17: difference: −79.8%; mean 4.7 Vs 0.9; p, Highlights • COronaVIrus Disease 19 (COVID-19) led to the reorganization of Cardiology Units • Interventional procedures during COVID-19 suffered a dramatic decrease in Piedmont • Structured clinical pathways should be created, together with awareness campaigns.

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400–0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02401-x.

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), is an ongoing global pandemic with high morbidity and mortality.1 Patients with preexist...

Introduction The impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined. Methods Consecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1–February 19, 2020) and previous-year control periods (February 20–May 3, 2019). ACS patients with Covid-19 were further compared with those without. Results Among 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively; p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%; p 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p Conclusion ACS patients presenting during the Covid-19 pandemic experienced increased all-cause mortality, driven by Covid-19 positive status due to higher rates of cardiogenic shock and sustained ventricular tachycardia. No differences in cardiovascular mortality compared to non-pandemic scenarios were reported.

Background Patient- and lesion-related factors may influence concordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR), potentially affecting safety of revascularization deferral. Methods Consecutive patients with at least an intermediate coronary stenosis evaluated by both iFR and FFR were retrospectively enrolled. Revascularization was at physician's discretion. The agreement between IFR and FFR at their diagnostic cut-offs (FFR 0.80, iFR 0.89) according to patient- and lesion-level characteristics was assessed. Multivariate analyses were carried to identify the independent predictors of discordance. Tailored iFR cut-offs according to predictors of discordance best matching an FFR of 0.80 were identified by receiver-operating characteristic (ROC) curves. The impact of reclassification according to tailored iFR cut-offs on major cardiovascular events (MACE: cardiovascular death, myocardial infarction or target lesion revascularization) among deferred lesions was investigated. Results 299 coronary stenosis (diameter stenosis 54±14%, FFR 0.84 [0.78–0.89], iFR 0.91 [0.87–0.95], left main/left anterior descending [LM/LAD] vessel 67.6%) of 260 patients were studied, and 46.5% were revascularized. Discordance rate was 23.4% (10.7% iFR-negative discordant, 12.7% iFR-positive discordant). Independent predictors of discordance were LM/LAD disease, multivessel disease, non-ST-elevation myocardial infarction presentation, smoking, reduced glomerular filtration rate and hypertension. Lesion reclassification with tailored iFR-cut-offs based on patient-level predictors carried no prognostic value among deferred lesions. Reclassification according to lesion location, which was entirely driven by LM/LAD lesions (iFR-cut-offs: 0.93 for LM/LAD, 0.89 for non-LM/LAD), identified increased MACE among lesions deferred based on a negative FFR, between patients with a positive as compared to a negative iFR (19.4% vs. 6.1%, p=0.044), while the same association was not observed with the conventional 0.89 iFR cut-off (15.0% vs 8.6%, p=0.303). Conclusion Tailored vessel-based iFR cut-offs carry prognostic value among FFR negative lesions, suggesting that iFR may more safely defer revascularization of LM/LAD lesions than FFR and that a single iFR cut-off might be clinically unsatisfactory. Funding Acknowledgement Type of funding source: None

Aims The role of antiplatelet therapy in patients with spontaneous coronary artery dissection (SCAD) undergoing initial conservative management is still a matter of debate, with theoretical arguments in favour and against its use. The aims of this article are to assess the use of antiplatelet drugs in medically treated SCAD patients and to investigate the relationship between single (SAPT) and dual (DAPT) antiplatelet regimens and 1-year patient outcomes. Methods and results We investigated the 1-year outcome of patients with SCAD managed with initial conservative treatment included in the DIssezioni Spontanee COronariche (DISCO) multicentre international registry. Patients were divided into two groups according to SAPT or DAPT prescription. Primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any unplanned percutaneous coronary intervention (PCI). Out of 314 patients included in the DISCO registry, we investigated 199 patients in whom SCAD was managed conservatively. Most patients were female (89%), presented with acute coronary syndrome (92%) and mean age was 52.3 ± 9.3 years. Sixty-seven (33.7%) were given SAPT whereas 132 (66.3%) with DAPT. Aspirin plus either clopidogrel or ticagrelor were prescribed in 62.9% and 36.4% of DAPT patients, respectively. Overall, a 14.6% MACE rate was observed at 12 months of follow-up. Patients treated with DAPT had a significantly higher MACE rate than those with SAPT [18.9% vs. 6.0% hazard ratios (HR) 2.62; 95% confidence intervals (CI) 1.22–5.61; P = 0.013], driven by an early excess of non-fatal MI or unplanned PCI. At multiple regression analysis, type 2a SCAD (OR: 3.69; 95% CI 1.41–9.61; P = 0.007) and DAPT regimen (OR: 4.54; 95% CI 1.31–14.28; P = 0.016) resulted independently associated with a higher risk of 12-month MACE. Conclusions In this European registry, most patients with SCAD undergoing initial conservative management received DAPT. Yet, at 1-year follow-up, DAPT, as compared with SAPT, was independently associated with a higher rate of adverse cardiovascular events (ClinicalTrial.gov id: NCT04415762).

Aims The recent coronavirus disease 19 (COVID‐19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID‐19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year. Methods and results We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter‐year period (21 February to 31 March 2019) and an intra‐year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra‐year period, and 192 during inter‐year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra‐year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56–0.89; P = 0.0037), or with inter‐year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45–0.72; P

Although oral P2YThe purpose of this study was to compare downstream and upstream oral P2YWe performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit).We randomized 1,449 patients to downstream or upstream oral P2YDownstream and upstream oral P2Y

Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels, Highlights • Impaired renal function, elevated C-reactive protein and advanced age were major indicators of death in COVID-19 patients. • These associations were substantially homogenous across all sub-groups analysed. • No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. • Death rates were higher in the Northern as opposed to Central-Southern Italian regions.

Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

Background: There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods: All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [ Results: Two thousand seven hundred forty-two patients were included. At 16 months (8–20) follow-up, inverse probability of treatment weighting adjusted rates of major adverse cardiac event were similar between FKI and no-FKI group (15.1% versus 15.5%; P =0.967), this result did not change with use of imaging, proximal optimization technique, or routine versus bail-out FKI. In the 2-stent subgroup, FKI was associated with lower rates of target vessel revascularization (7.8% versus 15.9%; P =0.030) and target lesion revascularization (7.3% versus 15.2%; P =0.032). Short overlap FKI was associated with a lower rate of target lesion revascularization compared with no FKI (2.6% versus 5.4%; P =0.034), while long overlap was not (6.8% versus 5.4%; P =0.567). Conclusions: In patients with bifurcations or unprotected left main treated with ultrathin stents, short overlap FKI is associated with less restenosis. In a 2-stent strategy, FKI was associated with less target vessel revascularization and restenosis. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03544294.