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Coronary artery disease is the predominant aetiology of heart failure and left ventricular dysfunction in industrialized countries. The pathophysiological substrate of hibernating myocardium constitutes the conceptual target of coronary revascularization by coronary artery bypass graft (CABG) or coronary angioplasty or percutaneous coronary intervention (PCI). Studies, mainly observational, conducted in the past have demonstrated a prognostic benefit of CABG on survival. These findings were confirmed by the long-term follow-up of the STICH study in which, however, documentation of inducible ischaemia or myocardial viability was not predictive of a prognostic benefit of CABG. Revascularization via PCI in the recent REVIVED-BCIS2 study did not demonstrate a significant benefit in terms of death or heart failure hospitalization compared with optimal medical therapy. Pending the long-term follow-up of the REVIVED-BCIS2 study, optimized medical therapy, cardiac resynchronization therapy, and the implantable cardioverter defibrillator, where indicated, are the mainstay of treatment in patients with dilated ischaemic cardiomyopathy. The decision for coronary revascularization is made in the individual patient, possibly with a higher bias in patients with angina, three-vessel coronary artery disease, severe left ventricular dysfunction, and cardiac remodelling.

Background Traditional cardiac rehabilitation (CR) is effective in improving physical performance and prognosis after myocardial infarction (MI). Anyway, it is not consistently recommended to older adults, and its attendance rate is low. Previous studies suggested that alternative, early and tailored exercise interventions are feasible and effective in improving physical performance in older MI patients. Anyway, the demonstration that they are associated also with a significant reduction of hard endpoints is lacking. Aim To describe rationale and design of the “Physical activity Intervention in Elderly patients with myocardial Infarction” (PIpELINe) trial. Methods The PIpELINe trial is a prospective, randomized, multicentre study with a blinded adjudicated evaluation of the outcomes. Patients aged ≥ 65 years, admitted to hospital for MI and with a low physical performance one month after discharge, as defined as short physical performance battery (SPPB) value between 4 and 9, will be randomized to a multi-domain lifestyle intervention (including dietary counselling, strict management of cardiovascular and metabolic risk factors, and exercise training) or health education. The primary endpoint is the one-year occurrence of the composite of cardiovascular death or re-hospitalization for cardiovascular causes. Results The recruitment started in March 2020. The estimated sample size is 456 patients. The conclusion of the enrolment is planned for mid-2023. The primary endpoint analysis will be available for the end of 2024. Conclusions The PIpELINe trial will show if a multi-domain lifestyle intervention is able to reduce adverse events in older patients with reduced physical performance after hospitalization for MI. Trial registration ClinicalTrials.gov NCT04183465.

Background. Diabetic patients presenting with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have an increased risk of contrast-induced-acute kidney injury (CI-AKI). It has been shown that sodium-glucose cotransporter-2 inhibitors (SGLT2-I) have a nephroprotective effect. Purpose. To analyze the association between chronic SGLT2-I treatment and the development of CI-AKI in diabetic patients with AMI (both ST- and non-ST segment elevation myocardial infarction) treated with PCI, in both patients with and without chronic kidney disease (CKD). Methods. In this multicenter international registry, consecutive patients with type 2 diabetes mellitus (T2DM) and AMI undergoing PCI between 2018 and 2021 were enrolled. The study population was stratified by the presence of CKD and anti-diabetic therapy at admission (SGLT2-I versus non-SGLT2-I users). CI-AKI was defined as an absolute (≥0.5 mg/dl) or relative increase (≥25%) in creatinine at 48-72 h after PCI compared to baseline values. Results. The study population consisted of 646 AMI patients: 111 SGLT2-I users [28 (25.2%) with CKD] and 535 non-SGLT2-I users [221 (41.3%) with CKD]. The median age was 70 [61-79] years, and more than 77% were males. Independently of creatinine at admission, SGLT2-I users exhibited significantly lower creatinine values at 72h after PCI, both in the non-CKD and CKD stratum. After PCI, the overall rate of CI-AKI was 76 (11.8%), significantly lower in SGLT2-I users compared to non-SGLT2-I patients (5.4% vs 13.1%, p=0.022). This finding was confirmed also in patients without CKD (p=0.040). In the CKD cohort, SGLT2-I users maintained significantly lower creatinine values at discharge, albeit without significant differences in CI-AKI rate compared to non-SGLT2-I patients. At multivariate analysis, the use of SGLT2-I was identified as an independent predictor of reduced rate of CI-AKI (OR 0.356; 95%CI 0.134-0.943, p=0.038). Patients with CI-AKI reported a longer hospital stay and higher incidence of adverse cardiovascular events at follow-up (p=0.001), mostly in the CKD cohort. Conclusion. In T2DM patients with AMI, the use of SGLT2-I was associated with a lower risk of CI-AKI during the index hospitalization, mostly in patients without CKD. Our results provide new insights into the cardio and nephroprotective effects of SGLT2-I in the setting of AMI. Trial Registration: data are part of the observational Registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT 05261867.

Contains fulltext : 291566.pdf (Publisher’s version ) (Open Access) BACKGROUND: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. METHODS: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. RESULTS: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.

Contains fulltext : 290798.pdf (Publisher’s version ) (Open Access) BACKGROUND: Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. METHODS: This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March-June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. RESULTS: We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825-0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31-2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96-1.34], p = 0.12). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous clinical entity and in its complex diagnostic approach cardiovascular magnetic resonance (CMR) plays a pivotal role. Purpose To characterize the differences of MINOCA patients with and without late gadolinium enhancement (LGE) at CMR and to identify the predictors for ischemic LGE development and extension. Methods We assessed 461 MINOCA cases from January 2016 to June 2021. MINOCA were defined according to the current European guidelines criteria. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR imaging findings, our cohort was divided into two CMR phenotypes based on regional myocardial necrosis detected throughout LGE (“LGE-positive MINOCA”) or regional ischemic injury without LGE (“LGE-negative MINOCA”). Extended LGE was considered as the presence of >2 segments with transmural LGE. Multivariate logistic regression analysis was used to determine the predictors of LGE and extended LGE. Results The final cohort included 175 MINOCA: 121 (69.1%) constituted the LGE-positive group. The mean time delay between acute clinical presentation and CMR was 6 ± 2.9 days. At admission, MINOCA LGE-patients more frequently presented angina and ST segment elevation (24% vs 7.4%, p = 0.01), compared to the LGE negative ones. Furthermore, the LGE positive group had a significantly greater infarct size, measured by peak hs-Troponin I values and left ventricular function. The only predictor of LGE was the peak troponin value (OR 1.64, 95% CI 1.18–2.28, p = 0.003), while predictors of extended LGE were ST-segment elevation at admission (OR 7.44, 95% CI 1.57–35.22, p = 0.01), peak troponin values (OR 1.07, 95% CI 1.02–1.13, p = 0.01) and the presence of non-obstructive coronary artery disease at coronary angiography (OR 5.49, 95% CI 1.20–25.09, p = 0.028). Conclusion The presence and extension of LGE at early CMR evaluation is an important feature in the setting of MINOCA. In addition, simple baseline characteristics (such as ST elevation, peak troponin value and LVEF) may aid the identification of a greater ischemic necrosis burden at CMR and therefore these high-risk MINOCA subjects could be benefit from a stricter management effort.

Background Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is a clinical condition that includes acute myocardial infarction (AMI) occurring with non-obstructive coronary disease. This entity accounts above 6% (from 1% to 14%) of all patients presenting with AMI and it's known to be more prevalent in females. However, differences in terms of clinical features and prognosis in MINOCA patients according to gender have been poorly understood. Purpose To evaluate differences in clinical characteristics at admission and during follow-up between males and females with MINOCA. Methods We included all consecutive patients with AMI undergoing coronary angiogram between 2016 and 2020 at our center. According to 2016 ESC Position Paper criteria, we considered as MINOCA all patients with AMI and coronary stenosis Results Among 289 patients affected by MINOCA according to the 2016 ESC criteria, 98 were male (34%) and 191 were female (66%). Females were older than males (68.9 ± 13.1 vs 58.4 ± 14.5 years, p =0.0001). About the traditional cardiovascular risk factors males were more frequently smokers (56.1% vs 33.9%, p=0.001) while there were no significant differences in others risk factors. Females were more frequently on beta-blockers (39% vs 20%, p=0.002) and statins (33% vs 19%, p=0.015) compared to males. No differences were found between the two groups regarding clinical characteristics and instrumental findings (EKG and echocardiography). At coronary angiography, males had more frequently severe coronary stenosis than females (15.5 ± 26.4 VS 9.1 ± 21.5, p =0.019). During follow up we did not find any differences in terms of death, reinfarction, stroke and heart failure while females had more MACEs than males (33% vs 19.4%, p=0.015); and this data was confirmed at Kaplan Meier curves (p = 0.014). Finally, the multivariate analysis showed that age is an independent predictor of MINOCA (HR 1.04, CI 1.01-2.07, p=0.006), rather than sex, diabetes, and hypertension. Conclusions In our MINOCA population we found that females were older than males, more frequently on statins and beta blockers at admission and they showed a lower degree of atherosclerotic disease. Nevertheless, after 36 ± 14.8 months of follow-up, we found a higher incidence of MACE in females than in males. We hypothesize that these findings could reflect the different pathogenesis of myocardial damage in our subgroups. Actually, statins and estrogens have a well-known protective role towards the progression of atherosclerosis, but they have no impact on other mechanisms of myocardial infarction which are more frequent in females, such as spontaneous coronary artery dissections, epicardial spasms or microvascular dysfunction.

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) receive intense clinical interest in patients with and without type 2 diabetes mellitus (T2DM) for their pleiotropic beneficial effects. Objectives To investigate in-hospital and long-term prognosis in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic (OAD) agents (non-SGLT2-I users). Methods In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. In-hospital outcomes included cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI). Long-term outcomes were cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization, and their composite (MACE). Results The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p Conclusions In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI.

Background Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor is the standard of care in patients with acute coronary syndromes. The optimal timing of the administration of oral P2Y12 inhibitors has been largely debated, particularly among patients with non-ST-segment elevation myocardial infarction (NSTEMI). The latest European Society of Cardiology guidelines, based on recent scientific evidence, do not recommend routine pre-treatment with a P2Y12 inhibitor before coronary angiography. However, the impact of pre-treatment on the incidence of peri-procedural myocardial infarction (MI) and myocardial injury has never been explored. Purpose To evaluate the impact of pre-treatment with a P2Y12 receptor inhibitor on periprocedural myocardial infarction and injury in NSTEMI patients undergoing invasive treatment. Methods We evaluated all consecutive patients admitted to our coronary care unit from 2016 to 2021 affected by NSTEMI undergoing invasive management with percutaneous coronary intervention (PCI). We enrolled only patients with stable (≤ 20% variation) or falling pre-procedure baseline cardiac troponin (cTn) values. The entire population was divided into two groups: patients pre-treated with dual antiplatelet therapy (an oral P2Y12 inhibitor in adjunct to aspirin) before performing coronary angiography (upstream group) and patients who started an oral P2Y12 inhibitor only after PCI (downstream group). All patients received aspirin and anticoagulant therapy before coronary angiography. The primary endpoint was the incidence rate of periprocedural MI and myocardial injury according to the fourth universal definition of myocardial infarction. Finally, a safety endpoint of major and minor bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria was evaluated for all bleeding episodes during hospitalization. Results A total of 878 patients with NSTEMI undergoing PCI and with pre-procedure stable cTn levels were analyzed: 615 (70%) constituted the upstream group. The mean age of the study population was 70.1±12.5 years and 71.3% were males. There were no significant differences regarding traditional cardiovascular risk factors, comorbidities, cTn and hemoglobin levels between the two groups. After PCI, the rate of periprocedural myocardial injury and MI did not significantly differ between the upstream and downstream groups (19.5% vs 24.7%, p=0.08 and 17.6% vs 19.4%, p=0.5, respectively). A trend of lower periprocedural myocardial injury and MI cumulative incidence was observed in the upstream group (37.1% vs 44.1%, p=0.051). Notably, major and minor bleedings during hospitalization occurred more frequently in the upstream group compared to the downstream one (5.2% vs 1.9%, p=0.02). Conclusions Among NSTEMI patients undergoing invasive management and with stable pre-procedure cTn levels, pretreatment with an oral P2Y12 inhibitor did not reduce the rate of periprocedural MI and myocardial injury but was associated with an increase in major and minor bleeding complications during hospitalization.

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients. Objectives To investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users). Methods Patients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization. Results The study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-I users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs.15.7%, p=0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually (p = 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR=0.35; 95%CI 0.14–0.86; p = 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-I therapy remained an independent predictor of VT/VF occurrence (OR=0.20; 95%CI 0.04–0.97; p = 0.046) but not of AF occurrence. Conclusions In T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control. Trial registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT05261867.

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) with pleiotropic beneficial effects. Nowadays, the inflammation response in the setting of acute myocardial infarction (AMI) has been proposed as a potential pharmacological intervention target. In this setting, we tested the hypothesis that the SGLT2-I displays anti-inflammatory effect along with glucose-lowering properties. We investigated the relationship between stress hyperglycemia, inflammation burden and infarct size in a cohort of type 2 diabetic AMI patients treated with SGLT2-I versus other oral anti-diabetic (OAD) agents alone. Methods In this multicenter international registry, all diabetic patients with AMI treated with percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the admission anti-diabetic therapy, patients were divided into those receiving SGLT2-I versus other OAD agents alone. Patients on insulin therapy alone or combined with OAD agents or with unavailable admission medical therapy were excluded from the study. Further exclusion criteria encompassed AMI (mostly NSTEMI) treated with coronary artery bypass grafting (CABG) after the CAG, severe valvular heart disease, prosthetic heart valves, severe anemia, major acute bleeding, pulmonary embolism, fever (38° C), chronic renal failure (glomerular filtration rate < 30 mL/min/1.73 m2), autoimmune diseases, malignancies and congenital heart disease. The following inflammatory markers were evaluated at different time points: total white blood cell, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR), C-reactive protein. Infarct size was assessed by peak troponin levels and echocardiographic parameters. Results The final study population consisted of 583 patients hospitalized for AMI (both STEMI and NSTEMI) classified as SGLT2-I users (n = 98) versus other OAD agents alone (n = 485). Admission hyperglycemia was more prevalent among the other OAD agents group. Reduced infarct size was detected in patients treated with SGLT2-I compared to those treated with other OAD agents alone. Both at admission, and after 24 hours, inflammatory indices were significantly higher in patients treated with other OAD agents alone, with a significant increase in neutrophils levels at 24 hours, compared to the SGLT2-I group. In multivariate analysis, SGLT2-I emerged as a significant predictor of reduced inflammatory response (OR 0.45, 95%CI 0.27–0.75, p = 0.002), together with peak troponin values, independently of age, admission creatinine values and admission glycemia. Conclusions Type 2 Diabetic patients hospitalized for AMI and receiving SGLT2-I exhibited modest inflammatory response and myocardial damage/infarct size compared to other OAD agents alone, independently of glucose-metabolic control. Our findings pave the way for new pathophysiological and therapeutic insights regarding the cardioprotective effect of SGLT2-I in the setting of coronary artery disease.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a significant proportion of acute myocardial infarction (AMI) population. MINOCA is a working diagnosis and an accurate investigation of the underlying causes should always be performed. In this setting, cardiac magnetic resonance (CMR) imaging plays a pivotal diagnostic role. However, a prognostic stratification based on the CMR findings in ischemic MINOCA is still unavailable. Purpose To evaluate the potential prognostic impact of specific CMR findings - especially ischemic late gadolinium enhancement (LGE) patterns - in order to look for measurable parameters that may guide the management of this still troubled clinical entity. Methods We assessed 461 MINOCA from January 2016 to June 2021. We excluded acute myocarditis, Tako-tsubo syndromes, cardiomyopathies, or non-pathological CMR. According to CMR findings, MINOCA were classified in two phenotypes: LGE-positive (an ischemic subendocardial or transmural LGE pattern) or LGE-negative (cases without LGE but exhibiting regional myocardial injury defined by myocardial edema in a coronary territory with a typically ischemic "wave-front" and/or regional wall motion abnormality consistent with coronary distribution). All-cause mortality, re-infarction, stroke, heart failure (HF) and the composite endpoint (MACE) were evaluated. Extended LGE was considered as the presence of >2 segments with transmural LGE. The mean follow-up was 36.1 ± 15.2 months and CMR was performed at a mean of 6 ± 2.9 days from the acute presentation. Results The final cohort included 175 MINOCA with a likely-ischemic etiology: 121 (69.1%) constituted the LGE-positive group. The mean age of the study population was 62.3 ± 12.9 years and more than 61% were females. During follow-up, HF (15.7% vs 1.9%, p=0.008) and MACE (20.7% vs 7.4%, p=0.029) occurred more frequently in MINOCA "LGE-positive" compared to the "LGE-negative" ones. Extended LGE was significantly more prevalent in patients with versus without subsequent HF. On multivariable Cox regression, extended LGE was an independent predictor of HF occurrence (HR 18.49, 95%CI 4.65–73.61, p < 0.001) and MACE (HR 14.64, 95%CI 3.91–54.86, p < 0.001). Conclusions Our data suggest that in MINOCA patients the detection of LGE is correlated with the incidence of major cardiovascular events and heart failure during long-term follow-up. In fact, LGE extension was identified as the strongest predictor of cardiac adverse events. The early execution of CMR is useful in the prognostic stratification of MINOCA and this could guide the subsequent clinical and therapeutic management.

Background Myocardial Infarction with Non-Obstructive Coronary Artery disease (MINOCA) is a heterogeneous entity with relevant long-term major adverse cardiovascular events (MACE). There is solid evidence that secondary prevention strategies improve prognosis of patients with obstructive myocardial infarction. However, evidence-based treatments for MINOCA are lacking as no published randomized clinical trials have ever exclusively enrolled this population. In fact, treatment recommendations in current guidelines are mainly based on expert opinions and MINOCA patients are frequently discharged with statins and dual antiplatelet therapy (DAPT). Purpose To evaluate the effects of statins and DAPT as secondary prevention treatments on long-term outcomes in MINOCA patients. Methods We enrolled all consecutive MINOCA patients admitted to our Centre from 2016 to 2021. The diagnosis of MINOCA was made according to the current European Society of Cardiology diagnostic criteria (angiographic conventional cut-off of < 50% coronary stenosis without a clinically apparent alternative diagnosis). Second-level diagnostic work-up including cardiac magnetic resonance was performed to exclude non-ischemic troponin elevation cause. All-cause mortality and MACE (a composite of all-cause mortality, hospitalization for heart failure, myocardial re-infarction and stroke) were collected during follow-up. The prognostic impact of statins and DAPT at discharge was assessed. The relationship between treatments and outcomes was evaluated by using Kaplan-Meier survival analysis. Results 278 MINOCA patients were enrolled, of whom 203 (73%) were discharged on statins and 123 (44.2%) on DAPT. After a median follow-up of 36 ± 14.8 months, the overall all-cause mortality was 11.8% and the composite endpoint (MACE) was achieved in 28.4% of the entire population. Kaplan-Meier curves showed that patients treated with statins had a significantly lower rate of all-cause mortality (9.3% vs 18.2%, p=0.04) and MACE (24.6% vs 39.2%, p=0.02). On the other hand, rates of death (9.8% vs 13.2%, p=0.4) and MACE (23.6% vs 31.6%, p=0.1) were similar in MINOCA patients treated with DAPT or single antiplatelet therapy. Conclusions Among MINOCA patients, DAPT at discharge neither reduced long-term all-cause mortality nor MACE. In contrast, statin treatment provided beneficial effects on long-term outcomes. These results should be considered preliminary and require confirmation from randomized clinical trials.

Background Coronary malperfusion due to type A aortic dissection is a life-threatening condition where timely recognition and treatment are mandatory. The International Registry of Acute Aortic Dissection (AAD) shows that only 5% of AAD patients present with ECG evidence of acute myocardial infarction, and prognosis is ominous due to the additional myocardial damage and missed or delayed diagnosis. The shark fin waveform is an uncommon but high-risk ECG pattern formed by fusion of QRS, ST-segment, and T waves. It is associated especially with the sub-occlusion of the left main coronary artery or proximal left anterior descending artery with a high risk of death due to cardiac arrest and cardiogenic shock. Case presentation A 61-year-old man was admitted to our cardiac cath-lab for typical chest pain and suspected acute ST segment elevation myocardial infarction (STEMI). A triangular pattern known as the ‘shark-fin’ sign in the precordial and inferior leads, and mirroring ST-segment depression in dI and aVL was detected. Unexpectedly coronary angiography revealed normal epicardial vessels, but a very-regular-shaped staining of the aortic sinus was observed. This finding was suspicious for acute aortic dissection. Bedside 2D-echocardiography within the cath-lab demonstrated an intimal flap in the aortic root and arch, with mild aortic regurgitation. Contrast-enhanced computerized tomography (CT) confirmed our diagnosis of Type A aortic dissection (AAD) highlighting the same dissection flap revealed by angiography arising from the left coronary cusp of the aortic root. The left main trunk was not directly involved, but the dissection extended from the ascending to the distal aorta involving both left and right external and internal iliac arteries with a thrombotic occlusion of the right femoral-iliac axis There was also a right inferior-pole renal infarction. Thus, the patient was immediately submitted to heart surgery. Conclusions Type A aortic dissection is a life-threatening disease in which early diagnosis and treatment are critical for survival. Occasionally it could mimic STEMI due to coronary involvement or dynamic obstruction of a coronary ostium. In our experience a bedside echocardiography performed before primary percutaneous coronary intervention (PCI) may confirm the clinical suspicious and avoid dangerous diagnostic delays.

Long term survival and its determinants after Percutaneous Coronary Intervention (PCI) on Unprotected Left Main Coronary Artery (ULMCA) remain to be appraised. In 9 European Centers 470 consecutive patients performing PCI on ULMCA between 2002 and 2005 were retrospectively enrolled. Survival from all cause and cardiovascular (CV) death were the primary end points, while their predictors at multivariate analysis the secondary ones. Among the overall cohort 81.5% of patients were male and mean age was 66 ± 12 years. After 15 years (IQR 13 to 16), 223 patients (47%) died, 81 (17.2%) due to CV etiology. At multivariable analysis, older age (HR 1.06, 95%CI 1.02 to 1.11), LVEF < 35% (HR 2.97, 95%CI 1.24 to 7.15) and number of vessels treated during the index PCI (HR 1.75, 95%CI 1.12 to 2.72) were related to all-cause mortality, while only LVEF

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older ( P = .002), less often active smokers ( P = .002), and hypercholesterolemic ( P = .006), they presented more often later than 12 h ( P = .037), more often to the hub and were more often in cardiogenic shock ( P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow ( P = .029) and more thrombectomy ( P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences.

The European Society of Cardiology guidelines on non-ST-elevation acute coronary syndromes suggest different temporal strategies for the angiographic study depending on the risk profile. The scientific evidence underlying the guideline recommendations and the critical issues currently existing in Italy, that often do not allow either an extended strategy of revascularization within 24 h or the application of the principle of the same day transfer from a spoke to a hub centre, are analysed. The position paper focuses, in particular, on the subgroup of patients with a defined diagnosis of non-ST-elevation myocardial infarction by proposing a timing of coronary angiography/revascularization that takes into account the available scientific evidence and the organizational possibilities of a considerable part of national cardiology services.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Objectives Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. Methods This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort (n = 761) included patients from the first three participating hospitals; validation cohort (n = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox’s regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. Results In the derivation cohort, the median age was 69 (IQR, 58–77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59–77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253–2.418], p p = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796–0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758–0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). Conclusion Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. Key Points •Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. •Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. •The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

Background The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. Objectives The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment. Methods This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. Results A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p, Central Illustration

Aims Our aim was to describe the electrocardiographic features of critical COVID-19 patients. Methods and results We carried out a multicentric, cross-sectional, retrospective analysis of 431 consecutive COVID-19 patients hospitalized between 10 March and 14 April 2020 who died or were treated with invasive mechanical ventilation. This project is registered on ClinicalTrials.gov (identifier: NCT04367129). Standard ECG was recorded at hospital admission. ECG was abnormal in 93% of the patients. Atrial fibrillation/flutter was detected in 22% of the patients. ECG signs suggesting acute right ventricular pressure overload (RVPO) were detected in 30% of the patients. In particular, 43 (10%) patients had the S1Q3T3 pattern, 38 (9%) had incomplete right bundle branch block (RBBB), and 49 (11%) had complete RBBB. ECG signs of acute RVPO were not statistically different between patients with (n = 104) or without (n=327) invasive mechanical ventilation during ECG recording (36% vs. 28%, P = 0.10). Non-specific repolarization abnormalities and low QRS voltage in peripheral leads were present in 176 (41%) and 23 (5%), respectively. In four patients showing ST-segment elevation, acute myocardial infarction was confirmed with coronary angiography. No ST-T abnormalities suggestive of acute myocarditis were detected. In the subgroup of 110 patients where high-sensitivity troponin I was available, ECG features were not statistically different when stratified for above or below the 5 times upper reference limit value. Conclusions The ECG is abnormal in almost all critically ill COVID-19 patients and shows a large spectrum of abnormalities, with signs of acute RVPO in 30% of the patients. Rapid and simple identification of these cases with ECG at hospital admission can facilitate classification of the patients and provide pathophysiological insights.

The so-called "smoking paradox", conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.

Background: Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI).Methods/Design: The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent's fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non–inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non–inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years.The PIONEER IV trial aims to demonstrate non–inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy.Clinical Trial Registration: ClinicalTrials.govUnique Identifier: NCT04923191Classifications: Interventional Cardiology

Aims: To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users). Methods: In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization. Results: The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33–0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21–0.98; p = 0.041). Conclusions: In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI. Registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT05261867.

Aims To evaluate the safety of a single and combined use of ultrasound-guided femoral puncture (U) and percutaneous arterial closure devices (P) in femoral artery procedures (FAP) compared to fluoroscopic guidance (F) and manual compression (M) in a large radial-focused interventional centre. U and P, taken individually, have improved safety in femoral arterial access procedures compared to traditional techniques. Methods and results All FAP performed between July 2017 and December 2018 in our centre were divided into three phases: (i) control period with F and M mainly performed; (ii) phase out period where U and P were introduced; and (iii) intervention period where a 6-month expertise on the novel techniques was acquired. The overall population was further stratified into subgroups: F/M, U/M, F/P, and U/P. The primary study endpoint was in-hospital access site bleeding events (BE) according to the BARC criteria. The secondary endpoint was vascular site complications (VASC). 418 procedures (14%) out of 3025 were performed via FA access during the study period. The overall access-site in-hospital BE were 97 (23%). Decreasing rates of BE (phase 1: n = 46, 29%; phase 2: n = 38, 22% e phase 3: n = 13, 15%; P = 0.027) and VASC were observed during the three periods. BE occurred significantly more often in F/M group (F/M: n = 48; 32%; U/M: n = 12, 16%; F/P: n = 18, 21%; U/P: n = 19, 17%; P = 0.008). F/M subgroup was an independent predictor of BE both in multivariable analysis and propensity score matching analysis. Conclusions The introduction of ultrasound-guided femoral puncture and percutaneous arterial closure devices has reduced access site bleeding with a progressive improvement after the first 6 months learning period.

Aims As known, Takotsubo Syndrome (TTS) can occur during stressful events that result in sympathetic overactivity. No studies have investigated the sympathetic activity and long-term prognosis in patients with TTS and admission hyperglycaemia vs. normoglycaemia. Moreover, whether hyperglycaemia may serve as a metabolic trigger to unbalance the sympathetic system axis as well as through over-inflammation is not fully understood. To investigate admission hyperglycaemia effects on the sympathetic system and long-term prognosis in Takotsubo syndrome (TTS). Methods and results In this multicentre study, we screened 4783 patients undergoing coronary angiography within the first 72 h of hospitalization for suspected acute coronary syndrome between January 2015 and January 2018. All enrolled patients met the InterTAK diagnostic criteria proposed in the European Society of Cardiology position statement for the diagnosis of TTS. Exclusion criteria encompassed patients with previous myocardial infarction, TTS events, or chronic kidney or liver disease. Patients with TTS were divided into those with hyperglycaemia vs. those with normoglycaemia according to a cutoff admission blood glucose value of 140 mg/dl. Sympathetic activity was assayed by blood values of norepinephrine and 123I-labelled metaiodobenzylguanidine (MIBG) cardiac scintigraphy with late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR), performed in 30 patients who did not present any contraindication to the examination, evaluated at baseline and at follow-up. Similarly, systemic inflammatory markers [C-reactive protein (CRP), white blood cell count (leukocytes and neutrophils), tumour necrosis factor-alpha (TNF-a)] and B-type natriuretic peptide (BNP) were assessed. Prespecified endpoints [heart failure (HF) and all-cause deaths] were assessed at long-term follow-up (12 and 24 months). At hospitalization, TTS patients with hyperglycaemia (N = 28) vs. those with normoglycaemia (M = 48) had significantly higher levels of inflammatory markers and B-type natriuretic peptide and lower left ventricular ejection fraction. Admission glucose values were correlated with norepinephrine levels (R2 = 0.39; P = 0.001). In 30 patients with TTS, 123I-MIBG cardiac scintigraphy showed lower late heart-to-mediastinum ratio values in the acute phase (P Conclusions Patients with TTS and hyperglycaemia exhibit sympathetic overactivity with a hyperglycaemia-mediated proinflammatory pathway, which could determine a worse prognosis during follow-up.

Aims In patients with acute myocardial infarction (AMI), hyperglycaemia is a common feature determining a worse prognosis. Few studies have examined the relationship between hyperglycemic status and atrial fibrillation in-hospital stay. To evaluate the relationship between admission hyperglycaemia (aHGL) and occurrence of atrial fibrillation (AF) in-hospital stay in patients with AMI, categorized as myocardial infarction with obstructive coronary artery disease (MIOCA) and myocardial infarction with nonobstructive coronary artery disease (MINOCA). Methods and results Hyperglycaemia was defined as a serum glucose level ≥140 mg/dl at the time of hospital admission. AF was defined as a beat-to-beat variability in cycle length and morphology with irregular fibrillatory waves on surface ECG. Among 2702 patients (32.1% were female, mean age was 70.1 ± 13.4 years), 24.2% were diabetic. Out of 2702 patients, 2457 were MIOCA and 245 (9.1%) were MINOCA patients. At admission, the mean value of serum glucose levels was 146 ± 66 mg/dl. At hospital admission, hyperglycemic status was present in 37.7% of patients and 8.3% presented atrial fibrillation. At hospital admission, atrial fibrillation (aAF) was significantly frequent in hyperglycemic than normoglycaemic patients (11.5% vs. 6.3%, respectively; P Conclusions Hyperglycaemia was an independent predictor of new atrial fibrillation during hospitalization in patients with AMI. Moreover, at hospital admission, patients with hyperglycemic status presented a higher incidence of atrial fibrillation, both in MIOCA and MINOCA subgroups. Further studies are needed to understand the biological mechanisms involved in these associations.

Aims The term acute myocardial infarction (AMI) reflects cell death of cardiac myocytes caused by ischaemia. The Fourth Universal Definition of Myocardial Infarction (UDMI) defined AMI by a typical rise and fall in the level of biochemical markers of myocardial necrosis together with criteria of myocardial ischaemia. However, the prognostic role of each single diagnostic criteria has never been explored. To evaluate the prognostic role of the different diagnostic criteria of AMI according to the Fourth UDMI. Methods and results We enrolled all consecutive patients with AMI admitted from 2016 to 2019. We used a combination of criteria, according to the current ESC guidelines, to meet the diagnosis, namely the detection of an increase and/or decrease of high-sensitivity cardiac troponin I, with at least one value above the 99th percentile of the upper reference limit and at least one of the following: symptoms of ischaemia; ECG changes (new ST-T changes or new left bundle branch block); development of pathological Q waves in the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, in our study evaluated by transthoracic echocardiogram. All-cause mortality and a composite endpoint of all-cause mortality, re-hospitalization for heart failure, and myocardial re-infarction were collected. The predictive value of diagnostic criteria alone and its association were evaluated using Kaplan–Meier survival curves and subsequent Cox-regression analysis to find independent predictors of adverse events. 2386 patients were evaluated. The median follow-up time was 23.3 ± 14.5 months. The total number of events was 703 (29.5%). Kaplan–Meier curves showed that major adverse cardiac events (MACEs) were statistically different depending on the diagnostic criteria of AMI at admission. Particularly, clinical criteria alone showed a better predictive value (P Conclusions Our data suggest that the prognosis is considerably better among patients with a diagnosis of AMI if clinical criteria alone are present at admission. We also demonstrated that clinical criteria are a strong prognostic predictor of good outcomes in patients with AMI. We hypothesize that the absence of electrocardiographic and echocardiographic alterations could indirectly indicate a smaller infarct sizes that contribute to patients’ outcome.

Aims Killip classification is a simple and fast clinical tool for risk stratification in patients with acute coronary syndrome (ACS). However, predictors of high Killip class at admission and its prognostic impact in the clinical contest of myocardial infarction with nonobstructive coronary artery (MINOCA) are still poorly known. To identify the clinical predictors of high Killip class and its potential prognostic role on in-hospital and follow-up outcomes in patients with MINOCA compared to patients with myocardial infarction with obstructive coronary artery (MIOCA). Methods and results We included all consecutive patients with myocardial infarction (MI) undergoing coronary angiogram between 2016 and 2019 at our hospital. According to 2016 ESC Position Paper criteria, we considered as MINOCA all patients with acute MI and with the angiographic conventional cut-off of 1 occurred in 24 patients in MINOCA group and 507 in MIOCA group (17.5% vs. 9.2%, P = 0.001). The KM survival distributions were significantly different across Killip class >1 (P Conclusions Our data suggest that Killip classification performed at the time of admission is a useful clinical marker of a high risk of early and late adverse cardiovascular events even in patients with MINOCA. The predictors of the high Killip class at time of presentation in MIOCA were older age, diabetes, ST elevation, left ventricle ejection fraction, and elevated cardiac troponin. Older age, ST elevation, and diabetes were predictors of high Killip class even in MINOCA, however left ventricle ejection fraction and elevated cardiac troponin did not predict the high Killip class in MINOCA patients. These results could reflect the different pathogenetic myocardial damage in MINOCA and MIOCA populations. Further studies are needed to evaluate these pathological mechanisms.

Aims Although an early invasive strategy (coronary angiography performed Methods and results From 2016 to 2020, all consecutive MINOCA patients diagnosed according to the current ESC diagnostic criteria (angiographic conventional cut-off of Conclusions We demonstrate for the first time that in the MINOCA population the prognosis was not influenced by an early vs. deferred coronary angiography, unlike in AMI patients with obstructive coronary arteries. These results add another piece to the puzzle and pave the way for the initial use of a non-invasive imaging strategy (e.g. Coronary-CT), mostly in patients with NSTEMI and high clinical suspicion of non-obstructive coronary arteries.

Aims Although patients with ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) share similar risk factors and similar pathophysiology, their outcomes differ considerably. The Fourth Universal Definition of Myocardial Infarction (UDMI) defined acute myocardial infarction (AMI) by an acute myocardial injury together with clinical evidence of acute myocardial ischaemia. However, the prognostic role of each single diagnostic criteria has never been explored. To evaluate the prognostic role of the different diagnostic criteria of AMI according to the Fourth UDMI in patients with STEMI vs. NSTEMI. Methods and results We enrolled all consecutive patients with AMI undergoing coronary angiogram at our Centre. We used a combination of criteria, according to the current ESC guidelines, to meet the diagnosis, namely the detection of an increase and/or decrease of high-sensitivity cardiac troponin I, with at least one value above the 99th percentile of the upper reference limit and at least one of the following: symptoms of ischaemia; ECG changes (new ST-T changes or new left bundle branch block); development of pathological Q waves in the ECG; echocardiographic evidence of new loss of viable myocardium, or new regional wall motion abnormality. According to the ECG presentation at admission, patients with AMI were divided into STEMI and NSTEMI subgroups. All-cause mortality and a composite endpoint of all-cause mortality, re-hospitalization for heart failure, and myocardial re-infarction were collected. The predictive value of diagnostic criteria alone and their association was evaluated using Kaplan–Meier survival curves and subsequent Cox-regression analysis to find independent predictors of adverse events. 2345 patients were evaluated (41.6% STEMI and 58.4% NSTEMI). The two groups had similar baseline characteristics. The total number of events was 689 (292 in STEMI group and 397 in NSTEMI group). We found that clinical criteria alone showed a positive predictive value in NSTEMI (P Conclusions Our data suggest that in NSTEMI the prognosis is considerably better if clinical criteria alone are present at admission. We hypothesize that the absence of electrocardiographic and echocardiographic alterations in NSTEMI could indirectly indicate smaller infarct sizes or other causes of acute myocardial injury.

In a letter in this issue of Diabetes Care , Madias suggests that norepinephrine, as mediator of admission hyperglycemia (AH), is an index of increased underlying sympathetic overactivity and/or diabetes comorbidity in patients with takotsubo syndrome (TTS) (1). Indeed, the 28 patients with AH versus the 48 patients without AH had a higher prevalence of diabetes (39.3% vs. 14.6%) (1,2). Notably, AH was a predictor of long-term prognosis in TTS patients (2). Moreover, the patients with AH showed lower left ventricular ejection fraction on admission and discharge and higher B-type natriuretic peptide and inflammatory markers, with the glucose values correlating with serum norepinephrine levels …

Background: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment.Methods: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients.Results: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p < 0.0001), consistently both in 2019 and in 2010.Conclusions: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection.Trial registration number: NCT04412655.

Background Sacubitril/Valsartan (SV) has recently been validated in the therapy of heart failure (HF) with reduced ejection fraction (EF). SV is effective on symptoms and heart remodeling. At the moment the best timing to EF assessment after SV initiation in order to proceed with defibrillator (ICD) implantation, it's unknown. Purpose Evaluate the timing of improvement of EF after SV initiation in patients (pts) with systolic HF, candidates to primary prevention ICD implantation. Methods We enrolled all consecutive pts candidates to primary prevention ICD implantation that underwent SV initiation from February 2018. We evaluated clinical and echo follow up (Fup). Results have been analyzed with paired T-test). Results The study involved 61 pts (mean age 67±10 years, 71% male, ischemic cardiopathy 44%, mean time from diagnosis 31 months) with mean EF at enrollment 30±5% (ED vol 94 ml/m2, ES vol 64 ml/m2, severe MR 21%) and mean NYHA 3±0.6. After a mean Fup of 6 months mean EF increased to 37±7% (ED vol 80 ml/m2, ES vol 51 ml/m2, severe MR 8%, p Conclusions After SV initiation in systolic HF, heart remodeling is already evident at 3 months Fup and better appreciable at 6 months Fup. Little non significant further EF improvement could be seen later. In our study best timing to decide for primary prevention ICD is likely between 3 and 6 months after SV initiation. Funding Acknowledgement Type of funding sources: None. Figure 1