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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.

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 A higher risk of death and major cardiovascular events, including Heart Failure (HF), after a Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) has been described. In particular, HF has a negative impact not only on survival but also on quality of life. In this context, strategies to identify subjects with a greater risk of developing HF are needed. Aims To assess the incidence and predictors of HF developing subsequently a MINOCA. Methods 461 subjects with suspected MINOCA from 2016 to 2021 were assessed. Acute myocarditis, Takotsubo syndromes, cardiomyopathies and patients with incomplete data were excluded. The final cohort consisted of 188 patients with a confirmed MINOCA diagnosis. After a mean follow-up of 36±14.8 months, 20 patients (10.6%) had hospital readmission for HF. Demographic, clinical, laboratory, and instrumental data were collected and analyzed. Results None among demographic characteristics, cardiovascular risk factors or comorbidities showed correlation with HF occurrences. Paroxysmal or permanent atrial fibrillation was more frequent among patients who developed HF (p .005), such as ST-elevation at onset (p .001). Higher glycemia at admission correlated with HF (p .012). In this regard, hyperglycemia could act as a direct toxic agent or as an indirect marker of a greater stress response. Cardiac troponin I (cTnI) at peak, but not first cTnI measurement, was significantly higher in patients who developed HF (p Conclusion In our cohort of patients with MINOCA, several clinical, laboratory and echocardiographic characteristics correlated with a higher frequency of HF occurrences. Moreover, a broader extent of cardiac damage, as testified by cTnI, wall motion abnormalities, reduced EF and transmural LGE, could predict HF development. Further studies to establish adequate follow-up programs and therapy to prevent HF progression in these patients are needed.

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 Differential diagnosis of cardiac masses represents a challenging issue with important implications for therapeutic management and patient's prognosis. Cardiac Magnetic Resonance (CMR) is a non-invasive imaging technique used to characterize morphologic and functional features of masses. Integration of these information can lead to an accurate diagnosis. Purpose To evaluate the diagnostic role of CMR in defining the nature of cardiac masses. Methods One hundred-fourteen patients with cardiac masses evaluated with CMR were enrolled. All masses had histological certainty. CMR sequences allowed a qualitative morphologic description as well as tissue characterization. Evaluation of masses morphology included localization, size and borders assessment, detection of potential multiple lesions and pericardial effusion. Tissue characterization resulted from an estimation of contrast enhancement - early gadolinium enhancement (EGE) and late gadolinium enhancement (LGE) sequences - and tissue homogeneity in T1 and T2 weighted acquisitions. The descriptive analysis was carried out by comparing benign vs malignant lesions as well as dividing patients into 4 subgroups: primitive benign tumours, primitive malignant tumours, metastatic tumours and pseudotumours. Results The descriptive analysis of morphologic features showed that diameter > 50 mm, invasion of surrounding planes, irregular margins and presence of pericardial effusion were able to predict malignancy (p < 0.001). As for tissue characteristics, heterogeneous signal intensity - independently from T1 and T2 weighted acquisitions - and EGE were more common in malignant lesions (p Furthermore, using classification and regression tree (CART) analysis, we developed an algorithm to differentiate masses: invasion of surrounding planes was a common characteristic of malignancy and identifies itself malignant tumours. In the absence of invasive features, gadolinium enhancement was evaluated: the lack of contrast uptake was able to increase the probability of a pseudotumour. Last step of decision algorithm included ejection fraction assessment to discriminate between benign tumours: a reduced ejection fraction increased the probability of pseudotumour diagnosis and reduced the probability of primary benign tumour diagnosis. Conclusions Cardiac magnetic resonance is a very powerful diagnostic tool for differential diagnosis of cardiac masses as it correctly addresses malignancy. Furthermore, an accurate evaluation of the several CMR features may discriminate primary benign masses and pseudotumours.

Background Cardiac masses (CM) are an extremely heterogeneous clinical scenario, including benign and malignant neoformations. After a first echocardiographic assessment, Cardiac Computed Tomography (CCT) together with Cardiac Magnetic Resonance (CMR) and 18-Fluorodeoxyglucose Positron Emission Tomography (18-FDG-PET) represent second-line and third-line imaging techniques to determine the nature of the mass. However, data regarding their diagnostic performance and a standardized imaging algorithm are lacking. Purpose To evaluate the different roles of CCT, CMR, and PET in defining the nature of CMs and to propose an evidence-based, stepwise, diagnostic approach. Materials and methods Out of 312 patients with suspected mass from January 2000 and August 2022, we enrolled 87 patients who underwent CCT, CMR and 18-FDG-PET within a month from the initial evaluation. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. For each imaging technique, we identified a model with the strongest predictors of malignancy at multivariate analysis and evaluated their ability to discriminate between benign and malignant neoformations. A multiple model with forwarding selection was performed to identify the strongest predictors of malignancy at CCT, CMR and 18-FDG-PET. Results CCT model included 4 variables (irregular margins, mass dimension, invasiveness and not-hypodense lesion) with an Area Under the Curve (AUC) of 0.972, 95% Confidence Interval (CI) 0.94-1.0; CMR model included 3 parameters (invasiveness, pericardial effusion and irregular margins, AUC 0.976 with 95% CI 0.95-1.0); PET model included only cardiac maximum Standardized Uptake Value (SUVmax), with an AUC 0.87 (95% IC 0.74-0.971). When implemented with SUVmax, CCT and CMR models showed only a slight improvement in their discrimination ability (AUC 0.975 and 0.986, respectively). No statistical difference was observed between CCT and CMR models regarding their discrimination ability (AUC 0.972 vs 0.976, p=0.26). However, on a multiple model with forwarding selection evaluating CCT, CMR and PET variables, only the 3 MR parameters remained significant predictors of malignancy. Conclusion After a first echocardiographic assessment, the application of the CMR model may be the most accurate second-level investigation to discriminate between benign and malignant lesions. When CMR is not available, or the patient has contraindications to CMR, the CCT model performs similarly, and 18-FDG-PET provides a negligible advantage.

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 Cardiac masses (CM) are an extremely heterogeneous clinical entity, including benign and malignant neoformations. 2D Echocardiography is, nowadays, the first-line approach to define nature and management of CM. Purpose The purpose of our study was to identify the echocardiographic predictors of malignancy and create a multiparametric score to further increase the diagnostic yield and accurately suggest the nature of CM. Materials and methods 249 consecutive patients undergoing a complete echocardiographic assessment for suspected cardiac mass in our center were enrolled from January 2004 to December 2020. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. Logistic regression was performed to evaluate the ability of echocardiography to discriminate benign versus malignant masses. Results A scoring system was developed in a derivation cohort of 178 (70%) and validated in 71 (30%) patients. A weighted score [Diagnostic Echocardiographic Mass (DEM) Score] ranging from 0 to 9 was obtained from 6 variables: infiltration, polylobate mass, moderate-severe pericardial effusion, inhomogeneity, sessile and non-left localization. The AUC for the score was 0.965 (95% CI 0.938-0.993). In a logistic regression analysis using the DEM score as a predictor, the likelihood of malignancy increased more than 4 times for a 1-unit increase of the score (OR=4.468; 95% CI 2.733-7.304). The prognostic validity of the score was confirmed by its ability to predict survival during follow-up (median time of 31 months). Conclusions The application of a multiparametric echocardiographic score in the approach to CM accurately predicts mass malignancy, thereby reducing the need for second-level investigations, and minimizing the diagnostic delay in such a complex clinical scenario.

Background Periprocedural myocardial damage and contrast-induced acute kidney injury (CI-AKI) are frequent complications of percutaneous coronary intervention (PCI) and impact prognosis. The possible associations and the prognostic role of these peri-procedural complications are still not well understood. Purpose To evaluate predictors and prognostic role of CI-AKI in patients with NSTEMI and the relationship between CI-AKI and periprocedural myocardial damage. Methods Patients with NSTEMI undergoing coronary angiography within 72 hours were enrolled from January 2016 to September 2021. To detect post-PCI acute myocardial damage in this setting of NSTEMI patients, we included only those with stable (≤ 20% variation) or falling pre-procedure baseline cardiac troponin (cTn) values. Serum cTnI were measured at baseline and at 3-6-12 hours after PCI in all patients. Periprocedural myocardial damage was evaluated according to postprocedural hsTnI criteria provided by most recent consensus documents. Renal injury was documented when absolute serume creatinine increased of ≥ 0.3 mg/dL or ≥ 50% within 72 hours or urine output reduced to ≤ 0.5 mL/Kg/hour for at least 6 hours. Results We enrolled 878 patients with NSTEMI undergoing PCI and with pre procedure stable cTn levels. 53 patients suffered from AKI post contrast and among these 8 patients exhibited myocardial periprocedural injury and 20 patients had periprocedural myocardial infarction according to European Society of Cardiology guidelines. Myocardial periprocedural damage occurred more frequently in the CI- AKI group compared to non-CI-AKI group (52% vs 38%, p = 0.01). Patients who experienced CI-AKI were significantly older (mean age 86 ± 4) and had more frequently cardiovascular risk factors such as diabetes (p < 0.001) and hypertension (p = 0.006), compared to non-CI-AKI group. Moreover NSTEMI patients with CI-AKI were more often on beta-blockers (p= 0.001) and statins (p < 0.001) and exhibited more frequently at admission ST-T segment (p < 0.000) and wall motion alterations at echocardiography evaluation (p = 0.004).Regarding intra-hospital outcomes, CI-AKI population experienced more frequently reinfarction (p = 0.02) and arrhythmias (p < 0.000) compared to others . Surprisingly, the multivariate logistic regression showed that the stronger predictor of CI-AKI was periprocedural myocardial infarction (p < 0.001). Finally, at 3 years of follow-up, in patients with CI-AKI there was more incidence of all-cause mortality (p = 0.001) and the composite of all-cause death, re-acute myocardial infarction and hospitalization for heart failure (p = 0.05) compared to non-CI-AKI group. Conclusion In NSTEMI patients, contrast-induced acute kidney injury was associated with majors adverse events, both intra-hospital and at long-term follow-up. Subjects who experienced acute kidney injury were older, had more comorbidities and had a worse clinical and instrumental profile at admission. CI-AKI was also associated with peri-procedural acute myocardial injury and infarction. More studies are needed to understand the patophysiological relations between these to post-PCI complications to improve their management.

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 Cardiac masses (CMs) are a diagnostic dilemma in clinical practice and require multimodality imaging to assess malignancy, which is essential to guide the proper treatment. Aim To define diagnostic accuracy and agreement between echocardiographic features and second-level imaging techniques (cardiac computed tomography – CCT or cardiac magnetic resonance – CMR) in patients with CMs. Methods All consecutive patients with histologically confirmed cardiac masses from January 2004 to December 2020, undergoing CCT and/or CMR after echocardiographic assessment were enrolled. Six echocardiographic variables, namely infiltration, polylobate mass, moderate-severe pericardial effusion, inhomogeneity, sessile and non-left localization, were used to predict malignancy. Patients with more than 3 of these features were considered at higher risk of malignancy. For the patients before 2017, the choice of which second-level imaging to perform was up to the clinical cardiologist. Since 2017, the indication has been the result of a multidisciplinary discussion by the Heart Team. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. The echo-vs-CCT agreement and echo-vs-CMR agreement were evaluated. Accuracy indicators (sensitivity, specificity, PPV, NPV, Cohen's Kappa coefficient) were calculated by standard formulas. Results Out of 249 patients with histologically confirmed CM, 138 underwent a CCT and 112 a CMR, after the standard echocardiographic assessment. A complete agreement between the echocardiographic assignment (using the cut-off of 3 parameters as a marker for malignancy) and CCT was reached in 104 out of 138 cases (75.4%), ranging from 85.1 to 70.3% for benign and malignant cardiac masses, respectively. On the other side, the agreement between the echocardiographic assignment and CMR report was in 93 out of 112 cases (83%), ranging from 88.7 to 82% for benign and malignant cardiac masses. The agreement between these imaging techniques expressed as Cohen's κ was higher for echocardiography versus CMR (k=0.73), compared to echocardiography versus CCT (k=0.61). These results were also confirmed by the higher diagnostic accuracy of echocardiography versus CMR compared to echocardiography versus CCT (87% vs 80%), with best values of sensitivity, and specificity, denoting good reliability between the first 2 techniques. Conclusions A multimodal imaging approach is mandatory in the diagnostic work-up of CMs. The CMR, after a standard echocardiographic assessment, turned out to be the most accurate second-level investigation to discriminate between benign and malignant masses. However, when CMR is not available or the patient has a contraindication, the CCT could still be reliable.

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.

The term cardiac mass refers to benign or malignant cardiac tumors and cardiac metastases but also to pseudotumors, which is a heterogeneous group consisting of thrombi, vegetations and normal variant structures. While primitive cardiac tumors are rare, metastases and pseudotumors are relatively common. The non-invasive diagnostic approach has not been well established in the literature yet. The first-line non-invasive approach consists of echocardiography, which provides good diagnostic accuracy for masses like thrombi, vegetations and some tumors (mainly myxoma and fibroelastoma). In contrast, for other masses, it does not provide information about the potential malignancy because of poor tissue characterization. Second-line (cardiac computed tomography and cardiac magnetic resonance) or third-line (positron emission tomography-computed tomography) evaluations have been validated in the diagnostic approach to cardiac masses by many studies. In fact, a comprehensive diagnostic approach may establish the diagnosis of malignancy without histological report, which is pivotal for the subsequent therapeutic strategy.The aim of this narrative review is to describe the commonly available non-invasive diagnostic techniques for cardiac masses, their potential and limitations and to suggest a diagnostic pathway for common practice.

The echocardiographic parameters required for a comprehensive assessment of cardiac masses (CMs) are still largely unknown.To identify and integrate the echocardiographic features of CMs that can accurately predict malignancy.Observational cohort study of 286 consecutive patients who underwent a standard echocardiographic assessment for suspected cardiac mass in Bologna University Hospital between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. Logistic and multivariable regression analysis was performed to confirm the ability of 6 echocardiographic parameters to discriminate malignant from benign masses. The unweighted count of these parameters was used as a numerical score, ranging from 0 to 6, with a cut-off of3 balancing sensitivity and specificity with respect to the histological diagnosis of malignancy. Classification tree analysis (CTA) was used to determine the ability of echocardiographic parameters to discriminate sub-groups of patients with a differential risk of malignancy.Benign masses were more frequently pedunculated, mobile, and adherent to the interatrial septum (p0.001). Malignant masses showed a greater diameter and exhibited a higher frequency of irregular margins, an inhomogeneous appearance, sessile implantation, polylobate shape, and pericardial effusion (p0.001). Infiltration, moderate-severe pericardial effusion, non-left localization, sessile, polylobate, and inhomogeneity were confirmed to be independent predictors of malignancy in both univariate and multivariable models. The predictive ability of the unweighted count of3 was very high (0.90) and similar to that of the previously published weighted score. The CTA generated an algorithm in which infiltration was the best discriminator of malignancy, followed by non-left localization and sessile shape. The percentage correctly classified by the CTA as malignant was 87.5%. Agreement between observer readings and cardiac mass histology ranged between 85.1-91.5%. The presence of at least 3 echocardiographic parameters was associated with a lower survival.In the approach to CM, some echocardiographic parameters can serve as markers to accurately predict malignancy, thereby informing the need for second-level investigations and minimizing the diagnostic delay in such a complex clinical scenario.

Background. Cardiac masses (CM) represent a heterogeneous clinical scenario, and sex-related differences of these patients remain to be established. Purpose: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. Material and Methods. The study cohort included 321 consecutive patients with CM enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause mortality at follow-up was evaluated. Multivariable regression analysis assessed the potential prognostic disparities between men and women. Results. Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p = 0.02) than men. Regarding CM histotypes, females were affected by benign masses more frequently (with cardiac myxoma above all), while metastatic tumours were more common in men (p < 0.001). At presentation, peripheral embolism occurred predominantly in women (p = 0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, in multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignant tumours and peripheral embolism were independent predictors of mortality. Conclusions. In a large cohort of cardiac masses, a significant sex-related difference in histotype prevalence was found: Benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex did not influence prognosis in benign and malignant masses.

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 Cancer is increasingly recognized as strictly related to atrial fibrillation (AF). In patients with AF, the relationship between cancer and cardioembolic or bleeding risk during oral anticoagulant therapy is unknown. To assess the bleeding and ischaemic burden of a baseline or newly diagnosed cancer in patients treated with direct oral anticoagulants (DOACs) for non-valvular AF (NVAF). Methods and results All consecutive patients treated with DOACs were enrolled among those with new-onset AF and indication for oral anticoagulant between January 2017 and March 2019. During follow-up, bleeding events, newly diagnosed primitive or metastatic malignancy and major cardiovascular events (MACEs) were evaluated. At baseline, CHA2DS2-VASc, HAS-BLED, ATRIA, and ORBIT scores were used to assess the haemorrhagic and ischaemic risk. Major bleedings (MBs) were defined according to the ISTH definition. Anaemia was defined as haemoglobin levels below 11 g/dl in women and 12 mg/dl in men. 1258 patients constituted the study population and followed for a mean time of 21.6 ± 9.5 months. Overall, 66 patients (5.2%) were affected by malignant neoplasia at baseline, whereas 59 (4.7%) were diagnosed with a malignancy during follow-up. Among baseline characteristics, anaemia was associated with cancer at enrolment (43.9% vs. 22.5%, P Conclusions Bleeding risk assessment is an ongoing challenge in patients with NVAF on DOACs. During follow-up, newly diagnosed primitive or metastatic cancer is a strong predictor of bleeding regardless of baseline haemorrhagic risk assessment. In contrast, such association is not observed with malignancy at baseline. A proper diagnosis and treatment could therefore decrease cancer-related bleeding risk. On the contrary, our study shows that cancer is not an ischaemic risk modifier, either diagnosed at baseline or follow-up.

SARS-CoV-2 vaccination is associated with potential side effects, particularly following second vaccine dose. Recent case series have reported a potential association between SARS-CoV-2 vaccination and acute myocarditis, predominantly in young males. We hereby describe a previously healthy 17-year-old man, with no past cardiac history, who presented to the emergency department with persistent chest pain and fever (up to 38 °C). The patient had received the first dose of Cominarty (BioNTech/Pfizer) vaccine 10 days before symptom onset and reported flu-like symptoms and conjunctivitis involving both eyes one week before administration of the first vaccine dose. On that occasion, no COVID test was performed and the patient was treated with anti-inflammatory drugs and antibiotic eye drops. On admission, laboratory tests were performed (Troponin-I Δ 19 500–23 270 ng/l. CRP 23 mg/dl, ESR 43 s, WBC 17 570 cell/mm3) as well as COVID-19 PCR, Serological tests and Autoimmune disorders panel all resulting negative. CT coronary angiogram did not reveal any spontaneous coronary artery dissection or anomalous origin of coronary arteries and Calcium Score was 0. Transthoracic echocardiography showed a depressed LVEF (36%) with concomitant posterior and inferior wall as well as posterior and anterior basal interventricular septum hypokinesia. Endomyocardial biopsy revealed multifocal lymphocytic myocarditis with sub-endomyocardial and interstitial fibrosis. CMR was also performed (1-week after presentation) demonstrating mildly depressed systolic function (LVEF 47%), with hypokinesia of the posterior and inferior wall, increased signal intensity on T2 maps (58 ms, n.v.

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.