Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking. METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs. RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 µg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 µg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001). CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

Impact of coronary CT image quality on the accuracy of the FFRCT Planner.

OBJECTIVE: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFRCT Planner) across different levels of image quality. MATERIALS AND METHODS: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFRCT Planner. Patient- and technical-related factors that could affect the FFRCT Planner accuracy were evaluated. The FFRCT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR. RESULTS: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFRCT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFRCT Planner was accurate across different levels of image quality with a mean difference between FFRCT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFRCT Planner (95%CI - 0.06 to - 0.001, p = 0.040). CONCLUSION: The FFRCT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality. CLINICAL RELEVANCE STATEMENT: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFRCT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFRCT Planner. KEY POINTS: • The fractional flow reserve derived from coronary CT angiography (FFRCT) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFRCT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFRCT Planner could potentially enhance and guide the invasive treatment.

Targeting high glucose-induced epigenetic modifications at cardiac level: the role of SGLT2 and SGLT2 inhibitors.

BACKGROUND: Sodium-glucose co-transporters (SGLT) inhibitors (SGLT2i) showed many beneficial effects at the cardiovascular level. Several mechanisms of action have been identified. However, no data on their capability to act via epigenetic mechanisms were reported. Therefore, this study aimed to investigate the ability of SGLT2 inhibitors (SGLT2i) to induce protective effects at the cardiovascular level by acting on DNA methylation. METHODS: To better clarify this issue, the effects of empagliflozin (EMPA) on hyperglycemia-induced epigenetic modifications were evaluated in human ventricular cardiac myoblasts AC16 exposed to hyperglycemia for 7 days. Therefore, the effects of EMPA on DNA methylation of NF-κB, SOD2, and IL-6 genes in AC16 exposed to high glucose were analyzed by pyrosequencing-based methylation analysis. Modifications of gene expression and DNA methylation of NF-κB and SOD2 were confirmed in response to a transient SGLT2 gene silencing in the same cellular model. Moreover, chromatin immunoprecipitation followed by quantitative PCR was performed to evaluate the occupancy of TET2 across the investigated regions of NF-κB and SOD2 promoters. RESULTS: Seven days of high glucose treatment induced significant demethylation in the promoter regions of NF-kB and SOD2 with a consequent high level in mRNA expression of both genes. The observed DNA demethylation was mediated by increased TET2 expression and binding to the CpGs island in the promoter regions of analyzed genes. Indeed, EMPA prevented the HG-induced demethylation changes by reducing TET2 binding to the investigated promoter region and counteracted the altered gene expression. The transient SGLT2 gene silencing prevented the DNA demethylation observed in promoter regions, thus suggesting a role of SGLT2 as a potential target of the anti-inflammatory and antioxidant effect of EMPA in cardiomyocytes. CONCLUSIONS: In conclusion, our results demonstrated that EMPA, mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects.

Relationship between coronary volume, myocardial mass, and post-PCI fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) carries prognostic information. Yet, myocardial mass subtended by a stenosis influences FFR. We hypothesized that a smaller coronary lumen volume and a large myocardial mass might be associated with lower post-PCI FFR. AIM: We sought to assess the relationship between vessel volume, myocardial mass, and post-PCI FFR. METHODS: This was a subanalysis with an international prospective study of patients with significant lesions (FFR ≤ 0.80) undergoing PCI. Territory-specific myocardial mass was calculated from coronary computed tomography angiography (CCTA) using the Voronoi's algorithm. Vessel volume was extracted from quantitative CCTA analysis. Resting full-cycle ratio (RFR) and FFR were measured before and after PCI. We assessed the association between coronary lumen volume (V) and its related myocardial mass (M), and the percent of total myocardial mass (%M) with post-PCI FFR. RESULTS: We studied 120 patients (123 vessels: 94 left anterior descending arteries, 13 left Circumflex arteries, 16 right coronary arteries). Mean vessel-specific mass was 61 ± 23.1 g (%M 39.6 ± 11.7%). The mean post-PCI FFR was 0.88 ± 0.06 FFR units. Post-PCI FFR values were lower in vessels subtending higher mass (0.87 ± 0.05 vs. 0.89 ± 0.07, p = 0.047), and with lower V/M ratio (0.87 ± 0.06 vs. 0.89 ± 0.07, p = 0.02). V/M ratio correlated significantly with post-PCI RFR and FFR (RFR r = 0.37, 95% CI: 0.21-0.52, p < 0.001 and FFR r = 0.41, 95% CI: 0.26-0.55, p < 0.001). CONCLUSION: Post-PCI RFR and FFR are associated with the subtended myocardial mass and the coronary volume to mass ratio. Vessels with higher mass and lower V/M ratio have lower post-PCI RFR and FFR.

Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry.

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.

Ambulatory pulmonary vein isolation workflow using the Perclose ProglideTM suture-mediated vascular closure device: the PRO-PVI study.

AIMS: The leading reason for delayed discharge after pulmonary vein isolation (PVI) is vascular complications. This study aimed to evaluate feasibility, safety, and efficacy of the Perclose Proglide™ suture-mediated vascular closure in ambulatory PVI, report complications, patient satisfaction, and cost of this approach. METHODS AND RESULTS: Patients scheduled for PVI were enrolled prospectively in an observational design. Feasibility was assessed as % discharged the day of procedure. Efficacy was analysed as acute access site closure rate, time to reach haemostasis, time to ambulate, and time to discharge. Safety analysis consisted of vascular complications at 30 days. Cost analysis was reported using direct and indirect cost analysis. A 1:1 propensity matched control cohort was used for comparing time to discharge to usual workflow. Of 50 enrolled patients, 96% were discharged on the same day. 100% of devices were successfully deployed. Immediate (<1 min) haemostasis was reached in 30 patients (62.5%). Mean time to discharge was 5:48 ± 1:03 h (vs. 10:16 ± 1:21 h in the matched cohort, P < 0.0001). Patients reported high level of satisfaction with the post-operative time. No major vascular complication occurred. Cost analysis showed a neutral impact compared to the standard of care. CONCLUSION: The use of the closure device for femoral venous access after PVI led to safe discharge of patients within 6 h from the intervention in 96% of the population. This approach could minimize the overcrowding of healthcare facilities. The gain in post-operative recovery time improved patients' satisfaction and balanced the economic cost of the device.

Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry.

BACKGROUND: The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents. METHODS: In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels. RESULTS: The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275-0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status. CONCLUSIONS: Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease. TRIAL REGISTRATION: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT. CLINICALTRIALS: gov Identifier: NCT05261867.

Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts.

BACKGROUND: High glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control. OBJECTIVES: We investigated the possible effects of GlycACE2 on the anti-remodeling pathways of the RAS inhibitors by evaluating the levels of Angiotensin (Ang) 1-9, Ang 1-7, and Mas receptor (MasR), Nuclear-factor of activated T-cells (NFAT), and fibrosis in human hearts. METHODS: We evaluated 197 first HTX recipients (107 non-T2DM, 90 T2DM). All patients were treated with angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) at hospital discharge. Patients underwent clinical evaluation (metabolic status, echocardiography, coronary CT-angiography, and endomyocardial biopsies). Biopsies were used to evaluate ACE2, GlycACE2, Ang 1-9, Ang 1-7, MasR, NAFT, and fibrosis. RESULTS: GlycACE2 was higher in T2DM compared tonon-T2DM cardiomyocytes. Moreover, reduced expressions of Ang 1-9, Ang 1-7, and MasR were observed, suggesting impaired effects of RAS-inhibition in diabetic hearts. Accordingly, biopsies from T2DM recipients showed higher fibrosis than those from non-T2DM recipients. Notably, the expression of GlycACE2 in heart biopsies was strongly dependent on glycemic control, as reflected by the correlation between mean plasma HbA1c, evaluated quarterly during the 12-month follow-up, and GlycACE2 expression. CONCLUSION: Poor glycemic control, favoring GlycACE2, may attenuate the cardioprotective effects of RAS-inhibition. However, the achievement of tight glycemic control normalizes the anti-remodeling effects of RAS-inhibition. TRIAL REGISTRATION: https://clinicaltrials.gov/ NCT03546062.

The usefulness of speckle tracking echocardiography in identifying subclinical myocardial dysfunction in young adults recovered from mild COVID-19.

BACKGROUND: Myocardial strain assessed with speckle tracking echocardiography is a sensitive marker of cardiac dysfunction. Both left-ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were affected by severe SARS-CoV-2 infection. However, data about cardiac involvement in patients with asymptomatic/mild Coronavirus disease-19 (COVID-19) is still lacking. AIM: To evaluate myocardial function using LV-GLS and RV-LS in patients with previous asymptomatic/mild COVID-19. METHODS: Forty young adults without previously known comorbidities/cardiovascular risk factors and with a confirmed diagnosis of asymptomatic or paucisymptomatic SARS-CoV-2 infection were retrospectively included. A 2D-transthoracic echocardiogram with speckle tracking analysis was performed at least 3 months after the diagnosis. Forty healthy subjects, matched for age, sex, and body surface area in a 1:1 ratio were used as the control group. RESULTS: Left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and RV-LS were comparable between the two groups. LV-GLS was significantly lower in the cases compared to the control group (-22.7 ± 1.6% vs. -25.7 ± 2.3%; p < .001). Moreover, the prevalence of regional peak systolic strain below -16% in at least two segments was three times higher in patients with previous COVID-19 compared to controls (30% vs. 10%, p = .02). In multivariable logistic regression, previous COVID-19 infection was independently associated with reduced LV-GLS values (p < .001). CONCLUSION: SARS-CoV-2 infection may affect left ventricular deformation in 30% of young adult patients despite an asymptomatic or only mildly symptomatic acute illness. Speckle-tracking echocardiography could help early identification of patients with subclinical cardiac involvement, with potential repercussions on risk stratification and management.

First report of totally robotically assisted hybrid coronary artery revascularization combining RE-MIDCAB and R-PCI: Case report.

A 62-year-old man presents to the Cardiology Department with a history of angina on exertion. Invasive coronary angiography revealed a severe three vessels coronary artery disease. The "Hybrid Heart Team" successfully performed a fully robotically assisted hybrid revascularization combining robotically enhanced-minimally invasive direct coronary artery bypass on the left anterior descending (LAD) and robotically assisted percutaneous coronary intervention on non-LAD lesions.

Hyperglycemia, inflammatory response and infarct size in obstructive acute myocardial infarction and MINOCA.

BACKGROUND: Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA. METHODS: Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF). RESULTS: The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients-obs-AMI and MINOCA-NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI (p < 0.001), a larger LVEDV (p = 0.003) and a lower LVEF (p < 0.001) compared to normoglycemic ones. Conversely, MINOCA patients showed a trivial myocardial damage, irrespective of admission glucose levels. CONCLUSIONS: Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.

Impact of admission hyperglycemia on short and long-term prognosis in acute myocardial infarction: MINOCA versus MIOCA.

BACKGROUND: The prognostic role of hyperglycemia in patients with myocardial infarction and obstructive coronary arteries (MIOCA) is acknowledged, while data on non-obstructive coronary arteries (MINOCA) are still lacking. Recently, we demonstrated that admission stress-hyperglycemia (aHGL) was associated with a larger infarct size and inflammatory response in MIOCA, while no differences were observed in MINOCA. We aim to investigate the impact of aHGL on short and long-term outcomes in MIOCA and MINOCA patients. METHODS: Multicenter, population-based, cohort study of the prospective registry, designed to evaluate the prognostic information of patients admitted with acute myocardial infarction to S. Orsola-Malpighi and Maggiore Hospitals of Bologna metropolitan area. Among 2704 patients enrolled from 2016 to 2020, 2431 patients were classified according to the presence of aHGL (defined as admission glucose level ≥ 140 mg/dL) and AMI phenotype (MIOCA/MINOCA): no-aHGL (n = 1321), aHGL (n = 877) in MIOCA and no-aHGL (n = 195), aHGL (n = 38) in MINOCA. Short-term outcomes included in-hospital death and arrhythmias. Long-term outcomes were all-cause and cardiovascular mortality. RESULTS: aHGL was associated with a higher in-hospital arrhythmic burden in MINOCA and MIOCA, with increased in-hospital mortality only in MIOCA. After adjusting for age, gender, hypertension, Killip class and AMI phenotypes, aHGL predicted higher in-hospital mortality in non-diabetic (HR = 4.2; 95% CI 1.9-9.5, p = 0.001) and diabetic patients (HR = 3.5, 95% CI 1.5-8.2, p = 0.003). During long-term follow-up, aHGL was associated with 2-fold increased mortality in MIOCA and a 4-fold increase in MINOCA (p = 0.032 and p = 0.016). Kaplan Meier 3-year survival of non-hyperglycemic patients was greater than in aHGL patients for both groups. No differences in survival were found between hyperglycemic MIOCA and MINOCA patients. After adjusting for age, gender, hypertension, smoking, LVEF, STEMI/NSTEMI and AMI phenotypes (MIOCA/MINOCA), aHGL predicted higher long-term mortality. CONCLUSIONS: aHGL was identified as a strong predictor of adverse short- and long-term outcomes in both MIOCA and MINOCA, regardless of diabetes. aHGL should be considered a high-risk prognostic marker in all AMI patients, independently of the underlying coronary anatomy. Trial registration data were part of the ongoing observational study AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation. ClinicalTrials.gov Identifier: NCT03883711.

SARS-COV-2 colonizes coronary thrombus and impairs heart microcirculation bed in asymptomatic SARS-CoV-2 positive subjects with acute myocardial infarction.

BACKGROUND: The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons has been equal to that of symptomatic patients. On the other hand, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. Therefore, we evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial blush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. METHODS: This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization. RESULTS: In the study population, ASAP vs. SANE showed a significant greater use of GP IIb/IIIa inhibitors and of heparin (p < 0.05), and a higher thrombus grade 5 and thrombus dimensions (p < 0.05). Interestingly, ASAP vs. SANE patients had lower MBG and left ventricular function (p < 0.001), and 39 (84.9%) of ASAP patients had thrombus specimens positive for SARS-COV-2. After PPCI, a MBG 2-3 was present in only 26.1% of ASAP vs. 97.7% of SANE STEMI patients (p < 0.001). Notably, death and nonfatal AMI were higher in ASAP vs. SANE patients (p < 0.05). Finally, in ASAP STEMI patients the thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (p < 0.005). Thus, multiple logistic regression analyses evidenced that thrombus SARS-CoV-2 infection and dimension were significant predictors of poorer MBG in STEMI patients. Intriguingly, in ASAP patients the female vs. male had higher thrombus viral load (15.53 ± 4.5 vs. 30.25 ± 5.51 CT; p < 0.001), and thrombus dimension (4.62 ± 0.44 vs 4.00 ± 1.28 mm2; p < 0.001). ASAP vs. SANE patients had a significantly lower in-hospital survival for MACE following PPCI (p < 0.001). CONCLUSIONS: In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG. These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.

Effect of SAcubitril/Valsartan on left vEntricular ejection fraction and on the potential indication for Implantable Cardioverter Defibrillator in primary prevention: the SAVE-ICD study.

PURPOSE: Sacubitril/valsartan has been associated with a positive reverse left ventricular remodelling in patients with heart failure with reduced ejection fraction (HFrEF). These patients may also benefit from an ICD implant. We aimed to assess EF improvement after 6 months of treatment with sacubitril/valsartan, evaluating when ICD as primary prevention was no longer indicated. METHODS: Multicentre, observational, prospective study enrolling all consecutive patients with HFrEF and EF ≤ 35% with an ICD as primary prevention and starting treatment with sacubitril/valsartan (NCT03935087). Resynchronization therapy and patients experiencing appropriate ICD therapies before sacubitril/valsartan were excluded. RESULTS: Two-hundred-and-thirty patients were enrolled (73.9% males, mean age 64.3 ± 12.1 years) After 6 months of treatment, a reduction in left ventricular end-diastolic and end-systolic volumes was noted and LVEF increased from 28.3 ± 5.6% to 32.2 ± 6.5% (p < 0.001). At 6 months, a non-ischemic aetiology of cardiomyopathy and a final dose of sacubitril/valsartan > 24/26 mg twice daily were associated with a higher probability of an absolute increase of > 5% in LVEF. A total of 5.3% of primary prevention patients still had an arrhythmic event in the first 6 months after treatment with sacubitril/valsartan started. CONCLUSIONS: Sacubitril/valsartan improves systolic function in HFrEF, mainly due to reverse left ventricular remodelling. Improvement in EF after 6 months of treatment could help prevent ICD implantation in nearly one out of four patients, with important clinical and economic implications. However, the risk of sudden cardiac death in this recovered HFrEF population has not been thoroughly studied, and the present data should be interpreted only as hypothesis-generating.

The value of ECG changes in risk stratification of COVID-19 patients.

BACKGROUND: There is growing evidence of cardiac injury in COVID-19. Our purpose was to assess the prognostic value of serial electrocardiograms in COVID-19 patients. METHODS: We evaluated 269 consecutive patients admitted to our center with confirmed SARS-CoV-2 infection. ECGs available at admission and after 1 week from hospitalization were assessed. We evaluated the correlation between ECGs findings and major adverse events (MAE) as the composite of intra-hospital all-cause mortality or need for invasive mechanical ventilation. Abnormal ECGs were defined if primary ST-T segment alterations, left ventricular hypertrophy, tachy or bradyarrhythmias and any new AV, bundle blocks or significant morphology alterations (e.g., new Q pathological waves) were present. RESULTS: Abnormal ECG at admission (106/216) and elevated baseline troponin values were more common in patients who developed MAE (p = .04 and p = .02, respectively). Concerning ECGs recorded after 7 days (159), abnormal findings were reported in 53.5% of patients and they were more frequent in those with MAE (p = .001). Among abnormal ECGs, ischemic alterations and left ventricular hypertrophy were significantly associated with a higher MAE rate. The multivariable analysis showed that the presence of abnormal ECG at 7 days of hospitalization was an independent predictor of MAE (HR 3.2; 95% CI 1.2-8.7; p = .02). Furthermore, patients with abnormal ECG at 7 days more often required transfer to the intensive care unit (p = .01) or renal replacement therapy (p = .04). CONCLUSIONS: Patients with COVID-19 should receive ECG at admission but also during their hospital stay. Indeed, electrocardiographic alterations during hospitalization are associated with MAE and infection severity.

MicroRNA-33 and SIRT1 influence the coronary thrombus burden in hyperglycemic STEMI patients.

Primary percutaneous coronary intervention (PPCI) is a pivotal treatment in ST-segment elevation myocardial infarction (STEMI) patients. However, in hyperglycemic-STEMI patients, the incidence of death is still significant. Here, the involvement of sirtuin 1 (SIRT1) and miR33 on the pro-inflammatory/pro-coagulable state of the coronary thrombus was investigated. Moreover, 1-year outcomes in hyperglycemic STEMI in patients subjected to thrombus aspiration before PPCI were evaluated. Results showed that hyperglycemic thrombi displayed higher size and increased miR33, reactive oxygen species, and pro-inflammatory/pro-coagulable markers. Conversely, the hyperglycemic thrombi showed a lower endothelial SIRT1 expression. Moreover, in vitro experiments on endothelial cells showed a causal effect of SIRT1 modulation on the pro-inflammatory/pro-coagulative state via hyperglycemia-induced miR33 expression. Finally, SIRT1 expression negatively correlated with STEMI outcomes. These observations demonstrate the involvement of the miR33/SIRT1 pathway in the increased pro-inflammatory and pro-coagulable state of coronary thrombi in hyperglycemic STEMI patients.

Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators.

OBJECTIVES: To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach. BACKGROUND: The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response. Therefore, we hypothesized that automatic CRTd optimization might improve clinical outcomes in T2DM patients. METHODS: We designed a prospective, multicenter study to recruit, from October 2016 to June 2019, 191 consecutive failing heart patients with T2DM, and candidate to receive a CRTd. Study outcomes were CRTd responders rate, hospitalizations for heart failure (HF) worsening, cardiac deaths and all cause of deaths in T2DM patients treated with CRTd and randomly optimized via automatic (n 93) vs. echocardiography-guided (n 98) approach at 12 months of follow-up. RESULTS: We had a significant difference in the rate of CRTd responders (68 (73.1%) vs. 58 (59.2%), p 0.038), and hospitalizations for HF worsening (12 (16.1%) vs. 22 (22.4%), p 0.030) in automatic vs. echocardiography-guided group of patients. At multivariate Cox regression analysis, the automatic guided approach (3.636 [1.271-10.399], CI 95%, p 0.016) and baseline highest values of atrium pressure (automatic SonR values, 2.863 [1.537-6.231], CI 95%, p 0.006) predicted rate of CRTd responders. In automatic group, we had significant difference in SonR values comparing the rate of CRTd responders vs. non responders (1.24 ± 0.72 g vs. 0.58 ± 0.46 g (follow-up), p 0.001), the rate of hospitalizations for HF worsening events (0.48 ± 0.29 g vs. 1.18 ± 0.43 g, p 0.001), and the rate of cardiac deaths ( 1.13 ± 0.72 g vs. 0.65 ± 0.69 g, p 0.047). CONCLUSIONS: Automatic optimization increased CRTd responders rate, and reduced hospitalizations for HF worsening. Intriguingly, automatic CRTd and highest baseline values of SonR could be predictive of CRTd responders. Notably, there was a significant difference in SonR values for CRTd responders vs. non responders, and about hospitalizations for HF worsening and cardiac deaths. Clinical trial ClinicalTrials.gov Identifier NCT04547244.

Primary malignant pericardial tumour in Lynch syndrome.

BACKGROUND: This case represents the first report of malignant primary cardiac tumour in a patient with Lynch Syndrome associated with MSH2 pathogenic variant. CASE PRESENTATION: A 57-year-old woman with previous ovarian cystadenocarcinoma was admitted to the emergency room for hematic pericardial effusion. Multimodal diagnostic imaging revealed two solid pericardial vascularized masses. After pericardiectomy, the final histological diagnosis was poorly differentiated pleomorphic sarcomatoid carcinoma. During follow-up she developed an ampulla of Vater adenocarcinoma. Genetic analysis identified an MSH2 pathogenic variant. CONCLUSION: This case contributes to expand the tumour spectrum of Lynch syndrome, suggesting that MSH2 pathogenic variants cause a more complex multi-tumour cancer syndrome than the classic Lynch Syndrome. In MSH2 variant carriers, symptoms such as dyspnoea and chest discomfort might alert for rare tumours and a focused cardiac evaluation should be considered.

Subacute pericardial abscess after aortic valve replacement: a case report.

BACKGROUND: Purulent pericarditis is an infectious disease, frequently caused by gram-positive bacteria, that is rarely observed in healthy individuals, and is often associated with predisposing conditions. CASE PRESENTATION: Here, we present the case of an Escherichia coli post-surgical localized purulent pericarditis complicated by transient constrictive pericarditis and its diagnostic and therapeutic management. CONCLUSIONS: Our case report focuses on the importance of imaging-guided treatment of purulent pericardial diseases, in particular on the emerging role of 18 F-labelled 2-fluoro-2-deoxy-D-glucose Positron Emission Tomography/Computed Tomography in pericardial diseases and on the management of transient constrictive pericarditis, often seen after thoracic surgery.

Cardiac resynchronization therapy with a defibrillator (CRTd) in failing heart patients with type 2 diabetes mellitus and treated by glucagon-like peptide 1 receptor agonists (GLP-1 RA) therapy vs. conventional hypoglycemic drugs: arrhythmic burden, hospitalizations for heart failure, and CRTd responders rate.

OBJECTIVES: To evaluate clinical outcomes in patients with diabetes, treated by cardiac resynchronization therapy with a defibrillator (CRT-d), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) in addition to conventional hypoglycemic therapy vs. CRTd patients under conventional hypoglycemic drugs. BACKGROUND: Patients with diabetes treated by CRTd experienced an amelioration of functional New York Association Heart class, reduction of hospital admissions, and mortality, in a percentage about 60%. However, about 40% of CRTd patients with diabetes experience a worse prognosis. MATERIALS AND METHODS: We investigated the 12-months prognosis of CRTd patients with diabetes, previously treated with hypoglycemic drugs therapy (n 271) vs. a matched cohort of CRTd patients with diabetes treated with GLP-1 RA in addition to conventional hypoglycemic therapy (n 288). RESULTS: At follow up CRTd patients with diabetes treated by GLP-1 RA therapy vs. CRTd patients with diabetes that did not receive GLP-1 RA therapy, experienced a significant reduction of NYHA class (p value < 0.05), associated to higher values of 6 min walking test (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). GLP-1 RA patients vs. controls at follow up end experienced lower AF events (p value < 0.05), lower VT events (p value < 0.05), lower rate of hospitalization for heart failure worsening (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). To date, GLP-1 RA therapy may predict a reduction of AF events (HR 0.603, CI [0.411-0.884]), VT events (HR 0.964, CI [0.963-0.992]), and hospitalization for heart failure worsening (HR 0.119, CI [0.028-0.508]), and a higher CRT responders rate (HR 3.707, CI [1.226-14.570]). CONCLUSIONS: GLP-1 RA drugs in addition to conventional hypoglycemic therapy may significantly reduce systemic inflammation and circulating BNP levels in CRTd patients with diabetes, leading to a significant improvement of LVEF and of the 6 min walking test, and to a reduction of the arrhythmic burden. Consequently, GLP-1 RA drugs in addition to conventional hypoglycemic therapy may reduce hospital admissions for heart failure worsening, by increasing CRTd responders rate. Trial registration NCT03282136. Registered 9 December 2017 "retrospectively registered".