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Aims Human epicardial adipose tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-protein–coupled receptors, such as those for glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG), and glucagon-like peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG, and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell-type localization specifically for GIP receptor (GIPR) and glucagon receptor (GCGR). Methods and results Epicardial adipose tissue samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2 ± 10.5 years mean ± SD). Microarray and immunohistochemistry analyses were performed. Microarray analysis showed that GIPR and GCGR messenger ribonucleic acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1 [3776 ± 1377 arbitrary unit (A.U.), 17.77 ± 14.91 A.U., and 3.41 ± 2.27 A.U., respectively]. The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated, and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in free fatty acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (P < 0.01). Epicardial adipose tissue GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (P < 0.01). Conclusions Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein–coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.

Left atrial (LA) function can be effectively assessed by measuring longitudinal LA strain (LAS) via two-dimensional speckle tracking echocardiography (2DSTE). Here, we test 2DSTE-based LAS as marker of different left ventricle (LV) remodeling patterns and as prognostic index in ischemic heart failure (HF) candidates to surgical ventricular reconstruction.We retrospectively considered ischemic HF patients with anterior (group A, n=130) or posterior (group P, n=48) LV remodeling. Based on 2D ultrasound, LV and LA morpho-functional parameters were quantified including reservoir (LASGroup A and group P displayed similar end-diastolic (p=0.89) and end-systolic (p=0.33) LV volume index, and LA volume index LAVi (p=0.44) corrected for the degree of mitral regurgitation. As compared to group P, group A revealed a significant reduction in LAS2DSTE-based LAS assessment is affordable, repeatable and non-invasive, and could add clinically-relevant mechanistic insight and prognostic value in the stratification of ischemic HF patients.

Over the last two decades there has been a significant shift towards the use of bioprostheses in the context of surgical aortic valve replacement, despite the well-known process of structural valve deterioration (SVD). This process has been extensively evaluated even though with many different definitions and methods, thus, the true long-term durability of surgical bioprostheses is not yet fully elucidated. Following the increasing implementation of the transcatheter aortic valve implantation (TAVI) technology, a better understanding of the long-term durability of transcatheter bioprostheses has become increasingly important as well, despite the limited availability of such data compared to the surgical experience. This lack of knowledge is a major barrier to the use of TAVI platforms to treat relatively younger patients. We thus aimed at providing an overview on long-term actual data concerning the durability of bioprostheses focusing on definition, incidence, and subsequent management of SVD of both surgical and transcatheter bioprosthetic aortic valves.

During the acute phase of COVID-19, many patients experience a complex coagulopathy characterized by a procoagulant pattern. The present study investigates the persistence of hemostatic changes in post-COVID patients at a long-term follow up, and the link with the persistence of physical and neuropsychological symptoms. We completed a prospective cohort study on 102 post-COVID patients. Standard coagulation and viscoelastic tests were performed, along with an assessment of persistent symptoms and recording of acute phase details. A procoagulant state was adjudicated in the presence of fibrinogen > 400 mg/dL, or D-dimer > 500 ng/mL, or platelet count > 450,000 cells/µL, or a maxim clot lysis at viscoelastic test < 2%. A procoagulant state was identified in 75% of the patients at 3 months follow up, 50% at 6 months, and 30% at 12–18 months. Factors associated with the persistence of a procoagulant state were age, severity of the acute phase, and persistence of symptoms. Patients with major physical symptoms carry a procoagulant state relative risk of 2.8 (95% confidence interval 1.17–6.7, p = 0.019). The association between persistent symptoms and a procoagulant state raises the hypothesis that an ongoing process of thrombi formation and/or persistent microthrombosis may be responsible for the main physical symptoms in long-COVID patients.

Objectives The quality of the outcome after cardiac surgery with cardiopulmonary bypass depends on the patient demographics, co-morbidities, complexity of the surgical procedure, and expertise of surgeons and the whole staff. The purpose of the present study is to analyze the timing of surgery (morning vs afternoon) with respect to morbidity and mortality in adult cardiac surgery. Methods: The primary end-point was the incidence of major morbidity defined according to a modified Society of Thoracic Surgeon criterion. We consecutively included all the adult (> 18 years) patients receiving a cardiac surgery operation at our Institution. Results From 2017 through 2019 a total of 4,003 cardiac surgery patients were operated. With a propensity-matching technique a final patient population of 1600 patients was selected, with 800 patients in the first-case surgery group and 800 in the second-case surgery group. Patients in the second-case group had a major morbidity rate of 13% vs 8.8% in the first-case group (P = 0.006), and a higher rate of 30-days mortality (4.1% vs 2.3%, P = 0.033). After correction for EuroSCORE and operating surgeon, the second-case group confirmed a higher rate of major morbidity (odds ratio 1.610, 95% confidence interval 1.16–2.23, P = 0.004). Conclusion Our study suggests that patients operated as second cases are exposed to an increased morbidity and mortality probably due to fatigue, loss of attention and hurriedness in the operating room, and decreased human resources in the intensive care unit.

OBJECTIVE The excess of visceral adipose tissue might hinder and delay immune response. How people with abdominal obesity (AO) will respond to mRNA vaccines against SARS-CoV-2 is yet to be established. We evaluated SARS-CoV-2 specific antibody responses after the first and second dose of the BNT162b2 mRNA vaccine comparing the response of individuals with AO to those without, discerning between individuals with or without prior infection. METHODS IgG neutralizing antibodies against the Trimeric-complex (IgG-TrimericS) were measured at four time points: at baseline, at day 21 after vaccine dose 1, at one and three months after dose 2. Nucleocapsid antibodies were assessed to detect prior SARS-CoV-2 infection. Waist circumference was measured to determine AO. RESULTS Between the first and third month after vaccine dose 2, the drop in IgG-TrimericS levels was more remarkable in individuals with AO compared to those without AO (2.44 fold [95%CI: 2.22-2.63] vs 1.82 fold [95%CI: 1.69-1.92], respectively, p

Background: Hospital mortality and admission to the Intensive Care Unit (ICU) are markers of disease severity in COVID-19 patients. Cardiovascular co-morbidities are one of the Academic Editor: Atsushi Tanaka Received: 17 June 2022 Accepted: 12 July 2022 Published: 15 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). main determinants of negative outcomes. In this study we investigated the impact of cardiovascular co-morbidities on mortality and admission to the ICU in first-wave COVID-19 patients. Methods: Amulticenter, retrospective, cohort study. A total of 1077 patients were analyzed for mortality and ICU admission. Cardiovascular risk factors were explored as determinants of the outcomes after correction for other confounders. Results: In the multivariable model, after correction for age, only a history of heart failure remained independently associated (p = 0.0013) with mortality (hazard ratio 2.22, 95% confidence interval 1.37 to 3.62). Age showed a mortality risk increase of 8% per year (hazard ratio 1.08, 95% confidence interval 1.05 to 1.10, p = 0.001). The transition from ward to the ICU had, as a single determinant, the age, but in a reversed fashion (hazard ratio 0.96, 95% confidence interval 0.94 to 0.98, p = 0.0002). Conclusions: Once adjusted for the main determinant of mortality (age) heart failure only remained independently associated with mortality. Admission to the ICU was less likely for elderly patients. This may reflect the catastrophic impact of the first wave of COVID-19 pandemic in terms of ICU bed availability in Lombardy, leading to a selection process for ICU admission.

Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6 months after STEMI.patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6 months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REMIn a contemporary cohort of STEMI patients studied by CMR, prevalence of LV-REM

Purpose Imaging of brain involvement in infective endocarditis can drive the clinical management of this serious condition. MRI is very sensitive, but CT is more readily available. In this retrospective study, we compared the detection rates of CT and MRI. Methods After Ethics Committee approval, we retrospectively reviewed a series of 20 patients (13 males, median age 64 years) who underwent both CT and MRI either before or after cardiac surgery for definite infective endocarditis. Plain CT and MRI were evaluated for acute ischemic lesions, both punctuate and large, intraparenchymal hemorrhages, cerebral microbleeds, subarachnoid hemorrhages, abscesses, microabscesses, and meningitis. Qualitative assessment and McNemar test were performed. The value of contrast-enhanced scans (MRI, n = 14; CT, n = 9) and cognitive status were also assessed. Results A total of 166 lesions were identified on either technique: 137 (83%) on MRI only, 4 (2%) on CT only, and 25 (15%) on both techniques (p Conclusion While CT rapidly excludes large hemorrhages in patients with infective endocarditis, MRI accurately distinguishes the whole spectrum of brain lesions, including small ischemic lesions, microbleeds, and microabscesses.

Purpose Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. Methods This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. Results Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P

BACKGRROUND The Left Ventricle Volume is one of the most important risk factor of mortality in follow-up, after an Acute Myocardial Infarction. AIMS Surgical Ventricular reconstruction reduces the volume of left ventricle to target of LVESI below 60 ml/m2. METHODS This can be achieved with different surgical techniques adapted to anatomy of left ventricle in the way to exclude the scared tissue from the cavity of left ventricle. New cavity has to have an elipsoide shape and normal volume. CONCLUSION This commentary stress out the importance using a sizer to guide the surgeons to acheive the target shape and volume using different techniques described in Calafiore and coworkers paper.

Aims Female sex and heart failure (HF) are considered poor prognostic factors for surgery. We aimed to investigate the association between sex and surgical outcomes in patients with ischaemic HF undergoing surgical ventricular reconstruction and coronary artery bypass grafting. Methods and results From July 2001 to June 2017, 648 patients [111 women (17%) and 537 men (83%)] were referred to our centre. Follow‐up continued through June 2018. All patients underwent surgical ventricular reconstruction; coronary artery bypass grafting was performed in 582 patients (90%). Primary outcome was defined as all‐cause mortality. Secondary outcome included all‐cause mortality or all‐cause hospitalization. Women were older (70 vs. 65 years, P

Objective To examine factors possibly involved in the resolution or persistence of restrictive filling pattern (RFP) after surgical ventricular restoration (SVR) in a series of patients with ischemic cardiomyopathy (ICM) and RFP. Methods Echocardiography was performed at baseline (pre-SVR), discharge, and follow-up in 43 patients with ICM and RFP (E/A ratio ≥2). Patients were divided into 2 groups based on E/A ratio at discharge: improved (E/A ratio Results The improved group had a significantly increased mean deceleration time (from 137 ± 22 ms to 194 ± 68 ms; P = .002) and mean A wave velocity (from 43 ± 10 cm/s to 92 ± 37 cm/s; P = .001), and decreased E/e′ ratio (from 27.7 ± 9.5 to 19.2 ± 7.8; P = .01) after SVR. The unchanged group did not show any significant variations in diastolic parameters. The only significant differences at baseline between the two groups were thinner left ventricle posterior wall and lower relative wall thickness (RWT) in the unchanged group. RWT was the sole baseline parameter independently associated with persistent RFP. Conclusions RFP was reversed after SVR in 22 of our 43 patients with ICM with a response that remained stable over time, associated with improved New York Heart Association class. RWT was the sole baseline echocardiographic parameter significantly associated with the evolution of RFP after SVR.

The natural history of secondary mitral regurgitation (MR) is unfavorable. Nevertheless, there are no evidence that its correction can improve the outcome. If from one side the original cause of secondary MR can be such to limit the possibilities of improvement, from the other side it is possible that the surgical technique widely applied to repair, restrictive mitral annuloplasty, is not adequate to correct the regurgitation. The addition of valvular and/or subvalvular techniques has been considered a possible technical solution. However, we do not know the prevalence of each technique, how many times mitral replacement is used to correct secondary MR. This aspect is of particular importance, as we know that a successful mitral repair causes a better left ventricular systolic remodeling than a unsuccessful repair or replacement. This study is a prospective, observational registry, conceived to understand what is done in the real world. Any surgeon will use the technique he thinks the most suitable for the patient. Every year, for 5 years, patients will have a clinical and echocardiographic follow-up, to evaluate the risk factors for a worse result (death, rehospitalization for heart failure, reoperation for MR return, moderate, or more MR return). This knowledge will give us the possibility to understand which is the technique, or the strategy, more efficient to treat this disease and the real efficacy of the surgical treatment.

Background Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. Objectives Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. Methods Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. Results At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 μg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2 = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). Conclusion The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.

This is an analysis involving 134 heart failure patients with reduced ejection fraction versus 80 controls investigated during functional evaluation with gas exchange and hemodynamic, addressing the severe mitral regurgitation phenotype and testing the hypothesis that the backward cardiac output redistribution to the lung during exercise impairs delivery and overexpresses peripheral extraction. This information is new and has important implications in the management of heart failure.

Background Time-resolved three-directional velocity-encoded (4D flow) magnetic resonance imaging (MRI) enables the quantification of left ventricular (LV) intracavitary fluid dynamics and energetics, providing mechanistic insight into LV dysfunctions. Before becoming a support to diagnosis and patient stratification, this analysis should prove capable of discriminating between clearly different LV derangements. Purpose To investigate the potential of 4D flow in identifying fluid dynamic and energetics derangements in ischemic and restrictive LV cardiomyopathies. Study Type Prospective observational study. Population Ten patients with post-ischemic cardiomyopathy (ICM), 10 patients with cardiac light-chain cardiac amyloidosis (AL-CA), and 10 healthy controls were included. Field Strength/Sequence 1.5 T/balanced steady-state free precession cine and 4D flow sequences. Assessment Flow was divided into four components: direct flow (DF), retained inflow, delayed ejection flow, and residual volume (RV). Demographics, LV morphology, flow components, global and regional energetics (volume-normalized kinetic energy [KEV] and viscous energy loss [ELV]), and pressure-derived hemodynamic force (HDF) were compared between the three groups. Statistical Tests Intergroup differences in flow components were tested by one-way analysis of variance (ANOVA); differences in energetic variables and peak HDF were tested by two-way ANOVA. AP-value of Results ICM patients exhibited the following statistically significant alterations vs. controls: reduced KEV, mostly in the basal region, in systole (−44%) and in diastole (−37%); altered flow components, with reduced DF (−33%) and increased RV (+26%); and reduced basal–apical HDF component on average by 63% at peak systole. AL-CA patients exhibited the following alterations vs. controls: significantly reduced KEVat the E-wave peak in the basal segment (−34%); albeit nonstatistically significant, increased peaks and altered time-course of the HDF basal–apical component in diastole and slightly reduced HDF components in systole. Data Conclusion The analysis of multiple 4D flow-derived parameters highlighted fluid dynamic alterations associated with systolic and diastolic dysfunctions in ICM and AL-CA patients, respectively.

We investigated the effect of the design of bioprosthetic pericardial valves on the downstream fluid flow pattern through four-dimensional flow magnetic resonance imaging (4D Flow). A dedicated in vitro test bench, including a paradigmatic aortic root phantom, was used to compare, under steady flow conditions, three commercially used pericardial bioprostheses (TrifectaTM, Carpentier-Edwards PERIMOUNT Magna, Crown PRT®), selecting the two smallest and comparable valve sizes. In-house 4D Flow post-processing provided the downstream flow pattern of velocity, the velocity profile at vena contracta, its effective orifice area (EOA) and the corresponding hydraulic diameter (DH). Trifecta reported the lowest peak of velocity for both the tested sizes, with vena contracta position being the most proximal to the free margin of leaflets. Conversely, in both Crown and Magna, jet flow continued to increase its downstream velocity, resulting in a farther position of vena contracta. EOA shape was trilobal for Magna, triangular for Crown and circular for Trifecta, the last one maximising EOA. The percentage of nominal luminal area effectively exploited by the flow was largely above 80% in Trifecta, below 75% in Crown and below 70% in Magna. Hence, the design of pericardial bioprostheses directly impacts on the downstream flow field pattern and its fluid dynamic performance.

Background: Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation. Methods: We employed high content imaging, 2-dimensional/3-dimensional culture, atomic force microscopy mapping, and molecular methods to prove the role of cell/nuclear straining in YAP-dependent fibrotic programming in a mouse model of ischemia-dependent cardiac fibrosis and in human-derived primitive cardiac stromal cells. We also tested treatment of cells with Verteporfin, a drug known to prevent the association of the YAP/TAZ complex with their cognate transcription factors TEADs. Results: Our experiments suggested that pharmacologically targeting the YAP-dependent pathway overrides the profibrotic activation of cardiac stromal cells by mechanical cues in vitro, and that this occurs even in the presence of profibrotic signaling mediated by TGF-β1 (transforming growth factor beta-1). In vivo administration of Verteporfin in mice with permanent cardiac ischemia reduced significantly fibrosis and morphometric remodeling but did not improve cardiac performance. Conclusions: Our study indicates that preventing molecular translation of mechanical cues in cardiac stromal cells reduces the impact of cardiac maladaptive remodeling with a positive effect on fibrosis.

Purpose The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. Methods We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n=5) or valvular replacement (VR) (n=5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. Results Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/104 adipocytes vs. 0,0 CLS/104 adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. Conclusion CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain.Level of evidence: No level of evidence; this is a basic science study.

According to the World Health Organization’s definition, long COVID is the persistence or development of new symptoms 3 months after the initial infection. Various conditions have been explored in studies with up to one-year follow-up but very few looked further. This prospective cohort study addresses the presence of a wide spectrum of symptoms in 121 patients hospitalized during the acute phase of COVID-19 infection, and the association between factors related to the acute phase of the disease and the presence of residual symptoms after one year or longer from hospitalization. The main results are as follows: (i) post-COVID symptoms persist in up to 60% of the patient population at a mean follow-up of 17 months; (ii) the most frequent symptoms are fatigue and dyspnea, but neuropsychological disturbances persist in about 30% of the patients (iii) when corrected for the duration of follow-up with a freedom-from-event analysis; only complete (2 doses) vaccination at the time of hospital admission remained independently associated with persistence of the major physical symptoms, while vaccination and previous neuropsychological symptoms remained independently associated with persistence of major neuropsychological symptoms.

The surgical ventricular restoration is an evolution of treatment of left ventricle aneurysm. The aetioloy of left ventricle aneurysm and the dilated post AMI cardiomiopaty is the same; the difference is in the extension of scarred tissue and in the quality of remote zone. Because in this anatomical situation the geometry of left left ventricle can be deeply affected, it can very difficult to have point of reference as position of apex or papillary mussles. Using a sizer and combine different surgical thecniques allow to rebuilt a ventricle with appropriate volume and shape.

Background Cardiac fibrosis is associated with inflammation and extracellular matrix (ECM) accumulation. A pro-fibrotic cytokine, IL11 induces cardiac fibroblasts conversion to myofibroblasts expressing α-smooth muscle actin (α-SMA) and ECM. MicroRNAs (miRNAs) are a class of small non-coding RNAs which participate in regulation of gene expression; Although mainly intracellular, miRNAs can be released into the blood stream where they can be readily detected. Purpose To screen miRNAs upregulated following IL11 triggered conversion of rat cardiac fibroblasts into myofibroblasts. To validate these miRNAs as potential diagnostic biomarkers of cardiac fibrosis by testing their level in blood plasma and septum of aortic valve stenosis (AVS) patients. Methods and results With a bioinformatical approach (Figure 1), we predicted miRNAs which can target proteins involved in TGFβ and IL-11 pathways of fibrosis progression. Of a vast number of miRNAs, we identified 7 strong candidates. After qPCR validation, we found miRNA-27b-5p and miRNA-497 to be significantly upregulated in rat cardiac fibroblasts treated by IL11 (5 ng/ul) but not TGFβ1 (100 ng/ul), values are 2–ΔΔCt: (3±1.5) and (5.2±2.2) (p-value Conclusions We found miRNA-497 and miRNA-27b-5p to be pro-fibrotic in rat fibroblasts. Importantly, we found both miRNAs to be up-regulated in the peripheral blood of AVS patients. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Roman Tikhomirov PhD studentship is supported by a fellowship from the University of Verona, ItalyEEU-Cardiac RNA cost action CA17129

The role of surgical ventricular reconstruction (SVR) in patients with ischemic cardiomyopathy is controversial. Observational series and the Surgical Treatment of IsChemic Heart failure (STICH) trial reported contradictory results. SVR is highly dependent on operator experience. The aim of this study is to compare the long-term results of SVR between a high-volume SVR institution and the STICH trial using individual patient data.Patients undergoing SVR at San Donato Hospital (Milan) were compared with patients undergoing SVR in STICH (as-treated principle) by inverse probability treatment-weighted Cox regression. The primary outcome was all-cause mortality.The San Donato cohort included 725 patients, whereas the STICH cohort included 501. Compared with the STICH-SVR cohort, San Donato patients were older (66.0, lower quartile, upper quartile [Q1, Q3: 58.0, 72.0] vs 61.9 [Q1, Q3: 55.1, 68.8], P .001) and with lower left ventricular end-systolic volume index at baseline (LVESVI: 77.0 [Q1, Q3: 59.0, 97.0] vs 80.8 [Q1, Q3: 58.5, 106.8], P = .02). Propensity score weighting yielded 2 similar cohorts. At 4-year follow-up, mortality was significantly lower in the San Donato cohort compared with the STICH-SVR cohort (adjusted hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .001). Greater postoperative LVESVI was independently associated with mortality (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03). At 4 to 6 months of follow-up, the mean reduction of LVESVI in the San Donato cohort was 39.6%, versus 10.7% in the STICH-SVR cohort (P .001).Patients with postinfarction LV remodeling undergoing SVR at a high-volume SVR institution had better long-term results than those reported in the STICH trial, suggesting that a new trial testing the SVR hypothesis may be warranted.

ObjectiveThe excess of visceral adipose tissue might hinder and delay the immune response. How people with abdominal obesity will respond to mRNA vaccines against SARS-CoV-2 is yet to be established. We evaluated SARS-CoV-2-specific antibody responses after the first and second dose of the BNT162b2 mRNA vaccine comparing the response of individuals affected by abdominal obesity (AO) to those without, discerning between individuals with or without prior infection.MethodsIgG neutralizing antibodies against the Trimeric complex (IgG-TrimericS) were measured at four time points: at baseline, at day 21 after vaccine dose-1, at one month and three months after dose-2. Nucleocapsid antibodies were assessed to detect prior SARS-CoV-2 infection. Waist circumference was measured to determine abdominal obesity.ResultsBetween the first and third month after vaccine dose-2, the drop in IgG-TrimericS levels was more remarkable in individuals with AO compared to those without AO (2.44 fold [95%CI: 2.22-2.63] vs 1.82 fold [95%CI: 1.69-1.92], respectively, pConclusionsOur findings highlight the need to extend the duration of serological monitoring of antibody levels in infection-naive individuals with abdominal obesity, a higher-risk population category in terms of possible weaker antibody response.

Both increased natriuretic peptide levels and restrictive filling pattern (RFP) are important risk predictors in patients with heart failure. The aim of this study was to examine the role of the combined use of natriuretic peptide and RFP for the prognostic stratification of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration in the Biomarker Plus study.A total of 186 patients (aged 64 ± 10 years) underwent echocardiographic study and N-terminal pro-B-type natriuretic peptide assay at baseline (before surgical ventricular restoration). Patients were divided into 4 groups depending on baseline diastolic filling pattern (RFP/no RFP) and N-terminal pro-B-type natriuretic peptide level (less than or greater than or equal to the upper tertile value of 2003 ŋg/L). RFP was defined as E/A ratio ≥2. All-cause death or heart failure hospitalizations within 36-month follow-up were analyzed.Despite similar ejection fraction, volumes, and mass, the 4 groups presented distinct clinical and structural pattern of presurgical ventricular restoration ventricular remodeling and significantly different clinical outcome after surgical unloading. During follow-up, 67 patients died or were hospitalized for heart failure (36%). High N-terminal pro-B-type natriuretic peptide levels and RFP, considered individually, were significantly associated with outcome (P .0001). The combination of both was associated with the highest adjusted hazard of adverse events (hazard ratio, 3.63; 95% CI, 1.73-7.6; P .0001).The simultaneous use of 2 markers, 1 biological and 1 echocardiographic, may allow better prognostic stratification and characterization of the distinct structural and clinical phenotypes in a population of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration. This approach could be useful in the decision-making process to guide treatment choices in patients with ischemic cardiomyopathy.

Congenital left ventricular aneurysm or diverticulum is very rare. Most congenital left ventricular aneurysms are asymptomatic but some cause systemic embolization, left ventricular free wall rupture, or ventricular arrhythmias causing sudden cardiac death. A 29-year-old woman with congenital left ventricular aneurysm and nonsustained ventricular tachycardia underwent surgical plication of the aneurysm with left ventricular reshaping to improve heart failure symptoms, prevent rupture of the aneurysm wall and the possibility of thrombus formation, and excise the fibrotic tissue of the left ventricular aneurysm, which could be a trigger for left ventricular aneurysm arrhythmias. The postoperative course was unremarkable.

Summary An increase in left ventricular volume after a myocardial infarction is a key component of the adverse remodelling process leading to chamber dysfunction, heart failure and an unfavourable outcome. Hence, the therapeutic strategies have been designed to reverse the remodelling process by medical therapy, devices or surgical strategies. Surgical ventricular reconstruction primarily combined with myocardial revascularization has been introduced as an optional intervention aimed to reduce the left ventricle through resection of the scar tissue and is recommended in selected patients with predominant heart failure symptoms, and with myocardial scarring and moderate left ventricular remodelling. This review outlines the rationale and the technique for reconstructing the left ventricle and the possible indications for using that technique, based on experiences from the centre with the largest international experience. The major contributions in the literature are briefly discussed.

PurposeChest x-ray (CXR) severity score and general obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored.MethodsThis retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19.ResultsPatients with abdominal obesity had significantly higher CXR severity scores and higher rates of these scores than those without abdominal obesity (P

Ischaemic chronic heart failure represents one of the cardiovascular diseases with the worst degree of morbidity and mortality in the Western world, along with the highest healthcare costs. Despite several retrospective studies demonstrating that surgical revascularization (coronary artery bypass grafting), especially in the presence of viable myocardium, improves heart function and therefore survival in this subgroup of patients, the matter remains unclear and controversial. This chapter discusses the available evidence in the literature, from observational studies to randomized trials, including operative techniques and controversial issues, in order to clarify the role of coronary artery bypass grafting in the current management of patients with ischaemic left ventricular dysfunction.