Pentraxin 3 in Myocarditis: Proof-of-Principle Assessment as a Diagnostic and Prognostic Biomarker.

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.

Subacute postoperative atrial fibrillation after heart surgery: Incidence and predictive factors in cardiac rehabilitation.

Background: Postoperative atrial fibrillation (POAF) is the most common arrhythmia following cardiac surgery (CS). It may occur between the 1st and the 4th postoperative day as acute POAF or between the 5th and the 30th as subacute (sPOAF). sPOAF is associated with higher thromboembolic risk, which consistently increase patients' morbidity. Neutrophil-to-lymphocyte ratio (NLR) is a low-cost inflammatory index proposed as possible POAF predictor. Identification of patients' risk categories might lead to improved postoperative outcomes. Methods: The aim was to assess the incidence of sPOAF and to identify possible predictors in patients performing cardiovascular rehabilitation (CR) after CS. A single-center cohort study was performed on 737 post-surgical patients admitted to CR on sinus rhythm. Continuous monitoring with 12-lead ECG telemetry was performed. We evaluated the predictive role of anamnestic, clinical, and laboratory data, including baseline NLR. Results: Subacute POAF was documented in 170 cases (23.1%). At the multivariate analysis, age (OR 1.03; p = .001), mitral valve surgery (OR 1.77; p = .012), acute POAF (OR 2.97; p < .001), and NLR at baseline (OR 1.13; p = .042) were found to be independent predictive factors of sPOAF following heart surgery. Conclusions: sPOAF is common after CS. Age, mitral valve procedures, acute POAF, and preoperative NLR were proved to increase sPOAF occurrence in CR. NLR is an affordable and reliable parameter which might be used to qualify the risk of arrhythmias at CR admission. Identification of new predictors of postoperative atrial fibrillation may allow to improve patients' prognosis.

[Eight reasons why cardiologists should not overlook the problem "obesity". Expert opinion for clinical practice]. / Otto motivi per i quali i cardiologi non dovrebbero trascurare il problema "obesità". Expert opinion per la pratica clinica.

This paper is addressed to the cardiologist, who in his or her clinical practice interacts with and treats cardiovascular risk factors associated with obesity and its complications; it may also be useful for other specialists, to whom patients with excess weight may be referred. We hope that the cardiologist will consider obesity as a preventable and treatable disease that contributes to overall cardiovascular risk, and will deploy a strong commitment to cope with this disease. To this purpose, the text is composed of 8 questions aimed to cover relevant topics for the clinical practice.

Imaging of the Diaphragm Following Cardiac Surgery: Focus on Ultrasonographic Assessment.

Diaphragm dysfunction is a common complication following cardiac surgery. Its clinical impact is variable, ranging from the absence of symptoms to the acute respiratory failure. Post-operative diaphragm dysfunction may negatively affect patients' prognosis delaying the weaning from the mechanical ventilation (MV), extending the time of hospitalization and increasing mortality. Ultrasonography is a valid tool to evaluate diaphragmatic impairment in different settings, like the Intensive Care Unit, to predict successful weaning from the MV, and the Cardiovascular Rehabilitation Unit, to stratify patients in terms of risk of functional recovery failure. The aim of this review is to describe the pathophysiology of post-cardiac surgery diaphragm dysfunction, the techniques used for its diagnosis and the potential applications of diaphragm ultrasound.

How cardiologists can manage excess body weight and related cardiovascular risk. An expert opinion.

Obesity is an important independent cardiovascular (CV) risk factor and a chronic inflammatory disease related to the development of insulin resistance, type 2 diabetes, dyslipidaemia, coronary artery disease, hypertension, heart failure, atrial fibrillation and obstructive sleep apnoea. Body Mass Index (BMI) values >27 kg/m2 are associated with an exponential increase in the risk for Major Adverse Cardiac Events (MACE). On the other hand, weight reduction can significantly reduce metabolic, CV and oncological risk. Orlistat, bupropion/naltrexone, liraglutide and semaglutide, combined with lifestyle changes, have proven to be effective in weight loss; the last two have been tested in randomized clinical trials (RCTs) with CV outcomes only in diabetic patients, and not in obese patients. To fill a fundamental gap of knowledge, the SELECT trial on patients with obesity and CV disease treated with semaglutide is ongoing, aiming at MACE as the primary endpoint. The battle against the social and clinical stigma towards obesity must be counteracted by promoting an awareness that elevates obesity to a complex chronic disease. Several actions should be implemented to improve the management of obesity, and cardiologists have a key role for achieving a global approach to patients with excess weight also through the correct implementation of available treatment strategies.

Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients.

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression. Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences. Conclusions: Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies.

Diaphragm Dysfunction after Cardiac Surgery: Insights from Ultrasound Imaging during Cardiac Rehabilitation.

Diaphragm dysfunction is common after cardiac surgery and can be evaluated with ultrasonography (US). We aimed at assessing with US the incidence of diaphragmatic dysfunction and the impact of cardiovascular rehabilitation (CR) on its recovery. A single-center cohort study was performed. Patients were enrolled after cardiac surgery. The 6-min walking test (6MWT) and diaphragm US were performed at CR admission and after 10 rehabilitative sessions. One hundred eighty-five patients were eligible for final analysis. One hundred thirty-one patients (70.8%) were found to have diaphragm dysfunction (excursion <2 cm). After CR, 68 patients regained normal diaphragmatic function; those with persistent dysfunction had a lower level of functional performance on the 6MWT (metabolic equivalents of tasks: 3.3 vs. 3.6, p = 0.013). The patients who underwent combined surgery (adjusted odds ratio [aOR] = 4.09, p = 0.001) and those with post-operative pneumothorax (aOR = 3.02, p = 0.042) were at increased risk of failure to improve diaphragmatic excursion. US parameters were more powerful tools in predicting diaphragmatic evolution compared with the 6MWT indexes: baseline diaphragm excursion and thickening fraction were associated with complete diaphragmatic functional recovery after CR (aOR = 9.101, p < 0.001, and aOR = 1.058, p = 0.020 respectively). US is a valuable tool for the assessment of post-operative diaphragmatic dysfunction and can identify patients at risk of diaphragmatic recovery failure.

Post-pericardiotomy syndrome: insights into neglected postoperative issues.

ABSTRACT OBJECTIVES: Pericardial effusion is a common complication after cardiac surgery, both isolated and in post-pericardiotomy syndrome (PPS), a condition in which pleuropericardial damage triggers both a local and a systemic inflammatory/immune response. The goal of this review was to present a complete picture of PPS and pericardial complications after cardiac surgery, highlighting available evidence and gaps in knowledge. METHODS: A literature review was performed that included relevant prospective and retrospective studies on the subject. RESULTS: PPS occurs frequently and is associated with elevated morbidity and significantly increased hospital stays and costs. Nevertheless, PPS is often underestimated in clinical practice, and knowledge of its pathogenesis and epidemiology is limited. Several anti-inflammatory drugs have been investigated for treatment but with conflicting evidence. Colchicine demonstrated encouraging results for prevention. CONCLUSIONS: Wider adoption of standardized diagnostic criteria to correctly define PPS and start early treatment is needed. Larger studies are necessary to better identify high-risk patients who might benefit from preventive strategies.

Cardiologist's approach to the diabetic patient: No further delay for a paradigm shift.

Type 2 diabetes mellitus (DM) is constantly increasing worldwide and its most critical determinant of morbidity and mortality is still represented by cardiovascular (CV) complications. For years, cardiologists' approach to diabetic patients has been focused on risk factors optimization, with positive results. However, the management of DM per se was never truly considered in order to obtain prevention from major CV events, because medications used for glycemic control were not expected to gain CV benefit. Early trials concerning intensive versus conventional glycemia control did not prove useful in reducing the number of CV events. The introduction of new molecules led to a game change in DM treatment, as some new glucose-lowering drugs (GLDs), such as sodium-glucose linked transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), showed not only to be safe but also to ensure CV benefit. A combination of anti-atherogenic effects and hemodynamic improvements are likely explanations of the observed reduction of CV events and mortality. These evidence opened a completely new era in the field of GLDs and of DM treatment. Nonetheless, the presence of residual cardiovascular risk despite optimal medical therapy remains an issue and an aggressive strategy against multiple risk factors is suggested. A paradigm shift toward a new approach to DM management should be made with no further delay with the use of medications that may prevent CV events in an integrated strategy of CV risk reduction.

Cardiac arrest due to acute thrombosis after surgical closure of coronary fistula: the role of anticoagulation.

Described herein the case of a 47-year-old woman who underwent surgical closure of a large fistula between the right coronary artery (RCA) and the superior vena cava with subsequent thrombosis of the ectatic RCA determining myocardial infarction and cardiac arrest. After resuscitation, rheolitic thrombectomy with AngioJet device was performed and anticoagulant treatment was started in addition to antiplatelet therapy. The type of antithrombotic therapy after coronary fistula closure is still debated but long-term anticoagulation should be considered in high-risk cases.

Glycaemic Control and Vascular Complications in Diabetes Mellitus Type 2.

Diabetes mellitus is constantly increasing worldwide. Vascular complications are the most common in the setting of long-standing disease, claiming the greatest burden in terms of morbidity and mortality. Glucotoxicity is involved in vascular damage through different metabolic pathways, such as production of advanced glycation end-products, activation of protein kinase C, polyol pathway activation and production of reactive oxygen species. Vascular complications can be classified according to the calibre of the vessels involved as microvascular (such as diabetic retinopathy, nephropathy and neuropathy) or macrovascular (such as cerebrovascular, coronary and peripheral artery disease). Previous studies showed that the severity of vascular complications depends on duration and degree of hyperglycaemia and, as consequence, early trials were designed to prove that intensive glucose control could reduce the number of vascular events. Unfortunately, results were not as satisfactory as expected. Trials showed good results in reducing incidence of microvascular complications but coronary heart diseases, strokes and peripheral artery diseases were not affected despite optimal glycemia control. In 2008, after the demonstration that rosiglitazone increases cardiovascular risk, FDA demanded stricter rules for marketing glucose-lowering drugs, marking the beginning of cardiovascular outcome trials, whose function is to demonstrate the cardiovascular safety of anti-diabetic drugs. The introduction of new molecules led to a change in diabetes treatment, as some new glucose-lowering drugs showed not only to be safe but also to ensure cardiovascular benefit to diabetic patients. Empaglifozin, a sodium-glucose cotransporter 2 inhibitor, was the first molecule to show impressing results, followed on by glucagon-like peptide 1 receptor agonists, such as liraglutide. A combination of anti-atherogenic effects and hemodynamic improvements are likely explanations of the observed reduction in cardiovascular events and mortality. These evidences have opened a completely new era in the field of glucose-lowering drugs and of diabetes treatment in particular with respect to vascular complications.

Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients with Type 2 Diabetes: A Novel Anti-Atherogenic Effect.

INTRODUCTION: Liraglutide has several non-glycemic effects, including those on plasma lipids and lipoproteins, contributing to its cardiovascular benefit; however, the exact underlying mechanisms remain unclear. We investigated a novel anti-atherogenic effect of liraglutide in a real-world prospective study on patients with type 2 diabetes (T2DM). METHODS: Sixty-two patients with T2DM (31 men, 31 women; mean age ± standard deviation 61 ± 9 years) naïve to incretin-based therapies were treated with liraglutide (1.2 mg/day) as add-on therapy to metformin (1500-3000 mg/day) for 4 months. Laboratory analyses included the assessment of lipoprotein subclass profile by gel electrophoresis (Lipoprint; Quantimetrix Corp., Redondo Beach, CA, USA). Carotid intima-media thickness (cIMT) was assessed by Doppler ultrasonography. Statistical analyses included the paired t test, Spearman correlation and multiple regression analysis. RESULTS: The addition of liraglutide to metformin monotherapy resulted in significant reductions in fasting glycemia, hemoglobin A1c, body mass index, waist circumference, total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol, as well as in cIMT. There was an increase in the large LDL-1 subfraction, with a concomitant reduction in atherogenic small dense LDL-3 and LDL-4 subfractions. Correlation analysis revealed a significant association between changes in cIMT and changes in small dense LDL-3 subfraction (r = 0.501; p < 0.0001). Multivariate analysis, including all of the measured anthropometric and laboratory parameters, revealed that only changes in the small dense LDL-3 subfraction were independent predictors of changes in cIMT (p < 0.0001). CONCLUSION: Our findings are the first to show that the vascular benefit of liraglutide in patients with T2DM is associated with reductions in atherogenic small dense LDL. This effect is independent of glycemic control and body weight reduction and may represent one of the key mechanisms by which liraglutide is able to reduce cardiovascular events. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01715428.

Lung Ultrasound in COVID-19 A Role Beyond the Acute Phase?

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2. With the increasing number of improved and discharged patients with COVID-19, the definition of an adequate follow-up strategy is needed. The purpose of this study was to assess whether lung ultrasound (LUS) is an effective indicator of subclinical residual lung damage in patients with COVID-19 who meet discharge criteria. METHODS: We prospectively enrolled 70 consecutive patients with COVID-19 who had a prolonged hospitalization with inpatient rehabilitation between April 6 and May 22, 2020. All of the patients underwent an LUS evaluation at discharge. Data of patients with more severe disease during the acute phase (ie, required ventilatory support) were compared to those of patients with milder disease. RESULTS: Among the 70 patients with COVID-19 (22 women and 48 men; mean age ± SD, 68 ± 13 years), the LUS score before discharge was still frankly pathologic and higher in patients who had more severe disease during the acute phase compared to patients with milder disease (median [interquartile range], 8.0 [5.5-13.5] versus 2.0 [1.0-7.0]; P < .001), even when both categories met internationally defined discharge criteria. CONCLUSIONS: Lung ultrasound can identify the persistence of subclinical residual lung damage in patients with severe COVID-19 even if they meet discharge criteria. Considering the low cost, easy application, and lack of radiation exposure, LUS seems the ideal tool to be adopted in outpatient and primary care settings for the follow-up of patients with COVID-19.