miRNA Regulation of Cell Phenotype and Parietal Remodeling in Atherosclerotic and Non-Atherosclerotic Aortic Aneurysms: Differences and Similarities.

Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) exhibit differences and similarities in their pathophysiological and pathogenetic features. AAA is a multifactorial disease, mainly associated with atherosclerosis, characterized by a relevant inflammatory response and calcification. TAA is rarely associated with atherosclerosis and in some cases is associated with genetic mutations such as Marfan syndrome (MFS) and bicuspid aortic valve (BAV). MFS-related and non-genetic or sporadic TAA share aortic degeneration with endothelial-to-mesenchymal transition (End-Mt) and fibrosis, whereas in BAV TAA, aortic degeneration with calcification prevails. microRNA (miRNAs) contribute to the regulation of aneurysmatic aortic remodeling. miRNAs are a class of non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report the involvement of deregulated miRNAs in the different aortic remodeling characterizing AAAs and TAAs. In AAA, miRNA deregulation appears to be involved in parietal inflammatory response, smooth muscle cell (SMC) apoptosis and aortic wall calcification. In sporadic and MFS-related TAA, miRNA deregulation promotes End-Mt, SMC myofibroblastic phenotypic switching and fibrosis with glycosaminoglycan accumulation. In BAV TAA, miRNA deregulation sustains aortic calcification. Those differences may support the development of more personalized therapeutic approaches.

miR-632 Induces DNAJB6 Inhibition Stimulating Endothelial-to-Mesenchymal Transition and Fibrosis in Marfan Syndrome Aortopathy.

Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 gene mutations leading to TGF-ß signaling hyperactivation, vascular wall weakness, and thoracic aortic aneurysms (TAAs). The pathogenetic mechanisms are not completely understood and patients undergo early vascular surgery to prevent TAA ruptures. We previously reported miR-632 upregulation in MFS TAA tissues compared with non-genetic TAA tissues. DNAJB6 is a gene target of miR-632 in cancer and plays a critical role in blocking epithelial-to-mesenchymal transition by inhibiting the Wnt/ß catenin pathway. TGF-ß signaling also activates Wnt/ß catenin signaling and induces endothelial-to-mesenchymal transition (End-Mt) and fibrosis. We documented that miR-632 upregulation correlated with DNAJB6 expression in both the endothelium and the tunica media of MFS TAA (p < 0.01). Wnt/ß catenin signaling, End-Mt, and fibrosis markers were also upregulated in MFS TAA tissues (p < 0.05, p < 0.01 and p < 0.001). Moreover, miR-632 overexpression inhibited DNAJB6, inducing Wnt/ß catenin signaling, as well as End-Mt and fibrosis exacerbation (p < 0.05 and p < 0.01). TGF-ß1 treatment also determined miR-632 upregulation (p < 0.01 and p < 0.001), with the consequent activation of the aforementioned processes. Our study provides new insights about the pathogenetic mechanisms in MFS aortopathy. Moreover, the high disease specificity of miR-632 and DNAJB6 suggests new potential prognostic factors and/or therapeutic targets in the progression of MFS aortopathy.

The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study.

The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-ß-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.

Circulating Levels of Ferritin, RDW, PTLs as Predictive Biomarkers of Postoperative Atrial Fibrillation Risk after Cardiac Surgery in Extracorporeal Circulation.

Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15-50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haematological parameters as POAF risk biomarkers in patients subjected to cardiac surgery. We enrolled 105 patients (mean age = 70.1 ± 7.1 years; 70 men and 35 females) with diverse heart pathologies and who were subjected to cardiothoracic surgery. Their blood samples were collected and used to determine hematological parameters. Electrocardiographic and echocardiographic parameters were also evaluated. The data obtained demonstrated significantly higher levels of serum ferritin, red cell distribution width (RDW), and platelets (PLTs) in POAF patients. However, the serum ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥148.5 ng/mL, identifies the subjects at the highest POAF risk, and with abnormal ECG atrial parameters, such as PW indices, and altered structural heart disease variables. Serum ferritin, RDW, and PTLs represent predictive biomarkers of POAF after cardiothoracic surgery in CECC; particularly, serum ferritin combined with anormal PW indices and structural heart disease variables can represent an optimal tool for predicting not only POAF, but also the eventual stroke onset.

Specific miRNA and Gene Deregulation Characterize the Increased Angiogenic Remodeling of Thoracic Aneurysmatic Aortopathy in Marfan Syndrome.

Marfan syndrome (MFS) is a connective tissue disease caused by mutations in the FBN1 gene, leading to alterations in the extracellular matrix microfibril assembly and the early formation of thoracic aorta aneurysms (TAAs). Non-genetic TAAs share many clinico-pathological aspects with MFS and deregulation of some microRNAs (miRNAs) has been demonstrated to be involved in the progression of TAA. In this study, 40 patients undergoing elective ascending aorta surgery were enrolled to compare TAA histomorphological features, miRNA profile and related target genes in order to find specific alterations that may explain the earlier and more severe clinical outcomes in MFS patients. Histomorphological, ultrastructural and in vitro studies were performed in order to compare aortic wall features of MFS and non-MFS TAA. MFS displayed greater glycosaminoglycan accumulation and loss/fragmentation of elastic fibers compared to non-MFS TAA. Immunohistochemistry revealed increased CD133+ angiogenic remodeling, greater MMP-2 expression, inflammation and smooth muscle cell (SMC) turnover in MFS TAA. Cultured SMCs from MFS confirmed higher turnover and α-smooth muscle actin expression compared with non-MFS TAA. Moreover, twenty-five miRNAs, including miR-26a, miR-29, miR-143 and miR-145, were found to be downregulated and only miR-632 was upregulated in MFS TAA in vivo. Bioinformatics analysis revealed that some deregulated miRNAs in MFS TAA are implicated in cell proliferation, extracellular matrix structure/function and TGFß signaling. Finally, gene analysis showed 28 upregulated and seven downregulated genes in MFS TAA, some of them belonging to the CDH1/APC and CCNA2/TP53 signaling pathways. Specific miRNA and gene deregulation characterized the aortopathy of MFS and this was associated with increased angiogenic remodeling, likely favoring the early and more severe clinical outcomes, compared to non-MFS TAA. Our findings provide new insights concerning the pathogenetic mechanisms of MFS TAA; further investigation is needed to confirm if these newly identified specific deregulated miRNAs may represent potential therapeutic targets to counteract the rapid progression of MFS aortopathy.

Intraoperative Transesophageal Echocardiography for Surgical Repair of Degenerative Mitral Regurgitation.

BACKGROUND: Segmental analysis of diseased mitral valves is important to predict a successful surgical valve repair. An assessment was made of the comparative accuracy of intraoperative three-dimensional (3D) and two-dimensional (2D) transesophageal echocardiography (TEE) in the evaluation of mitral valve lesions when compared with intraoperative surgical segmental analysis. METHODS: A total of 42 consecutive patients (12 females, 30 males; mean age 70.5 ± 14 years) with severe mitral valve regurgitation due to degenerative disease and who underwent mitral valve repair was enrolled in the study. Complete 2D- and 3D-TEE were performed before surgery. The findings obtained using the different echocardiographic techniques were compared with intraoperative segmental analysis performed by a single operator who was blinded to the 2D- and 3D-TEE findings until the end of the inspection. The sensitivity and specificity of echocardiographic evaluations of involved scallops were compared with surgical inspection. RESULTS: 3D-TEE allowed an accurate identification of all mitral lesions. Thirty-three patients had simple lesions at 3D-TEE and underwent a simple surgical procedure, while nine patients had complex lesions; in these latter cases complex surgical procedures were performed. 3D-TEE showed more sensitivity than 2D-TEE in the analysis of the anterior leaflet (A), in particular for A3 lesion (100% versus 25%, p <0.001) and for complex lesion (100% versus 33.3%, p <0.009). CONCLUSIONS: 3D-TEE allowed a more accurate identification of mitral valve lesions compared with 2D-TEE. The greatest accuracy was achieved for analysis of the anterior leaflet. 3D-TEE should be regarded as an important adjunct to standard 2D-TEE in decisions regarding mitral valve repair.

Cardiovascular Disease in Ageing: An Overview on Thoracic Aortic Aneurysm as an Emerging Inflammatory Disease.

Medial degeneration associated with thoracic aortic aneurysm and acute aortic dissection was originally described by Erdheim as a noninflammatory lesion related to the loss of smooth muscle cells and elastic fibre fragmentation in the media. Recent evidences propose the strong role of a chronic immune/inflammatory process in aneurysm evocation and progression. The coexistence of inflammatory cells with markers of apoptotic vascular cell death in the media of ascending aorta with aneurysms and type A dissections raises the possibility that activated T cells and macrophages may contribute to the elimination of smooth muscle cells and degradation of the matrix. On the other hand, several inflammatory pathways (including TGF-ß, TLR-4 interferon-γ, chemokines, and interferon-γ) seem to be involved in the medial degeneration related to aged and dilated aorta. This is an overview on thoracic aortic aneurysm as an emerging inflammatory disease.

Matrix Metalloproteinases (MMPs), Their Genetic Variants and miRNA in Mitral Valve Diseases: Potential Biomarker Tools and Targets for Personalized Treatments.

Mitral valve diseases (MVD)s, comprising congenital and acquired forms, are characterized by a diverse etiology, pathophysiology, prevalence, and incidence. In industrialized countries, the acquired forms represent 2.5% of all cardiovascular diseases, with a marked augmentation after the age of 65 years. In addition, all forms of MVDs (i.e., degenerative forms) have a difficult clinical management. The major challenge is 'the early diagnosis', and echocardiographic analysis has been shown inappropriate for diagnosing MVD in moderate forms. Thus, there is a strong need to identify more appropriate biomarker tools to diagnose MVDs at early clinical stage before complications occur and worsen the prognosis. Innovative biomarker tools may particularly be appropriate for the complex treatment of elderly patients, the clinical management of which is very difficult due to the high risk of surgical interventions and no clear benefits in terms of life expectancy or quality of life compared to younger patients. These biomarker tools may be identified as genetic factors and/or components of cellular and molecular pathways related to the mechanisms of MDV pathophysiology. In this review, emphasis is placed on the possibility of proposing matrix metalloproteinase (MMP) pathways, their genetic variants and microRNA as promising predictive, diagnostic and prognostic biomarkers and targets for personalized treatments. Evidence is also provided of the lack of any consistent evidence which actually hampers their clinical application. Thus, criticisms and concerns are underlined, as well as suggestions to close the existing gaps.

Acute Type A Aortic Dissection: Beyond the Diameter.

Aortic dissection is a life-threatening condition in which early diagnosis, treatment and close follow up are critical for survival. Between 60% and 70% of patients with acute aortic dissection are affected at the ascending aorta, classified as Stanford type A (TAD). Preventive surgery of the aorta in asymptomatic patients on the basis of aortic size alone remains controversial among patient populations without known risk factors for aortic dissection. In fact, many dissection patients do not appear to have markedly dilated aortas at the time of presentation. In contrast, previous studies have indicated that the incidence of aortic dissection did not decrease, regardless of elective aortic replacement therapy. An increased aortic size as a follow up parameter is not sufficient to predict aortic dissection and rupture. Here, published evidence is reported regarding the limited role of aortic size in the genesis of TAD. Currently, a need exists to develop new markers to prevent aortic complications, especially in patients with sporadic ascending aneurysms (S-TAAs). It is important to emphasize this interesting aspect to the scientific cardiothoracic surgery forum in an attempt to improve guidelines for this disease.

Impact of Prosthesis-Patient Mismatch after Mitral Valve Replacement.

BACKGROUND: The study aim was to determine the impact of prosthesis-patient mismatch (PPM) on early and late clinical outcomes, left atrial and ventricular remodeling, late tricuspid valve regurgitation and pulmonary hypertension (PH) in patients after mitral valve replacement (MVR). METHODS: A total of 46 patients (mean age 66 ± 9.3 years) with mitral valve diseases and undergoing isolated MVR was enrolled in the study. The mitral valve effective orifice area (EOA) was determined using the continuity equation and indexed for the patient's body surface area (EOAi). PPM was defined as EOAi ≤1.2 cm2/m2. PH was defined as a systolic pulmonary artery pressure (sPAP) >40 mmHg. Both, clinical and echocardiographic follow up were performed. RESULTS: PPM was identified in 25% of patients, but no significant differences were observed in baseline and operative characteristics when comparing patients with and without PPM. The NYHA class was improved in most cases after surgery. Indeed, significant decreases in mean transvalvular gradient (from 8.6 ± 2.8 mmHg to 5 ± 1.3 mmHg, p = 0.001), left atrial dimension (LAD) (from 31.9 ±9.8 mm to 29.5 ± 7 mm, p = 0.011), left ventricular end-systolic diameter (from 42.6 ± 18.1 mm to 35.5 ± 6.6 mm, p = 0.044) and left ventricular end-diastolic diameter (from 55.8 ± 19.2 mm to 48.7 ± 6.1 mm, p = 0.024) were observed over time when comparing preoperative and postoperative echocardiographic data. In addition, at follow up (mean 6.9 ± 1.8 years) there were significant decreases in LAD (from 31.9 ± 9.8 mm to 28 ± 11.1 mm, p = 0.001), left ventricular enddiastolic volume (from 106.9 ± 32.9 ml to 92.3 ± 21.9 ml, p = 0.024), tricuspid regurgitation (TR) (from 87% to 27%, p = 0.002) and PH (from 78.3% to 58.7%, p = 0.043) in all patients. No significant differences were observed in hemodynamic, clinical outcome and atrial natriuretic peptide levels of patients with and without PPM. CONCLUSIONS: Mitral PPM does not appear to have any negative effect on ventricular and atrial remodeling, TR and PH during the early and late postoperative periods.

Penn classification in acute aortic dissection patients.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of the Penn classification in predicting in-hospital mortality after surgery in acute type A aortic dissection patients. METHODS: We evaluated 58 patients (42 men and 16 women; mean age 62.17 ± 10.6 years) who underwent emergency surgery for acute type A aortic dissection between September 2003 and June 2010 in our department. We investigated the correlation between the pre-operative malperfusion and in-hospital outcome after surgery. RESULTS: Twenty-eight patients (48%) were Penn class Aa (absence of branch vessel malperfusion or circulatory collapse), 11 (19%) were Penn class Ab (branch vessel malperfusion with ischaemia), 5 (9%) were Penn class Ac (circulatory collapse with or without cardiac involvement) and 14 (24%) were Penn class Abc (both branch vessel malperfusion and circulatory collapse). The number of patients with localized or generalized ischaemia or both, Penn class non-Aa, was 30 (52%). In-hospital mortality was 24%. In-hospital mortality was significantly higher in Penn class Abc and Penn class non-Aa. Intensive unit care stay, hospital ward stay and overall hospital stay was longer in Penn class non-Aa vs Penn class Aa. De Bakey type I dissection and type II diabetes mellitus were associated with in-hospital mortality. CONCLUSION: Preoperative malperfusion is important for the evaluation of patients with acute aortic type A dissection. The Penn classification is a simple and quick method to apply and predict in-hospital mortality and outcomes.

Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"?

Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

Role of TGF-ß pathway polymorphisms in sporadic thoracic aortic aneurysm: rs900 TGF-ß2 is a marker of differential gender susceptibility.

Thoracic aortic aneurysm (TAA) is a progressive disorder involving gradual dilation of ascending and/or descending thoracic aorta with dissection or rupture as complications. It occurs as sporadic or defined syndromes/familial forms.Genetic, molecular and cellular mechanims of sporadic TAA forms are poorly characterized and known. Thus, our interest has been focused on investigating the role of genetic variants of transforming growth factor-ß (TGF-ß) pathways in TAA risk. On the other hand, no data on the role of genetic variants of TGF-ß pathway in sporadic TAA exist until now. In addition, other cytokines, including IL-10, orchestrate TAA pathophysiology. Their balance determines the ultimate fate of the aortic wall as healing atherosclerosis or aneurysm formation. Thus, in this paper it was analyzed the role of ten polymorphisms of genes encoding TGF-ß isoforms and receptors, and IL-10 in sporadic TAA. Our study included cases affected by sporadic TAA and two control groups. The most relevant finding obtained allows us to propose that rs900 TGF-ß2 SNP is associated with sporadic TAA in women. This might open new perspectives for the analysis of sporadic TAA susceptibility factors and prevention.

CAR, mGPS and hs-mGPS: What is among them the best gero-biomarker for age-related diseases? And for what clinical application?

The identification of biomarkers linked to the onset, progression, and prevention of age-related diseases (ARD), in the era of personalized medicine, represents the best goal of geroscience. Geroscience has the fundamental role of exploring and identifying the biological mechanisms of aging to suggest interventions capable of stopping/delaying the many pathological conditions and disabilities related to age. Therefore, it has become its key priority, as well as that of clinical practice and research, based on identifying and validating a range of biomarkers, geromarkers, which can be used to diagnostic, prognostic, or predictive clinical purposes. Indeed, geromarkers have, the potential to predict ARD trajectories and facilitate targeted interventions to slow down the related disabilities. Here our attention is paid to the inflammatory indexes (CAR, mGPS, hs-mGPS) linked to the relationship between the plasma levels of two inflammatory analytes, the typical positive protein of the acute phase, and the negative one, i.e. c-reactive protein (CRP) and albumin, respectively. These indexes allow us to understand the magnitude of the two main mechanisms predicted to influence the aging process, including inflammation and immunosenescence, as well as the degree of ARD severity. Evidence on their relationship with ARD is widely reported and discussed, to understand which can represent the best ARD geromarker, and its clinical application.

The role of the female gender on mid-term outcome after coronary artery bypass grafting: a retrospective study.

Background: Data on female gender differences on clinical prognosis after coronary artery bypass grafting (CABG) are still controversial. We evaluated retrospectively the impact of women patients in comparison with men undergoing CABG on mid-term outcome. Methods: Between December 2014 and March 2022, 1,044 consecutive patients (162 females, 15.5%, 882 males, 84.5%) underwent isolated CABG. The mean follow-up was 40±27 (median 38) months. Logistic and Cox model analysis regressions were used to assess the risk of female gender and other variables, Kaplan-Meier estimates to assess survival rates. Results: Women did not have a significant higher operative mortality than men (3.09% vs. 1.93%; P=0.37). There was no difference in the use of left internal mammary artery (97.5% vs. 94.9%; P=0.85). Independent predictors of early mortality were emergency CABG (P<0.0001), percutaneous coronary intervention (PCI) within 30 days (P=0.0026), and higher EuroSCORE II (P=0.0155). At 7.5 years, actuarial survival was 87%±3.6% for female gender vs. 88%±1.9% in male gender (P=0.41), freedom from cardiac death 97%±1.8% vs. 96.6%±1.0% (P=0.6), freedom from major adverse cardiac events (MACE) 87%±6.2% vs. 89.7%±2.5% (P=0.96). Independent predictor of all-causes death and cardiac death was the advanced age (74 years in dead patients vs. 67 years in survivors) (P<0.0001). Female gender was not a predictor of either operative mortality (P=0.34) or worse mid-term outcome (P=0.41). Conclusions: Women undergoing CABG with the same surgical techniques currently adopted for men, do not appear to be associated with worse early prognosis. Freedom from late all-causes mortality, cardiac death and adverse cardiac events are comparable and equally satisfactory, highlighting the positive protective effect of CABG over time also in women.

Early-Staged Carotid Artery Stenting Prior to Coronary Artery Bypass Grafting: Analysis of the Early and Mid-Term Results in Comparison with a Consecutive Cohort of Isolated Coronary Artery Surgery Patients.

AIM: The aim of the present study was to analyze retrospectively the results of patients who underwent early-staged, i.e., within 24-48 h, carotid artery stenting (e-s CAS) before coronary artery bypass grafting (CABG). METHODS: Between December 2014 and December 2022, 1046 consecutive patients underwent CABG; 31 of these patients (3%) were subjected to e-s CAS prior to CABG (e-s CAS + CABG group). Preoperative and intraoperative variables and early and mid-term results of the e-s CAS + CABG group were compared with those of patients who underwent isolated CABG (CABG group). RESULTS: As compared with the CABG group, the e-s CAS + CABG group showed a worse clinical risk profile due to higher Euroscore-2 values and incidence of obstructive pulmonary disease and bilateral carotid artery and peripheral artery diseases (p < 0.05, for all comparisons). The combined end point of operative mortality, periprocedural myocardial infarction, and stroke was 3.2% (0%/0%/3.2%) in the e-s CAS + CABG group vs. 5.9% (2.2%/2.8%/0.9%) in the CABG group (p > 0.5, for all measurements). At 5 years, actuarial survival was 74% ± 16% in the e-s CAS + CABG group vs. 93% ± 4.0% in the CABG group, freedom from cardiac death was 100% vs. 98% ± 1.0% (p = 0.6), and freedom from MACCEs was 85% ± 15% vs. 97% ± 2.5% (p > 0.1, for all comparisons). Independent predictors of all-causes death were advanced age at the operation (p < 0.0001), a lower value for left ventricular ejection fraction (p = 0.05), and a high Euroscore-2 (p = 0.04). CONCLUSIONS: CABG preceded by e-s CAS appears to be associated with satisfactory early outcomes while limiting the risk of myocardial infarction to a very short time interval between the two procedures. Freedom from late all-causes death, cardiac death, and MACCEs were comparable and equally satisfactory, underscoring the positive protective effects of CAS and CABG on the carotid and coronary territories over time.

A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: The Elabela/Apela/Toddler peptide.

Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its high homology with apelin, the first ligand of APJ receptor, ELA likely mediates similar effects. Increasing evidence shows that ELA has a critical function not only in embryonic development, but also in adulthood, contributing to physiological and pathological conditions, such as the onset of age-related diseases (ARD). However, still little is known about the mechanisms and molecular pathways of ELA, as well as its precise functions in ARD pathophysiology. Here, we report the mechanisms by which ELA/APJ signaling acts in a very complex network of pathways for the maintenance of physiological functions of human tissue and organs, as well as in the onset of some ARD, where it appears to play a central role. Therefore, we describe the possibility to use the ELA/APJ pathway, as novel biomarker (predictive and diagnostic) and target for personalized treatments of ARD. Its potentiality as an optimal peptide candidate for therapeutic ARD treatments is largely described, also detailing potential current limitations.

Cerebrovascular events after cardiovascular surgery: diagnosis, management and prevention strategies.

Introduction: Cerebrovascular events after cardiac surgery are among the most serious complications, related to a greater risk of patient mortality. This problem can occur following the formation of gas emboli during open heart surgery. Aim: To address all the mechanisms that can lead to embolic events after cardiovascular surgery, how to manage them and how to possibly prevent them. Material and methods: A search of the PubMed database was conducted. We reviewed the clinical literature and examined all aspects to identify the root causes that can lead to the formation of emboli. Results: Among the studies reviewed, it was found that the main causes include manipulation of the aorta, inadequate deaeration after cardiac surgery, and blood-component contact of extracorporeal circulation. It has been reported that gas emboli can lead to deleterious damage such as damage to the cerebral vascular endothelium, disruption of the blood-brain barrier, complement activation, leukocyte aggregation, increased platelet adhesion, and fibrin deposition in the microvascular system. Conclusions: Stroke after cardiovascular surgery is one of the most important complications, with a great impact on operative mortality and patient survival. Efforts have been made over time to understand all the pathophysiological mechanisms related to this complication, with the aim of reducing its incidence. One of the goals should be to improve both the surgical technique and the perfusion modality and minimize the formation of air bubbles or to facilitate their elimination during the cardiopulmonary bypass procedure.

How Refined Surgical Technical Solutions Can Make Bentall Operation a Low-Risk Procedure: 20-Year Personal Experience at the "Root" of the Aortic Diseases-It Is Time to Change Surgical Guidelines.

(1) Objective: Twenty years' experience of Bentall-De Bono operations by one surgeon. (2) Methods: From January 2003 to September 2023, four-hundred-and-two patients aged 65.9 ± 15 years underwent a Bentall operation. The EuroScore-2 was 5.0% ± 3.8%. Associated procedures were performed on 113 patients (28.1%). Results: Operative mortality was 1.2% (n = 5), in particular 0.69% (n = 2/289) for isolated Bentall operation, 2.65% (n = 3/113) for combined procedures (p < 0.05). Postoperative acute heart failure occurred in 38 patients (9.45%). Preoperative pulmonary hypertension (44 ± 14 vs. 33 ± 7 mmHg), cardiopulmonary bypass time (169 ± 61 min. vs. 124 ± 42 min.) and aortic cross-clamp time (133 ± 45 min. vs. 107 ± 34 min.) have been recognized as independent predictors of mortality and cardiac complications (p < 0.05). Conclusions: In our experience, the Bentall operation was associated with low operative mortality and low rate of complications. For this reason, in agreement with the patients, we have modified surgical indication for ascending aortic aneurysms and now we think that it is time to change surgical guidelines.

Transcatheter aortic valve replacement in the management of aortic insufficiency secondary to left ventricular assist device implantation: a case report.

Background: Left ventricular assist device (LVAD) is considered either a destination therapy for patients with end-stage heart failure or heart transplantation bridging. LVAD implantation often causes aortic insufficiency (AI), which requires aortic valve repair. However, severe acute AI does not respond well to medication, and re-operation means higher risk to the patients; the most effective therapeutic strategies for LVAD-induced AI still need further exploration. In this report, we present the first described case of new-onset, severe LVAD-induced AI in China with a patient who underwent transcatheter aortic valve replacement (TAVR) and achieved significant improvement in functional capacity and symptoms with lower operation risk. Case Description: A 55-year-old male patient was diagnosed with dilated cardiomyopathy for 14 years. The effect of the medication gradually deteriorated, LVAD (HeartCon®) was implanted one year earlier. The patient complained of intermittent chest tightness for one week, which had been aggravated for two days before hospitalization. Echocardiographic findings revealed new-onset, severe LVAD-induced AI. TAVR was performed with a self-expandable stent-valve (TAV30, Vitaflow Liberty). Within minutes, the patient recovered with rapid disappearance of chest tightness and stable vital signs. Before discharge, the position of the artificial valve was fixed without incomplete closure nor thrombus attachment, yielding a left ventricular ejection fraction (LVEF) of 35%. The patient was hospitalized for 38 days, and followed up with outpatient treatment, the condition was stable until 19 June 2023. Conclusions: TAVR could be an effective, safe, and less invasive means of restoring ejection fraction for patients with a LVAD who develop severe AI.