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.

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.

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.

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.

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.

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.

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.

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.

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.

Initial Surgical Strategy for the Treatment of Type A Acute Aortic Dissection: Does Proximal or Distal Extension of the Aortic Resection Influence the Outcomes?

(1) Background: We sought to analyze and compare the outcomes in terms of early and late mortality and freedom from a redo operation in patients undergoing surgical treatment for a type A acute aortic dissection in relation to the initial surgical treatment strategy, i.e., proximal or distal extension of the aortic segment resection, compared with isolated resection of the supracoronary ascending aorta. (2) Methods: This is a retrospective study in which we included 269 patients who underwent operations for a type A acute aortic dissection in the Department of Cardiac Surgery of Tor Vergata University from May 2006 to May 2016. The patients were grouped according to the extent of the performed surgical treatment: isolated replacement of the supracoronary ascending aorta (NE, no extension), replacement of the aortic root (PE, proximal extension), replacement of the aortic arch (DE, distal extension), and both (BE, bilateral extension). The analyzed variables were in-hospital mortality, postoperative complications (incidence of neurological damage, renal failure and need for prolonged intubation), late mortality and need for a redo operation. (3) Results: Unilateral cerebral perfusion was performed in 49.3% of the patients, and bilateral perfusion-in 50.6%. The overall in-hospital mortality was 31.97%. In the multivariate analysis, advanced age, cardiopulmonary bypass time and preoperative orotracheal intubation were independent predictors of in-hospital mortality. In the population of patients who survived the surgery, the probability of survival at 92 months was 70 ± 5%, the probability of freedom from a redo operation was 71.5 ± 5%, the probability of freedom from the combined end-point death and a redo operation was 50 ± 5%. The re-intervention rate in the general population was 16.9%. The overall probability of freedom from re-intervention was higher in patients undergoing aortic root replacement, although not reaching a level of statistical significance. Patients who underwent aortic arch treatment showed reduced survival. (4) Conclusions: In the treatment of type A acute aortic dissection, all the surgical strategies adopted were associated with satisfactory long-term survival. In the group of patients in which the aortic root had not been replaced, we observed reduced event-free survival.

Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms.

Aorta diseases, such as ascending aorta aneurysm (AsAA), are complex pathologies, currently defined as inflammatory diseases with a strong genetic susceptibility. They are difficult to manage, being insidious and silent pathologies whose diagnosis is based only on imaging data. No diagnostic and prognostic biomarkers or markers of outcome have been known until now. Thus, their identification is imperative. Certainly, a deep understanding of the mechanisms and pathways involved in their pathogenesis might help in such research. Recently, the key role of oxidative stress (OS) on the pathophysiology of aorta disease has emerged. Here, we describe and discuss these aspects by revealing some OS pathways as potential biomarkers, their underlying limitations, and potential solutions and approaches, as well as some potential treatments.

Bentall Operation: Early Surgical Results, Seven-Year Outcomes, and Risk Factors Analysis.

Aim: To analyze early and mid-term outcomes of the Bentall operation. Methods: Two hundred and seventeen patients (mean age 65.6 ± 15.9 years, males/females 172/45) underwent Bentall operation in a 7-year period (January 2015−December 2021), on average, 30 Bentall operations occurred per year, using biological (n = 104) or mechanical (n = 113) valved conduits for the treatment of ascending aorta−aortic root aneurysms. Associate procedures were performed in 58 patients (26.7%); coronary artery bypass grafting (CABG) in 35 (16%). Mean follow-up was 55.2 ± 24 (median 60.2) months. Cox model analysis was used to assess risk factors, Kaplan−Meier and log-rank tests were used to assess different survival rates. Results: Operative mortality was 1.38%. At 7 years, survival, freedom from cardiac death, and event-free survival were 93% ± 2%, 99% ± 1%, and 81% ± 5%. NYHA class (p < 0.0001), trans-aortic valve mean (p < 0.0001) and maximum (p < 0.000) gradients, left ventricular hypertrophy (p < 0.05), and pulmonary arterial pressure (p = 0.002) significantly improved vs. preoperative values. Concomitant CABG during Bentall operation independently affected late outcomes (HR 1.9−2.3; p-values < 0.05). Late survival was affected by concomitant CABG (84% ± 8% vs. 95% ± 2%, p = 0.04), preoperative myocardial infarction (91% ± 9% vs. 97% ± 2%, p = 0.02), and biological vs. mechanical prostheses valved conduits (91% ± 9% vs. 95% ± 3%, p = 0.02). Event-free survival also was affected by concomitant CABG (62% ± 14% vs. 85% ± 5%, p = 0.005) and biological prostheses (78% ± 8% vs. 84% ± 6%, p = 0.06). Freedom from endocarditis−redo operation was 83% ± 9% for biological prostheses vs. 89% ± 6% for mechanical prostheses (p = 0.49). Conclusions: Low rates of operative mortality and late complications make Bentall operation the gold standard for the treatment of ascending aorta−aortic root aneurysms. Coronary ischemic disease affects late outcomes. Biological prostheses should be preferred for the elderly.

Medial tunica degeneration of the ascending aortic wall is associated with specific microRNA changes in bicuspid aortic valve disease.

Ascending aortic diameter is not an accurate parameter for surgical indication in patients with bicuspid aortic valve (BAV). Thus, the present study aimed to identify specific microRNAs (miRNAs/miRs) and their expression levels in aortic wall aneurysm associated with BAV according to severity of medial degeneration and to elucidate the association between the tissue expression levels of the miRNAs with their expression in plasma. Aortic wall and blood specimens were obtained from 38 patients: 12 controls and 26 patients with BAV with ascending aortic aneurysm. Of the patients with BAV, 19 had cusp fusions of right and left, 5 of right and non­coronary, and 2 of left and non­coronary. Two groups of patients were identified according to the grade of medial degeneration (MD): Low­grade D group (LGMD) and high­grade MD group (HGMD). Expression level of miR­122, miR­130, miR­718 and miR­486 were validated by reverse transcription­quantitative PCR in plasma and tissue samples. MD grade was found to be independent from the BAV phenotype. The HGD group showed increased expression levels of MMP­9 and MMP­2, and an increase in the number of apoptotic cells. Tissue expression levels of miR­718 and miR­122 were lower in the LGMD and HGD groups compared with expression in the control group; the HGD group showed increased levels of miR­486. Plasma expression levels of miR­122 were decreased in the LGMD and HGD groups, and miR­718 was only reduced in the HGD group. On the contrary, expression of miR­486 was increased in the LGMD and HGD groups. The data suggested that miR­486 may be considered as a non­invasive biomarker of aortic wall degeneration. Dysregulation of this putative biomarker may be associated with high risk of dissection and rupture in patients with BAV.

The impact of dual antiplatelet therapy administration on the risk of bleeding complications during coronary artery bypass surgery.

INTRODUCTION: Dual antiplatelet therapy reduces the risk of cardiovascular death, myocardial infarction and recurrence of adverse ischemic events in patients affected by acute coronary syndromes, but in patients urgently needing coronary artery surgery it can increase the risk of severe perioperative bleeding complications. AIM: We evaluated the impact of dual antiplatelet therapy (DAPT) based on acetylsalicylic acid plus clopidogrel or ticagrelor in patients undergoing coronary artery bypass grafting (CABG). MATERIAL AND METHODS: Three hundred and thirty-three patients underwent coronary artery bypass grafting with DAPT discontinuation > 72 hours or 3-4 days (group A, n = 159), 48-72 hours or 2-3 days (group B, n = 126), < 24 hours or 0-1 day (group C, n = 24) prior to CABG. RESULTS: Operative mortality was 1.87% (group A), 0.79% (group B), absent (group C). The incidence of mediastinal re-exploration was 1.25% or 2 patients (group A), 1.59% or 2 patients (group B), 8.33% or 4 patients (group C) (p = 0.01). Group C showed postoperatively a greater incidence of a blood loss greater than 500 ml at 6 hours and a blood loss from chest tube drainages significantly higher at 6 and 24 hours (p < 0.01). Multivariate analysis showed that ongoing ticagrelor intake in group C (HR = 42.4; p = 0.02) and group C (HR = 6.9; p = 0.04) were the only independent predictors of surgical re-exploration. In group C, surgical re-exploration was 2.56% or 1/39 patients taking clopidogrel, 33.3% or 3/9 patients taking ticagrelor (p = 0.002). CONCLUSIONS: Dual antiplatelet therapy ongoing until 1 day or 24 hours before CABG showed a significantly increased risk of bleeding complications in comparison with its discontinuation at 2-3 and > 3-4 days before, respectively. Major blood loss and surgical re-exploration were not associated with increased risk of operative all-cause or bleeding-related mortality. As expected, taking ticagrelor compared with clopidogrel in the short interval confers a higher risk of bleeding complications.