Perceval sutureless bioprosthesis versus Trifecta sutured bioprosthesis for aortic valve replacement: immediate results of the Perfecta study.

Introduction: The Perceval sutureless biological prosthesis for aortic valve replacement has been introduced with the rationale for shortening surgical, extracorporeal circulation and aortic cross-clamping times, in order to reduce postoperative complications. Aim: To evaluate early hemodynamic performance and immediate outcomes of implantation of the Perceval sutureless bioprosthesis in comparison with the St. Jude Trifecta sutured bioprosthesis for aortic valve replacement (Perfecta study). Material and methods: Between December 2014 and June 2023, 281 patients underwent St. Jude Trifecta implantation (n = 220, mean age: 75.2 ±6.5 years) and Perceval implantation, when indicated (n = 61, mean age: 77.9 ±5.1 years). Concomitant CABG was performed in 73 (33%) and in 27 (44%) patients, respectively. Results: Extracorporeal circulation and cross-clamp times were significantly shorter in Perceval patients in all aortic valve replacements (61 ±23 and 49 ±18 minutes vs. 96 ±36 and 67 ±21 minutes), and in isolated procedures (54 ±10 and 43 ±8 minutes vs. 84 ±28 and 66 ±21 minutes) (p < 0.0001, for all comparisons). Operative mortality was absent and 2.7%, respectively (p = 0.2). Postoperatively, low output cardiac syndrome (0% vs. 4.5%) and total rate of major cardiac and non-cardiac related complications (6.6% vs. 18.6%) were significantly lower in Perceval patients (p = 0.01). Echocardiography at discharge in comparison with preoperatively showed a relevant and similar decrease of mean and peak trans-aortic valve gradients for the Trifecta prosthesis (11.6 ±4.3 vs. 50 ±15.2 mm Hg; 21.6 ±7.3 vs. 78.8 ±24 mm Hg) and for the Perceval prosthesis (12.6 ±4.8 vs. 52 ±12.5 mm Hg; 22.6 ±7.9 vs. 77.8 ±16 mm Hg) (p < 0.00001, for all comparisons). Better global cardiac function was observed in Perceval patients. Concomitant multi-vessel and left main coronary artery disease (p = 0.046; HR = 4.6) and chronic pulmonary disease (p = 0.006; HR = 5.6) were detected as independent predictors of death and postoperative major complications. Conclusions: Early hemodynamic performance appears to be satisfactory with the use of Trifecta sutured and Perceval sutureless bioprostheses. Perceval implantation allows reduction of surgical times, better preservation of myocardial contractile function and, consequently, reduction of the risk of postoperative complications.

Sutureless Aortic Prosthesis Valves versus Transcatheter Aortic Valve Implantation in Intermediate Risk Patients with Severe Aortic Stenosis: A Literature Review.

Aortic stenosis remains the most frequently occurring valvular pathology in the elderly population of Western countries. According to the latest guidelines, the therapeutic choice of aortic stenosis depends on the age of the patient (<75 years or >75 years) and the risk class (STS-Prom/Euroscore II < o >4%). Therefore, if the surgical indication is clear in young and low-risk patients and percutaneous treatment is the gold standard in older and high-risk patients, the therapeutic choice is still debated in intermediate-risk patients. In this group of patients, aortic valve stenosis treatment depends on the patient's global evaluation, the experience of the center, and, no less importantly, the patient's will. Two main therapeutic options are debated: surgical aortic valve replacement with sutureless prosthesis versus transcatheter aortic valve implantation. In addition, the progressive development of mininvasive techniques for aortic valve surgery (right-anterior minithoracotomy) has also reduced the peri- and post-operative risk in this group of patients. The purpose of this review is to compare sutureless aortic valve replacement (SuAVR) versus TAVI in intermediate-risk patients with severe aortic stenosis.

miRNA-Driven Regulation of Endothelial-to-Mesenchymal Transition Differs among Thoracic Aortic Aneurysms.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

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.

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.

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.

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.