Endothelium-Derived Relaxing Factors and Endothelial Function: A Systematic Review.

BACKGROUND: The endothelium plays a pivotal role in homeostatic mechanisms. It specifically modulates vascular tone by releasing vasodilatory mediators, which act on the vascular smooth muscle. Large amounts of work have been dedicated towards identifying mediators of vasodilation and vasoconstriction alongside the deleterious effects of reactive oxygen species on the endothelium. We conducted a systematic review to study the role of the factors released by the endothelium and the effects on the vessels alongside its role in atherosclerosis. METHODS: A search was conducted with appropriate search terms. Specific attention was offered to the effects of emerging modulators of endothelial functions focusing the analysis on studies that investigated the role of reactive oxygen species (ROS), perivascular adipose tissue, shear stress, AMP-activated protein kinase, potassium channels, bone morphogenic protein 4, and P2Y2 receptor. RESULTS: 530 citations were reviewed, with 35 studies included in the final systematic review. The endpoints were evaluated in these studies which offered an extensive discussion on emerging modulators of endothelial functions. Specific factors such as reactive oxygen species had deleterious effects, especially in the obese and elderly. Another important finding included the shear stress-induced endothelial nitric oxide (NO), which may delay development of atherosclerosis. Perivascular Adipose Tissue (PVAT) also contributes to reparative measures against atherosclerosis, although this may turn pathological in obese subjects. Some of these factors may be targets for pharmaceutical agents in the near future. CONCLUSION: The complex role and function of the endothelium is vital for regular homeostasis. Dysregulation may drive atherogenesis; thus, efforts should be placed at considering therapeutic options by targeting some of the factors noted.

Patients with Bicuspid Aortopathy and Aortic Dilatation.

(1) Background: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. Alteration of ascending aorta diameter is a consequence of shear stress alterations due to haemodynamic abnormalities developed from inadequate valve cusp coaptation. (2) Objective: This narrative review aims to discuss anatomical, pathophysiological, genetical, ultrasound, and radiological aspects of BAV disease, focusing on BAV classification related to imaging patterns and flux models involved in the onset and developing vessel dilatation. (3) Methods: A comprehensive search strategy was implemented in PubMed from January to May 2022. English language articles were selected independently by two authors and screened according to the following criteria. (4) Key Contents and Findings: Ultrasound scan is the primary step in the diagnostic flowchart identifying structural and doppler patterns of the valve. Computed tomography determines aortic vessel dimensions according to the anatomo-pathology of the valve. Magnetic resonance identifies hemodynamic alterations. New classifications and surgical indications derive from these diagnostic features. Currently, indications correlate morphological results, dissection risk factors, and genetic alterations. Surgical options vary from aortic valve and aortic vessel substitution to aortic valve repair according to the morphology of the valve. In selected patients, transcatheter aortic valve replacement has an even more impact on the treatment choice. (5) Conclusions: Different imaging approaches are an essential part of BAV diagnosis. Morphological classifications influence the surgical outcome.

Thromboembolic Disease and Cardiac Thrombotic Complication in COVID-19: A Systematic Review.

The coronavirus 2019 pandemic has affected many healthcare systems worldwide. While acute respiratory distress syndrome (ARDS) has been well-documented in COVID-19, there are several cardiovascular complications, such as myocardial infarction, ischaemic stroke, and pulmonary embolism, leading to disability and death. The link between COVID-19 and increasing thrombogenicity potentially occurs due to numerous different metabolic mechanisms, ranging from endothelial damage for direct virus infection, associated excessive formation of neutrophil extracellular traps (NETs), pathogenic activation of the renin-angiotensin-aldosterone system (RAAS), direct myocardial injury, and ischemia induced by respiratory failure, all of which have measurable biomarkers. A search was performed by interrogating three databases (MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations, and EMBASE). Evidence from randomized controlled trials (RCT), prospective series, meta-analyses, and unmatched observational studies were evaluated for the processing of the algorithm and treatment of thromboembolic disease and cardiac thrombotic complications related to COVID-19 during SARS-CoV-2 infection. Studies out with the SARS-Cov-2 infection period and case reports were excluded. A total of 58 studies were included in this analysis. The role of the acute inflammatory response in the propagation of the systemic inflammatory sequelae of the disease plays a major part in determining thromboembolic disease and cardiac thrombotic complication in COVID-19. Some of the mechanisms of activation of these pathways, alongside the involved biomarkers noted in previous studies, are highlighted. Inflammatory response led to thromboembolic disease and cardiac thrombotic complications in COVID-19. NETs play a pivotal role in the pathogenesis of the inflammatory response. Despite moving into the endemic phase of the disease in most countries, thromboembolic complications in COVID-19 remain an entity that substantially impacts the health care system, with long-term effects that remain uncertain. Continuous monitoring and research are required.

Cardiotoxicity of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Pathophysiology, Clinical Implications, and Echocardiographic Assessment.

Contemporary anticancer immunotherapy with chimeric antigen receptor T-cell (CAR-T) therapy has dramatically changed the treatment of many hematologic malignancies previously associated with poor prognosis. The clinical improvement and the survival benefit unveiled the risk of cardiotoxicity, ranging from minimal effects to severe cardiac adverse events, including death. Immunotherapy should also be proposed even in patients with pre-existing cardiovascular risk factors, thereby increasing the potential harm of cardiotoxicity. CAR-T therapy frequently results in cytokine release syndrome (CRS), and inflammatory activation is sustained by circulating cytokines that foster a positive feedback mechanism. Prompt diagnosis and treatment of CAR-T cardiotoxicity might significantly improve outcomes and reduce the burden associated with cardiovascular complications. Clinical and echocardiographic examinations are crucial to perform a tailored evaluation and follow-up during CAR-T treatment. This review aims to summarize the pathophysiology, clinical implications, and echocardiographic assessment of CAR-T-related cardiotoxicity to enlighten new avenues for future research.

Biomechanics of Transcatheter Aortic Valve Implant.

Transcatheter aortic valve implantation (TAVI) has grown exponentially within the cardiology and cardiac surgical spheres. It has now become a routine approach for treating aortic stenosis. Several concerns have been raised about TAVI in comparison to conventional surgical aortic valve replacement (SAVR). The primary concerns regard the longevity of the valves. Several factors have been identified which may predict poor outcomes following TAVI. To this end, the lesser-used finite element analysis (FEA) was used to quantify the properties of calcifications which affect TAVI valves. This method can also be used in conjunction with other integrated software to ascertain the functionality of these valves. Other imaging modalities such as multi-detector row computed tomography (MDCT) are now widely available, which can accurately size aortic valve annuli. This may help reduce the incidence of paravalvular leaks and regurgitation which may necessitate further intervention. Structural valve degeneration (SVD) remains a key factor, with varying results from current studies. The true incidence of SVD in TAVI compared to SAVR remains unclear due to the lack of long-term data. It is now widely accepted that both are part of the armamentarium and are not mutually exclusive. Decision making in terms of appropriate interventions should be undertaken via shared decision making involving heart teams.

miRNAs in Cardiac Myxoma: New Pathologic Findings for Potential Therapeutic Opportunities.

MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, contributing to all major cellular processes. The importance of miRNAs in cardiac development, heart function, and valvular heart disease has been shown in recent years, and aberrant expression of miRNA has been reported in various malignancies, such as gastric cancer and breast cancer. Different from other fields of investigation, the role of miRNAs in cardiac tumors still remains difficult to interpret due to the scarcity publications and a lack of narrative focus on this topic. In this article, we summarize the available evidence on miRNAs and cardiac myxomas and propose new pathways for future research. miRNAs play a part in modifying the expression of cardiac transcription factors (miR-335-5p), increasing cell cycle trigger factors (miR-126-3p), interfering with ceramide synthesis (miR-320a), inducing apoptosis (miR-634 and miR-122), suppressing production of interleukins (miR-217), and reducing cell proliferation (miR-218). As such, they have complex and interconnected roles. At present, the study of the complete mechanistic control of miRNA remains a crucial issue, as proper understanding of signaling pathways is essential for the forecasting of therapeutic implications. Other types of cardiac tumors still lack adequate investigation with regard to miRNA. Further research should aim at investigating the causal relationship between different miRNAs and cell overgrowth, considering both myxoma and other histological types of cardiac tumors. We hope that this review will help in understanding this fascinating molecular approach.

Exploring the Operative Strategy for Secondary Mitral Regurgitation: A Systematic Review.

BACKGROUND: Mitral valve disease surgery is an evolving field with multiple possible interventions. There is an increasing body of evidence regarding the optimal strategy in secondary mitral regurgitation where the pathology lies within the ventricle. We conducted a systematic review to identify the benefits and limitations of each surgical option. METHODS: A systematic review of the literature was performed to identify pertinent randomized controlled trials (RCTs), propensity-matched observational series, and meta-analyses which were considered initially and followed by unmatched observational series using the MEDLINE, Ovid EMBASE, and Cochrane Library. RESULTS: We identified 6 different strategies for treating secondary mitral valve regurgitation: mitral valve replacement, restrictive mitral annuloplasty, surgical revascularization (with and without mitral annuloplasty), subvalvular procedures (papillary muscle approximation, papillary muscle relocation, ring and string procedure), and procedures directly targeting the mitral valve (edge-to-edge repair and anterior leaflet enlargement) alongside transcatheter heart valve therapy. We also highlighted the role of left ventricular assist devices in the management of this condition. The benefits and limitations of each intervention are highlighted. CONCLUSION: There is currently no unanimous and shared strategy for the optimal treatment of patients with secondary IMR. The management of patients with secondary mitral regurgitation must be entrusted to a multidisciplinary Heart Team to ensure ideal intervention and patient matching for the best outcomes.

Percutaneous versus Surgical Intervention for Severe Aortic Valve Stenosis: A Systematic Review.

Aortic stenosis is a disease that is increasing in prevalence and manifests as decreased cardiac output, which if left untreated can result in heart failure and ultimately death. It is primarily a disease of the elderly who often have multiple comorbidities. The advent of transcatheter aortic valve therapies has changed the way we treat these conditions. However, long-term results of these therapies remain uncertain. Recently, there has been an increasing number of studies examining the role of both surgical aortic valve replacement and transcatheter aortic valve replacement. We therefore performed a systematic review using Ovid MEDLINE, Ovid Embase, and the Cochrane Library. Two investigators searched papers published between January 1, 2007, and to date using the following terms: "aortic valve stenosis," "aortic valve operation," and "transcatheter aortic valve therapy." Both strategies in aortic stenosis treatment highlighted specific indications alongside the pitfalls such as structural valve degeneration and valve thrombosis which have a bearing on clinical outcomes. We propose some recommendations to help clinicians in the decision-making process as technological improvements make both surgical and transcatheter therapies viable options for patients with aortic stenosis. Finally, we assess the role of finite element analysis in patient selection for aortic valve replacement. THVT and AVR-S are both useful tools in the armamentarium against aortic stenosis. The decision between the two treatment strategies should be best guided by a strong robust evidence base, ideally with a long-term follow-up. This is best performed by the heart team with the patient as the center of the discussion.

The Choice of Pulmonary Autograft in Aortic Valve Surgery: A State-of-the-Art Primer.

The Ross procedure has long been seen as an optimal operation for a select few. The detractors of it highlight the issue of an additional harvesting of the pulmonary artery, subjecting the native PA to systemic pressures and the need for reintervention as reasons to avoid it. However, the PA is a living tissue and capable of adapting and remodeling to growth. We therefore review the current evidence available to discuss the indications, contraindications, harvesting techniques, and modifications in a state-of-the-art narrative review of the PA as an aortic conduit. Due to the lack of substantial well-designed randomized controlled trials (RCTs), we also highlight the areas of need to reiterate the importance of the Ross procedure as part of the surgical armamentarium.

Predictors of adherence to composite therapy after acute coronary syndromes.

AIMS: Adherence to medical therapy following acute coronary syndrome (ACS) affects a patient's prognosis. In this cohort study, we sought to assess the factors that could affect a patient's adherence to therapy after ACS. METHODS: We prospectively collected information from patients (N = 964) hospitalized at the coronary care unit of the Federico II University Hospital, from 1 January 2015 to 30 June 2017, for ACS. Adherence to three classes of drugs including statins, antiplatelets [dual or single antiplatelet agent (SAPT)] and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE-I/ARB) and their composites were assessed at 1 month, 1 and 2 years after discharge. RESULTS: At 30 days adherence to prescribed therapy was 94.4% for dual antiplatelet therapy (DAPT), 78.2% for statins, 92.7% for ACE-I/ARB and 70.7% for multitherapy. At 1 year, it was 91.1% for DAPT, 81.2% for ACE-I/ARB, 84.9% for statins and 71.4% for multitherapy. At 2 years, it was 97.1% for SAPT, 78.1% for ACE-I/ARB, 91.8% for statins, 72.8% for multitherapy. Multivariable logistic analysis demonstrated that at each time point, a telephone follow-up assessment predicts nonadherence to multitherapy and that a percutaneous coronary intervention at the index hospitalization is an independent predictor of adherence to composite therapy at 1 month and 1 year. CONCLUSION: Up to 2 years after ACS, three out of four patients are adherent to multitherapy prescription; percutaneous coronary intervention during the index hospitalization improves a patient's adherence, whereas telephone follow-up is associated with reduced adherence to multitherapy.Campania Salute Network Registry (Clinical Trials.gov Identifier: NCT02211365).

The Use of Radial Artery for CABG: An Update.

We used the radial artery as a second target conduit for coronary artery bypass grafting since 1971. However, randomized clinical studies have demonstrated differences in clinical outcomes between the radial artery and other grafts because these trials are underpowered. As we proceed toward 50 years of experience with radial artery grafting, we examined the literature to define the best second-best target vessel for coronary artery bypass grafting. The literature was reviewed with emphasis, and a large number of randomized controlled trials, propensity-matched observational series, and meta-analyses were identified with a large patient population who received arterial conduit and saphenous vein grafts. The radial artery has been shown to be effective and safe when used as a second target conduit for coronary artery bypass grafting. Results and patency rates were superior to those for saphenous vein grafting. It has also been shown that the radial artery is a safe and effective graft as a third conduit into the territory of the artery right coronary artery. However, there is little evidence based on a few comparable series limiting the use of the gastroepiploic artery. In its fifth decade of use, we can finally deduced that the aorto-to-coronary radial bypass graft is the conduit of choice for coronary operations after the left internal thoracic artery to the left anterior descending artery.

Heart Valve Endocarditis.

Heart valve replacement is the most common cardiac surgical operation performed worldwide for infective endocarditis (IE). Long-term durability and avoidance of infection relapse are the goals of the procedure. However, no detailed guidelines on prosthesis selection and surgical strategies are available, which should be guided by a comprehensive evaluation of the extent of the infection and its microbiological characteristics, the clinical profile of the patient and the risk of infection recurrence. Conventional mechanical or stented xenografts are the preferred choice for localized heart infection. In cases of complex IE with involvement of the root or the aorto-mitral continuity, the use of homograft is suggested according to the surgeon's and center's experience. The use of homograft needs to be balanced against the risk of structural degeneration. Prosthetic bioroot and prosthetic valved conduit with a mechanical or bioprosthetic valve are also considered acceptable alternatives in patients with aortic valve endocarditis. The further development of preservation techniques to enable the longer durability of allogeneic substitutes is required. We discuss current evidence for the use of valve substitutes in heart valve endocarditis and propose an evidence-based algorithm for the choice of treatment.

Transcatheter Tricuspid Valve Interventions: Current Approaches and Future Perspectives.

Tricuspid valve regurgitation is generally functional in nature due to right-sided dysfunction in the setting of left-sided concomitant cardiac disease or pulmonary hypertension. Patients living with tricuspid regurgitation often experience numerous limitations as a result of right-sided heart failure symptoms. Patients with significant tricuspid disease, whether native, repaired, or replaced valve, often present with significant symptoms but may not be ideal candidates for operation or, eventually, reoperation. Transcatheter techniques to either repair or replace the tricuspid valve are a burgeoning frontier in structural cardiac interventions. Anatomical challenges include the large and asymmetrical annulus, paucity of calcification, adjacency of the right coronary artery system, and fragility of the valve tissue. Current approaches under investigation in feasibility and early phase clinical trials include edge-to-edge repair, coaptation enhancement, annuloplasty, heterotopic caval valve implantation, and percutaneous tricuspid valve replacement. Although there are limitations to the currently available transcatheter options for the patients, the initial data demonstrate the relative safety of using existing devices with good results and functional improvement. Hopefully, the emerging interest into interventional therapy of tricuspid valve disease will bring back the "forgotten valve" into the conscience of the cardiological and surgical community. This review intends to summarize the current strategies and evidences in transcatheter tricuspid valve intervention and enlightening new avenues for future clinical studies.