Bicuspid Aortic Valve in Children and Young Adults for Cardiologists and Cardiac Surgeons: State-of-the-Art of Literature Review.

Bicuspid aortic valve disease is the most prevalent congenital heart disease, affecting up to 2% of the general population. The presentation of symptoms may vary based on the patient's anatomy of fusion, with transthoracic echocardiography being the primary diagnostic tool. Bicuspid aortic valves may also appear with concomitant aortopathy, featuring fundamental structural changes which can lead to valve dysfunction and/or aortic dilatation over time. This article seeks to give a comprehensive overview of the presentation, treatment possibilities and long-term effects of this condition. The databases MEDLINE, Embase, and the Cochrane Library were searched using the terms "endocarditis" or "bicuspid aortic valve" in combination with "epidemiology", "pathogenesis", "manifestations", "imaging", "treatment", or "surgery" to retrieve relevant articles. We have identified two types of bicuspid aortic valve disease: aortic stenosis and aortic regurgitation. Valve replacement or repair is often necessary. Patients need to be informed about the benefits and drawbacks of different valve substitutes, particularly with regard to life-long anticoagulation and female patients of childbearing age. Depending on the expertise of the surgeon and institution, the Ross procedure may be a viable alternative. Management of these patients should take into account the likelihood of somatic growth, risk of re-intervention, and anticoagulation risks that are specific to the patient, alongside the expertise of the surgeon or centre. Further research is required on the secondary prevention of patients with bicuspid aortic valve (BAV), such as lifestyle advice and antibiotics to prevent infections, as the guidelines are unclear and lack strong evidence.

Sternal fixation and autologous bone grafting for post sternotomy non-union: a case series.

Background: Sternal non-union is a rare but serious complication post cardiac surgery. It is defined as sternal pain with clicking, instability or both, lasting for more than 6 months in the absence of infection. It usually presents in an outpatient setting and is confirmed on computed tomography (CT) scanning. Despite many corrective methods described in the literature, there is a lack of consensus amongst cardiac surgeons as to the ideal surgical management of sternal non-union post cardiac surgery. We describe our experience of sternal plating combined with autologous iliac crest bone grafting (AICBG) for sternal fixation and explore its safety and feasibility in patients with non-union post cardiac surgery. Case Description: Patients who underwent sternal non-union surgery between 2015 and 2020 were included. Their primary cardiac surgical interventions occurred between 2011-2018. Demographic, clinical and outcome data obtained from a local database was analyzed retrospectively. Surgical procedure: sternal edge debridement, plate fixation with screws, filling with AICBG. Due to variable pathoanatomy of non-union, residual wires and multiple fragments of poor bone quality were cut and the sternal halves were stabilised by titanium plates and screws. These were reinforced with AICBG applied in the residual sternal gap created after debridement. Seven patients were included in the study. Median age was 65 years (54-75 years). Four patients (57.1%) were male. Demographic risk factors for sternal non-union prior to their initial cardiac surgery included diabetes (N=6), smoking history (N=3), and a median body mass index (BMI) of 31.2 kg/m2. The median interval between primary surgery and sternal fixation was 2.2 years. There were no perioperative deaths. Complications post sternal plating such as iliac crest pain (n=3) and acute tubular necrosis (n=1) were managed conservatively with long-term resolution. None of the patients required further intervention post sternal fixation after a mean follow-up of 18.0 months. Conclusions: The use of AICBG in addition to sternal plating is a viable and innovative method of treating sternal non-union post-cardiac surgery with lasting effects and without any serious long-term complications. However, further larger studies are required to validate our results.

Treating Spontaneous Pneumothorax Using an Innovative Surgical Technique Called Capnodissection Pleurectomy: Case Report.

Spontaneous pneumothorax is one of the most common conditions encountered in thoracic surgery. This condition can be treated conservatively or surgically based on indications and guidelines. Traditional surgical management includes pleurodesis (mechanical or chemical) in addition to bullectomy if the bullae can be identified. Mechanical pleurodesis is usually performed by surgical pleurectomy or pleural abrasion. In this case report, we present a case of a young patient with spontaneous pneumothorax who needed a surgical intervention. We performed a new, innovative surgical technique for surgical pleurectomy where we used carbon dioxide for dissection of the parietal pleura (capnodissection). This technique may provide similar efficiency to the traditional procedure but with less risk of bleeding and complications.

Lactate-Based Difference as a Determinant of Outcomes following Surgery for Type A Acute Aortic Dissection: A Multi-Centre Study.

Type A acute aortic dissection (TAAAD) is a serious condition within the acute aortic syndromes that demands immediate treatment. Despite advancements in diagnostic and referral pathways, the survival rate post-surgery currently sits at almost 20%. Our objective was to pinpoint clinical indicators for mortality and morbidity, particularly raised arterial lactate as a key factor for negative outcomes. METHODS: All patients referred to the three cardiovascular centres between January 2005 and December 2022 were included in the study. The inclusion criteria required the presence of a lesion involving the ascending aorta, symptoms within 7 days of surgery, and referral for primary surgical repair of TAAAD based on recommendations, with consideration for other concomitant major cardiac surgical procedures needed during TAAAD and retrograde extension of TAAAD. We conducted an analysis of both continuous and categorical variables and utilised predictive mean matching to fill in missing numeric features. For missing binary variables, we used logistic regression to impute values. We specifically targeted early postoperative mortality and employed LASSO regression to minimise potential collinearity of over-fitting variables and variables measured from the same patient. RESULTS: A total of 633 patients were recruited for the study, out of which 449 patients had complete preoperative arterial lactate data. The average age of the patients was 64 years, and 304 patients were male (67.6%). The crude early postoperative mortality rate was 24.5% (110 out of 449 patients). The mortality rate did not show any significant difference when comparing conservative and extensive surgeries. However, malperfusion had a significant impact on mortality [48/131 (36.6%) vs. 62/318 (19.5%), p < 0.001]. Preoperative arterial lactates were significantly elevated in patients with malperfusion. The optimal prognostic threshold of arterial lactate for predicting early postoperative mortality in our cohort was ≥2.6 mmol/L. CONCLUSION: The arterial lactate concentration in patients referred for TAAAD is an independent factor for both operative mortality and postoperative complications. In addition to mortality, patients with an upper arterial lactate cut-off of ≥2.6 mmol/L face significant risks of VA ECMO and the need for dialysis within the first 48 h after surgery. To improve recognition and facilitate rapid transfer and surgical treatment protocol, more diligent efforts are required in the management of malperfusion in TAAAD.

Current Knowledge on the Interaction of Human Cytomegalovirus Infection, Encoded miRNAs, and Acute Aortic Syndrome.

Aortic dissection is a clinicopathological entity caused by rupture of the intima, leading to a high mortality if not treated. Over time, diagnostic and investigative methods, antihypertensive therapy, and early referrals have resulted in improved outcomes according to registry data. Some data have also emerged from recent studies suggesting a link between Human Cytomegalovirus (HCMV) infection and aortic dissection. Furthermore, the use of microRNAs has also become increasingly widespread in the literature. These have been noted to play a role in aortic dissections with elevated levels noted in studies as early as 2017. This review aims to provide a broad and holistic overview of the role of miRNAs, while studying the role of HCMV infection in the context of aortic dissections. The roles of long non-coding RNAs, circular RNAs, and microRNAs are explored to identify changes in expression during aortic dissections. The use of such biomarkers may one day be translated into clinical practice to allow early detection and prognostication of outcomes and drive preventative and therapeutic options in the future.

Bridging Molecular and Clinical Sciences to Achieve the Best Treatment of Enterococcus faecalis Endocarditis.

Enterococcus faecalis (E. faecalis) is a commensal bacterium that causes various infections in surgical sites, the urinary tract, and blood. The bacterium is becoming a significant concern because it tends to affect the elderly population, which has a high prevalence of undiagnosed degenerative valvular disease and is often subjected to invasive procedures and implanted medical devices. The bacterium's actions are influenced by specific characteristics like pili activity and biofilm formation. This resistance significantly impedes the effectiveness of numerous antibiotic therapies, particularly in cases of endocarditis. While current guidelines recommend antimicrobial therapy, the emergence of resistant strains has introduced complexity in managing these patients, especially with the increasing use of transcatheter therapies for those who are not suitable for surgery. Presentations of the condition are often varied and associated with generalised symptoms, which may pose a diagnostic challenge. We share our encounter with a case study that concerns an octogenarian who had a TAVI valve and developed endocarditis. We also conducted a literature review to identify the essential treatment algorithms for such cases.

The Roles of microRNAs in the Cardiovascular System.

The discovery of miRNAs and their role in disease represent a significant breakthrough that has stimulated and propelled research on miRNAs as targets for diagnosis and therapy. Cardiovascular disease is an area where the restrictions of early diagnosis and conventional pharmacotherapy are evident and deserve attention. Therefore, miRNA-based drugs have significant potential for development. Research and its application can make considerable progress, as seen in preclinical and clinical trials. The use of miRNAs is still experimental but has a promising role in diagnosing and predicting a variety of acute coronary syndrome presentations. Its use, either alone or in combination with currently available biomarkers, might be adopted soon, particularly if there is diagnostic ambiguity. In this review, we examine the current understanding of miRNAs as possible targets for diagnosis and treatment in the cardiovascular system. We report on recent advances in recognising and characterising miRNAs with a focus on clinical translation. The latest challenges and perspectives towards clinical application are discussed.

Host-Bacterium Interaction Mechanisms in Staphylococcus aureus Endocarditis: A Systematic Review.

Staphylococci sp. are the most commonly associated pathogens in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations, and the protracted infection courses, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid's version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. Thirty-five studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored, giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. The goal of this study is to attain a better understanding on the molecular pathways involved in infective endocarditis supported by S. aureus and whether therapeutic avenues for the prevention and treatment of IE can be obtained. The use of antibiotic-treated allogeneic tissues have marked antibacterial action, thereby becoming the ideal substitute in native and prosthetic valvular infections. However, the development of effective vaccines against S. aureus still requires in-depth studies.

The Use of the Cryopreserved Aortic Homograft for Aortic Valve Replacement: Is It Still an Option?

The indications for cryopreserved allografts in aortic valve replacement are still debatable. We aim to identify factors influencing early and long-term durability of the aortic homograft and to define subgroups of patients with an improved long-term quality of life, survival, and freedom from structural valve degeneration (SVD). We evaluated our series of 210 patients who underwent allograft implantation with a retrospective cohort study design over a period of 20 years. Endpoints were overall mortality, cardiac mortality related to SVD, the incidence of SVD, reoperation, and a composite endpoint comprising major adverse cardiac and cerebrovascular events (MACCEs), which includes cardiac death both related and not related to SVD, subsequent aortic valve surgery, new or recurrent infection of implanted allograft, recurrent aortic regurgitation, rehospitalization for heart failure, an increase in New York Heart Association (NYHA) class of ≥1, or cerebrovascular events. The primary indication for surgery was endocarditis (48%), which was also a predisposing factor for increased cardiac mortality. Overall mortality was 32.4% with a 27% incidence of SVD and mortality associated with SVD of 13.8%. Reoperation occurred in 33.8% and MACCEs in 54.8%. Long-term NYHA functional class and echocardiographic parameters improved over time. Statistical analysis demonstrated that root replacement technique and adult age were protective factors for SVD. We found no statistically significant difference in the clinical outcomes analyzed between women of childbearing age who had children after surgery and the rest of the women. The cryopreserved allograft is still a valid option in aortic valve replacement, providing acceptable durability and clinical outcomes with optimal hemodynamic performance. SVD is influenced by the implantation technique. Women of childbearing age might have additional benefits from this procedure.

Surgical Strategy for the Repair of Acute Type A Aortic Dissection: A Multicenter Study.

Type A acute aortic dissection is associated with significant morbidity and mortality, with prompt referral imaging and management to tertiary referral centers needed urgently. Surgery is usually needed emergently, but the choice of surgery often varies depending on the patient and the presentation. Staff and center expertise also play a major role in determining the surgical strategy employed. The aim of this study was to compare the early- and medium-term outcomes of patients undergoing a conservative approach extended only to the ascending aorta and the hemiarch to those of patients subjected to extensive surgery (total arch reconstruction and root replacement) across three European referral centers. A retrospective study was conducted across three sites between January 2008 and December 2021. In total, 601 patients were included within the study, of which 30% were female, and the median age was 64.4 years. The most common operation was ascending aorta replacement (n = 246, 40.9%). The aortic repair was extended proximally (i.e., root n = 105; 17.5%) and distally (i.e., arch n = 250; 41.6%). A more extensive approach, extending from the root to the arch, was employed in 24 patients (4.0%). Operative mortality occurred in 146 patients (24.3%), and the most common morbidity was stroke (75, 12.6%). An increased length of ICU admission was noted in the extensive surgery group, which comprised younger and more frequently male patients. No significant differences were noted in surgical mortality between patients managed with extensive surgery and those managed conservatively. However, age, arterial lactate levels, "intubated/sedated" status on arrival, and "emergency or salvage" status at presentation were independent predictors of mortality both within the index hospitalization and during the follow-up. The overall survival was similar between the groups.

SARS-CoV-2-Induced Myocarditis: A State-of-the-Art Review.

In this review, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly cause myocarditis with severe myocardial damage induced by viral particles. A review of the major data published from 2020 to 2022 was performed by consulting the major databases alongside first-hand experiences that emerged from the cardiac biopsies and autopsy examinations of patients who died of SARS-CoV-2 infections. From this study, a significantly large amount of data suggests that the Dallas criteria were met in a residual percentage of patients, demonstrating that SARS-CoV-2 myocarditis was a rare clinical and pathological entity that occurred in a small percentage of subjects. All cases described here were highly selected and subjected to autopsies or endomyocardial biopsies (EMBs). The most important discovery, through the detection of the SARS-CoV-2 genome using the polymerase chain reaction, consisted in the presence of the viral genome in the lung tissue of most of the patients who died from COVID-19. However, the discovery of the SARS-CoV-2 viral genome was a rare event in cardiac tissue from autopsy findings of patients who died of myocarditis It is important to emphasize that myocardial inflammation alone, as promoted by macrophages and T cell infiltrations, can be observed in noninfectious deaths and COVID-19 cases, but the extent of each cause is varied, and in neither case have such findings been reported to support clinically relevant myocarditis. Therefore, in the different infected vs. non-infected samples examined, none of our findings provide a definitive histochemical assessment for the diagnosis of myocarditis in the majority of cases evaluated. We report evidence suggesting an extremely low frequency of viral myocarditis that has also been associated with unclear therapeutic implications. These two key factors strongly point towards the use of an endomyocardial biopsy to irrefutably reach a diagnosis of viral myocarditis in the context of COVID-19.

Sex-Based Difference in Aortic Dissection Outcomes: A Multicenter Study.

BACKGROUND: Type A Acute Aortic Dissection (TAAAD) repair is a surgical emergency associated with high morbidity and mortality. Registry data have noted several sex-specific differences in presentation with TAAAD which may account for the differences in men and women undergoing surgery for this condition. METHODS: A retrospective review of data from three departments of cardiac surgery (Centre Cardiologique du Nord, Henri-Mondor University Hospital, San Martino University Hospital, Genoa) between January 2005 and 31 December 2021 was conducted. Confounders were adjusted using doubly robust regression models, a combination of regression models with inverse probability treatment weighting by propensity score. RESULTS: 633 patients were included in the study, of which 192 (30.3%) were women. Women were significantly older with reduced haemoglobin levels and pre-operative estimated glomerular filtration rate compared to men. Male patients were more likely to undergo aortic root replacement and partial or total arch repair. Operative mortality (OR 0.745, 95% CI: 0.491-1.130) and early postoperative neurological complication results were comparable between the groups. The adjusted survival curves using IPTW by propensity score confirmed the absence of a significant impact of gender on long-term survival (HR 0.883, 95% CI 0.561-1.198). In a subgroup analysis of women, preoperative levels of arterial lactate (OR 1.468, 95% CI: 1.133-1.901) and mesenteric ischemia after surgery (OR 32.742, 95% CI: 3.361-319.017) were significantly associated with increased operative mortality. CONCLUSIONS: The advancing age of female patients alongside raised preoperative level of arterial lactate may account for the increasing preponderance among surgeons to perform more conservative surgery compared to their younger male counterparts although postoperative survival was similar between the groups.

Primary graft dysfunction following lung transplantation: From pathogenesis to future frontiers.

Lung transplantation is the treatment of choice for patients with end-stage lung disease. Currently, just under 5000 lung transplants are performed worldwide annually. However, a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction. It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant. This review aims to provide an in-depth analysis of the epidemiology, patho physiology, risk factors, outcomes, and future frontiers involved in mitigating primary graft dysfunction. The current diagnostic criteria are examined alongside changes from the previous definition. We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion. Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality, ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.

Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review.

Endothelial integrity plays a major role in homeostasis and is responsive to the numerous endogenous factors released. While its functional role in vascular tone is well described, its role in the pathophysiology of cardiovascular disease is of interest as a potential therapeutic target. We performed a systematic review to provide an overview of new therapeutic and diagnostic targets for the treatment of coronary artery disease related to endothelial dysfunction. Databases of PubMed, Ovid's version of MEDLINE, and EMBASE were interrogated with appropriate search terms. Inclusion criteria have been met by 28 studies that were included in the final systematic review. We identified inflammation, pulmonary hypertension, diabetes mellitus and Fabry disease as pathophysiological mechanisms and explored the therapeutic options related to these conditions including medications such as Canakinumab. Endothelial dysfunction has a key role in several different pathophysiological processes which can be targeted for therapeutic options. Ongoing research should be targeted at making the transition to clinical practice. Further research is also needed on understanding the amelioration of endothelial dysfunction with the use of cardiovascular medications.

Impact of Mitral Regurgitation Recurrence on Mitral Valve Repair for Secondary Ischemic Mitral Regurgitation.

OBJECTIVES: The current guidelines still do not include specific recommendations on the use of subvalvular repair (SV-r) for treatment of ischemic mitral regurgitation (IMR). Therefore, the objective of our study was to evaluate the clinical impact of mitral regurgitation (MR) recurrence and ventricular remodeling on long-term outcomes after SV-r combined with restrictive annuloplasty (RA-r). METHODS: We performed a subanalysis of the papillary muscle approximation trial, studying 96 patients with severe IMR and coronary artery disease undergoing restrictive annuloplasty alongside subvalvular repair (SV-r + RA-r group) or restrictive annuloplasty alone (RA-r group). We analyzed treatment failure differences, the influence of residual MR, left ventricular remodeling, and clinical outcomes. The primary endpoint was treatment failure (composite of death; reoperation; or recurrence of moderate, moderate-to-severe, or severe MR) within 5 years of follow-up after the procedure. RESULTS: A total of 45 patients showed failure of the treatment within 5 years, of which 16 patients underwent SV-r + RA-r (35.6%) and 29 underwent RA-r (64.4%, p = 0.006). Patients with significant residual MR presented with a higher rate of all-cause mortality at 5 years compared with trivial MR (HR 9.09, 95% CI 2.08-33.33, p = 0.003). MR progression occurred earlier in the RA-r group, as 20 patients in the RA-r group vs. 6 in SV-r + RA-r group had a significant MR 2 years after surgery (p = 0.002). CONCLUSIONS: RA-r remains a surgical mitral repair technique with an increased risk of failure and mortality at 5 years compared with SV-r. The rates of recurrent MR are higher, and recurrence occurs earlier, with RA-r alone compared to SV-r. The addition of the subvalvular repair increases the durability of the repair, thus extending all of the benefits of preventing MR recurrence.

Worsening Thrombotic Complication of Atherosclerotic Plaques Due to Neutrophils Extracellular Traps: A Systematic Review.

Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries alongside propagating and amplifying the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases. In response to disease-relevant stimuli, neutrophils undergo a specialized series of reactions that culminate in NET formation. DNA derived from either nuclei or mitochondria can contribute to NET formation. The DNA liberated from neutrophils forms a reticular mesh that resembles morphologically a net, rendering the acronym NETs particularly appropriate. The DNA backbone of NETs not only presents intrinsic neutrophil proteins (e.g., MPO (myeloperoxidase) and various proteinases) but can congregate other proteins found in blood (e.g., tissue factor procoagulant). This systematic review discusses the current hypothesis of neutrophil biology, focusing on the triggers and mechanisms of NET formation. Furthermore, the contribution of NETs to atherosclerosis and thrombosis is extensively addressed. Again, the use of NET markers in clinical trials was considered. Ultimately, given the vast body of the published literature, we aim to integrate the experimental evidence with the growing body of clinical information relating to NET critically.

Pathophysiology and Outcomes of Endothelium Function in Coronary Microvascular Diseases: A Systematic Review of Randomized Controlled Trials and Multicenter Study.

BACKGROUND: Coronary macrovascular disease is a concept that has been well-studied within the literature and has long been the subject of debates surrounding coronary artery bypass grafting (CABG) vs. Percutaneous Coronary Intervention (PCI). ISCHEMIA trial reported no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management, while in the ORBITA trial PCI did not improve angina frequency score significantly more than placebo, albeit PCI resulted in more patient-reported freedom from angina than placebo. However, these results did not prove the superiority of the PCI against OMT, therefore do not indicate the benefit of PCI vs. the OMT. Please rephrase the sentence. We reviewed the role of different factors responsible for endothelial dysfunction from recent randomized clinical trials (RCTs) and multicentre studies. METHODS: A detailed search strategy was performed using a dataset that has previously been published. Data of pooled analysis include research articles (human and animal models), CABG, and PCI randomized controlled trials (RCTs). Details of the search strategy and the methods used for data pooling have been published previously and registered with Open-Source Framework. RESULTS: The roles of nitric oxide (NO), endothelium-derived contracting factors (EDCFs), and vasodilator prostaglandins (e.g., prostacyclin), as well as endothelium-dependent hyperpolarization (EDH) factors, are crucial for the maintenance of vasomotor tone within the coronary vasculature. These homeostatic mechanisms are affected by sheer forces and other several factors that are currently being studied, such as vaping. The role of intracoronary testing is crucial when determining the effects of therapeutic medications with further studies on the horizon. CONCLUSION: The true impact of coronary microvascular dysfunction (CMD) is perhaps underappreciated, which supports the role of medical therapy in determining outcomes. Ongoing trials are underway to further investigate the role of therapeutic agents in secondary prevention.

Basic pathophysiology and options of treatment for surgical management of functional tricuspid regurgitation: a systematic review.

Background: Functional tricuspid regurgitation (TR) appears frequently in the presence of left-sided heart valve diseases, combined with symptoms of heart failure, worsens if left untreated, and is associated with poor patient survival. Correct indications for surgery and the choice of suitable technique, which should be based on pathophysiology of disease are of utmost importance to ensure longevity and durability of repair; particularly given the risky nature of reoperations due to residual/recurrent TR. Methods: A systematic review was performed using Embase, Ovid Medline, Cochrane, Web of Science, and Google to deepen knowledge of major and controversial aspects of the subject. Results: A total of 1,579 studies were reviewed, and 32 of these were enclosed in the final review: 13 studies were primarily focused on pathophysiology and preoperative assessment of functional TR; 19 studies on surgical treatment of functional TR. A total of 15,509 patients were included. Conclusions: Indications for treatment of TR are based on the severity of regurgitation (grading), as well as on the presence of signs and symtoms of right-sided heart failure and on the extent of tricuspid annular dilation, leaflet tethering, and pulmonary hypertension (staging of disease). Despite improved knowledge of the underlying pathophysiology of TR, issues regarding indications for treatment and options of repair remain present. There is no consensus within the scientific community, for the preferred method to quantify the severity of TR; the recently introduced 5-grade TR classification based on objective quantitative parameters has not yet become common practice. The assessment of TR during stress exercise is rarely performed, though it takes into account the changes in severity of regurgitation that occur under different physiological conditions. Magnetic resonance imaging, which is the gold standard for the right heart evaluation is occasionally carried out before surgery. The threshold beyond which the tricuspid annular dilation should be repaired is unclear and recent studies put forward the idea that it may be lower than current recommendations. Tricuspid valve annuloplasty is the most adopted surgical option today. However, the ideal annuloplasty device remains elusive. In addition, as severe leaflet tethering cannot be addressed by annuloplasty alone, the addition of new techniques further increasing leaflet coaptation might optimize long-term valve continence. Further investigations are needed to address all these issues, alongside the potential of percutaneous options.

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.