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Abstract Background Type A acute aortic dissection (TAAAD) is a deadly condition that demands immediate surgery, because it involves a critically. The mortality and morbidity associated with it are significant, and it is vital that the patient’s conditions and treatment strategies are fully understood to ensure the appropriate management of TAAAD. This study aims to ascertain whether hemiarch repair (HAR) versus extended arch repair (EAR) with or without descending aortic intervention results in better perioperative and late outcomes for patients with TAAAD. Methods Four leading centers of cardiac surgery from two European countries have joined forces to create a groundbreaking multicenter observational registry (AoArch). This study was approved by the institutional review board (IRB 202201173). We conducted a retrospective review (NCT 0591263) of our prospectively maintained database for patients who underwent operative repair of DeBakey type I or type II dissection from January 1, 2005 to March 2024 (NCT 05927090). We will analyze how patient co-morbidities, referral conditions, and surgical strategies involving hemi-arch repair (HAR) and extended arch repair (EAR) impact early and late adverse events. We have developed a procedure urgency algorithm based on the severity of preoperative hemodynamic conditions and malperfusion due to TAAAD, and we will use it to assess the primary clinical outcomes: in-hospital mortality, late mortality, and reoperations on the aorta. We will define secondary outcomes as permanent neurologic deficit, the need for new dialysis, respiratory failure, a composite of major adverse events (myocardial infarction, cerebrovascular accidents, the need for dialysis, or the need for tracheostomy), and a composite of major adverse pulmonary events (intubation over 48 h, pneumonia, reintubation, tracheostomy), and reoperation due to bleeding. Discussion This multicenter registry will definitively determine the prognostic significance of critical preoperative conditions and the efficacy of extended arch interventions and hemiarch repair in reducing the risk of early adverse events after surgery for TAAAD. This registry will provide insights into the long-term durability of different strategies of surgical repair for TAAAD.

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.

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.

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.

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.

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.

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.

Saline injection into the left ventricle trough mitral valve (saline test) is the most commonly used intraoperative assessment method in mitral valve repair. However, potential discrepancies between the saline test findings and intraoperative transesophageal echocardiography results after the weaning of cardiopulmonary by-pass, remain significant. Here, we describe a new antegrade reperfusion test, reproducing intraoperatively, the physiologic conditions of loaded and beating heart for direct transatrial evaluation of valve tightness. The proposed test is performed by perfusing warm oxygenated blood into the aortic root under cross-clamping. From February 2016 to December 2018, 91 patients (mean age: 63 ± 11 years) underwent mitral valve repair for mitral regurgitation. In all of them, the classic saline test was completed with the newly proposed antegrade test. We report our results with this combined approach. Data were obtained from the medical records and our mitral valve repair database. In 32 (35.1%) patients, evident or undetectable minor regurgitation at the saline test were respectively unconfirmed or detected by the antegrade reperfusion test leading to their complete correction. In only three patients (3.2%) major discrepancies was present between the intraoperative evaluation and the post-pump transesophageal echocardiography. Two of them (2.1%) required a second cardiopulmonary bypass run to fix the residual regurgitation. The antegrade reperfusion test is a simple dynamic intraoperative approach mimicking the physiological conditions of ventricular systole for mitral valve repair evaluation. Combined with the classic saline test, it seems to be a valuable additional intraoperative tool, enabling a more predictable repair result.

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.

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.

OBJECTIVES: To evaluate the use of CABG utilising an isolated pedicled Right Internal Thoracic Artery (RITA) or Left Internal Thoracic Artery (LITA) or the Pure Internal Thoracic Artery (PITA) technique to treat anomalous aortic origin of coronary artery (AAOCA). METHODS: A retrospective review of all patients at our institution over an 8-year period (2013–2021) who underwent surgery for AAOCA was performed. Data assessed included patient demographics, initial presentation, morphology of coronary anomaly, surgical procedure, cross-clamp time, cardiopulmonary bypass time, and long-term outcome. RESULTS: A total of 14 patients underwent surgery, including 11 males (78.5%) with a median logistic EuroSCORE of 1.605 (IQR 1.34). The median age was 62.5 years (IQR 48.75). Presentation was angina (7 patients), acute coronary syndrome (5 patients), incidental findings in aortic valve pathology (2 patients). AAOCA morphology varied: RCA from left coronary sinus (6), RCA from left main stem (3), left coronary artery from the right coronary sinus (1), left main stem arising from right coronary sinus (2) and circumflex artery arising from the right coronary sinus (2). Overall, 7 patients had co-existing flow-limiting coronary artery disease. CABG was performed using either a pedicled skeletonized RITA, LITA or PITA technique. There was no perioperative mortality. Overall median follow-up time was 43 months. One patient presented with recurrent angina secondary to graft failure at 2 years and there were two non-cardiac-related deaths at 4 and 35 months. CONCLUSION: The use of internal thoracic artery grafts can provide a durable treatment option in patients with anomalous coronary arteries. The potential risk of graft failure in patients with no flow-limiting disease should be very carefully considered. However, a proposed benefit of this technique is the use of a pedicle flow to increase the long-term patency. More consistent results are obtained when ischaemia can be demonstrated preoperatively.

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.

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.

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.

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.

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.

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.

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.

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.

Introduction: The choice of valve substitute for aortic valve surgery is tailored to the patient with specific indications and contraindications to consider. The use of an autologous pulmonary artery (PA) with a simultaneous homograft in the pulmonary position is called a Ross procedure. It permits somatic growth and the avoidance of lifelong anticoagulation. Concerns remain on the functionality of a pulmonary autograft in the aortic position when exposed to systemic pressure. Methods: A literature review was performed incorporating the following databases: Pub Med (1996 to present), Ovid Medline (1958 to present), and Ovid Embase (1982 to present), which was run on 1 January 2022 with the following targeted words: biomechanics of pulmonary autograft, biomechanics of Ross operation, aortic valve replacement and pulmonary autograph, aortic valve replacement and Ross procedure. To address the issues with heterogeneity, studies involving the pediatric cohort were also analyzed separately. The outcomes measured were early- and late-graft failure alongside mortality. Results: a total of 8468 patients were included based on 40 studies (7796 in pediatric cohort and young adult series and 672 in pediatric series). There was considerable experience accumulated by various institutions around the world. Late rates of biomechanical failure and mortality were low and comparable to the general population. The biomechanical properties of the PA were superior to other valve substitutes. Mathematical and finite element analysis studies have shown the potential stress-shielding effects of the PA root. Conclusion: The Ross procedure has excellent durability and longevity in clinical and biomechanical studies. The use of external reinforcements such as semi-resorbable scaffolds may further extend their longevity.

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.

Infective endocarditis remains an illness that carries a significant burden to healthcare resources. In recent times, there has been a shift from Streptococcus sp. to Staphylococcus sp. as the primary organism of interest. This has significant consequences, given the virulence of Staphylococcus and its propensity to form a biofilm, rendering non-surgical therapy ineffective. In addition, antibiotic resistance has affected treatment of this organism. The cohorts at most risk for Staphylococcal endocarditis are elderly patients with multiple comorbidities. The innovation of transcatheter technologies alongside other cardiac interventions such as implantable devices has contributed to the increased risk attributable to this cohort. We examined the pathophysiology of infective endocarditis carefully. Inter alia, the determinants of Staphylococcus aureus virulence, interaction with host immunity, as well as the discovery and emergence of a potential vaccine, were investigated. Furthermore, the potential role of prophylactic antibiotics during dental procedures was also evaluated. As rates of transcatheter device implantation increase, endocarditis is expected to increase, especially in this high-risk group. A high level of suspicion is needed alongside early initiation of therapy and referral to the heart team to improve outcomes.

Both the European Society of Cardiology (ESC) and the American College of Cardiology (ACC/AHA) have recently released guidelines on the management of patients with secondary mitral regurgitation. This includes defining, classifying, and assessing the severity of secondary mitral regurgitation. These guidelines are also the first to incorporate the use of transcatheter edge-to-edge repair in decision-making based on recent studies. The review highlights the strengths and shortcomings of these studies and the applicability and generalisability of these results to assist in decision-making for the heart time. It also emphasises the importance of shared decision-making via the heart team. Echocardiography plays an important role in the assessment of these patients although these may be specifically for primary mitral insufficiency. The optimal guideline-directed medical therapy should be the first line of treatment followed by mechanical intervention. The choice of intervention is best directed by a specialist multidisciplinary team. Concomitant revascularization should be performed in a subgroup of patients with severe secondary mitral regurgitation given the role of adverse LV remodelling in propagation of the dynamic secondary MR. The guidelines need further confirmation from high-quality studies in the near future to decision-making towards either TEER, mitral valve replacement, or mitral valve repair with or without a subvalvular procedure.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has resulted in significant mortality and burdening of healthcare resources. While initially noted as a pulmonary pathology, subsequent studies later identified cardiovascular involvement with high mortalities reported in specific cohorts of patients. While cardiovascular comorbidities were identified early on, the exact manifestation and etiopathology of the infection remained elusive. This systematic review aims to investigate the role of inflammatory pathways, highlighting several culprits including neutrophil extracellular traps (NETs) which have since been extensively investigated. Method: A search was conducted using three databases (MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations and EMBASE). Data from randomized controlled trials (RCT), prospective series, meta-analyses, and unmatched observational studies were considered for the processing of the algorithm and treatment of inflammatory response during SARS-CoV-2 infection. Studies without the SARS-CoV-2 Infection period and case reports were excluded. Results: A total of 47 studies were included in this study. The role of the acute inflammatory response in the propagation of the systemic inflammatory sequelae of the disease plays a major part in determining outcomes. Some of the mechanisms of activation of these pathways have been highlighted in previous studies and are highlighted. Conclusion: NETs play a pivotal role in the pathogenesis of the inflammatory response. Despite moving into the endemic phase of the disease in most countries, COVID-19 remains an entity that has not been fully understood with long-term effects remaining uncertain and requiring ongoing monitoring and research.

One of the hallmarks of the SARS-CoV-2 infection has been the inflammatory process that played a role in its pathogenesis, resulting in mortality within susceptible individuals. This uncontrolled inflammatory process leads to severe systemic symptoms via multiple pathways; however, the role of endothelial dysfunction and thrombosis have not been truly explored. This review aims to highlight the pathogenic mechanisms of these inflammatory triggers leading to thrombogenic complications. There are direct and indirect pathogenic pathways of the infection that are examined in detail. We also describe the case of carotid artery thrombosis in a patient following SARS-CoV-2 infection while reviewing the literature on the role of ACE2, the endothelium, and the different mechanisms by which SARS-CoV-2 may manifest both acutely and chronically. We also highlight differences from the other coronaviruses that have made this infection a pandemic with similarities to the influenza virus.

Coronavirus disease 2019 is characterized by its severe respiratory effects. Data early on indicated an increased risk of mortality in patients with cardiovascular comorbidities. Early reports highlighted the multisystem inflammatory syndrome, cytokine storm, and thromboembolic events as part of the disease processes. The aim of this review is to assess the association between COVID-19 and its thrombotic complications, specifically related to the cardiovascular system. The role of neutrophil extracellular traps (NETs) is explored in the pathogenesis of the disease. The structure and anatomy of the virus are pivotal to its virulence in comparison to other α and β Coronaviridae (HCoV-229E, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1). In particular, the host interaction and response may explain the variability of severity in patients. Angio tensin-converting enzyme 2 (ACE2) activation may be implicated in the cardiovascular and throm bogenic potential of the disease. The virus may also have direct effects on the endothelial lining affecting hemostasis and resulting in thrombosis through several mechanisms. Dipyridamole may have a therapeutic benefit in NET suppression. Therapeutic avenues should be concentrated on the different pathophysiological steps involving the virus and the host.

Until recently, conventional mitral valve surgery has been the treatment of choice even in secondary mitral regurgitation. Recent evidence, however, advocates the use of transcatheter edge-to-edge mitral valve repair (TEER) of the mitral valve. This has been reflected by the change in guidelines of the American College of Cardiology/American Heart Association. We reviewed the literature to shed light on the risks and benefits of all interventions, surgical, transcatheter and guideline-directed medical therapy. Secondary mitral regurgitation occurs due to an imbalance between closing forces and tethering forces. Given the pathology extends beyond the valve alone, treatment should be directed at restoring the geometrical shape of the left ventricle alongside the valve. Myocardial revascularization plays a pivotal role in preventing recurrence. The role of papillary muscle approximation in addition to restrictive mitral annuloplasty should be considered in a select group of patients. We also reviewed the current literature on TEERs from the COAPT and Mitra-FR trials while highlighting the concept of proportionate/disproportionate MR which may help identify which patients benefit from mitral valve restoration. Treatment of this condition will require robust randomized trials alongside the use of state-of-the-art imaging technologies available with the full complement of the multidisciplinary team to ensure the best outcomes for each patient.

The COVID-19 pandemic has resulted in a complex clinical challenge, caused by a novel coronavirus, partially similar to previously known coronaviruses but with a different pattern of contagiousness, complications, and mortality. Since its global spread, several therapeutic agents have been developed to address the heterogeneous disease treatment, in terms of severity, hospital or outpatient management, and pre-existing clinical conditions. To better understand the rationale of new or old repurposed medications, the structure and host–virus interaction molecular bases are presented. The recommended agents by EDSA guidelines comprise of corticosteroids, JAK-targeting monoclonal antibodies, IL-6 inhibitors, and antivirals, some of them showing narrow indications due to the lack of large population trials and statistical power. The aim of this review is to present FDA-approved or authorized for emergency use antivirals, namely remdesivir, molnupinavir, and the combination nirmatrelvir-ritonavir and their impact on the cardiovascular system. We reviewed the literature for metanalyses, randomized clinical trials, and case reports and found positive associations between remdesivir and ritonavir administration at therapeutic doses and changes in cardiac conduction, relatable to their previously known pro-arrhythmogenic effects and important ritonavir interactions with cardioactive medications including antiplatelets, anti-arrhythmic agents, and lipid-lowering drugs, possibly interfering with pre-existing therapeutic regimens. Nonetheless, safety profiles of antivirals are largely questioned and addressed by health agencies, in consideration of COVID-19 cardiac and pro-thrombotic complications generally experienced by predisposed subjects. Our advice is to continuously adhere to the strict indications of FDA documents, monitor the possible side effects of antivirals, and increase physicians’ awareness on the co-administration of antivirals and cardiovascular-relevant medications. This review dissects the global and local tendency to structure patient-based treatment plans, for a glance towards practical application of precision medicine.

Aortic valve replacement is the commonest cardiac surgical operation performed worldwide for infective endocarditis (IE). Long-term durability and avoidance of infection relapse are goals of the procedure. However, no detailed guidelines on prosthesis selection and surgical strategies guided by the comprehensive evaluation of the extension of the infection and its microbiological characteristics, clinical profile of the patient, and risk of infection recurrence are currently available. Conventional mechanical or stented xenografts are the preferred choice for localized aortic infection. However, in cases of complex IE with the involvement of the root or the aortomitral continuity, the use of homograft is suggested according to the surgeon and center experience. Homograft use should be counterbalanced against the risk of structural degeneration. Prosthetic bioroot or prosthetic valved conduit (mechanical and bioprosthetic) are also potentially suitable alternatives. Further development of preservation techniques enabling longer durability of allogenic substitutes is required. We evaluate the current evidence for the use of valve substitutes in aortic valve endocarditis and propose an evidence-based algorithm to guide the choice of therapy. We performed a systemic review to clarify the contemporary surgical management of aortic valve endocarditis.

miRNAs have recently attracted investigators’ interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease and the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out of the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms of thrombosis following vaccination were also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

Over the years, there has been an increasing number of cardiac and orthopaedic implanted medical devices, which has caused an increased incidence of device-associated infections. The surfaces of these indwelling devices are preferred sites for the development of biofilms that are potentially lethal for patients. Device-related infections form a large proportion of hospital-acquired infections and have a bearing on both morbidity and mortality. Treatment of these infections is limited to the use of systemic antibiotics with invasive revision surgeries, which had implications on healthcare burdens. The purpose of this review is to describe the main causes that lead to the onset of infection, highlighting both the biological and clinical pathophysiology. Both passive and active surface treatments have been used in the field of biomaterials to reduce the impact of these infections. This includes the use of antimicrobial peptides and ionic liquids in the preventive treatment of antibiotic-resistant biofilms. Thus far, multiple in vivo studies have shown efficacious effects against the antibiotic-resistant biofilm. However, this has yet to materialize in clinical medicine.

Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is a recently identified positive sense single-strand RNA (ssRNA) β-coronavirus. The viral spike proteins infect human hosts by binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2). The infection causes a systemic illness involving cell metabolism. This widespread involvement is implicated in the pathophysiology of the illness which ranges from mild to severe, requiring multi organ support, ranging from oxygen supplementation to full cardiovascular and respiratory support. Patients with multiple co-existing comorbidities are also at a higher risk. The aim of this review is to explore the exact mechanisms by which COVID-19 affects patients systemically with a primary focus on the bleeding and thrombotic complications linked with the disease. Issues surrounding the thrombotic complications following administration of the ChAdOx1 nCoV-19 (Astra-Zeneca-Oxford) vaccine have also been illustrated. Risk stratification and treatment options in these patients should be tailored according to clinical severity with input from a multidisciplinary team.

Coronary heart disease remains one of the leading causes of death in most countries. Healthcare improvements have seen a shift in the presentation of disease with a reducing number of ST-segment elevation myocardial infarctions (STEMIs), largely due to earlier reperfusion strategies such as percutaneous coronary intervention (PCI). Stents have revolutionized the care of these patients, but the long-term effects of these devices have been brought to the fore. The conceptual and technologic evolution of these devices from bare-metal stents led to the creation and wide application of drug-eluting stents; further research introduced the idea of polymer-based resorbable stents. We look at the evolution of stents and the multiple advantages and disadvantages offered by each of the different polymers used to make stents in order to identify what the stent of the future may consist of whilst highlighting properties that are beneficial to the patient alongside the role of the surgeon, the cardiologist, engineers, chemists, and biophysicists in creating the ideal stent.

Background: Transcatheter aortic valve replacement has proved its safety and effectiveness in intermediate- to high-risk and inoperable patients with severe aortic stenosis. However, despite current guideline recommendations, the use of transcatheter aortic valve replacement (TAVR) to treat severe aortic valve stenosis caused by degenerative leaflet thickening and calcification has not been widely adopted in low-risk patients. This reluctance among both cardiac surgeons and cardiologists could be due to concerns regarding clinical and subclinical valve thrombosis. Stent performance alongside increased aortic root and leaflet stresses in surgical bioprostheses has been correlated with complications such as thrombosis, migration and structural valve degeneration. Materials and Methods: Self-expandable catheter-based aortic valve replacement (Medtronic, Minneapolis, MN, USA), which was received by patients who developed transcatheter heart valve thrombosis, was investigated using high-resolution biomodelling from computed tomography scanning. Calcific blocks were extracted from a 250 CT multi-slice image for precise three-dimensional geometry image reconstruction of the root and leaflets. Results: Distortion of the stent was observed with incomplete cranial and caudal expansion of the device. The incomplete deployment of the stent was evident in the presence of uncrushed refractory bulky calcifications. This resulted in incomplete alignment of the device within the aortic root and potential dislodgment. Conclusion: A Finite Element Analysis (FEA) investigation can anticipate the presence of calcified refractory blocks, the deformation of the prosthetic stent and the development of paravalvular orifice, and it may prevent subclinical and clinical TAVR thrombosis. Here we clearly demonstrate that using exact geometry from high-resolution CT scans in association with FEA allows detection of persistent bulky calcifications that may contribute to thrombus formation after TAVR procedure.

Ischemic mitral regurgitation (IMR) occurs as an adverse consequence of left ventricle remodeling post-myocardial infarction. A change in mitral valve configuration with an imbalance between closing and tethering forces underlie this pathological condition. These abnormalities lead to impaired leaflet coaptation and a variable degree of mitral regurgitation, which can in turn influence the ventricular filling status, the heart rhythm and the afterload regardless of the residual ischemic insult. The IMR correction can be pursued through under-sizing mitral annuloplasty and papillary muscle approximation to restore the mitral valve and left ventricle physiological geometry to, consequently, achieve normalization of the engaged physical forces. Because the structures involved undergo extremely large deformations, a biomechanics model based on the Euler’s Elastica −the mitral leaflet− interlaced with nonlinear chordae tendineae anchored on papillary muscles has been constructed to elucidate the interactions between closing and tethering forces. The model takes into account the actual updated geometrical and mechanical features of the valvular and subvalvular apparatuses in physiological and IMR conditions, as well as in case of papillary muscle approximation, finally furnishing ad hoc geometry-based mathematical relations that could be utilised to support—and optimize—the relevant choices in cardiac surgery.

Context: Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports. Evidence Acquisition: Evidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles. Results: Pharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF. Conclusions: Despite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.