Intestinal Microbiota and Derived Metabolites in Myocardial Fibrosis and Postoperative Atrial Fibrillation.

The high incidence of atrial fibrillation (AFib) following cardiac surgery (postoperative atrial fibrillation, POAF) relies on specific surgical features. However, in the setting of POAF, the role of the microbiome in the modulation of cardiac fibrosis is still not clear. This study aimed to analyze the effect of the microbiome and its main metabolic product (trimethylamine-N-oxide, TMAO) in the fibrosis of myocardial tissue, to investigate its role in POAF. Patients undergoing elective cardiac surgery with cardiopulmonary bypass, central atrio-caval cannulation and no history of AFib, were included. A fragment of the right atrium was analyzed for qualitative and mRNA-quantitative evaluation. A preoperative blood sample was analyzed with enzyme-linked immunosorbent assay (ELISA). A total of 100 patients have been included, with POAF occurring in 38%. Histologically, a higher degree of fibrosis, angiogenesis and inflammation has been observed in POAF. Quantitative evaluation showed increased mRNA expression of collagen-1, collagen-3, fibronectin, and transforming growth factor beta (TGFb) in the POAF group. ELISA analysis showed higher levels of TMAO, lipopolysaccharide and TGFb in POAF, with similar levels of sP-selectin and zonulin. TMAO ≥ 61.8 ng/mL (odds ratio, OR 2.88 [1.35-6.16], p = 0.006), preoperative hemoglobin < 13.1 g/dL (OR 2.37 [1.07-5.24], p = 0.033) and impaired right ventricular function (OR 2.38 [1.17-4.83], p = 0.017) were independent predictors of POAF. Also, TMAO was significantly associated with POAF by means of increased fibrosis. Gut microbiome product TMAO is crucial for myocardial fibrosis, which is a key factor for POAF. Patients in preoperative sinus rhythm who will develop POAF have increased genetic expression of pro-fibrotic genes and enhanced fibrosis in histological staining. Elevated TMAO level (≥61.8 ng/mL) is an independent risk factor for POAF.

Treatment and Prophylaxis of Post-pericardiotomy Syndrome in Cardiac Surgery Patients: a Systematic Review.

PURPOSE: Post-pericardiotomy syndrome (PPS) is a common complication of cardiac surgery. This systematic review aimed to investigate the efficacy of colchicine, indomethacin, and dexamethasone in the treatment and prophylaxis of PPS. METHODS: Literature research was carried out using PubMed. Studies investigating ≥ 10 patients with clinically PPS treated with colchicine, dexamethasone, and indomethacin and compared with placebo were included. Animal or in vitro experiments, studies on < 10 patients, case reports, congress reports, and review articles were excluded. Cochrane risk-of-bias tool for randomized trials (RoB2) was used for the quality assessment of studies. RESULTS: Seven studies were included. Among studies with postoperative colchicine treatment, two of them demonstrated a significant reduction of PPS. In the single pre-surgery colchicine administration study, a decrease of PPS cases was registered. Indomethacin pre-surgery administration was linked to a reduction of PPS. No significant result emerged with preoperative dexamethasone intake. CONCLUSION: Better outcomes have been registered when colchicine and indomethacin were administered as primary prophylactic agents in preventing PPS and PE. Further RCT studies are needed to confirm these results.

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

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

Cardiovascular Effects of Cosmic Radiation and Microgravity.

Recent spaceflights involving nonprofessional people have opened the doors to the suborbital space tourism business. However, they have also drawn public attention to the safety and hazards associated with space travel. Unfortunately, space travel involves a myriad of health risks for people, ranging from DNA damage caused by radiation exposure to the hemodynamic changes that occur when living in microgravity. In fact, the primary pathogenetic role is attributed to cosmic radiation, since deep space lacks the protective benefit of Earth's magnetic shielding. The second risk factor for space-induced pathologies is microgravity, which may affect organ function and cause a different distribution of fluid inside the human body. Both cosmic radiation and microgravity may lead to the alteration of cellular homeostasis and molecular changes in cell function. These, in turn, might have a direct impact on heart function and structure. The aim of this review is to draw attention to the fact that spaceflights constitute a novel frontier in biomedical research. We summarize the most important clinical and experimental evidence regarding the cardiovascular effects of cosmic radiation and microgravity. Finally, we highlight that unraveling the mechanisms underlying how space radiation and microgravity affect the cardiovascular system is crucial for identifying potential countermeasures and developing effective therapeutic strategies.

Heart Disease and Microgravity: The Dawn of a New Medical Era?: A Narrative Review.

After a decline in interest in space missions following the cessation of the Apollo missions, there has been a recent resurgence. Activities on the International Space Station have raised awareness of a positive resumption of space travel to more challenging destinations such as Mars and a possible adaptation of human life on the Moon. The biological and physiological studies conducted on these stations in low Earth orbit are crucial in familiarizing humanity with the potential problems that can arise during long journeys. Cosmic rays and microgravity are the 2 main negative phenomena in space flights. Microgravity in the interplanetary environment plays a special role in altering normal organic processes. These studies are compared to studies conducted on Earth with laboratory technologies that mimic the space environment. To date, the molecular and physiological adaptations of the human body to this unnatural environment are very poor. The aim of this review is therefore to provide an overview of the most important findings on the molecular and physiological anomalies that develop during microgravity in short and long space flights.

Perioperative Right Ventricular Dysfunction and Abnormalities of the Tricuspid Valve Apparatus in Patients Undergoing Cardiac Surgery.

Right ventricular (RV) dysfunction frequently occurs after cardiac surgery and is linked to adverse postoperative outcomes, including mortality, reintubation, stroke, and prolonged ICU stays. While various criteria using echocardiography and hemodynamic parameters have been proposed, a consensus remains elusive. Distinctive RV anatomical features include its thin wall, which presents a triangular shape in a lateral view and a crescent shape in a cross-sectional view. Principal causes of RV dysfunction after cardiac surgery encompass ischemic reperfusion injury, prolonged ischemic time, choice of cardioplegia and its administration, cardiopulmonary bypass weaning characteristics, and preoperative risk factors. Post-left ventricular assist device (LVAD) implantation RV dysfunction is common but often transient, with a favorable prognosis upon resolution. There is an ongoing debate regarding the benefits of concomitant surgical repair of the RV in the presence of regurgitation. According to the literature, the gold standard techniques for assessing RV function are cardiac magnetic resonance imaging and hemodynamic assessment using thermodilution. Echocardiography is widely favored for perioperative RV function evaluation due to its accessibility, reproducibility, non-invasiveness, and cost-effectiveness. Although other techniques exist for RV function assessment, they are less common in clinical practice. Clinical management strategies focus on early detection and include intravenous drugs (inotropes and vasodilators), inhalation drugs (pulmonary vasodilators), ventilator strategies, volume management, and mechanical support. Bridging research gaps in this field is crucial to improving clinical outcomes associated with RV dysfunction in the near future.

Nosocomial Extracardiac Infections After Cardiac Surgery.

Purpose of Review: Nosocomial extracardiac infections after cardiac surgery are a major public health issue affecting 3-8.2% of patients within 30-60 days following the intervention. Recent Findings: Here, we have considered the most important postoperative infective complications that, in order of frequency, are pneumonia, surgical site infection, urinary tract infection, and bloodstream infection. The overall picture that emerges shows that they cause a greater perioperative morbidity and mortality with a longer hospitalization time and excess costs. Preventive interventions and corrective measures, diminishing the burden of nosocomial extracardiac infections, may reduce the global costs. A multidisciplinary team may assure a more appropriate management of nosocomial extracardiac infections leading to a reduction of hospitalization time and mortality rate. Summary: The main and most current data on epidemiology, prevention, microbiology, diagnosis, and management for each one of the most important postoperative infective complications are reported. The establishment of an antimicrobial stewardship in each hospital seems to be, at the moment, the more valid strategy to counteract the challenging problems.

Cosmic Radiations and the Cardiovascular System: A Narrative Review.

In recent times, space flights receive continued interest. Humankind's next two goals are to return to the Moon and, a few years later, to land on the surface of Mars. Although technology will improve enough to enable long voyages, there are still some unresolved questions about the effects of the space environment on human health, including the effects of such long voyages on organs. Specifically, there is no information on the effects of radiation in space on the human cardiovascular system. To better understand the adaptation of the cardiovascular system to radiation exposure, the physical properties of radiation and the cellular and molecular mechanisms underlying tissue changes are essential. To this end, this article aims to provide an overview of the effects of radiation on the cardiovascular system by analyzing the physical properties of radiation and their relationship to cellular and molecular mechanisms and potential changes. Each type of radiation triggers different responses in the cardiovascular system. Radiation plays a relevant role in altering endothelial function and arterial wall stiffness by inducing vascular changes that accelerate atherosclerosis and affect endothelial adhesiveness. Clinical studies have shown that vascular changes due to radiation depend on the delayed manifestations of early radiation damage. To reduce the effects of radiation in space, some pharmacological treatments that seem to be able to counteract oxidative stress during flight are being used. At the same time, new shielding systems that can reduce or eliminate radiation exposure must be developed. Future studies should aim to replicate flights in the deep space environment to study in more detail the harmful effects of radiation on the whole cardiovascular system.

Association between COVID-19 Diagnosis and Coronary Artery Thrombosis: A Narrative Review.

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 ß 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.

Patients with Bicuspid Aortopathy and Aortic Dilatation.

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

Inflammatory Response and Endothelial Dysfunction Following Cardiopulmonary Bypass: Pathophysiology and Pharmacological Targets.

BACKGROUND: Endothelial injury occurring during cardiopulmonary bypass is a major contributing factor in the development of organ dysfunction, which leads to many of the postoperative complications occurring during cardiac surgery. OBJECTIVE: This narrative review aims to summarize the main mechanisms of cardiopulmonary bypass - related disease, evaluating the unfavorable events leading to tissue injury, with a description of current pharmacologic and non-pharmacologic mechanisms to reduce CPB-related injury. METHODS: A Medline/Pubmed/Scopus search was conducted using clinical queries with the key terms "cardiac surgery", "cardiopulmonary bypass", "inflammation" and "endothelial injury", and related MeSH terms, until July 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the same key terms from https://patents.google.com/, www.uspto.gov, and www.freepatentsonline.com. RESULTS: In this review, we discuss the current knowledge of the mechanisms of vascular endothelial cell injury, the acute inflammatory response, and the regulatory factors that control the extent of vascular injury during extracorporeal circulation, summarizing the main target of anti-inflammatory pharmacologic and non-pharmacologic strategies. CONCLUSION: Inflammatory response and endothelial dysfunction following cardiopulmonary bypass are the prices to pay for the benefits offered during cardiac surgery procedures. Counteracting the detrimental effect of extracorporeal circulation appears to be crucial to improve clinical outcomes in pediatric and adult cardiac surgery. The intrinsic complexity and the tight interplay of the factors involved might require a holistic approach against inflammation and endothelial response.

Preoperative atorvastatin reduces bleeding and blood transfusions in patients undergoing elective isolated aortic valve replacement.

OBJECTIVES: Minimization of bleeding to reduce the use of blood products is of utmost importance in cardiac surgery. Statins are known for their pleiotropic effects beyond lipid-lowering properties, and the use of atorvastatin preoperatively is associated with reduced risk of bleeding and blood product use after coronary surgery. However, no studies have investigated if this beneficial effect also extends to aortic valve surgery. METHODS: In this retrospective cohort study, 1145 consecutive patients undergoing elective primary isolated aortic valve replacement meeting the inclusion and exclusion criteria were selected from January 2009 to December 2017 (547 in the atorvastatin group, 598 in the control group). Postoperative bleeding, blood product use, and complications were monitored during hospitalization. RESULTS: Postoperative bleeding was significantly lower in the atorvastatin group compared with the controls in the first 12 h after surgery (372 ± 137 vs 561 ± 219 ml; P = 0.001) and considering overall bleeding (678 ± 387 vs 981 ± 345 ml, P = 0.001). A total of 32.3% of controls and 26.3% of atorvastatin users received packed red blood cells (P = 0.027), and major surgical complications were similar between the groups. Postoperative length of stay was shorter in the atorvastatin group with an average reduction of 1 day of hospitalization (6.0 ± 1.4 vs 6.9 ± 2.1 days; P = 0.001). Postoperative bleeding among the atorvastatin-treated patients was significantly greater in those taking lower doses compared to those taking higher doses of atorvastatin with a 20% between-group difference (P = 0.001). CONCLUSIONS: Preoperative treatment with atorvastatin might reduce postoperative bleeding and transfusion of packed red blood cells in patients undergoing elective isolated aortic valve replacement. This result might translate into faster recovery after surgery and reduced hospitalization costs.

Preoperative atorvastatin reduces bleeding and blood products use in patients undergoing on-pump coronary artery bypass grafting.

AIMS: Statins are a widely recognized weapon in the primary and secondary prevention of coronary artery disease for their pleiotropic effects. However, recent reports from the cerebrovascular and pharmacological literature are insinuating concerns about a potential increase in the haemorrhagic risk among statin users.The effect of statins in postoperative bleeding should be carefully investigated in major cardiac surgery that exposes per se to risk of bleeding. METHODS: In this retrospective cohort study, we evaluated 441 patients who received atorvastatin until surgery and 213 patients who had never been treated with statins, undergoing elective primary isolated on-pump coronary artery bypass grafting. Postoperative bleedings, blood products use and complications were monitored during hospitalization. RESULTS: Preoperative and intraoperative variables were similar between groups. Early and overall postoperative bleedings were reduced among statin users, who had lower C-reactive protein values in the first postoperative day. Atorvastatin carries a strong protective effect against major bleedings, with a propensity score-adjusted odds ratio of 0.28 (P < 0.01). Also, blood products use for statin-treated patients was lower compared with controls, with fewer transfused patients and fewer red-packed cells units per transfused patient. CONCLUSION: Preoperative atorvastatin use is associated with reduced risk of bleeding and blood products use after coronary artery bypass grafting, likely due to a reduction in the postoperative inflammatory response. Statin continuation at the highest tolerable dose should be encouraged before cardiac surgery. The preoperative use of statins in cardiac surgery as 'bleeding-preventers' might have profound clinical implications.