Virulence of beta-hemolytic streptococci in infective endocarditis.

BACKGROUND: Streptococci involved in infective endocarditis (IE) primarily comprise alpha- or non-hemolytic streptococci (ANHS). Moreover, beta-hemolytic streptococci (BHS) can be involved, and guidelines recommend the addition of gentamicin for the first 2 weeks of treatment and the consideration of early surgery in such cases. This study compared the morbidity and mortality associated with IE depending on the microorganisms involved (BHS, ANHS, staphylococci, and enterococci). METHODS: We conducted a retrospective observational study between 2012 and 2017 in a single hospital in France. The endpoints were overall in-hospital mortality, 1-year mortality and the occurrence of complications. RESULTS: We analyzed 316 episodes of definite IE including 150 (38%), 96 (25%), 46 (12%), and 24 cases (6%) of staphylococcal, ANHS, enterococcal, and BHS IE, respectively. In-hospital mortality was significantly higher in the staphylococcal (n = 40; 26.7%) and BHS groups (n = 6; 25.0%) than in the ANHS (n = 9; 9.4%) and enterococcal groups (n = 5; 10.9%) (all p < 0.01). The rates of septic shock and cerebral emboli were also higher in the BHS group than in the ANHS group [n = 7 (29.2%) vs. n = 3 (3.1%), p < 0.001; n = 7 (29.2%) vs. n = 12 (12.5%); p = 0.05, respectively]. CONCLUSION: This study confirmed that BHS IE has a more severe prognosis than ANHS IE. The virulence of BHS may be similar to that of staphylococci, justifying increased monitoring of these patients and more 'aggressive' treatments such as early surgery.

Serotonin contribution to cardiac valve degeneration: new insights for novel therapies?

Heart valve disease (HVD) is a complex entity made by different pathological processes that ultimately lead to the abnormal structure and disorganization of extracellular matrix proteins resulting to dysfunction of the leaflets. At its final evolutionary step, treatments are limited to the percutaneous or surgical valve replacement, whatever the original cause of the degeneration. Understanding early molecular mechanisms that regulate valve interstitial cells remodeling and disease progression is challenging and could pave the way for future drugs aiming to prevent and/or reverse the process. Some valve degenerative processes such as the carcinoid heart disease, drug-induced valvulopathy and degenerative mitral valve disease in small-breed dogs are clearly linked to serotonin. The carcinoid heart is typically characterized by a right-sided valve dysfunction, observed in patients with carcinoid tumors developed from serotonin-producing gut enterochromaffin cells. Fenfluramine or ergot derivatives were linked to mitral and aortic valve dysfunction and share in common the pharmacological property of being 5-HT2B receptor agonists. Finally, some small-breed dogs, such as the Cavalier King Charles Spaniel are highly prone to degenerative mitral valve disease with a prevalence of 40% at 4 years-old, 70% at 7 years-old and 100% in 10-year-old animals. This degeneration has been linked to high serum serotonin, 5-HT2B receptor overexpression and SERT downregulation. Through the comprehension of serotonergic mechanisms involved into these specific situations, new therapeutic approaches could be extended to HVD in general. More recently, a serotonin dependent/ receptor independent mechanism has been suggested in congenital mitral valve prolapse through the filamin-A serotonylation. This review summarizes clinical and molecular mechanisms linking the serotonergic system and heart valve disease, opening the way for future pharmacological research in the field.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Concomitant repair of tetralogy of Fallot and an aortic root aneurysm in an adult.

We reported the case of a 56-year-old male with tetralogy of Fallot associated with an aneurysm of the aortic root and severe aortic insufficiency. Repair of the aortic aneurysm along with a complete tetralogy repair was performed.

Left ventricular rupture after embolic myocardial infarction due to mitral valve endocarditis.

We report a very rare case of a 43-year-old patient with fatal left ventricular subepicardial aneurysm rupture complicating embolic myocardial infarction due to mitral valve infective endocarditis.

Early chest tube removal on the 1st postoperative day protocol of an enhanced recovery after cardiac surgery programme is safe.

OBJECTIVES: The aim of this study was to assess the safety of early chest tube removal (CTR) protocol on the 1st postoperative day (POD1) of our Enhanced Recovery After Surgery (ERAS) programme by comparing the risk of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality. METHODS: All consecutive patients undergoing elective coronary revascularization and/or valve surgery between 2015 and 2021 were assessed in terms of their perioperative management pathways: conventional standard of care (control group) versus standardized systematic perioperative ERAS programme including an early CTR on POD1 (ERAS group). A propensity score matching was applied. The primary end-point was a composite of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality. RESULTS: A total of 3153 patients were included. Propensity score analysis resulted in 2 groups well-matched pairs of 1026 patients. CTR on POD1 was significantly increased from 29.5% in the control group to 70.3% in the ERAS group (P < 0.001). The incidence of the primary end-point was 6.4% in the control group and 6.9% in the ERAS group (P = 0.658). Patients in the ERAS group, as compared with control group, had significant lower incidence of bronchopneumonia (9.0% vs 13.5%; P = 0.001) and higher incidence of mechanical ventilation ≤6 h (84.6% vs 65.2%; P < 0.001), length of intensive care unit ≤1 day (61.2% vs 50.8%; P < 0.001) and hospital ≤6 days (67.3% vs.43.2%; P < 0.001). CONCLUSIONS: CTR on POD1 protocol can be safely incorporated into a standardized systematic ERAS programme, enabling early mobilization, and contributing to the improvement of postoperative outcomes. CLINICAL TRIAL REGISTRATION NUMBER: Ethics committee of the French Society of Thoracic and Cardio-Vascular Surgery (CERC-SFCTCV-2022-09-13_23140).

Infectious Mediastinitis: A Retrospective Cohort Study.

Background: This study aimed to characterize the demographics, microbiology, management and treatment outcomes of mediastinitis according to the origin of the infection. Methods: This retrospective observational study enrolled patients who had mediastinitis diagnosed according to the criteria defined by the Centers for Disease Control and Prevention and were treated in Strasbourg University Hospital, France, between 1 January 2010 and 31 December 2020. Results: We investigated 151 cases, including 63 cases of poststernotomy mediastinitis (PSM), 60 cases of mediastinitis due to esophageal perforation (MEP) and 17 cases of descending necrotizing mediastinitis (DNM). The mean patient age (standard deviation) was 63 (14.5) years, and 109 of 151 patients were male. Microbiological documentation varied according to the origin of the infection. When documented, PSM cases were mostly monomicrobial (36 of 53 cases [67.9%]) and involved staphylococci (36 of 53 [67.9%]), whereas MEP and DNM cases were mostly plurimicrobial (38 of 48 [79.2%] and 8 of 12 [66.7%], respectively) and involved digestive or oral flora microorganisms, respectively. The median duration of anti-infective treatment was 41 days (interquartile range, 21-56 days), and 122 of 151 patients (80.8%) benefited from early surgical management. The overall 1-year survival rate was estimated to be 64.8% (95% confidence interval, 56.6%-74.3%), but varied from 80.1% for DNM to 61.5% for MEP. Conclusions: Mediastinitis represents a rare yet deadly infection. The present cohort study exhibited the different patterns observed according to the origin of the infection. Greater insight and knowledge on these differences may help guide the management of these complex infections, especially with respect to empirical anti-infective treatments.

Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.

An enhanced recovery programme significantly improves postoperative outcomes after surgical aortic valve replacement.

OBJECTIVES: Evidence regarding the benefits of an enhanced recovery after cardiac surgery (ERACS) programme is lacking. The aim of this study was to analyse the impact of a systematic standardized ERACS programme for patients undergoing isolated elective surgical aortic valve replacement (SAVR) for aortic stenosis in terms of hospital mortality and morbidity, patient blood management and length of stay. METHODS: Patients undergoing isolated elective SAVR for aortic stenosis between 2015 and 2020 were identified from our database (n = 941). The standardized systematic ERACS programme was implemented in November 2018. Propensity score matching indicated that 259 patients would receive standard perioperative care (control group) and 259 patients would receive the ERACS programme (ERACS group). The primary outcome was hospital mortality. The secondary outcomes were hospital morbidity, patient blood management and length of stay. RESULTS: Both groups had similar hospital mortality rates (0.4%). The ERACS group had a significantly lower troponin I peak level (P < 0.001), a larger proportion of improved perioperative left ventricular ejection fractions (P = 0.001), a lower incidence of bronchopneumonia (P = 0.030), a larger proportion of patients with mechanical ventilation <6 h (P < 0.001), a lower incidence of delirium (P = 0.028) and less acute renal failure (P = 0.013). The ERACS group had a significantly lower rate of red blood cell transfusions (P = 0.002). The intensive care unit stay was significantly shorter in the ERACS group than in the control group (P = 0.039). CONCLUSIONS: The standardized systematic ERACS programme significantly improved postoperative outcomes and should become the reference for the perioperative care pathway for patients undergoing SAVR.

Enhanced recovery after surgery program for patients undergoing isolated elective coronary artery bypass surgery improves postoperative outcomes.

OBJECTIVE: To evaluate the effect of a perioperative systematic standardized enhanced recovery after surgery (ERAS) program for patients undergoing isolated elective coronary artery bypass grafting (CABG) in terms of mortality, hospital morbidities, and length of stay. METHODS: From January 2015 to September 2020, 1101 patients underwent isolated elective CABG. Our standardized systematic ERAS program was implemented in November 2018. Propensity score matching resulted in well-matched pairs of 362 patients receiving standard perioperative care (control group) and 362 patients on the ERAS program (ERAS group). There were no significant intergroup differences in preoperative and operative data except for the normothermia rate, which was significantly greater in the ERAS group (P < .001). The primary outcome was 3-year mortality. The secondary outcomes were hospital morbidities and length of stay. RESULTS: In-hospital and 3-year mortality did not differ between the 2 groups. The ERAS program was associated with a significant relative risk decrease in mechanical ventilation duration (-53.1%, P = .003), length of intensive care unit stay (-28.0%, P = .015), length of hospital stay (-10.5%, P = .046), bronchopneumonia (-51.5%, P < .001), acute respiratory distress syndrome (-50.8%, P = .050), postoperative delirium (-65.4%, P = .011), moderate-to-severe acute kidney injury (-72.0%, P = .009), 24-hour chest tube output (-26.4%, P < .001), and overall red blood cell transfusion rate (-32.4%, P = .005) compared with the control group. CONCLUSIONS: A systematic standardized ERAS program for low-risk patients undergoing isolated elective CABG was associated with a significant improvement in postoperative outcomes, reduction in red blood cell transfusion, shorter lengths of intensive care unit and hospital stays, and comparable long-term mortality.

Remote and local ischemic postconditioning further impaired skeletal muscle mitochondrial function after ischemia-reperfusion.

OBJECTIVE: Muscular injuries contribute to perioperative and long-term morbidity after vascular surgery in humans. We determined whether local and remote ischemic postconditioning might similarly decrease muscle mitochondrial dysfunction through reduced oxidative stress. METHODS: Eighteen male Black-6 mice were divided in three groups: (1) sham mice had no ischemia (sham), (2) ischemia-reperfusion (IR) mice underwent 2-hour tourniquet-induced ischemia on both hind limbs, followed by 2-hour reperfusion, and (3) postconditioning (PoC) mice underwent four bouts of 30-second reperfusion and 30-second ischemia at the onset of reperfusion on the right limb; thus, the right limb underwent local PoC and left limb underwent remote PoC (rPoC). Maximal oxidative capacity (V(max)) of the gastrocnemius muscle mitochondrial respiratory chain was measured. Oxidative stress was evaluated by dihydroethidium staining. Expressions of genes involved in antioxidant defense (superoxide dismutase [SOD1], SOD2, glutathione peroxidase [GPx]), apoptosis (Bax, BclII), and inflammation (interleukin-6) were determined by quantitative real-time polymerase chain reaction. Muscle inflammation was determined using immunohistochemistry. RESULTS: IR reduced V(max) (8.5 ± 2.2 vs 10.2 ± 1.8 µmol O(2)/min/g dry weight; P = .034), and increased dihydroethidium staining (134.8%; P = .039). IR decreased GPx expression (-47.9%; P = .048) and increased the proapoptotic marker Bax (255.5%; P = .020). Local PoC and rPoC further increased these deleterious effects. PoC decreased V(max) to 4.4 ± 1.4 µmol O(2)/min/g dry weight (sham vs PoC, -56.9% [P < .001]; IR vs PoC, -48.2% [P < .001]). rPoC similarly reduced V(max) to 5.1 ± 1.9 µmol O(2)/min/g dry weight (sham vs PoC, -50.0% [P < .001]; IR vs PoC, -40.0% [P = .001]). Dihydroethidium staining was further increased by PoC (207.2%; P = .002) and rPoC (305.4%; P < .001) compared with sham and was associated with macrophage infiltration. Local PoC increased SOD1, SOD2, and the antiapoptotic Bcl-2, and rPoC increased Bax (391.6%; P < .001) and the Bax/BclII ratio (621.7%; P < .001). CONCLUSIONS: Local and remote ischemic postconditioning further increased injury by enhancing mitochondrial dysfunction, oxidative stress production, and inflammation. Caution should be applied when considering ischemic postconditioning in vascular surgery.

A 2-Stage Surgical Approach for Adrenocortical Carcinoma With Intracardiac Extension.

Direct intracardiac extension of abdominal malignant diseases represents a rare but challenging situation. Removal of the intracardiac extension requires cardiopulmonary bypass with systemic anticoagulation, which could potentially increase the risk of bleeding if it is associated with liver resection. This report describes a 2-stage surgical approach for malignant disease with intracardiac extension in a high-risk patient. Atrial thrombectomy was performed first, followed by right portal vein embolization. Four months after the cardiac surgical procedure, the patient underwent right hepatectomy extended to segment 1, the right adrenal gland, and the retrohepatic inferior vena cava under venovenous bypass. The advantages and drawbacks of this approach are discussed.

Peripheral Blood Mononuclear Cells Mitochondrial Respiration and Superoxide Anion after Heart Transplantation.

INTRODUCTION: The mitochondrial function of circulating peripheral blood mononuclear cells (PBMCs) is an interesting new approach to cardiac diseases. Thus, PBMC's mitochondrial respiration decreases in relation to heart failure severity. However, no data are available on heart-transplanted patients (Htx). POPULATION AND METHODS: We determined PBMCs mitochondrial respiration by high-resolution respirometry (Oroboros Instruments) and superoxide anion production using electron paramagnetic resonance (Bruker-Biospin) in 20 healthy subjects and 20 matched Htx and investigated clinical, biological, echocardiographic, coronarography and biopsy characteristics. RESULTS: PBMCs mitochondrial respiratory chain complex II respiration was decreased in Htx (4.69 ± 0.84 vs. 7.69 ± 1.00 pmol/s/million cell in controls and Htx patients, respectively; p = 0.007) and complex IV respiration was increased (24.58 ± 2.57 vs. 15.68 ± 1.67 pmol/s/million cell; p = 0.0035). Superoxide anion production was also increased in Htx (1.47 ± 0.10 vs. 1.15 ± 0.10 µmol/min; p = 0.041). The leucocyte-to-lymphocyte ratio was increased in Htx, whom complex II correlated with leucocyte number (r = 0.51, p = 0.02) and with the left ventricular posterior wall peak early diastolic myocardial velocity (r = -0.62, p = 0.005). Complex IV was increased in the two patients with acute rejection and correlated negatively with Htx's isovolumetric relation time (r = -0.45, p = 0.045). DISCUSSION: Although presenting with normal systolic function, Htx demonstrated abnormal PBMC's mitochondrial respiration. Unlike immunosuppressive therapies, subclinical diastolic dysfunction might be involved in these changes. Additionally, lymphopenia might reduce complex II, and acute rejection enhances complex IV respirations. CONCLUSION: PBMC's mitochondrial respiration appears modified in Htx, potentially linked to cellular shift, mild diastolic dysfunction and/or acute rejection.

Minimally invasive surgery for left ventricular assist device implantation is safe and associated with a decreased risk of right ventricular failure.

BACKGROUND: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with significant mortality and morbidity. The objective of this study was to determine pre- and postoperative risk factors associated with the occurrence of RVF after LVAD implantation. METHODS: This retrospective study included 68 patients who received LVADs between 2010 and 2018 either for bridge to transplant (40 patients, 58.8%) or bridge to destination therapy (28 patients, 41.2%). RVF after LVAD implantation was defined according to the INTERMACS classification. The primary endpoint was the occurrence of RVF. The secondary endpoints were hospital mortality and morbidity and long-term survival. RESULTS: The majority of patients (61.8%) had an INTERMACS profile 1 (36.8%) or 2 (25.0%). The LVAD was implanted either by sternotomy (37 patients, 54.4%) or thoracotomy (31 patients, 45.6%). RVF after LVAD implantation was observed in 32 patients (47.1%). In univariate analysis, an elevated serum glutamic oxaloacetic transaminase (SGOT) (P=0.028) and a high preoperative vasoactive inotropic score (VIS) (P=0.028) were significantly associated with an increased risk of RVF, whereas the implantation of LVAD through a thoracotomy approach was associated with a significant reduction in this risk (P=0.006). The multivariate analysis demonstrated that only the thoracotomy approach was significantly associated with decreased risk of RVF (odds ratio =0.33, 95% confidence interval: 0.17-0.96; P=0.042). Hospital mortality was 53.1% and 5.6% in the RVF and control groups, respectively (P<0.0001). The incidence of stroke and postoperative acute renal failure were significantly increased in the RVF group compared with the control group. The survival after LVAD implantation was 33.5%±9.0% and 85.4%±6.0% at 1 year in the RVF and control groups, respectively (P<0.0001). CONCLUSIONS: LVAD implantation by thoracotomy significantly reduced the risk of postoperative RVF. This surgical approach should, therefore, be favored.

Left ventricular assist device-associated infections: incidence and risk factors.

BACKGROUND: Left ventricular assist device (LVAD)-associated infections are major complications that can lead to critical outcomes. The aims of this study were to assess the incidence of and to determine the risk factors for LVAD-associated infections. METHODS: We included all consecutive patients undergoing LVAD implantation between January 1, 2010, and January 1, 2019, in a single institution. Infection-related data were retrospectively collected by review of patient's medical files. LVAD-associated infections were classified into three categories: percutaneous driveline infections, pocket infections and pump and/or cannula infections. RESULTS: We enrolled 72 patients. Twenty-one (29.2%) patients presented a total of 32 LVAD-associated infections. Eight (38.1%) patients had more than one infection. Five (62.5%) pocket infections and one (50.0%) pump and/or cannula infection were preceded by a driveline infection. The median delay between the operation and LVAD-associated infection was 6.5 (1.4-12.4) months. The probability of having a LVAD-associated infection at one year after receiving an implant was 26.6% (95% CI: 17.5-40.5%). Percutaneous driveline infections represented 68.7% of all LVAD-associated infections. Staphylococcus aureus and coagulase-negative staphylococci were the predominant bacteria in LVAD-associated infections (53.1% and 15.6%, respectively). Hospital length of stay (sdHR =1.22 per 10 days; P=0.001) and postoperative hemodialysis (sdHR =0.17; P=0.004) were statistically associated with infection. Colonization with multidrug-resistant bacteria was more frequent in patients with LVAD-associated infections than in others patients (42.9% vs. 15.7%; P=0.013). CONCLUSIONS: LVAD-associated infections remain an important complication and are mostly represented by percutaneous driveline infections. Gram-positive cocci are the main pathogens isolated in microbiological samples. Patients with LVAD-associated infections are more frequently colonized with multidrug-resistant bacteria.

Lower circulating Sta-Liatest D-Di levels in patients with aortic intramural hematoma compared with classical aortic dissection.

OBJECTIVE: To compare the diagnostic value of circulating Sta-Liatest D-Di levels in classic acute aortic dissection (AAD) and in aortic intramural hematoma (AIH), a variant of AAD without a patent false lumen. DESIGN: Single-center retrospective case-control study. SETTING: University Hospital of Strasbourg, France. PATIENTS: Ninety-four consecutive patients with both confirmed AAD and d-dimer measurements at entry were included. d-dimer levels were assayed by the immunoturbidimetric method Sta-Liatest D-Di (Diagnostica Stago, Asnieres sur Seine, France). INTERVENTION: Patient characteristics and clinical evolution were analyzed. MEASUREMENTS AND MAIN RESULTS: Eighty-four patients (89%) presented a classic AAD with patent false lumen and ten (11%) presented an AIH. Clinical presentation did not differ between the two groups. The mortality rate was 0% in AIH and 26% in classic AAD. d-dimer levels were significantly lower in patients with AIH (median, 1230 ng/mL; interquartile range, 685-2645 ng/mL) than in patients with AAD with patent false lumen (median value, 9290 ng/mL; interquartile range, 3890-20,000 ng/mL; p = 0.008). All patients with AAD and patent false lumen had d-dimer levels above the threshold of 400 ng/mL (sensitivity 100%). However, one patient with AIH presented d-dimer levels below the threshold. Therefore, the sensitivity of the d-dimer test in detecting AIH was 90%. CONCLUSIONS: Sta-Liatest D-Di levels are lower in AIH than in AAD with patent false lumen. This test can quite possibly be negative in the case of intramural hematoma. This feature must be considered when interpreting d-dimer levels in patients with acute aortic syndrome.

EPA:DHA 6:1 is a superior omega-3 PUFAs formulation attenuating platelets-induced contractile responses in porcine coronary and human internal mammary artery by targeting the serotonin pathway via an increased endothelial formation of nitric oxide.

At arterial sites of endothelial denudation and dysfunction, activated platelets contribute to vascular injury through the release of potent contracting factors such as serotonin (5-HT). This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs), known to protect the vascular system, are able to prevent platelets-induced contractile responses in isolated arteries and, if so, to investigate the underlying mechanism and the importance of the omega-3 PUFAs formulation. Porcine coronary arteries (PCA), human internal mammary arteries (IMA) and washed human platelets were prepared and vascular reactivity was studied in organ chambers. In PCA rings, aggregating platelets caused concentration-dependent contractions that were significantly inhibited by the 5-HT2A receptor antagonist ketanserin, and by EPA:DHA 6:1 but not EPA:DHA 1:1 at 0.4% v/v. EPA:DHA 6:1 also prevented the 5-HT-induced contractions but affected only slightly those to the thromboxane A2 analogue U46619. The inhibitory effect of EPA:DHA 6:1 on platelets-induced contractions was not observed in rings without endothelium, and prevented by an eNOS inhibitor but not by inhibitors of endothelium-dependent hyperpolarization. In IMA rings, EPA:DHA 6:1 but not EPA:DHA 1:1 at 0.4% v/v significantly prevented the 5-HT-induced contraction, and induced greater endothelium-dependent relaxations than bradykinin and acetylcholine sensitive to an eNOS inhibitor. EPA:DHA 6:1 strongly inhibits platelets- and 5-HT-induced contractions in PCA rings and those to 5-HT in IMA rings most likely through an increased endothelial formation of NO. These findings suggest that the omega-3 PUFAs EPA:DHA 6:1 formulation may be of interest to prevent platelets-induced vascular injury at arterial sites of endothelial dysfunction.

Atrial Fibrillation Progression Is Associated with Cell Senescence Burden as Determined by p53 and p16 Expression.

BACKGROUND: Whilst the link between aging and thrombogenicity in atrial fibrillation (AF) is well established, the cellular underlying mechanisms are unknown. In AF, the role of senescence in tissue remodeling and prothrombotic state remains unclear. AIMS: We investigated the link between AF and senescence by comparing the expression of senescence markers (p53 and p16), with prothrombotic and inflammatory proteins in right atrial appendages from patients in AF and sinus rhythm (SR). METHODS: The right atrial appendages of 147 patients undergoing open-heart surgery were harvested. Twenty-one non-valvular AF patients, including paroxysmal (PAF) or permanent AF (PmAF), were matched with 21 SR patients according to CHA2DS2-VASc score and treatment. Protein expression was assessed by tissue lysates Western blot analysis. RESULTS: The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, p = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, p = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, p = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, p = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. Conclusions: The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.

Impact of Setting up an "Endocarditis Team" on the Management of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) remains a severe disease with a high mortality rate. Therefore, guidelines encourage the setup of a multidisciplinary group in reference centers. The present study evaluated the impact of this "Endocarditis Team" (ET). METHODS: We conducted a monocentric observational study at Strasbourg University Hospital, Strasbourg, France, between 2012 and 2017. The primary end point was in-hospital mortality. Secondary end points were 6-month and 1-year mortality, surgery rate, time to surgical procedure, duration of effective antibiotic therapy, length of in-hospital stay, and sequelae. We also assessed predictors of in-hospital mortality. RESULTS: We analyzed 391 episodes of IE. In the post-ET period, there was a nonsignificant decrease in in-hospital mortality (20.3% vs 14.7%, respectively; P = .27) and sequelae, along with a significant reduction in time to surgery (16.4 vs 10.3 days, respectively; P = .049), duration of antibiotic therapy (55.2 vs 47.2 days, respectively; P < .001), and length of in-hospital stay (40.6 vs 31.9 days, respectively; P < .01). In a multivariate analysis, the post-ET period was positively associated with survival (odds ratio, 0.45; 95% confidence interval, 0.20-0.96; P = .048). CONCLUSIONS: This multidisciplinary approach exerted a positive impact on the management of IE and should be considered in all hospitals managing IE.

Twenty-seven-year experience with composite valve graft replacement of the aortic root.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess early and late outcome in patients undergoing composite valve graft replacement (CVGR) of the aortic root by means of the Bentall procedure, and to identify predictors of early and late death associated with this surgical approach. METHODS: Between August 1975 and July 2002, 162 consecutive patients underwent a Bentall procedure for CVGR. Demographic, treatment and clinical outcome data from these patients were gathered, reviewed, and analyzed. Potential predictors of early and late mortality were analyzed. RESULTS: The study population was predominantly male (n = 132; 81.5%) and middle-aged (mean age 51.3 +/- 15.8 years; range: 10-79 years). The main indications for surgery were annuloaortic ectasia (n = 75; 46.3%), aortic dissection (n = 44; 27.2%) and Marfan syndrome (n = 34; 21%). Reoperation was required in 37 cases (22.8%). The mean follow up was 74 months. Early (in-hospital) mortality was 1.9% (n = 3). The only independent determinant of early mortality was cardiopulmonary bypass time (p = 0.025). Late mortality was 27.7% (n = 44). On multivariate analysis, the only independent risk factors for late mortality were age >60 years (p = 0.044) and left ventricular ejection fraction <50% (p = 0.037). Actuarial survival rates were 92.9%, 77%, 56.2%, and 47.1% at one, five, 10, and 15 years, respectively. Rates of freedom from reoperation on the aortic root and ascending aorta were 90.6% and 72.5% at five and 15 years, respectively. No false aneurysms were observed at any coronary reimplantation sites. CONCLUSION: In this series, the Bentall procedure was associated with low operative mortality and good early and late results. This suggests that the procedure may be considered as a reference to other operations on the aortic root, at least in adult patients.